Environmental conflicts might arise out of clashes of different interests or because of the existence of different values. Take mangroves for instance, on the coast of Ecuador. Some people want to preserve them against the shrimp industry because they appreciate their ecological and aesthetic values. Other people want to preserve them because they make their livelihood and survive from them, and/or because they understand their practical role in coastal defence and as fish breeding grounds. Other people (or the same people, in other contexts) might appeal to the sense of culture and place that mangroves provide for their traditional inhabitants. They might even argue that there are sacred mangroves.
In all cases, environmental conflicts are expressed as conflicts of valuation, either within the parameters of one single standard of valuation or across plural values (Munda, 2008). Thus, in a gold mining conflict, the company will probably argue in terms of the money to be gained (and shared locally for employment, taxes and royalties), while the opposition may argue in terms of the uncertain risks to health from cyanide used in open cast mining, in terms of damage to water availability, in terms of the infringement of indigenous rights to the territory under Convention 169 of ILO, or in terms of the sacredness of a mountain or a river.
Which then is the true value of 1 pound of farm-raised shrimp or the true value of an ounce of gold? Who has the power to simplify complexity, ruling some viewpoints as out of order? These questions demonstrate that conventional conflict resolution through cost-benefit analysis and monetary compensation is inappropriate, because in simplifying complex value systems related to the environment into monetary units, it denies the legitimacy of other languages.
Munda, G. (2008) Social Multi-criteria Evaluation for a Sustainable Economy, Heidelberg, Springer.


Situated alongside the White Bay Passenger terminal, opposite the White bay Power Station and right beside the Anzac Bridge leading into the CBD, Oxford Agency are pleased to present this unique warehouse/showroom opportunity to the market.
This warehouse occupies an unbeatable 100m frontage along Mullens Street Rozelle, which operates as the main thoroughfare for motorists off the Anzac Bridge into the heart of Balmain.
Capitalise on this Inner West emerging market and the upcoming Bays precinct development which is going to provide unlimited growth opportunity over the coming years.
Parking Facilities are available along Robert Street.


text:
package org.mycontroller.standalone.db.tables;

import org.apache.commons.lang.builder.ToStringBuilder;

import com.fasterxml.jackson.annotation.JsonIgnoreProperties;
import com.j256.ormlite.field.DatabaseField;
import com.j256.ormlite.table.DatabaseTable;

/**
 * @author Jeeva Kandasamy (jkandasa)
 * @since 0.0.1
 */
@DatabaseTable(tableName = "settings")
@JsonIgnoreProperties(ignoreUnknown = true)
public class Settings {
    public static final String AUTO_NODE_ID = "auto-node-key";
    public static final String MC_VERSION = "mc-version";
    public static final String MC_DB_VERSION = "mc-db-version";
    public static final String LAST_ONE_DAY_AGGREGATION = "last_one_day_aggregation";
    public static final String SUNRISE_TIME = "timer-sunrise";
    public static final String SUNSET_TIME = "timer-sunset";
    public static final String CITY_NAME = "city_name";
    public static final String CITY_LATITUDE = "city_latitude";
    public static final String CITY_LONGITUDE = "city_longitude";
    public static final String DEFAULT_FIRMWARE = "default_firmware";
    public static final String ENABLE_NOT_AVAILABLE_TO_DEFAULT_FIRMWARE = "not_available_to_default_firmware";

    public static final String EMAIL_SMTP_HOST = "email_smtp_host";
    public static final String EMAIL_SMTP_PORT = "email_smtp_port";
    public static final String EMAIL_SMTP_USERNAME = "email_smtp_username";
    public static final String EMAIL_SMTP_PASSWORD = "email_smtp_password";
    public static final String EMAIL_ENABLE_SSL = "email_enable_ssl";
    public static final String EMAIL_FROM = "email_from";

    public static final String SMS_AUTH_ID = "sms_auth_id";
    public static final String SMS_AUTH_TOKEN = "sms_auth_token";
    public static final String SMS_FROM_PHONE_NUMBER = "sms_from_phone_number";

    public static final String SERIALPORT_NAME = "serialport_name";
    public static final String SERIALPORT_BAUD_RATE = "serialport_baud_rate";
    public static final String SERIALPORT_DRIVER_TYPE = "serialport_driver_type";

    public static final String GRAPH_INTERPOLATE_TYPE = "graph_interpolate_type";

    public static final String DEFAULT_UNIT = "du_";

    public static final String ENABLE_SEND_PAYLOAD = "enable_send_payload";

    public static final String MY_SENSORS_CONFIG = "mys_config";

    public static final String MC_LANGUAGE = "mc_language";

    public static final String MC_TIME_12_24_FORMAT = "mc_time_12_24_format";

    public Settings() {

    }

    public Settings(String key, String value, String frindlyName) {
        this(key, value, frindlyName, null);
    }

    public Settings(String key, String value, String frindlyName, Boolean userEditable) {
        this.key = key;
        this.value = value;
        this.frindlyName = frindlyName;
        if (userEditable == null) {
            this.userEditable = false;
        } else {
            this.userEditable = userEditable;
        }

