PICTURE this scenario: A terrorist carefully negotiates city streets, moving ever closer to his target, an air force base on the outskirts of town. In the rear of his van, a homemade bomb—containing plutonium and high explosives—waits for the signal to explode. As one of the "good guys," you've received information that the attack is imminent, but your sources don't know its timing, the direction from which the vehicle will come, or what route it will take. What can you do to detect, identify, and track the van and its contents so that you can prevent the attack? At Lawrence Livermore, researchers in the Nonproliferation, Arms Control, and International Security (NAI) Directorate have been exploring responses to this threat and others like it.
The researchers are focusing on systems for detecting and tracking threats. The systems go by many names—correlated sensor networks, wide-area tracking systems, sensor or network fabrics—but the concept behind them is the same. Take a number of wireless sensors (for instance, seismic, magnetic, pressure, acoustic, nuclear, or particle-counting), tie them together with a communications network, develop a scheme for fusing the data (that is, converting the data into forms easily interpreted by users), and make the system easy to deploy.
Such correlated sensor networks can help detect a nuclear terrorist attack, track the movement and characteristics of a wildfire, assist military operations in taking out a target, determine earthquake damage to large structures such as bridges, and even protect the president.
Most of today's wireless sensors are big and heavy. They have large power requirements and limited intelligence. Thus, large networks of such sensors are impractical. In the Nonproliferation, Arms Control, and International Security (NAI) Directorate, researchers are working to create sensors that use less energy, are more intelligent, and scale better to large networks.
The energy issue, notes engineer Rob Hills, is a big concern for sensors that are networked. "We have a saying that power is everything," he explains. "Power requirements make a network feasible—or not." For instance, the Joint Biological Remote Early Warning System (JBREWS) prototype network used 132 commercial sensors, each requiring two batteries (one in the sensor, one in the charger) to operate continuously, for a grand total of nine tons of batteries. To address this problem, the Laboratory developed a communication system that requires an average power of only 1 watt. "And we're pushing the power requirement down from there," says Hills.
In a back-to-basics project, Laboratory engineer Dave Harris is researching the underlying physics that is key to creating microsensors for seismic networks. "I believe that Dave's work—along with our data-fusion techniques—will allow us to create cheap and small sensors, which can be delivered from a remote platform such as unmanned aerial vehicles," says Hills. Harris has been been working with engineer Bruce Henderer, who has developed a prototype sensor about 3 centimeters thick and 6 centimeters square— small enough to hold in the palm of your hand—and containing a low-power communications device that allows the sensors to network and to configure themselves. "In other words," says Hills, "once laid down, the sensors would talk to each other and, by determining their neighbors, build a network and paths back to control." The data processing would take place out in the network, with the network sensors themselves being capable of pattern recognition, information fusion, and decision making.
The prototype sensor being developed at Livermore.
One solution is to network the sensors, that is, have them share the information they gather. "Networked sensors allow the user to 'see' more by creating a more complete picture of the situation, something that stand-alone sensors cannot do," says Niemeyer. For this article's opening scenario, for instance, a correlated sensor network could do double duty. First, it could provide a way to discard signals that are false alarms. Second, it could pick up on signals that might be real alarms but would have been ignored by stand-alone sensors because the signals were under a preset threshold of sensitivity.
The figure below shows how correlated network and stand-alone systems differ. In the figure, the truck carries a device that emits signals averaging 50 counts per second; signals in the natural background are on average 300 counts per second. Three stand-alone sensors are set to register detections, or hits, of 350 or more counts, which would reduce false alarms caused by background variations.
The truck passes the first sensor, which detects 355 counts—a possible hit. It goes on its route and the stand-alone sensors detect five other instances of over 350-count signals. The detections provide no information to the person at the central command post as to whether they are real alarms or not.
In the correlated sensor case, the 355-count signal at sensor one is noted as a possible hit. This information is shared with sensor two, and then the system clock starts to track travel time. The travel time between sensors one and three is assumed to be about 5 minutes. Sensor two is on the alert for signals above background that appear within a certain window of time centered on a predetermined time mark, say, 2.5 minutes. The closer a signal is detected to that 2.5-minute mark, the more weight is given to the probability that the signal is from a real source, rather than some random hiccup from background.
The ensuing signals at sensors one and three are discounted as false alarms because they are uncorrelated, that is, they show no relation to previously recorded data. If the truck is proceeding forward, it would not register at sensor one, which it just passed, and the signal at sensor three comes much too soon. However, the 340 counts detected at sensor two, even though a trifle low, is viewed as a possible hit because it falls within the allotted window of time and is considerably higher than background. This information is passed along to sensor three.
Three signals follow and are discounted as false alarms because of their location and timing. However, the 348-count signal at sensor three is recorded and its probability of being real is calculated and correlated with the preceding hits.
Performing these kinds of calculations for three networked sensors is one thing, but widen a network to include 100 sensors and it becomes extraordinarily challenging. The computer algorithms needed to track and follow more than one likely pattern and calculate all of the probabilities are extremely complex (see box below) and are only now possible with the increases in computing power.
This illustration shows the different results produced by stand-alone sensors versus a correlated sensor network. Here, the sensors are set to register signals of 350 or more counts per second from a truck carrying a signal-emitting device. The stand-alone sensor system simply detects six instances of over-350 signal counts (blue boxes). The networked system, having access to more information, correlates the information to discount all but the first detection as false alarms and to register two others that are under the 350-count threshold as likely "hits," which are then correlated to the first hit.
Livermore researchers have been working on many applications of correlated sensor networks. For instance, the Laboratory has developed a prototype correlated sensor network for detecting and tracking a ground-delivered nuclear material. The Wide-Area Tracking System (WATS) is a network of gamma and neutron detectors and communications links, with information continuously evaluated by Laboratory-developed data-fusion algorithms. The sensors can be permanently deployed at chosen locations or mounted in vans for deployment on demand to protect specific areas for specific situations or events.
The individual sensors share their data with neighboring sensors, process the data, integrate and combine them with other available information (for example, data gathered previously; observed radiation signatures, spectra, and backgrounds; road maps), and finally determine the probability that the signal comes from a real source—all while the system is in the field. In this way, a WATS sensor network can drastically reduce false alarms and detect the entry of a nuclear device or radioactive material into the protected area and track its movement.
The analysis could be performed by a centralized computer at, say, command headquarters, but researchers have found that communications limitations—latencies, available bandwidth, and so on—can be a significant bottleneck for these types of networks. When data are processed in the field, it is necessary to send only bits of information between neighbors, with the final result going to the human user. This type of operation makes the network much more scalable.
Another example of correlated sensor network development involves a recently concluded project called Joint Biological Remote Early Warning System (JBREWS). For JBREWS, the Laboratory was responsible for developing the command, control, communications, computers, and intelligence systems for a network of biodetectors that could provide U.S. field troops with early warning of a biological attack. Although the project is not continuing, it has allowed the Laboratory to make important progress in developing data-fusion solutions that could be applied to any type of correlated sensor network. The communications paradigms that were developed in JBREWS let Laboratory researchers take a big step toward solving one part of the data-fusion problem—that is, how to quickly and automatically establish a communications fabric for data fusion to work within.
In this communications scheme, the array of sensors forms an automatically reconfiguring, or self-healing, network, as follows. Once the sensors are in place, they communicate with each other via radio frequencies so each sensor can map where its neighboring sensors are. The sensors then radio-test each other and develop an efficient communications path back to the central command post. If, for example, one sensor can't communicate directly with the command post on the other side of a hill, it passes its data to its neighbors, to be relayed with the neighbors' data to other units, and so on, until the information reaches its destination. If a unit is knocked out by a malfunction or hostile action, its communication relay functions are picked up by surrounding units and a secondary path is formed. In short, the system quickly recognizes and adjusts to the absence of any sensor units. A big plus for this type of network and others like it, Hills notes, is that there are no single-point failures.
Yet another application for such networks is in tactical engagement systems. With sensor networks as part of these systems, a soldier would never be alone in the field. The sensor network could supply information not just to people in the field, but to those who are out of harm's way as well. They would all be tied together in a collaborative environment. With such a system, the electronic network would be displayed in a chest-top system so that a soldier could "see" the environment and watch his back—all from one small device.
Correlated sensor networks could also be used in nonmilitary applications to provide temporary communication infrastructures after a destructive earthquake or to provide information during large firestorms. For example, there are microclimates within a large fire. A correlated sensor network could track temperatures, humidity, and wind in three dimensions, providing valuable information to firefighters.
David McCallen, director for Livermore's Engineering Center for Complex Distributed Systems, notes that current research to develop self-healing, self-configuring networks of seismic sensors would be useful in studying how large structures respond in earthquakes. "Once these networks are developed, it's a small step to apply them to large structures, such as bridges, to gather data on how these structures vibrate and respond under various circumstances," he explains. "When you consider that to densely instrument a structure like the Golden Gate Bridge takes hundreds of sensors, having a system that's wireless and self-configuring is very attractive." He adds that the California Department of Transportation is also interested in using such networks to monitor steep hillsides for possible landslides.
While developing the computer algorithms to perform distributed decision making for a sensor network, a team of researchers, including physicist Chris Cunningham, came up with an approach based on Bayesian algorithms. As Cunningham explains it, the Bayesian approach has a couple of pluses. First, it is energy-efficient because communication only occurs when there is a sufficient probability that a target has been detected. Second, each sensor independently extracts features from its raw sensor signals, compares these features with the targets, calculates the likelihood of detection, fuses the likelihoods received from neighboring nodes, and communicates only the new likelihoods to its neighboring nodes. This statistical data fusion can allow each sensor platform to make decisions based on the total information in the network, while reducing the volume of communications among sensors.
addresses the question, "Given that an event has occurred that may have been the result of any of two or more causes, what is the probability that the event was the result of a particular cause?" The answer lies not in an absolute yes or no, but in the set of probabilities that the various causes are at play. Bayesian methods allow scientists to combine prior information about a population parameter with information contained in a sample to guide a statistical inference process. A prior probability distribution for a parameter of interest is specified first. Sample information is then obtained and combined through an application of Bayes's theorem to confirm the prior assumptions. Bayesian methods are used extensively in statistical decision theory.
Livermore's Wide-Area Tracking System (WATS) is one example of a correlated sensor network that uses algorithms based on Bayesian constructs. In WATS, each sensor computes and exchanges information with its near neighbors in the form of Bayesian probabilities for possible sources. Algorithms reduce the sensor data to probability estimates and then fuse the estimates among the multiple sensors.
One of the challenges to using these networks is getting them in place, in real terrain. "In a battlefield scenario, for instance, or during a wildfire, you can't have people tromping in to set down sensors," says Hills. One answer is to use unmanned aerial vehicles (UAVs), such as the U.S. Air Force's Predator or even smaller, 2-meter-wingspan UAVs. In one project, researchers are evaluating the use of UAVs to rapidly place, operate, and maintain sensor networks in rugged terrain. Such vehicles could drop the sensors in predetermined locations and then act as airborne routers. Once in place, the sensors would form a network, communicate with each other, and send information skyward to be collected and transmitted by the planes.
to position ourselves for the future," says Hills.
Researchers at Livermore are exploring the possibility of using unmanned aerial vehicles (UAVs) to place, operate, and maintain sensor networks in rugged terrain. In the figure, the sensors in the network are shown sending their information.
Key Words: Bayesian statistics, correlated sensor networks, Counterproliferation Analysis and Planning System (CAPS), gamma detector, Joint Biological Remote Early Warning System (JBREWS), neutron detector, nuclear terrorism, seismic detector, sensor or network fabrics, tactical engagement systems, unmanned aerial vehicle (UAV), Wide-Area Tracking System (WATS).
For further information contact Rob Hills (925) 423-7344 (hills1@llnl.gov).
ROB HILLS is the acting associate division leader for the Tactical Systems Section in the Nonproliferation, Arms Control, and International Security Directorate. He leads a variety of projects that include research and development for sensors and sensor networks, military systems analysis, and computer-based battlefield conflict simulation models. Hills received a B.S. in electrical engineering from the Michigan Technological University in 1983. He joined Livermore in 1988 to perform research that involved automating the transfer of existing digital designs to new implementation technologies. Thereafter, he participated in several projects to develop sensor systems and image-processing technologies for astronomical telescopes. For example, he was a member of the team that developed the camera system to detect dark matter; the system won an R&D 100 Award for being one of the most technologically significant new products in 1993. Hills has led research and development efforts for microtechnology tools, such as a polymerase chain reaction system, used both in medical and national security applications. And he has engineered optical interconnects for parallel computer systems as well as overall architectures for self-configuring and self-healing communications networks.