    }

    public Settings(String key) {
        this.key = key;
    }

    @DatabaseField(generatedId = true)
    private Integer id;
    @DatabaseField(canBeNull = false, unique = true)
    private String key;
    @DatabaseField(canBeNull = false)
    private String frindlyName;
    @DatabaseField(canBeNull = true)
    private String value;
    @DatabaseField(canBeNull = true)
    private Boolean userEditable = false;

    public String toString() {
        return ToStringBuilder.reflectionToString(this);
    }

    public String getKey() {
        return key;
    }

    public void setKey(String id) {
        this.key = id;
    }

    public String getValue() {
        return value;
    }

    public void setValue(String value) {
        this.value = value;
    }

    public String getFrindlyName() {
        return frindlyName;
    }

    public void setFrindlyName(String frindlyName) {
        this.frindlyName = frindlyName;
    }

    public Boolean getUserEditable() {
        return userEditable;
    }

    public void setUserEditable(Boolean userEditable) {
        this.userEditable = userEditable;
    }

    public Integer getId() {
        return id;
    }

    public void setId(Integer id) {
        this.id = id;
    }
}

redpajama_set_name: RedPajamaGithub


Monitored vital signs, such as temperature, weight, height, blood pressure and pulse.
Performed procedures and uses equipment as delegated by a licensed professional, including EKGs.
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This page lists and includes all events and ideas out of the city of Lille. The outing ideas are sorted by date and available in English and French. You can also follow us on Twitter to be informed of the latest developments and ideas out on the town.