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(WO202036655) Methods of using genetic markers associated with endometriosis 机翻标题: 暂无翻译,请尝试点击翻译按钮。
(WO202036655) Methods of using genetic markers associated with endometriosis
WO2020/036655WO2020/036655WO2020/036655 / 2020-06-042020-04-022020-02-20
ALBERTSEN HANSCHETTIER RAKESH NWARD KENNETH;
JENU BIOSCIENCES;
A61K-031/56 A61K-031/566 A61K-039/395 A61P-015/00 C07H-021/04 C12N-015/09
(WO2020/036655) Disclosed herein are methods of using genetic markers associated with endometriosis, for example via a computer-implemented program to predict risk of developing endometriosis, and methods of preventing or treating endometriosis or a symptom thereof. For example, the present disclosure provides a method of testing for endometriosis and treating a subject having at least one genetic mutation in at least one gene of UGT2B28, USP17L2 (alias DUB3), and METTL11B such that the subject is prevented from developing endometriosis or such that endometriosis in the subject is prevented from progressing. The treatment may be a surgical intervention, a hormone treatment, a pharmaceutical treating, or a combination thereof.
(WO202036655) ARONIN, Caren P. ([US])
(WO2020/036655) CLAIMS  WHAT IS CLAIMED: 1. A method comprising assaying a genetic sample of a subject, the method comprising detecting in the sample a genetic mutation in UGT2B28, USP17L2, or METTL1 IB; and applying at least one endometriosis therapeutic to the subject. 2. The method of claim 1, wherein the assaying comprises sequencing, array comparative genomic hybridization (CGH), polymerase chain reaction (PCR), or the use of a DNA microarray. 3. The method of claim 1 or 2, wherein the at least one genetic mutation comprises a hemizygous deletion mutation or a rare missense mutation. 4. The method of any one of claims 1-3, wherein the at least one genetic mutation comprises at least one of a hemizygous deletion mutation in UGT2B28 or USP17L2 and a rare missense mutation in METTL11B. 5. The method of any one of claims 1-4, wherein the subject manifests a pelvic pain, infertility, or dysmenorrhea. 6. The method of any one of claims 1-5, wherein the endometriosis therapeutic comprises a   hormonal treatment, canceling a contemplated hormonal treatment, a surgical procedure, or canceling a contemplated surgical procedure. 7. The method of claim 6, wherein the hormonal treatment comprises at least one of an estrogen containing composition, a progesterone containing composition, a progestin containing composition, a gonadotropin releasing-hormone (GnRH) agonist, a GnRH antagonist, or any combination thereof. 8. A method comprising applying a endometriosis therapeutic to a subject having a genetic mutation in UGT2B28, USP17L2, or METTLl IB in DNA of the subject. 9. The method of claim 8, wherein the genetic mutation comprises a hemizygous deletion mutation or a rare missense mutation. 10. The method of claim 8 or 9, wherein the genetic mutation comprises at least one of a hemizygous deletion mutation UGT2B28 or USP17L2 and a rare missense mutation in METTLl IB. 11. The method of any one of claims 8-10, wherein the subject manifests a pelvic pain, infertility, or dysmenorrhea. 12. The method of any one of claims 8-11, wherein the endometriosis therapeutic comprises a   hormonal treatment, canceling a contemplated hormonal treatment, surgical procedure, or canceling a contemplated surgical procedure. 13. The method of claim 12, wherein the hormonal treatment comprises an estrogen containing   composition, a progesterone containing composition, a progestin containing composition, a gonadotropin releasing-hormone (GnRH) agonist, orany combination thereof. 14. The method of any one of claims 1-13, wherein the genetic sample is obtained from a blood sample. 15. The method of any one of claims 1-14, further comprising providing a treatment for the subject, wherein the treatment comprises a recommendation for the treatment. 16. The method of any one of claims 1-15, wherein the detecting comprises comparing a data set obtained from the genetic sample to a control data set of a control sample. 17. The method of claim 16, wherein the data set comprises sequencing data. 18. The method of claim 16, wherein at least a portion of data from the data set is removed. 19. The method of claim 16, wherein at least a portion of data from the control data set is removed. 20. The method of claim 18 or claim 19, wherein an accuracy of the detecting is improved after a removal of the portion of data. 21. The method of claim 18 or claim 19, wherein a false positive rate of the detecting is reduced after a removal of the portion of data. 22. The method of claim 19, wherein the portion of data removed from the control data set is data of a sample that is familial to the genetic material. 23. The method of any one of claims 16-2, wherein the control sample is selected based on one or more parameters of associated with the genetic material. 24. The method of claim 23, wherein the one or more parameters comprise an ethnicity, an age, a gender, a geographical location, a diet, a medical history, a familial history, a sample preparation, or any combination thereof. 25. A method comprising:   (a) hybridizing a nucleic acid probe to a nucleic acid sample from a human subject suspected of having or developing endometriosis; and   (b) detecting a genetic variant in a panel comprising two or more genetic variants defining a minor allele listed in Tables 1 and 2. 26. The method of claim 25, wherein the nucleic acid sample comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof. 27. The method of claim 25, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from cDNA or mRNA. 28. The method of claim 25, wherein the nucleic acid sample comprises PCR amplified nucleic acids produced from genomic DNA. 29. The method of any one of claims 25-28, wherein the nucleic acid probe is a sequencing primer. 30. The method of any one of claims 25-28, wherein the nucleic acid probe is an allele specific probe. 31. The method of any one of claims 25-30, wherein the detecting comprises sequencing,   hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof. 32. The method of any one of claims 25-31, wherein the detecting yields a data set. 33. The method of claim 32, further comprising inputting the data set into a programmed computer having a trained algorithm. 34. The method of any one of claims 25-33, further comprising outputting an electronic report that comprises a result. 35. The method of claim 31, wherein the detecting comprises the sequencing and wherein the   sequencing comprises next-gen sequencing. 36. The method of claim 31, wherein the detecting comprises the sequencing and wherein the   sequencing comprises nanopore sequencing. 37. The method of claim 36, wherein the nanopore sequencing is performed with a biological   nanopore, a solid state nanopore, a hybrid nanopore, or any combination thereof. 38. The method of claim 25, wherein the detecting comprises labeling the one or more SNPs. 39. The method of claim 38, wherein the labeling comprises associating a fluorescent label with the one or more SNPs. 40. The method of claim 38 or 39, wherein the labeling comprises covalently labeling the one or more SNPs. 41. The method of any one of claims 25-40, wherein the nucleic acid sample is at least partially isolated from a blood sample. 42. The method of any one of claims 25-41, wherein the nucleic acid sample is at least partially isolated from a cell -free sample. 43. The method of any one of claims 25-42, wherein the nucleic acid sample is comprised in a cell- free DNA. 44. The method of any one of claims 25-43, wherein the panel comprises at least: 5, 10, 15, or 20 genetic variants defining minor alleles listed in Tables 1 and 2. 45. The method of any one of claims 25-44, wherein the genetic variant comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. 46. The method of any one of claims 25-45, wherein the genetic variant comprises a protein   damaging mutation. 47. The method of any one of claims 25-46, wherein the panel comprises one or more protein   damaging or loss of function variants in one or more genes selected from the group consisting of UGT2B28, USP17L2, METTL11B , and any combinations thereof. 48. The method of claim 47, further comprising sequencing the one or more genes to identify the one or more protein damaging or loss of function variants. 49. The method of claim 47, wherein the one or more protein damaging or loss of function variants is identified based on a predictive computer algorithm. 50. The method of claim 47, wherein the one or more protein damaging or loss of function variants is identified based on reference to a database. 51. The method of claim 46, wherein the one or more protein damaging or loss of function variants comprises a stop-gain mutation, a splice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof. 52. The method of any one of claims 25-51, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with a specificity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 53. The method of any one of claims 25-52, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with a sensitivity of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 54. The method of any one of claims 25-53, wherein the panel is capable of identifying a human subject as having or being at risk of developing endometriosis with an accuracy of at least: 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. 