text:
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A New Perspective on the Past, Present and Future of Toxicity Testing
Home / New Perspectives / Overarching Challenges / A New Perspective on the Past, Present and Future of Toxicity Testing
Overarching Challenges
Sunita Shukla, NIH Chemical Genomics Center Published: December 4, 2009
Dr. Shukla received her B.A. in 1999 from Saint Louis University with a major in English and minor in Biology. Upon graduation, she completed a Master of Public Health at Saint Louis University in 2001 with a focus on Epidemiology and Environmental/Occupational Health. During her MPH, Sunita held a fellowship at Washington University School of Medicine looking at worker compliance with isoniazid therapy. From 2002-2007, Sunita earned a PhD in Human Genetics, with a focus on pharmacogenetics of anticancer agents, from the University of Chicago in the lab of Dr. Eileen Dolan. During this period, Sunita contributed to several peer-reviewed publications that reported on the use of lymphoblastoid cell lines in order to identify genetic determinants of resistance or toxicity to various chemotherapeutic agents, including cisplatin and carboplatin. During the last year of her PhD, Sunita held an internship at Abbott Laboratories and worked on clinical trial protocols pertaining to concurrent therapies. In 2007, Sunita began a postdoctoral fellowship at the NIH Chemical Genomics Center and is working in various areas including pregnane X receptor, signaling pathways, and high content imaging under the guidance of Drs. Menghang Xia and Douglas Auld. In the area of toxicology, Sunita is working on in vitro toxicological assays which may be useful to generate predictive models. These models may be used to predict toxicity of chemical compounds in vivo in order to develop more cost effective alternatives to animal testing.
Sunita J. Shukla, MPH, Ph.D.
NIH Chemical Genomics Center
Email: shuklasu@mail.nih.gov
(Editors' note: In December 2008, the founders of AltTox—the Procter & Gamble Company and the Humane Society of the United States—bestowed the North American Alternatives Award on the principal architects of the US government's "Tox21" program (North American Alternative Awards Announced). The winners included Christopher Austin of the NIH Chemical Genomics Center (NCGC), Raymond Tice of the National Toxicology Program (NTP), and Robert Kavlock of the Environmental Protection Agency (EPA). They decided to use the $25,000 prize money to partially fund a post-doctoral fellow working on the Tox21 program at the NCGC (Tox21: Putting a Lens on the Vision of Toxicity Testing in the 21st Century). The AltTox Management Team recently invited this post-doctoral fellow—Sunita Shukla—to contribute an essay to The Way Forward series, providing her perspective as a young scientists contributing to the transformation of toxicology as it moves into the 21st century.)
This is an exciting time to be young post-doctoral fellow at the NIH Chemical Genomics Center (NCGC), especially as we carry out our share of the research associated with the Tox21 program. I have the opportunity to reflect on a unique point in time with regard to toxicity testing. Regardless of the advancements made in recent years, the resonating goal in the international toxicology community is the reduction of in vivo testing and the development of alternative in vitro methods.
Traditionally, animal models have been used to extrapolate potentially harmful events in humans. These models have been specifically developed to evaluate toxicological endpoints such as oral, dermal and ocular toxicity; immunotoxicity; genotoxicity; reproductive and developmental toxicity; and carcinogenicity. However, there are major initiatives, outlined below, which have sought to combine existing methods with new technologies in order to utilize in vitro methods as predictive models for in vivo response.
As someone who has a background in public health and genetics, I agree with the need to move the field towards translational toxicology. In other words, the current paradigm should focus on using new tools and technologies to make population risk decisions regarding hazardous environmental and chemical agents. Broadly speaking, this paradigm shift will ultimately require an intersection between toxicology, genetics, informatics, and public health.
The intersection of various disciplines should enable researchers to focus on a battery of in vitro methods that will test detect changes in the underlying biology involved in toxicity pathways resulting from environmental perturbation (Andersen and Krewski, 2009). Furthermore, this paradigm shift may be a welcomed movement away from traditional high dose hazard studies in vivo (Andersen and Krewski, 2009). In order to appreciate the scientific and technological advancements which are shaping toxicity testing today, it is important to appreciate where this fits in the context of historical testing.
A Review of Traditional Testing Methods
As a newcomer to the field of toxicology, I have been reading about the challenges and proposed solutions to reducing animal testing. Previous toxicity testing has relied on animal models treated at high doses over a period time, with the results extrapolated to human health outcomes at lower doses. This approach dates back to the 1950s, when the utilization of animal models and knowledge of the underlying response was primitive (Krewski, et al., 2009). Furthermore, in vivo testing has been costly, time consuming and low throughput (Xia, et al., 2008). Previously, complete toxicological profiling of one chemical in standard whole-animal toxicity assays consisted of 8 toxicity tests: acute, sub-chronic, and chronic toxicity; reproductive toxicity; developmental toxicity, ocular and skin irritation, hypersensitivity; phototoxicity; and toxicokinetic studies (Goldberg and Frazier, 1989).
Despite the disadvantages associated with animal testing, the majority of our understanding regarding chemical toxicity has come from animal data (Zurlo, et al., 1993). However, extensive animal testing did not provide a mechanistic understanding of chemical toxicity, and knowledge concerning adverse risks to humans was still inadequate (Rowan, 1983). Hence, a need for more mechanistic data and "theoretical framework for rational decision making" was noted in the early 1980s (Rowan, 1983).
More recently, there have been numerous studies highlighting the intra- and inter-species differences in mammals, including humans. Williams and Weisburger (1993) pointed out that intra-species differences between different strains of mouse affect the severity and incidence of neoplasms and can affect extrapolation of various cancers from mice to humans. Inherent resistance to spontaneous and malignant tumors in nonhuman primate models has also led to the variation in the manifestation of disease across these species (Beniashvili, 1994). In addition to inter and intra-species differences in disease models, other species differences which affect disease outcome and extrapolations include differences in basal metabolic rate, metabolic pathways, cancer type (sarcomas in mice versus carcinomas in humans), genetic aberrations associated with tumors, and telomere biology (Rangarajan and Weinberg, 2003).
In order for a new generation of toxicologists to understand how new approaches will advance the field, it is appropriate to understand previous strategies and origins of current regulatory agencies (National Research Council (NRC), 2007). In 1938, the Food, Drug, and Cosmetic Act (FDCA) was passed in order to monitor drug safety prior to marketing, based on animal toxicity studies (NRC, 2007). In the following years, clinical trials became more prevalent and the Food and Drug Administration (FDA) developed its first protocols pertaining to toxicity testing during the 1950s (NRC, 2007). Since this time, there have been several critical pieces of legislation which have established standards for food and pesticide levels.
Agencies such as the Environmental Protection Agency (EPA, 1970) and the National Toxicology Program (NTP, 1978) were created to evaluate pesticides and environmental pollutants, coordinate toxicology-based testing programs within the federal government and provide scientific information regarding toxicity testing to appropriate health agencies, professionals and the public (NRC, 2007). The role of the NTP is especially pertinent because of its ability to evaluate toxicity testing strategies based on new tests and approaches, such as its initiation of the development of high throughput screening to assess a large number of chemical entities. Furthermore, the NTP and its activities could be seen as a successful program that takes a multi-disciplinary approach regarding the initiation and implementation of new methods in toxicity testing.
NIH Roadmap for Medical Research and Toxicity Testing in the 21st Century: A Paradigm Shift
A recent report from the National Academy of Sciences termed Toxicity Testing in the 21st Century (NRC, 2007) has become the vision and roadmap for toxicology by calling for the development and utilization of more predictive in vitro models of biological response. Furthermore, the advent of technological innovations in molecular biology has prompted the NTP to incorporate these advances into new testing strategies encompassing broader scientific knowledge from other sources. The NTP created its roadmap titled "A National Toxicology Program for the 21st Century" (National Toxicology Program, 2004) where the goal is to take advantage of emerging research opportunities and provide a framework for setting research priorities. The NTP Roadmap has identified three main areas for toxicity testing in the 21st century including refining traditional toxicology assays, developing rapid mechanism-based predictive screens, and improving the overall utility of NTP products for public health decisions (National Toxicology Program, 2004). The NTP Roadmap places an increased emphasis on the use of alternative assays for identifying key pathways and molecular mechanisms linked to disease. These less expensive, higher throughput assays can be used to screen a larger number of compounds and prioritize them for testing programs. Furthermore, high throughput testing of compounds may allow for the rapid and more accurate prediction of in vivo biological responses.
In order to meet the goals outlined in the Roadmap and to address the needs outlined in the NRC report, the NTP partnered with the NIH Chemical Genomics Center (NCGC) in 2004 and the EPA in 2006. The major goals of the collaboration rest upon the identification of mechanisms involved in chemical-induced biological activity, prioritization of chemicals of further toxicological evaluation and the development of more in vitro predictive models of in vivo response (Austin, et al., 2008).
A central aspect of the Tox21 collaboration is NCGC's ability to utilize its robotic automation technology to test hundreds of thousands of compounds in titration-based format over a short period of time (Austin, et al., 2008). To fully appreciate the scope of NCGC's role in Tox21, it is important to understand its relationship with the Molecular Libraries Initiative (MLI). The MLI is a component of the NIH Roadmap for Medical Research, established in 2004, to respond to challenges facing biomedical research and expand the availability and use of chemical probes (Austin, et al., 2004; http://nihroadmap.nih.gov/molecularlibraries/). The MLI was born from the need for new approaches to determine function and therapeutic potential for newly sequenced genes and the need to accelerate the pace at which basic research is translated into new therapeutics (Austin, et al., 2004).