55. The method of any one of claims 25-54, further comprising administering a therapeutic to the human subject. 56. The method of claim 55, wherein the therapeutic comprises a regenerative therapy, a medical device, a pharmaceutical composition, a medical procedure, or any combination thereof. 57. The method of claim 55, wherein the therapeutic comprises a non-steroidal anti-inflammatory, a hormone treatment, a dietary supplement, a cannabis-derived therapeutic or any combination thereof. 58. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises an at least partially hemp-derived therapeutic, an at least partially cannabis-derived therapeutic, a cannabidiol (CBD) oil derived therapeutic, or any combination thereof. 59. The method of claim 55, wherein the therapeutic comprises the medical procedure, and wherein the medical procedure comprises a laparoscopy, a laser ablation procedure, a hysterectomy or any combination thereof. 60. The method of claim 55, wherein the therapeutic comprises the regenerative therapy, and wherein the regenerative therapy comprises a stem cell, a cord blood cell, a Wharton's jelly, an umbilical cord tissue, a tissue, or any combination thereof. 61. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition comprises cannabis, cannabidiol oil, hemp, or any combination thereof. 62. The method of claim 55, wherein the therapeutic comprises the pharmaceutical composition, and wherein the pharmaceutical composition is formulated in a unit dose. 63. The method of claim 54, wherein the therapeutic comprises hormonal therapy, an advanced   reproductive therapy, a pain managing medication, or any combination thereof. 64. The method of claim 54, wherein the therapeutic comprises a hormonal contraceptive,   gonadotropin-releasing hormone (GnRH) agonist, gonadotropin-releasing hormone (GnRH) antagonist, progestin, danazol, or any combination thereof. 65. The method of any one of claims 25-64, further comprising administering an imaging procedure to a subject. 66. The method of claim 64, wherein the imaging procedure comprises an ultrasound, an x-ray, a magnetic resonance imaging (MRI), a computed tomography (CT) scan, or any combination thereof. 67. The method of any one of claims 25-66, wherein the human subject is asymptomatic for   endometriosis. 68. The method of any one of claims 25-67, wherein the human subject is a teenager. 69. A method comprising detecting one or more genetic variants defining a minor allele listed in Tables 1 and 2 in genetic material from a human subject suspected of having or developing endometriosis. 70. The method of claim 69, wherein the genetic material comprises mRNA, cDNA, genomic DNA, or PCR amplified products produced therefrom, or any combination thereof. 71. The method of claim 69 or 70, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, of any combination thereof. 72. The method of claim 69 or 70, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material. 73. The method of any one of claims 69-72, wherein the detecting comprises testing for the presence or absence of at least: 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 genetic variants defining a minor allele listed in Table 1 and Table 2. 74. The method of any one of claims 69-73, further comprising administering a therapeutic to the human subject. 75. A method comprising:   (a) sequencing all or a portion of one or more genes or gene expression products selected from the group consisting of UGT2B28, USP17L2 , METTL1 IB and any combinations thereof to identify one or more protein damaging or loss of function variants in a human subject suspected of having or developing endometriosis; and   (b) identifying the human subject as having or being at risk of developing endometriosis when the one or more protein damaging or loss of function variant is identified. 76. The method of claim 75, wherein the one or more protein damaging or loss of function variants comprises a deletion of all or a portion of the one or more genes. 77. The method of claim 75, wherein the one or more protein damaging or loss of function variants is identified based on a predictive computer algorithm, reference to a database, or a combination thereof. 78. The method of claim 75, wherein the one or more protein damaging or loss of function variants comprises a stop-gain mutation, a splice-site mutation, a frameshift mutation, a missense mutation, or any combination thereof. 79. The method of any one of claims 75-78, further comprising administering a hormonal therapy to the human subject. 80. The method of claim 79, wherein the hormonal therapy comprises administration of hormonal contraceptives, gonadotropin-releasing hormone (GnRH) agonists, gonadotropin-releasing hormone (GnRH) antagonists, progestin, danazol, or any combination thereof. 81. The method of any one of claims 75-80, further comprising administering to the human subject an assisted reproductive therapy. 82. The method of claim 81, wherein the assisted reproductive therapy comprises in vitro fertilization, intrauterine insemination, ovulation induction, gamete intrafallopian transfer, or any combination thereof. 83. The method of any one of claims 75-82, further comprising administering to the human subject a pain medication. 84. The method of claim 83, wherein the pain medication comprises a nonsteroidal anti-inflammatory drug (NS AID), ibuprofen, naproxen, an opioid, a cannabis-based therapeutic, or any combination thereof. 85. The method of any one of claims 75-84, further comprising detecting the at least one genetic   variant in a genetic material from the human subject. 86. The method of claim 85, wherein the detecting comprises DNA sequencing, hybridization with a complementary probe, an oligonucleotide ligation assay, a PCR-based assay, or any combination thereof. 87. The method of claim 85, wherein the detecting comprises hybridizing a nucleic acid probe to the genetic material. 88. The method of claim 87, wherein the nucleic acid probe is a sequencing primer or an allele- specific probe. 89. The method of any one of claims 75-88, wherein the human subject has at least one genetic   variant that comprises a synonymous mutation, a non-synonymous mutation, a nonsense mutation, an insertion, a deletion, a splice-site variant, a frameshift mutation, or any combination thereof. 90. A kit comprising: one or more probes for detecting one or more single nucleotide   polymporphisms (SNPs) of Table 1, Table 2, or a combination thereof in a sample. 91. The kit of claim 90, further comprising a control sample. 92. The kit of claim 90, wherein the control sample comprises one or more of SNPs of Table 1, Table 2, or a combination thereof. 93. The kit of any one of claims 90-92, wherein a probe of the one or more probes comprises a   sequence having at least 80% sequence complementarity to a sequence adjacent thereto a SNP of the one or more SNPs of Table 1 , Table 2, or a combination thereof. 94. The kit of any one of claims 90-93, wherein the one or more probes comprise a hybridization probe or amplification primer. 95. The kit of any one of claims 90-94, wherein the one or more probes is configured to detect a   variant allele in the sample. 96. The kit of any one of claims 90-95, wherein the one or more probes is configured to hybridize to a portion of a nucleic acid of the sample when a variant allele is present in the nucleic acid. 97. The kit of any one of claims 90-96, wherein the one or more probes is configured to associate with a solid support. 98. The kit of any one of claims 90-97, wherein the kit further comprises instructions for use and wherein the instructions for use comprise high stringent hybridization conditions. 99. The kit of any one of claims 90-98, wherein the one or more probes is configured to hybridize to a target region of a nucleic acid of the sample, wherein the target region comprises one or more SNPs. 100. A system comprising: (a) a computer processor configured to receive sequencing data obtained from assaying a sample, wherein the computer processor is configured to identify a presence or an absence of one or more SNPs comprising one or more SNPs of Table 1, Table 2, or a combination thereof in the sample, and (b) a graphical user interface configured to display a report comprising the identification of the presence or the absence of the one or more SNPs in the sample. 101. The system of claim 100, wherein the computer processor comprises a trained algorithm. 102. The system of claim 100 or 101, wherein the computer processor communicates a result. 103. The system of claim 102, wherein the result comprises an identification of the presence or the absence of one or more SNPs in the sample.
USE OF A CHIMERIC PROTEIN COMPRISING Met-GnRH IN THE PREPARATION OF A PHARMACEUTICAL COMPOSITION FOR TREATING ADENOCARCINOMA OR HEPATOCARCINOMA
Chimeric toxins for targeted therapy
Treatment of disease conditions through modulation of hydrogen sulfide produced by small intestinal bacterial overgrowth
CHIMERIC TOXINS COMPRISING GnRH FOR TARGETED THERAPY
Heterocyclic cytokine inhibitors
Epha2 vaccines
(US20190358216) Heteroaryl inhibitors of pad4
(EP3490989) Covalent inhibitors of pad4

redpajama_set_name: RedPajamaCommonCrawl


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North | Follow Category: None July 12, 2019 - 11:43 PDT | Last Edited: July 12, 2019 - 11:43 PDT 1 46
Will there be another war?
The United States, UK and Iran all agree:they don't want war, but tensions are rising by the day. Iran accuses Britain of being a servant of the U.S. as it demands the return of an oil tanker seized off Gibraltar. It's been suggested British Royal Marines boarded the vessel at the request of America. And the UK is looking at boosting its military presence in the Gulf after an apparent close encounter with Iran's Revolutionary Guard just days later. The U.S. meantime is turning the screw further on Iran's already faltering economy, and Britain finds itself in an awkward position. It's working with Europe to try and save the 2015 Iran nuclear deal, which the U.S. has abandoned. But it also needs to maintain close ties with Washington as it seeks to leave the European Union. The situation with the tanker has infuriated Iran with the foreign minister demanding Britain return the ship or face what he called 'the consequences'.
GR | Follow | 3 days ago
Professor Charandi gets angrier by the minute. Enjoyed watching his blood pressure rise towards the end of the clip. I doubt he has a son serving in the armed forces.
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Walk for Women set for weekend
SANDCASTLE MANIA: Island, Clayton's prepare for weekend event
New info emerges in body's discovery
By HEATHER C. COX
Special to the PRESS
The lifeless body of a man later identified as Jeremy Tyrone Eyster, of Irving TX, washed ashore last weekend near public Beach Access 6. At this time, a gunshot wound to the head has caused investigators to treat Eyster's death as a homicide.
Eyster's body was discovered by a passerby who alerted the constable's office near 9:30 p.m. on Saturday, September 29. He was reportedly clothed in a blue t-shirt, shorts and tennis shoes but had no identification or personal effects on his person.
Members of ICE used specialized fingerprinting equipment which reportedly identified Eyster and alerted authorities to his most current geographic location.
Cameron County Sheriff Omar Lucio said, "We don't know exactly what happened; however, he did have a hole or gunshot wound through the top of his head. We don't know the type of caliber yet." He added that the death is still under investigation at this time and is being treated as a homicide until evidence from a pathologist report indicates otherwise.
Eyster had not been reported missing at the time officials contacted his family. No known reason regarding the victim's whereabouts or possible cohorts has surfaced at this time, and investigators do not know why or with whom Eyster was visiting the Island.
"We're still working on other details," said Lucio of more specific details which remain either unknown or undisclosed as of presstime.
Access 6 is a rather undeveloped portion of South Padre Island, though according to Lucio, past records indicate that criminal mischief and death occurrences at this public access "are few and far between." When asked whether the sheriff's office will be altering security measures in the area, Lucio stated, "The constables are there. We have no plans to increase security [at this part of the island] anymore at this time."
Read this story in the October 4 edition of the Port Isabel-South Padre Press, or subscribe to our E-Edition by clicking here.
Permanent link to this article: https://www.portisabelsouthpadre.com/2012/10/04/new-info-emerges-in-bodys-discovery/


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MercyMe Set to Release inhale (exhale) April 30th
March 26, 2021 Absolutely Gospel Music News & Scoops 0
March 26, 2021… Nashville, TN – GRAMMY® nominated, multiple American Music Award, Billboard Music Award and Dove Award-winning band MercyMe is set to release inhale (exhale) on April 30, and it is available across all DSPs for preorder today. In anticipation, MercyMe is also releasing a new instant grat track and lyric video for "On Our Way," featuring Millard's son Sam Wesley, along with previously released tracks, "Almost Home," "Say I Won't," and "Hurry Up & Wait."
The fast-rising current radio single "Say I Won't," which is currently #7 on the Billboard National Christian Airplay chart and #9 on the Mediabase Christian Audience chart, is spinning on a vast majority of Christian radio stations across the country – including KLOVE, SiriusXM The Message, KLTY/Dallas, KSBJ/Houston, Z88.3/Orlando, WGTS/Washington DC, The Fish/Atlanta, The Joy FM/Tampa, KTIS/Minneapolis, and JoyFM/St. Louis. The track is a potent declaration of faith and perseverance colored by tragedy. Gary Miracle, a longtime friend that worked with MercyMe for many years, contracted an infection that resulted in having both his arms and legs amputated. His indomitable spirit in the face of such challenges was inspiring. Good Morning America's third hour, GMA3, will be featuring MercyMe and Miracle in a special segment on April 15th. FoxNews.com originally premiered the song's powerful music video last December. More of Gary's story can also be seen here.
The 16-song collection (produced by Tedd T., Brown Bannister and Jordan Mohilowski) includes "Almost Home," a stunningly poignant anthem that topped the charts for a combined total of 17 weeks. There's also the buoyant "A Little Love" featuring Millard's close friend Gary LeVox, lead vocalist for award-winning country super group Rascal Flatts. Disco legend and friend Gloria Gaynor lends her signature vocals to "Brand New."
inhale (exhale) is the latest chapter in MercyMe's creative adventure, and Millard admits this one was a long time in coming together. "It was two years and one month to the day that we started writing for this new record until we finally finished," Millard says. "'Almost Home,' which is the first single, will be out a year and a half before the record releases. We would have had it done a year or so ago, but when the pandemic hit, it slowed everything down. We practically re-wrote the album two or three different times."
The band began writing and wound up with more than 40 songs. Millard admits having the new record to focus on offered a welcome sense of purpose during pandemic life, and the opportunity to inhale (exhale). "It's been a life saver working on this record during the pandemic when you can't do shows and everything else. I love being with my family but I think my wife is like, 'Yeah you function better when there is an outside purpose going along with this.' I agree," he says with a laugh. The pandemic—as awful as it's been—has been amazing for our family, just getting to spend so much time together. It's been such a scary place, but at the same time, it's been great to have this much time with family, to push pause and not have a deadline. Everything has stopped. That's a crazy feeling and after a few weeks or a month of me freaking out like, 'What's going to happen?' I realized that we're all freaking out together. Music has been put on hold and so once I realized that, I kind of let go and started enjoying the fact that some days my most important decision was what flavor of ice cream I'm getting with my youngest daughter."
"One reason we're calling the album inhale (exhale) is we all just want to sit back for a second and take a deep breath and be like, 'Okay this is what matters. This is what matters,'" Millard concludes. "I'm grateful that messages like that seem to resonate with people on a consistent basis because there is hope in that, and if they can still get fired up about what's to come then not all is lost."
inhale (exhale) Track Listing:
1- Inhale
2 – Blessed
3 – On Our way (feat. Sam Wesley)
4 – So Yesterday
5 – A Little Love (feat. Gary LeVox)
6 – Whiplash
7 – Bright Side Of Broken
8 – Let Yourself Be Loved
9 – Hurry Up and Wait
10 – Brand New (feat. Gloria Gaynor)
11 – Uh Oh (Here I Go)
12 – The Moment
13 – Then Christ Came (Demo)
14 – Say I Won't
15 – Almost Home
16 – Exhale
About MercyMe:
It continues to be a landmark time for the multi-platinum selling, GRAMMY® nominated, multiple American Music Award, Billboard Music Award and Dove Award winners MercyMe. They were recently named Billboard's Top Christian Artist of the 2010 decade, and in 2020 received their eighth American Music Award nomination. A major motion picture based on the life of frontman Bart Millard who wrote the mega-hit song "I Can Only Imagine" after the loss of his father, opened at a remarkable No. 3 at the box office on Mar. 16, 2018 (Lionsgate, Roadside Attractions). In conjunction with the movie release, Millard penned a memoir and the band released a collection of hits titled I Can Only Imagine – The Very Best Of MercyMe. In 2018 MercyMe was named Top Christian Artist at the Billboard Music Awards, was the top winner at the fan-fueled K-LOVE Fan Awards including a win for Artist of the Year, and was the GMA Dove Award Winner for Artist Of The Year. Since their debut in 2001, the band has sold more than 9 million units in CD, single and DVD sales, garnered more than 48 No. 1 multi-format radio singles, and had four consecutive mainstream radio hits. MercyMe made history in 2014 as "I Can Only Imagine" surpassed 2 million digital downloads, making it the first song in Christian music to go platinum and double-platinum in the digital domain. The song has now gone has gone 4x platinum. In 2009, Billboard named MercyMe's "Word Of God Speak" the No. 1 Song of The Decade and the group the No. 1 Artist of the Decade in both the Christian Songs and Christian AC Songs categories, recognizing them as one of the industry's most notable talents. They have sold out venues throughout the US and Canada, including Radio City Music Hall, Red Rocks Amphitheatre, and have appeared on the Macy's Thanksgiving Day Parade, Good Morning America, The Today Show, CBS This Morning, FOX New Channel's FOX & Friends, CNN, ABC News and in the pages of Entertainment Weekly, The New York Times, USA Today and more.
FairTrade Service
Christmas Music Guide 2015


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Q: Display arabic correctly on ip phones i am facing an issue on cisco ip phones, when trying to display arabic characters it displays corrupted as ???????? so i was wondering How to display arabic correctly on ip phones ?

A: Issue fixed using the following code:
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            str.getBytes("iso-8859-1"), "utf-8");

redpajama_set_name: RedPajamaStackExchange


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Etrusia - The Celts
Celts and Britain
Who were...
Celtic Myths
Maiden Castle
Cattle Raid
Celtic Shop
Etrusia
Normans
Modified: 30 Jul 06
XHTML 1.1 CSS 2.1 W3 Sites CC Licence
The Celtic Web Site
NEW: Celtic Shop - Now you can support the Celtic World website while you do your shopping. In the Celtic World Shop we have a variety of items, have a look and see if there is anything you like.
There is a section on Celtic / British iron age hill forts now being built. The first one is dedicated to Maiden Castle.
We have added a contact form for people who wish to get in touch - either to say hello or even suggest articles / information on the site. If you would like to send us a message then please do so.
As part of the Etrusia British History Site, the Celtic World subdomain will look at the origins and history of the Celtic Peoples. Ranging from the proto-Celtic bronze age societies that spread out of central Europe to the last strongholds of the ancient culture today; this site will look at how the Celtic people have explored and expanded and adapted to the world around them.
This site is undergoing large scale, offline, development but it is planned to have reached version 1.0 by 1 Jan 07. If you have any articles or information you would like to submit for publishing here please contact us and let us know.
During their travels around Europe and eastern Asia, the Celts were known by a variety of names, all adding to the confusion around their origins. In the Odyssey (c.800 BC), Homer makes a reference to the "Cimmerians" as living somewhere north nest of Greece, which may well be an early reference to the proto-Celtic Urnfield culture.
By 435 BC Herodotus wrote in his Histories of the Celts living along the River Rhône and beyond the "Pillars of Hercules" (Gibraltar). At this point, the Celts were truly the dominant European culture.
-- The Celtic World WebSite --
This page was created by Halkyn Consulting Ltd for www.etrusia.co.uk. It has been placed on the internet under a creative commons licence.