Additional components of the MLI include: (i) the establishment of a nation-wide consortium of small molecule screening centers, including NCGC, with access to over 300,000 chemically diverse small molecules; (ii) a comprehensive database of chemical structures and their biological activities from HTS assays (www.pubchem.ncbi.nlm.nih.gov); (iii) technology development supporting the development of new chemically diverse libraries, the development of new high-throughput instrumentation and assay diversity enabling the design of pharmacologically relevant tools to explore cellular function (http://nihroadmap.nih.gov/molecularlibraries/); and (iv) development of datasets and algorithms for improved prediction of ADME/toxicity of small molecules in various assays/tissue types (Austin, et al., 2004).
Traditional biological assays have been low-throughput, employing animal models and labor-intensive testing of samples. However, the growth of small molecule collections required the development of high throughput screening (HTS) technologies (Schnecke and Bostrom, 2006). NCGC has built upon the HTS technology and developed its own quantitative high throughput screening (qHTS) paradigm, in which a titration-based screening approach is used to test upward of a million small molecules, while reducing false negative and positive rates. Furthermore, qHTS was developed to increase the rate and efficiency of chemical probe development in addition to providing valuable publicly available data through PubChem against various cell-based and biochemical assays. As outlined above, NCGC is an example of how technology-driven translational research has been successfully used to characterize toxicity endpoints in cell-based assays.
Various assays that are part of Tox21 are performed at NCGC. These assays are primarily focused on general toxicity/cytotoxicity (Huang, et al., 2008; Xia, et al., 2008), pathway-specific toxicological mechanisms (Xia, et al., 2009a; Xia, et al., 2009b; Xia, et al., 2009c) and target-specific toxicological mechanisms. In one example study, cytotoxicity across various human and rodent cell lines was assessed for 1,353 compounds from the NTP collection (Xia, et al., 2008). Within the subgroup of active compounds, multiple effects from the compounds were identified within and across compound types, cell types and species. For example, there were human and rodent-derived cells that were most sensitive to compound-induced cytotoxicity, whereas human fibroblast and skin cells were the least sensitive. Overall, rodent cells demonstrated more sensitivity than human cells. A striking finding was the lack of concordance in the patterns of compound activity in cells derived from the same tissue but from different species (there were also instances where cells with similar tissue origin in the same species showed discordance in compound activity profiles), highlighting intra-tissue differences in response. Variation in cellular differentiation may be one reason why specific cell types are more sensitive to compounds than others.
To examine the specific mechanism of cytotoxicity in various tissue types, two different endpoints (cell viability and caspase activation) were assessed with regard to testing 1,353 compounds in human and rat cell types using a qHTS platform (Huang, et al., 2008). Hierarchical clustering based on compound EC50/IC50 patterns revealed similar clustering based on endpoints rather than cell type, indicating that viability and caspase assays provide distinct sets of information and that most compounds induce toxicity through mechanisms in addition to caspase activation.
Although attractive, target-based screens may lead to the identification of active compounds which do not retain their activity in a physiological environment (Xia, et al., 2009b). Thus, cell-based cell signaling assays offer an alternative assay format in which the readout is dependent on specific components acting on a single signaling pathway. Consequently, NCGC has utilized qHTS in such assays, which was most recently demonstrated in the identification of compounds that potentiate the cyclic-AMP Response Element Binding (CREB) pathway (Xia, et al., 2009b). CREB is a protein involved in learning and long-term memory through binding to cAMP Responsive Elements (CRE) in order to regulate the transcription of genes. Over 73,000 compounds were screened in 7-15 concentration points for CREB enhancer activity in a cell-based CRE reporter gene assay. Approximately 1,800 compounds were classified as potentiators of CREB activity, allowing for structure-activity relationships (SAR) to be deciphered on active compounds. Several chemical series were identified containing compounds with known and novel biological activities. Furthermore, multiple mechanisms of the CREB signaling pathway were interrogated using qHTS to better characterize compound mechanism of action. This particular study highlights the use of qHTS coupled with various assay formats (cell-based and enzymatic), follow-up assays, SAR and multiple pathway targets in order to accelerate the development of chemical probes for drug discovery in this pathway.
Future Directions and Responsibilities
The MLI and Tox21 endeavors have become increasingly important initiatives by paving the way for new collaborations and technologies to accelerate scientific discoveries. In addition, these initiatives generated public interest in next-generation testing methods and in alternative approaches to existing ones. In the midst of these initiatives, NCGC is playing a critical role in utilizing and validating in vitro approaches for modeling in vivo responses.
The examples given here are only a few of the studies that utilize qHTS and various in vitro models to study specific endpoints or pathways in humans and rodents. Furthermore, the combination of qHTS and in vitro methods has allowed the screening of hundreds of thousands of compounds in millions of wells in an efficient manner and short amount of time. Most importantly, the production of concentration response curves for every compound tested provides a data rich resource for SAR analysis, computational modeling and chemical prioritization for more extensive toxicological evaluation. NCGC has recently developed a fragment-based approach to modeling toxicity, which is designed to achieve good prediction with structurally diverse sets of compounds (Huang, et al., 2009). Ultimately, this process enables the rapid development of chemical probes which may ultimately become novel therapeutics in a variety of diseases.
Through collaborative efforts and expertise found at NCGC, future goals include the inclusion of new platforms for qHTS (such as high content screening and nanotechnology), assessment of genetic variation involved in human and rodent toxicity, prioritization of toxicity assays which assess key human toxicity endpoints, expansion of compounds tested, and creation of public databases harboring the aforementioned screening data.
The future of toxicology and testing in the 21st century will be a community-wide effort and will warrant continual improvements in technology and development of alternative animal models to better predict public health outcomes. We are headed in the right direction, but must not lose sight of how to bridge the enormous gap between data and regulatory practice. Thus, it is especially important for young toxicologists to continually interrogate models, methods and data from all platforms. Additionally, it is important to become involved in international efforts of refining practices and incorporating new strategies which may one day become the very foundation for toxicity testing.
©2009 Sunita Shukla
Andersen, M.E. & Krewski, D. (2009). Toxicity testing in the 21st century: Bringing the vision to life. Toxicol. Sci. 107, 324-330.
Austin, C.P., Kavlock, R. & Tice, R.R. (2008). Tox21: Putting a Lens on the Vision of Toxicity Testing in the 21st Century. Tox21: Putting a Lens on the Vision of Toxicity Testing in the 21st Century
Austin, C.P., Brady, L.S., Insel, T.R. & Collins, F.S. (2004). NIH Molecular Libraries Initiative. Science. 306, 1138-1139.
Beniashvili, D. (1994). Experimental Tumors in Monkeys, CRC Press.
Goldberg, A.M. & Frazier, J.M. (1989). Alternatives to animals in toxicity testing. Sci. Am. 261, 24-30.
Huang, R., Southall, N., Cho, M.H., Xia, M., Inglese, J. & Austin, C.P. (2008). Characterization of diversity in toxicity mechanism using in vitro cytotoxicity assays in quantitative high throughput screening. Chem. Res. Toxicol. 21, 659-667.
Huang, R., Southall, N., Xia, M., Cho, M.H., Jadhav, A., Nguyen, D.T., Inglese, J., Tice, R.R. & Austin, C.P. (2009). Weighted feature significance: A simple, interpretable model of compound toxicity based on the statistical enrichment of structural features. Toxicol. Sci. 112, 385-393.
Krewski, D., Andersen, M.E., Mantus, E. & Zeise, L. (2009). Toxicity testing in the 21st century: Implications for human health risk assessment. Risk Anal. 29, 474-479.
National Research Council (NRC). (2007). Toxicity Testing in the 21st Century: A Vision and a Strategy, National Academy Press, Washington, D.C.
National Toxicology Program. (2004). A National Toxicology Program for the 21st Century: A Roadmap for the Future. http://ntp.niehs.nih.gov/files/NTPrdmp.pdf
Rangarajan, A. & Weinberg, R.A. (2003). Opinion: Comparative biology of mouse versus human cells: Modelling human cancer in mice. Nat. Rev. Cancer. 3, 952-959.
Rowan, A.N. (1983). Alternatives: Interaction between science and animal welfare. In: Product Safety Evaluation (ed. AM Goldberg), pp 113-133. Mary Ann Liebert, Inc., New York.
Schnecke, V. & Bostrom, J. (2006). Computational chemistry-driven decision making in lead generation. Drug Discov. Today. 11, 43-50.
Williams, G. & Weisburger, G. (1993). Chemical carcinogenesis. Toxicology, The Basic Science of Poisons, McGraw-Hill, New York.
Xia, M., Huang, R., Witt, K.L., Southall, N., Fostel, J., Cho, M.H., Jadhav, A., Smith, C.S., Inglese, J., Portier, C.J., Tice, R.R. & Austin, C.P. (2008). Compound cytotoxicity profiling using quantitative high-throughput screening. Environ. Health Perspect. 116, 284-291.
Xia, M., Guo, V., Huang, R., Inglese, J., Nirenberg, M. & Austin, C.P. (2009a). A Cell-based beta-Lactamase Reporter Gene Assay for the CREB Signaling Pathway. Curr. Chem. Genomics. 3, 7-12.
Xia, M., Huang, R., Guo, V., Southall, N., Cho, M.H., Inglese, J., Austin, C.P. & Nirenberg, M. (2009b). Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory. Proc. Natl. Acad. Sci. U.S.A. 106, 2412-2417.
Xia, M., Huang, R., Sun, Y., Semenza, G.L., Aldred, S.F., Witt, K.L., Inglese, J., Tice, R.R. & Austin, C.P. (2009c). Identification of chemical compounds that induce HIF-1alpha activity. Toxicol. Sci. 112, 153-163.
Zurlo, J., Rudacille, D. & Goldberg, A.M. (1993). Animals and Alternatives in Testing: History, Science, and Ethics, Mary Ann Liebert, Inc.
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redpajama_set_name: RedPajamaCommonCrawl