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Target tries to capitalize on Victoria's Secret's struggles
February 28, 2019	Off	By WhoThatCelebsRS
New York (CNN Business) Victoria's Secret is struggling. That's an opportunity for Target.
Target (TGT) is attempting to woo customers weary of Victoria's Secret's push-up bras and sexy supermodel image. Its new brand will come in a broad range of sizes and its marketing campaign will feature women "in all different shapes and sizes." The company is also launching Stars Above, a pajama brand, and Colsie, a brand for teens to rival Pink.
Target is following a strategy similar to what other lingerie companies are doing. Startups ThirdLove and Lively, along with Aerie, which is owned byAmerican Eagle Outfitters (AEO), have broken Victoria's Secret's grip on the industryby selling better-fitting bras and using inclusive advertising.
Victoria's Secret, owned by L Brands (LB), is still the biggest player in the lingerie business, but it has bled market share lately. The company has lost 3.8 million customers over the two past years to rivals like Amazon (AMZN) and Aerie, according to an estimate from Neil Saunders, analyst at GlobalData Retail.
Victoria's Secret has mostly stuck to the same playbook that helped it dominate the lingerie business: flashy fashion shows, sexy push-up bras and celebrity models. It continues to run an annual fashion show with skinny supermodel "Angels" in wings, despite record low ratings.
That marketing has fallen out of favor with many women.
"The people in charge of the brand are completely out of touch with what their customers want to see," said Cora Harrington, author of "In Intimate Detail: How to Choose, Wear & Love Lingerie." "They didn't feel an urgency to stay on top of consumer trends."
Victoria's Secret's weaknesses opened the door for online upstarts and traditional retailers, analysts say. To draw a sharp contrast against Victoria's Secret, Aerie started showing natural-looking women in ads and stopped airbrushing photos in 2014. The decision energized the brand, and it has grown sales by double digits for 15 straight quarters.
"Aerie hit it right at a time when people were tiring of what Victoria's Secret and PINK were portraying as overtly sexy and really unattainable beauty standards," said Janine Stichter, analyst at Jefferies.
Online startups like ThirdLove have marshaled tech tools online to offer custom sizes to shoppers.
Target says 80% of women in the United States wear the wrong bra size, so it will offer an online "fit finder" to help customers get the right size.
It is also trying to undercut Victoria's Secret with lower prices. Victoria's Secret bras go for around $50 and overonline. Target's $22 and under prices will make Auden "an easy impulse buy" for shoppers, Harrington said.
But other big retailers could block Target's path to Victoria's Secret shoppers.
Aerie, which only has stores in 15 states, plans to expand its brick-and-mortar presence to draw customers. Calvin Klein parent PVH (PVH) acquired lingerie startup True & Co. in 2017 and has expanded its distribution. Lululemon (LULU) launched its first bra. And Walmart (WMT)bought online lingerie retailer Bare Necessities last year, giving it a foothold in the market.
Read more: http://edition.cnn.com/
Tagsbusiness news Target launches new lingerie brands - CNN
MOWGLI Trailer (2019)
This billionaire reportedly paid $60K for a portrait of Trump. He was allegedly reimbursed by Trump's charity.


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Ten El Paso schools ranked top in the U.S.
Lindsey Anderson
Ten El Paso schools made U.S. News & World Report's list of the 2,673 best high schools in the country.
All El Paso schools that made the cut are charter schools or in the El Paso and Ysleta school districts.
El Paso's Harmony Science Academy, a charter school, ranked highest at 232nd nationwide. Also ranked were:
Valle Verde Early College: 717
Charter school Harmony School of Innovation-El Paso: 874
El Paso High: 1,192
Silva Health Magnet: 1,432
Charter school Davinci School for Science and the Arts: 1,573rd
Coronado High: 1,671
Del Valle High: 2,177
Eastwood High: 2,466
Hanks High: 2,562
U.S. News & World Report rated Dallas' School for Talented and Gifted the best in the country and the best in Texas.
The schools also made the list of the 204 best high schools in Texas, with Harmony Science Academy clocking in at 38th in the state, Valle Verde at 83rd, Harmony School of Innovation at 95th, El Paso High at 121st, Silva Health Magnet at 141st, Davinci School at 147th, Coronado at 155th, Del Valle at 184th, Eastwood at 199th and Hanks at 203rd.
The schools are ranked based on student performance on state tests, graduation rates and how well they prepare students for college.


The mission of the School of Science and Technology (SST) is to build and sustain high quality and broad-based teaching and research programs in science, communication and technology; to prepare graduates by equipping them with knowledge, skills, and attitudes relevant for professional success in science, communications, and technology related careers; and to provide exemplary service to the community. Further, the SST is committed to promoting the generation, dissemination and application of knowledge of science, communication and technology in order to create a better world.
As par t of their growth and development, students formulate and articulate the ethical standards and develop the leadership skills which will guide their professional and personal lives. This is accomplished through formal courses in discipline areas and active engagement of students in leadership roles both inside and outside the classroom.


High-polish stainless steel and clear glass make this large candle lantern a standout. Place your favorite candle inside or fill it with a collection of beautiful things to create a stunning display. Set it on your tabletop or hang it from its generous top-mounted loop.
Item weight: 4 lbs. 7 3/4" x 7 1/2" x 15 3/8" high; 19 1/4" high with handle. Stainless steel, iron and glass. Candle not included.


Sunny Anderson's Grilled Fennel with Grilled Jalapeno Sauce – Paleo!
Yesterday was awful, but today's not so bad. I think it's all a matter of withdrawal and normalization, this "coming off of antidepressants" thing. Sure, I drop down again tomorrow, but at least today, I'm not feeling so bad. I'll take a good day where I can get it.
Today, I'm trying to get a bag packed for the hospital next week and get the house neatened up so that it's good to go.
Oh! And here's some news! Our foster kittens got adopted! We drop them off to their new owners tomorrow afternoon.
Other than that, not much is going on. I'm really enjoying going through Food Network's website and trying to get at least 1 paleo recipe for each of their chefs.
It's pretty awesome to me that each of their celebrity chefs has at least 1 (if not more) paleo recipe in their top 100 most popular recipes featured on the website. So without further ado, here's today's recipe.
Guy Fieri's Turkey Hash Recipe – Paleo (if you eat potatoes)!
Got a lot of leftover turkey from Thanksgiving?
Me too. In fact, Adam and I bought an extra turkey since they were on sale, so we have a whole extra turkey's worth of meat to use up.
Here's a great way to use 2 pounds of it!
This recipe got 5 stars on the Food Network website, and is one of those recipes that you really look forward to on a cold fall morning when it's so cold outside that you're just sure that it's going to snow.
Some people say that potatoes aren't paleo – and for them I say, "Great! Make em sweet potatoes, it'll still taste good! Or, in the alternative, don't make this recipe.
Adam and I eat potatoes. They grow out of the ground. Grok wouldn't say no to them.
In medium saute pan, add 2 ounces olive oil, onions, peppers and saute until translucent.
Add turkey and brown on all sides.
In a separate pan, add 2 ounces of oil, and fry potatoes in oil until crispy.
On a serving plate layer the turkey mixture on top of the crispy potatoes.
Top with diced roma tomatoes and fresh squeezed lime juice.
Paula Deen's Baked Tilapia with Tomato and Basil – Paleo!
I'm sure everyone's busy getting all of their holiday shopping taken care of today, so I wanted to feature a recipe that was absolutely mouth-watering and easy to fix up for supper tonight.
Today, I'm bringing you one of Paula Deen's top recipes that got 5 stars on Food Network's website. It honestly amazes me that with all of the totally healthy recipes that I don't even have to change at all that the Food Network doesn't have their own section of paleo recipes. Maybe I should suggest it to them!
Spray a shallow 1-quart baking dish with nonstick spray.
Arrange the tilapia in a baking dish and sprinkle evenly with basil, oregano, onion powder and garlic.
Drizzle with 2 tablespoons of the olive oil.
Arrange the tomato slices evenly over the fish, and drizzle with the remaining 1 tablespoon of olive oil.
Bake until fish flakes easily with fork, about 20 to 25 minutes.
Squeeze the lemon juice over fish and serve immediately.
Bobby Flay's Grilled Chicken Paillard with Lemon and Black Pepper and Arugula-Tomato Salad – Paleo!
Things here at home are great. We've just had a delicious breakfast of sweet potato hashed browns, center-cut, thick-cut bacon, and eggs, and are about to start our day. We've got to hit Costco for some staples, and then we're going to go to the YMCA to work out.
I found the cutest presents to buy my niece on Amazon.com, and I'm getting really excited for the holidays. This weekend we're setting up the Decemberween bush of lights, and I'm going to start working on our paleo gingerbread recipe.
Today, I'm bringing you a recipe that we'll probably be making for dinner in a couple of nights. Thanks for another great paleo-friendly recipe, Food Network!
Whisk together lemon juice, shallot, olive oil and black pepper in a large baking dish. Add the chicken, turn to coat and marinate in the refrigerator for 30 minutes.
Preheat grill to high. Remove chicken from marinade, season with salt on both sides and grill for 2 to 3 minutes per side or until golden brown and just cooked through.
Combine arugula, tomatoes and onions in a large bowl, toss with the vinegar and oil and season with salt and pepper, to taste. Place each paillard on a large plate, drizzle with extra-virgin olive oil and top with some of the arugula-tomato salad. Garnish with lemon halves.
Chef Robert Irvine's Pork Chops with Apples And Onions – Paleo!
Ah, Black Friday – the day you either avoid shopping altogether, or go out and brave the stores to get the best deals possible for Chanukkah and Christmas presents. Today, Adam and I are huddled up in our apartment because it is cold outside, and we are choosing to enjoy the convenience of online shopping of Amazon.com .
Today, I'm featuring Chef Robert Irvine's Pork Chops with Apples and Onions – a delicious recipe that is paleo as you can get. It's perfect for this day-after-Thanksgiving when all you want is to have leftovers, but instead you can give yourself something good for your body and just as delicious as the meal you had yesterday.
In a large saute pan over high heat, add the oil and allow to heat to the verge of smoking.
Then add the onions and reduce the heat to medium.
Allow the onions to cook, stirring throughout, until light brown in color, about 2 minutes.
Then add the bacon and allow to cook until the bacon has begun to brown.
Then add the apples. After adding the apples, allow all the ingredients to blend in flavor for a final 2 minutes.
Add the wine to deglaze the pan and allow the alcohol to cook off.
After reducing the wine, reduce the heat to low and whisk in the butter and optional spices, stirring for 1 to 2 minutes to create a sauce.
Finish with the mint and hold warm until serving.
In large a saute pan over medium-high heat, add the oil and allow to warm.
Sprinkle the chops with salt and pepper equally on both sides and add to the warm oil.
Allow the chops to brown on the first side for 3 to 4 minutes, and then flip and repeat cooking on the second side for a final 3 to 4 minutes.
Once cooked, remove from the pan and serve with potatoes of choice.
Finish with the apple compote.


At fifteen most guys only have to worry about the style of their shoes, or mustering up the courage to talk to the pretty girl sitting across the room. Gabe Perkins isn't most guys. After being diagnosed with a terminal illness, he begins to make friends with a girl so ethereal that he starts to question his own sanity.
The concept of this book was an interesting one, which is why I was originally drawn to it.
There are a lot of obvious grammatical mistakes such as commas in the wrong place, the misuse of words - such as 'your', and other issues along those lines. Then there's some content issues - the dialog, the narrator giving detailed explanation of conversations that happened between two people when he was a toddler - as if he were there participating in it, mixing up character names, the list goes on.
Despite that, I did enjoy this story - but it needs work. There's some pretty heavy stuff going on in this book. The author is able to portray the emotions pretty well. Normally when a book has this many editing issues I cannot finish it, but this story was able to keep me captivated.
I give this 2.5 platypires. I would read it again and would be willing to increase my rating if the author made the necessary changes.


Lasting Impact of the "Great Recession"
This purpose of this article is to briefly analyze and discuss the impact of the global economic recession spanning the years 2007 to 2009 on the operations of ultra-luxury resorts in the Caribbean Basin. For purposes of this analysis, we sampled via questionnaire and/or interviewed selected representatives of ownership and management at a group of Caribbean resorts which we identified, based on our research, as being those with the likely highest average rate performance. We have, for purposes of this article, used the term "ultra-luxury" to describe these properties. Smith Travel Research (STR) supplied us with two Trend reports for our analysis – one comprising approximately 264 properties categorized as "Luxury Class" hotels in the Caribbean region and a second "Custom Trend" report for our chosen subset – comprising 29 of those properties. To lend perspective to the difference in strata, the chosen ultra luxury subset achieved an average daily rate of $648 in 2011, more than 80% higher than the $358 ADR reported for the overall STR Luxury Class set.
The impact of downturns in performance at all resorts is problematic to hosting area economies, but the impact of business slowdowns at this sub-set of ultra-luxury properties has, based on input received during our research, more direct implications. Many of the top-tier ultra-luxury resorts are located on islands with relatively small economies. In many cases, the economy of the hosting island is driven almost entirely by tourism and a drop in the fortunes of the major employers -the resorts – reverberates through the economy of the entire island. In many cases, ultra-luxury level resorts comprise a very large percentage of the resort inventory.
In terms of occupancy, the broader-based Luxury sample began its slide during the period 2006 into 2007 while the ultra-luxury properties peaked in 2007 and then began declining. Moving from 2007 to 2008 and onward, the occupancy progression pattern was very similar. Of note when examining the chart is the fact that the gap between occupancy levels reached at luxury properties and occupancy at ultra-luxury properties was quite wide in 2006 – 8 points. The gap narrowed to only 1 occupancy point in 2008 and 2009 before beginning to widen again. There is a 4-point gap in 2011 data.
Average daily rate progression was similar with the Luxury properties almost paralleling the Ultra-Luxury in terms of rate movement. Interesting, the margin between the two tiers stayed very similar with Ultra-luxuries remaining in a narrow band between 81% and 85% higher in rate than the Luxury segment in every year of the analysis.
Overall performance as measured by RevPAR also ran fairly parallel. The beginning of the business downturn from 2007 to 2008 can be seen clearly. Based on information provided during our interviews and the survey conducted, the brunt of the decline began to be felt in late 2008 subsequent to the collapse of Lehman Brothers in September, 2008.
In terms of future performance, the outlook is guardedly positive for the ultra-luxuries.
Based on information from our survey, more than 20% of the GMs surveyed/interviewed expect 2012 occupancy to increase by 1 to 3 points and an additional 30%+ expect an increase of between 4 and 6 points. While this is a positive trend for the ultra-luxuries, it is important to point out that 2012 occupancy, based on that prognostication, would still be well below the 2007 peak of 65%.
Increases in average daily rate are, in general, expected to be healthy. More than 40% of those interviewed said that they expect average daily rate to increase between 4% and 6% in 2012 with another 10%+ indicating that rate increases might be in the 7% to 10% range.
Based upon what we have discussed thus far, it is clear that the Ultra Luxury properties were not, in any significant way, immune to the difficulties presented by the Great Recession. In fact, their performance during the downturn paralleled, in many ways, the performance in the broader Luxury segment.
One of the most common responses involved selective cuts in payroll of regular employees. There was reluctance to decrease payroll levels severely in that service levels must be maintained and consistent for the ultra-luxury guest. Some properties – primarily smaller ones – recruited temporary help (albeit quickly and heavily trained temporary help) as needed during peak season times such as Presidents week, Christmas week, Easter week etc. The limited selection of branded properties appears to have been able to take advantage of "sister" properties in order to borrow qualified staff.
Another measure taken by the management of the properties was to cut expenses in utilities. By mainland US standards, the cost of utilities in most island locations can, without hesitation, be described as "enormous". In addition to standard utility costs, many of the ultra-luxury resorts must produce their own supply of potable water. Some of the strategies implemented at ultra-luxury properties include investment is solar panels which proved to be both a money saver and even a revenue generator in some cases; switch to low consumption lighting fixtures that included LED lighting for common areas and fluorescent lighting for guest rooms; and low water consumption plumbing fixtures in guest rooms and public areas.
Based on our interviews, operators of ultra-luxury properties seem guardedly optimistic that the current business recovery will continue. European travelers comprise a very large portion of visitors to the Caribbean at the ultra-luxury end of the market. With the concurrent reliance on European economic health, operators are anxious about the painful deleveraging and resulting economic contraction currently taking place in key demand-generating countries in the Euro Zone. However, there seems to be consensus that they ultra-luxury market in the Caribbean has survived the effects of the "Great Recession" and has emerged as a stronger contender than before in the global market to capture luxury travelers.