For most people, peanuts and tree nuts are yummy protein rich foods, though for an increasing number of Canadian children with serious allergies, peanuts and tree nuts might as well be arsenic, radioactive waste, or the kryptonite to an otherwise healthy and carefree childhood. First of all, when it comes to discussing nut allergies, the most common question is why the separate referencing between peanuts and other nuts? The reason is because a true nut grows in trees, whereas peanuts grow in the ground and are thus placed in a different categorical family. An allergy to both peanuts and tree nuts is common, as the protein in peanuts is similar in structure to tree nut protein. Nevertheless, there are cases where a person can safely consume peanuts but not tree nuts and vice versa.
According to the York Region Health Services Department, genetics is the prime factor in determining whether a child will develop a nut allergy. If a baby has at least one parent or sibling with a diagnosed food allergy, then she would be considered a high-risk for also developing an allergy. On the other hand, if neither parent nor sibling has a food allergy, then it would be considered unnecessary to restrict certain foods from your baby's diet for groundless worrying.
Some women have tried to prevent the onset of a food allergy in their unborn baby by avoiding the particular allergen foods during pregnancy. There is no proof that this practice works, but there is evidence to justify that it can lead to malnutrition for both the mother and unborn baby. Breastfeeding, on the other hand, is proven to be a preventative against food allergies. Health Canada recommends that mothers exclusively breastfeed their babies for the first six months and continue with supplemental breastfeeding until age two at a minimum. No research has confirmed that avoiding allergen foods while breastfeeding will reduce the risk of developing a food allergy. When it comes to introducing nuts into a high-risk baby's diet, the jury is still out. Researcher have not quite agreed on the best time to try your baby on the potential allergens, but the general advice is that peanuts and tree nuts should not be offered to your child until she is three years old. That being said, it must be noted that delaying a child's exposure to peanuts and nuts will not prevent the development of an allergy, only postpone it. When introducing peanuts and nuts, only give a teaspoon amount to your baby in the morning, while keeping tabs on her throughout the day to monitor for an allergic reaction. If there is no reaction, you can up the amount of the food as the week goes on. Medical experts advise that only one new food item should be introduced to your baby each week. Make sure that it is either pure peanuts or nuts your baby is consuming. However, in case your baby has a mild allergic reaction to any of the nuts, wait a month before trying her out on nuts again. Obviously, a severe allergic response requires immediate emergency, medical attention. If a month has past and your baby still has the mild allergy to nuts, go see your doctor.