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Home/The History of the American Flag
The History of the American Flag
Today the American flag consists of thirteen horizontal stripes; seven red stripes alternating with six white stripes representing the original 13 colonies. The stars represent the 50 states of the Union.
The colors of the flag are symbolic as well: Red symbolizes Hardiness and Valor, White symbolizes Purity and Innocence and Blue represents Vigilance, Perseverance and Justice.
The first legislation of the Continental Congress, on October 18, 1775, established a Federal navy, but, as far as is known, without a national ensign. Ships are reported to have been sent to sea under the pine-tree flag or possibly hoisted the colors of their originating State.
Two days later on October 20, 1775, Washington writes to Colonel Glover and Stephen Moyland, "Please fix upon some particular flag, and a signal by which our vessels may know one another. What do you think of a flag with a white ground, a tree in the middle, the motto, "Appeal to Heaven". This is the flag of our floating batteries. We are fitting out two vessels at Plymouth and when I next hear from you on this subject, I will let them know them know the flag and the signal, that we may distinguish our friends from our foes'.
Dr. Franklin, Mr. Lynch and Mr. Harrison, convening at the camp at Cambridge, were appointed to consider the subject. The result was the retention of the union jack (king's colors) representing the still-recognized sovereignty of England, but coupled to thirteen stripes, alternating red and white in place of the loyal red ensign. This symbolized the union of the thirteen colonies against the tyranny and oppression of Great Britain.
While not known with great certainty, it has been suggested that the origin of the stripes came from the ragtag Continental soldiers. The continental army of 1775 was without uniforms, and cloths of a stripe or ribbon distinguished the different grades. The daily view of these distinguishing marks of rank would naturally represent the United Colonies.
It will probably never be known who designed our union of stars. Neither Congressional records nor the public and private voluminous correspondence or diaries of the time refer to the creation of the stars.
It has been asked why the stars on our banner are five-pointed while, historically, those on our coins have been six-pointed. While there is a wonderful story about Betsy Ross favoring a five pointed star because of it's ease in construction (see further on), the answer is, that the designers of our early coins followed the English, and the designer of our flag the European custom. In the heraldic language of England, the star has six points; in the heraldry of Holland, France and Germany, the star is five-pointed.
The first unofficial national flag, called the Grand Union Flag or the Continental Colours, was raised at the behest of General Washington near his headquarters outside Boston, Massachusetts, on January 1, 1776 over the Cambridge camp when the Continental Army was reorganized in accordance with a Congressional resolution, which placed American forces under George Washington's control.
On that New Year's Day, the Continental Army was laying siege to Boston which had been taken over by the British Army. Washington ordered the Grand Union flag hoisted above his base at Prospect Hill. The flag had 13 alternating red and white horizontal stripes and the British Union Flag (a predecessor of the Union Jack) in the canton (the upper left-hand corner). Another early flag had a rattlesnake and the motto "Don't Tread on Me".
An anonymous letter, written January 2, 1776, says: "The grand union flag of thirteen stripes was raised on a height near Boston. The regulars did not understand it; and as the king's speech had just been read, as they supposed, they thought the new flag was a token of submission."
General Washington, writing to Joseph Reed on January 4th says: "We are at length favored with the sight of his Majesty's most gracious speech, breathing sentiments of tenderness and compassion for his deluded American subjects; the speech I send you [a volume of them was sent out by the Boston gentry] and, farcical enough, we have great joy to them without knowing or intending it, for on that day [the 2nd] which gave being to our new army, but before the proclamation came to hand, we hoisted the union flag in compliment to the United Colonies. But behold! It was received at Boston as a token of the deep impression the speech had made upon us, and as a signal of submission. By this time I presume they begin to think it strange that we have not made a formal surrender of our lines."
The first official national flag, also known as the Stars and Stripes, was approved by the Continental Congress on June 14, 1777. The blue canton contained 13 stars, representing the original 13 colonies, but the layout varied. Although nobody knows exactly who designed the flag, it most likely was Continental Congress member Francis Hopkinson. (See Francis Hopkinson & the Design of the American Flag in "American Flag Stories" at the end of this article.)
In May of 1776, Betsy Ross reported that she sewed the first American flag.
According to popular legend, the first American flag was made by Betsy Ross, a Philadelphia seamstress who was acquainted with George Washington, leader of the Continental Army and other influential Philadelphians. In May 1776, so the story goes, General Washington and two representatives from the Continental Congress visited Ross at her upholstery shop and showed her a rough design of the flag. Although Washington initially favored using a star with six points, Ross advocated a five-pointed star, which she demonstrated could be cut with just one quick snip of the scissors; the gentlemen were won over.
Unfortunately, historians have never been able to verify this version of events. Although it is known that Ross made flags for the Pennsylvania Navy. The story of Washington's visit to the flag maker became popular about the time of the country's first centennial after William Canby, a grandson of Ross, told about her role in shaping U.S. history in a speech given at the Philadelphia Historical Society in March 1870. He claimed that his maternal grandmother, Mrs. John Ross, was the maker and partial designer of the first flag combining the stars and stripes. Three of Mrs. Ross's daughters were living when Mr. Canby wrote his paper confirming its content. (See Betsy Ross and the First American Flag under "American Flag Stories' at the end of this article.)
He asserts that, in June 1776, a committee of Congress accompanied by General Washington called upon Mrs. Ross, an upholsterer. They engaged her to make the flag from a rough drawing which was redrawn, at her suggestion, by General Washington in pencil in her back parlor. This flag was adopted by Congress and was, according to Mr. Canby, the first star-spangled banner. Mrs. Ross was employed as flag maker for the government for many years.
On July 4, 1776 the Declaration of Independence was adopted. The document was authenticated, like other papers of Congress, by the signatures of the President and Secretary. It was also signed by the members present with the exception of Mr. Dickenson, of New York who refused to sign. It did not yet bear the names of the members of Congress as we are familiar with it. Some days after the Declaration had been passed it was ordered to be engraved on parchment and signed by every member. It was not until the 2nd of August that these signatures were affixed. It is this copy which has been preserved as the first-signed paper does not exist and was probably destroyed.
The Declaration was not actually signed on the fourth of July. Mr. Read, whose name appears among the signers, was then actually against it; and Morris, Rush, Clymer, Smith, Taylor, and Ross, whose names also appear, were not members on that day, and were not appointed delegates until the 20th of July. Thornton, of New Hampshire, who entered Congress in November, then signed it and Judge McKeen who was present and voted for it, did not sign until after his return from Washington's camp. The Declaration was read in New York in the presence of Washington by one of his aids on July 9, 1776. In the center of a square of the troops in New York. It was not until September 9, 1776 that Congress ordered "all continental commissions and instruments should be made to read 'United States', where heretofore the words "United Colonies" had been used'.
In Philadelphia, the Committee of Safety proclaimed it from the old State House and the king's arms were taken from this courthouse and burned outside. On the 10th the Declaration was read at the head of the several brigades.
Thursday, July 18, 1776, it was proclaimed from the balcony of the State House in Boston, the king's arms and every similar sign be taken down and burned.
On June 14, 1777, Congress "Resolved that the flag of the United States be thirteen stripes alternate red and white, that the Union be thirteen stars white in a blue field, representing a new constellation". As the exact arrangement of the stripes and stars was not specified, individual flag makers used their own judgment, producing several variants. Meanwhile other flags appeared, vessels of war are said to have worn a jack displaying a rattlesnake across thirteen red and white stripes, and merchantmen to have flown a flag having only thirteen stripes.
The first anniversary of the Declaration of Independence, July 4, 1777, was celebrated in Philadelphia, with demonstrations of joy and festivity. About noon, all the armed ships and galleys in the river were drawn up before the city, with the colors of the United States and streamers flying. At one o'clock they celebrated the day by a discharge of thirteen cannon from each ship and one from each of the thirteen galleys, in honor of the thirteen United States. In the afternoon, Congress provided an elegant dinner, when toasts were drank and guns were fired. Congress and the General Officers reviewed the troops and the day closed with the ringing of bells and exhibition of fireworks, which began and ended with thirteen rockets.
At Charleston, South Carolina, at sunrise the same day, American colors were displayed from all the forts, batteries and vessels in the harbor and at one o'clock the forts discharged seventy-six pieces, celebrating the glorious year of 1776.
The thirteen stars and thirteen stripes were unfurled at the battle of Brandywine, September 11, 1777, eight days after the official announcement of them at Philadelphia, and at Germantown on the 4th of October; they witnessed the operations against and the surrender of Burgoyne, after the battle of Saratoga, October 17, 1777. The sight of this new flag helped to cheer the patriots of the army amid their sufferings around the camp fires at Valley Forge the ensuing winter. The Stars and stripes waived triumphant at the surrender of Cornwallis at Yorktown September 19, 1781; looked down upon the evacuations of New York, November 25, 1783; and shared in all the glories of the latter days of the Revolution.
When Vermont and Kentucky were admitted into the Union in 1791 and 1792 respectively, the American flag had to be altered and Congress enacted that "from and after May 1, 1795 the flag of the United States be fifteen stripes and the Union be fifteen stars'. It was this flag which inspired Francis Scott Key when he saw it flying over Fort McHenry, to write what is now the national anthem, "The Star Spangled Banner".
In 1818 after five more states had gained admittance, The Congressional Act of April 4, 1818, signed by President Monroe, fixed the number of stripes at 13 and required that the number of stars equal the number of states; one star for each state, to be added to the flag on the 4th of July following the admission of each new state. The last new star, bringing the total to 50, was added on July 4, 1960, after Hawaii became a state.
Between 1818 and 1960, Congress passed several acts that changed the shape, design and arrangement of the flag and allowed for additional stars and stripes to be added to reflect the admission of each new state.
By Executive Order of President Taft (June 24, 1912), the proportions of the flag were established. Also provided for were the arrangement of the stars in six horizontal rows of eight each, a single point of each star to be upward.
The Executive Order of President Eisenhower (January 3, 1959) provided for the arrangement of the stars in seven rows of seven stars each, staggered horizontally and vertically.
President Eisenhower's Executive Order (August 21, 1959) provided for the arrangement of the stars in nine rows of stars staggered horizontally and eleven rows of stars staggered vertically.
The Stars and Stripes is the national and merchant flag and ensign of the United States of America with thirteen stripes (seven red and six white) of the first Union and 50 stars representing the fifty states of the union.
The flag of the President of the United States, is the National Ensign, the flag of the sovereign people of whom he is the popular representative, and from whom he derives power and authority. The President is empowered to design his own flag, but its field is always blue. As presently in use, it displays the presidential seal; this shows the American Eagle grasping in its talons the emblems of peace and war, thirteen arrows and an olive branch, having thirteen leaves. Thirteen stars appear around its head and it is surrounded by a circle of fifty stars, symbolizing the original and the present number of states in the Union. A shield of the national colors bearing seven white and six red stripes also appears, and the Latin motto E Pluribus Unum signifies "From Many, One". It is hoisted at the main and denotes his presence on board a war ship.
The Vice-President and members of the Cabinet (the Secretary of Navy excepted) are also designated by the national flag worn at the fore during their presence on board a vessel of war, and it always floats at the Capitol over the Senate-Chamber and House of Representatives whenever those bodies are in session, - a custom followed in all or most of the States of the Union whenever their legislative bodies are in session.
A special mark for the Secretary of the Navy, established in 1866, was a square blue flag having a white foul anchor placed vertically in the center with four white stars surrounding it, one in each corner of the flag.
Each of the States of our Union and the Territories have flags of their own. This flag is carried by the State militia into battle or on parade side by side with the national standard.
AMERICAN FLAG STORIES
"Old Glory!"