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White House has held multiple pardon meetings since the election
Posted December 3, 2020 3:23 p.m. EST
By Pamela Brown and Gloria Borger, CNN
CNN — With a rush of pardons expected before President Donald Trump leaves office, the White House has been holding multiple pardon meetings since the election, involving the White House counsel's office and other staff, two senior administration officials told CNN.
The meetings include a list of potential pardon cases to be considered and ideas of who else should be included. White House officials such as Trump's son-in-law Jared Kushner have weighed in, but the White House counsel's office runs the meetings, one of the sources said.
While such meetings are not unusual and past presidents have issued pardons on their way out, the President's past clemency for allies, such as Michael Flynn and Roger Stone, and potential preemptive pardon considerations for his family, bring an added dimension.
The Trump White House also acts fast once the President makes a decision, at times without Justice Department involvement, according to sources.
The White House declined to comment when reached out to by CNN.
Three sources with knowledge of the situation told CNN Kushner has not been personally involved in advocating for his own father, Charles Kushner, to get a pardon for his felony, but two of the sources said outside criminal justice groups who worked with Jared Kushner in the past have petitioned the White House to consider the pardon.
It's known Kushner would like one, according to one source, and it's so evident it doesn't need to be discussed since the President is aware.
In 2004, Charles Kushner pleaded guilty to 16 counts of tax evasion, one count of retaliating against a federal witness -- his brother-in-law -- and another count of lying to the Federal Election Commission.
CNN previously reported that associates in Trump's orbit, including his personal lawyer Rudy Giuliani, have approached the President to seek preemptive pardons. The President has also been talking with advisers about preemptively pardoning several people close to him, including his children and Jared Kushner.
The President has told advisers he feels he and his family have been unfairly targeted and that he's concerned the legal pursuits could continue under the Biden Justice Department. Lawyers and allies of the President have been lobbying him for pardons ranging from their personal clients to people who Vice President-elect Kamala Harris put behind bars, according to multiple people. She was a state prosecutor and pardons only apply to federal crimes.
CNN reported Wednesday that the public should expect a "flurry" of pardons before Trump leaves office, a source close to the White House says, as has happened at the end of previous administrations.
This source, familiar with discussions on the matter, told CNN some of the President's advisers believe that it would perfectly fine for Trump to pardon his family members and other associates preemptively, even though they haven't been charged with any crimes.


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Ctrls
CtrlS appoints Royce Thomas as President and Chief Business Officer
Royce joins CtrlS from Equinix, where he served as Senior Vice President, Strategic Alliances and Global Account Management. Earlier, he held senior leadership roles at Level 3 Communications and Sprint.
India's Northeast gets first Rated-4 Datacenter
The government of Assam invites CtrlS to build a Rated-4 Datacenter in Tech City Park
Is the cloud really cheaper than in-house IT?
In this week's story, we discuss why the cloud ends up being more expensive and why enterprises still want to continue using it. More importantly, what are the ways in which you can control your expenses on the cloud and make it a more viable alternative to on-premise setups?
CtrlS to set up its third and largest data centre in Hyderabad
The new data centre will be coming up in Financial District in the neighbourhood of the ICICI Regional Centre, Microsoft, Capgemini, Amazon, among others, and is slated to come up over the next 12 months or so.
Is it enough to rely on the cloud for backups?
You can perhaps take a leaf out of some of the leading enterprises' playbooks on how best to deal with cloud backups as we go through the same in detail in this week's newsletter.
CtrlS appoints Dillip Guru as SVP International DC Expansion, Renewable Energy & Edge Strategy
At CtrlS, he will be responsible for providing strategic direction in the company's efforts to expand in international markets.
CtrlS to deploy 1.2GW gas insulated substations to power data centers
CtrlS Datacenters, the Hyderabad-headquartered data centre player, is deploying one of Asia's largest gas insulated substations (GIS) to power its cluster of 10 data centres coming up at Navi Mumbai.
KFin Technologies achieved competitive advantages with CtrlS
Sreekanth Nadela, CEO, KFintech Technologies talks about new-age technologies and the company's business strategy. He along with the company's CTO highlighted a few competitive advantages and benefits gained after working with CtrlSKFin Technologies achieved competitive advantages with CtrlS
CtrlS appoints former RCom executive Bill Barney to its Board of Directors
"We look forward to Bill advising the company as we continue to build and scale our business by establishing hyperscalar data centers around the world," said Sridhar Pinnapureddy, Founder and CEO, CtrlS.
CtrlS building world class Hyperscale Tier-4 Data center facility in India
Company lines up 2,000 crore to build three hyperscale facilities in the country.
CtrlS to invest Rs 2,000 cr to set up world's largest tier-4 datacentre footprint in India
The demand for data storage has boomed in the country and data localisation is also creating huge demand for hyperscale datacentre in India.
We are gearing up to build hyper scale data centres: Sridhar Pinnapureddy, CtrlS
After meeting its geographical expansion target in India, CtrlS is now looking to ride the next wave of datacentre trend – building large scale datacentre campuses.
CtrlS plans to invest Rs 1,500 cr in datacentre expansion
"We are going to set-up a hyper scale datacentre in Hyderabad with 100 megabyte capacity equivalent to about 1 million square feet in tier 4 category.
CtrlS Tier-4 Datacentre to lend huge advantages to businesses in India's Silicon Valley
The facility is expected to provide India's growing tech giants with reliable, robust data management and distribution networks, with near zero downtime, 100% redundancy and industry's lowest PUE.
CtrlS plans to invest Rs 1,200 crore in next 3 years
Funds to be used for Research and Development (R&D) activities and upgradation of infrastructure at its data centres at Hyderabad, Noida, Chennai and Mumbai.
Bengaluru gets one of the world's biggest Tier4 datacenters
Comprehending SaaS Apps can help CIOs add unique value to business: CEO, CtrlS
According to Sridhar Pinnapureddy, Founder and CEO of CtrlS Datacenters, for a CIO to deliver value to his organization, he would have to develop a thorough understanding of the cloud ecosystem and the interesting services that have come up because of SaaS.
IT strategy should focus on ensuring the infrastructure availability: Anil Nama, CIO – CtrlS
In this interview, Anil Nama, CIO – CtrlS Datacenter talks about company's IT strategy, the challenges of managing and driving the datacenter infrastructure as a CIO and trends in the datacenter space
CtrlS announces partnership with SAP for SAP HANA Enterprise Cloud
Under this partner, SAP plans to leverage CtrlS's IT infrastructure and managed services to expand the reach of its HEC platform across the Asia Pacific region including India