This famous name was coined by Captain William Driver, ship master of Salem, Massachusetts, in 1831. As he was leaving on one of his many voyages aboard the brig Charles Doggett friends presented him with a beautiful American flag of twenty four stars. As the banner opened to the ocean breeze for the first time, he exclaimed "Old Glory!" (This voyage would climax with the rescue of the mutineers of the Bounty).
Captain Driver retired to Nashville in 1837, taking his treasured American flag from his sea days with him. By the time the Civil War erupted, most everyone in and around Nashville recognized Captain Driver's "Old Glory." When Tennessee seceded from the Union, Rebels were determined to destroy his flag, but repeated searches revealed no trace of the hated banner.
Then on February 25th, 1862, Union forces captured Nashville and raised the American flag over the capital. It was a rather small ensign and immediately folks began asking Captain Driver if "Old Glory" still existed. Happy to have soldiers with him this time, Captain Driver went home and began ripping at the seams of his bed cover. As the stitches holding the quilt-top to the batting unraveled, the onlookers peered inside and saw the 24-starred original "Old Glory"!
Captain Driver gently gathered up the flag and returned with the soldiers to the capitol. Though he was sixty years old, the Captain climbed up to the tower to replace the smaller banner with his beloved flag. The Sixth Ohio Regiment cheered and saluted - and later adopted the nickname "Old Glory" as their own, telling and re-telling the story of Captain Driver's devotion to the flag we still honor today.
Captain Driver's grave is located in the old Nashville City Cemetery and is one of three (3) places authorized by act of Congress where the Flag of the United States may be flown 24 hours a day.
A caption above a faded black and white picture in the book, The Stars and the Stripes, states that 'Old Glory' may no longer be opened to be photographed, and no color photograph is available." Visible in the photo in the lower right corner of the canton is an applique anchor, Captain Driver's very personal note. "Old Glory" is the most illustrious of a number of flags - both Northern and Confederate - reputed to have been similarly hidden, then later revealed as times changed. The flag was given to his granddaughter or niece who later donated it to the Smithsonian.
Betsy Ross Maker of the First American Flag
According to popular legend, the first American flag was made by Betsy Ross, a Philadelphia seamstress who was acquainted with George Washington, leader of the Continental Army and other influential Philadelphians. In May 1776, so the story goes, General Washington and two representatives from the Continental Congress visited Ross at her upholstery shop and showed her a rough design of the flag. Although Washington initially favored using a star with six points, Ross advocated a five-pointed star, which she demonstrated, could be cut with just one quick snip of the scissors, and the gentlemen were won over. Thus, in May of 1776, Betsy Ross reported that she sewed the first American flag.
Unfortunately, historians have never been able to verify this version of events. Although it is known that Ross made flags for the Pennsylvania Navy. The story of Washington's visit to the flag maker became popular about the time of the country's first centennial, after William Canby, a grandson of Ross, told about her role in shaping U.S. history in a speech given at the Philadelphia Historical Society in March 1870.
What follows is the true story, to the best of our understanding.
Betsy would often tell her children, grandchildren, relatives and friends of the fateful day when three members of a secret committee from the Continental Congress came to call upon her. Those representatives, George Washington, Robert Morris and George Ross, asked her to sew the first flag. This meeting occurred in her home some time late in May 1776. George Washington was then the head of the Continental Army. Robert Morris, an owner of vast amounts of land, was perhaps the wealthiest citizen in the Colonies.
Colonel George Ross was a respected Philadelphian and also the uncle of her late husband, John Ross. Naturally, Betsy Ross already knew George Ross as she had married his nephew. Furthermore, Betsy was also acquainted with the great General Washington. Not only did they both worship at Christ Church in Philadelphia, but Betsy's pew was next to George and Martha Washington's pew.
Her daughter recalled, "That she was previously well acquainted with Washington, and that he had often been in her house in friendly visits, as well as on business. That she had embroidered ruffles for his shirt bosoms and cuffs, and that it was partly owing to his friendship for her that she was chosen to make the flag."
In June 1776, brave Betsy was a widow struggling to run her own upholstery business. Upholsterers in colonial America not only worked on furniture but did all manner of sewing work, which included making flags. According to Betsy, General Washington showed her a rough design of the flag that included a six-pointed star. Betsy, a standout with the scissors, demonstrated how to cut a five-pointed star in a single snip. Impressed, the committee entrusted Betsy with making our first flag.
Betsy Ross is often credited for creating the first American flag, yet, most probably she was the person responsible for sewing the first American flag. According to the legend, George Washington himself approached Elizabeth Ross in 1777 and asked her to create a flag from a sketch he drew. She then sewed this first flag for the new country. However, the story is open to interpretation. There is no record of this inciden discussed in any official or anecdotal documents of the time. In fact, the story was not told until 94 years after the event took place by one of Betsy Ross' grandsons, William J. Canby.
During the Revolutionary War, several patriots made flags for our new nation. Among them were Cornelia Bridges, Rebecca Young, and Elizabeth (Betsy) Ross, all of whom were from Pennsylvania, and John Shaw of Annapolis, Maryland.
Although Betsy Ross, the best known of these persons, made flags for 50 years, there is no proof that she made the first Stars and Stripes. It is known that she made flags for the Pennsylvania State Navy in 1777. The flag popularly known as the "Betsy Ross flag", which arranged the stars in a circle, did not appear until the early 1790's.
The claims of Betsy Ross were first brought to the attention of the public in 1870 by one of her grandsons, William J. Canby. In a paper he read before the meeting of the Historical Society of Pennsylvania, Canby stated:
"It is not tradition, it is report from the lips of the principal participator in the transaction, directly told not to one or two, but a dozen or more living witnesses, of which I myself am one, though but a little boy when I heard it. ... Colonel Ross with Robert Morris and General Washington, called on Mrs. Ross and told her they were a committee of Congress and wanted her to make a flag from the drawing, a rough one, which, upon her suggestions, was redrawn by General Washington in pencil in her back parlor. This was prior to the Declaration of Independence. I fix the date to be during Washington's visit to Congress from New York in June, 1776 when he came to confer upon the affairs of the Army, the flag being no doubt, one of these affairs."
More interesting than this legend, however, is the origin of the original flag having a circle of stars. An artist named Charles Weisgerber actually designed the flag in this manner for the painting, "Birth of Our Nation's Flag." This painting was eventually copied into American History texts and became 'fact'.
So what is the true origin of the flag?
It is believed that Francis Hopkinson, a Congressman from New Jersey and patriot, was the true designer of the flag. In fact, the journals of the Continental Congress show that he designed the flag.
Francis Hopkinson and the Design of the American Flag
Francis Hopkinson was a popular patriot, lawyer, Congressman from New Jersey, signer of the Declaration of Independence, poet, artist and distinguished civil servant. He almost certainly was the person who designed the first Stars and Stripes.
He was appointed to the Continental Navy Board on November 6,1776. It was while serving on the Continental Navy Board that he turned his attention to designing the United States flag. The use of stars in that design is believed to have been the result of an experience in the war directly related to his property.
A book in Hopkinson's library at his home in Bordentown was taken by a Hessian soldier in December 1776, a dark year of the war. The book, Discourses on Public Occasions in America (London, 1762) by William Smith,D.D., had been a gift to him by the author. The soldier, one I. Ewald, wrote on the inside cover that he had seen the author near Philadelphia and that he, Ewald, had taken the book from a fine country seat near Philadelphia. The book was subsequently given to someone in Philadelphia who returned it to Hopkinson. The soldier had written above and below Hopkinson's bookplate, which had three six pointed stars and his family motto, "Semper Paratus", or "Always Ready". The safe return of the book may well have symbolized to Hopkinson the revival of the Americans hope.
In a letter to the Board of Admiralty in 1780 Hopkinson asserted that he had designed "the flag of the United States of America" as well as several ornaments, devices and checks appearing on bills of exchange, ship papers, the seals of the boards of Admiralty and Treasury, and the Great Seal of the United States. Hopkinson had received nothing for this work and now he submitted a bill and asked "whether a Quarter Cask of the public wine" would not be a reasonable and proper reward for his labors.
The Board forwarded the letter to Congress, which referred it to the Board of Treasury. Apparently acting on a request from Congress, Hopkinson sent a detailed bill on June 6th, and it was sent to the auditor general, James Milligan. Milligan sent it to the commissioners of the Chamber of Accounts, who replied six days later on June 12th that they were of the opinion that the charges were reasonable and ought to be paid. Milligan gave the report a favorable endorsement and passed it on to the Board of Treasury. The board now raised objections and returned the bill to the auditor general on the grounds that no vouchers were included with the bill.
Hopkinson now submitted a new copy of his bill and itemized each charge but it was rejected once again and the auditor asked once more for its favorable consideration. After another round of referral through the departments, the board filed the correspondence and did nothing for two and half months. Fed up with the delay, Hopkinson wrote to Charles Lee, the secretary of the Board of Treasury, accusing him of lying about having received the amended bill and delaying the settlement of his claim. Lee failed to satisfy Hopkinson and the latter sent to Congress a list of charges against the board.
Just as in our modern times, Congress appointed a committee to investigate the matter. The various government officers concerned with the claim appeared before the committee at its request. Only the men of the Board of Treasury ignored the summons. In its report to Congress, the committee recommended that the present board be dismissed.
Congress sent the report back to the committee for further consideration and another investigation and another report followed. In its second report the committee noted that this time the members of the Board of Treasury answered the summons, but frequently tried to dictate the way in which the investigation should be made. The committee felt that the Treasury should be directed by a single individual responsible to Congress, but made no recommendation in regard to Hopkinson's claim. The matter remained unsettled until August 23rd,1781, when Congress passed a resolution asking that the claim be acted on. Meanwhile, Hopkinson had grown weary of the controversy and on July 23rd, 1781, he resigned his office as Treasurer of Loans. One of Hopkinsons chief opponents on the board of Treasury resigned the same day.
Between the first and second report of the committee, the Board of Treasury gave its own report to Congress on the history of the Hopkinson claim. Aside from the lack of vouchers, the members of the board knew that "Hopkinson was not the only person consulted" on the matter of designs and therefore could not rightly claim the whole amount and in addition, the board felt that the public was entitled to these extra services from men who drew high salaries.
Though Hopkinson's political adversaries blocked all attempts to have him paid for his services, they never denied that he made the designs. The journals of the Continental Congress clearly show that he designed the flag.
The design of the first Stars and Stripes by Hopkinson had the thirteen stars arranged in a "staggered" pattern technically known as quincuncial because it is based on the repetition of a motif of five units. This arraignment inevitably results in a strongly diagonal effect. In a flag of thirteen stars, this placement produced the unmistakable outline of the crosses of St. George and of St. Andrew, as used together on the British flag. Whether this similarity was intentional or accidental, it may explain why the plainer fashion of placing the stars in three parallel rows was preferred by many Americans over the quincuncial style.


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Q: Compactness Theorem- Why not Counterexample? The compactness theorem states that if every finite subset of a set of logical statements is consistent, then the overall set of statements is consistent.
So, why is the following set of statements (each of which could be formalized under the rules of predicate logic) about a given universe not a counterexample?

*

*There exists at least one distinct object in our universe.

*There exist at least two distinct objects in our universe.

*There exist at least three distinct objects in our universe.

*There exist at least four distinct objects in our universe.

...

*

*There exist finitely many distinct objects in our universe.

Any finite subset of these statements is consistent, yet the overall set is inconsistent.  Is this not a counterexample because the last sentence cannot be formalized in first-order predicate logic?

A:
(each of which could be formalized under the rules of predicate logic)

...

There exist finitely many distinct objects in our universe.

Are you sure that last statement is actually appropriately expressible? Indeed, the compactness theorem shows that it isn't.
(In other words, the very last line of your post is exactly right.)