Do not ever buy the combination lock and the bike vm-02 models!!! WARNING!!!
okay, so you want to know what i think of the combination lock model? the combination lock model does not work at all because parts do not fit together very well because ugears is cheap ukrainian rubbish designed to relieve people of their wallets. the same can also be said of the bike vm-02 model as well. the only positive thing i can say is that you get free rubber bands and free cocktail sticks. it would be so much better if models did not require the fitting of rubber bands and the cutting of cocktail sticks to specific lengths. i want a refund (for the commbination lock model, two lots because i purchased two of the combination lock models because one of the parts snapped the first time round, and the bike vm-02 model, because i have junked them and put them in the bin), and i am never ever buying another thing from ugears. f*** you.
I cannot actually review your product as I purchased it for a friend but I will say that dealing with your company was a pleasant experience. The online ordering was acceptionally easy. The item arrived earlier than was expected which is always a plus. I'm waiting to hear back from my friend once he finds time in his busy life to put it together. Will write another review when that happens.
Ordered two different models from Ugears, both arrived from the UK to the US intact and in excellent time (one had to be sent on to New Zealand), and both produced exactly the fascinated and engrossed facial expressions on their adult male recipients that I had been hoping for as they put them together.


With broad experience in all aspects of commercial real estate law, Tessa represents developers of multi-family residential, office and retail developments. Her work includes working with developers and their lenders through all phases of a project—from forming an organizational structure, to property acquisition, to financing and leasing. An accountant prior to becoming an attorney, Tessa has experience with Fannie Mae, Freddie Mac and HUD financing, and serves as a title and escrow agent for several title companies.
While commercial real estate is the foundation of Tessa's practice, she also uses her keen understanding of overall business law to help her clients with all manner of transactions, agreements and dispute resolution. And in recent years, she has expanded her practice to assist clients with matters related to estate planning and administration.
Past member of the Law Related Education Committee of the North Carolina Bar Association; contributor to the committee's publication of "The North Carolina Constitution Explained," a text book for North Carolina high school students.


Dentures differ from the rest of the work that we do instead of restoring and building on your natural teeth, they replace missing or loose teeth entirely. This happens; it's not something to be embarrassed or worried about. Denture technology has come a long way, and even with dentures, you will be able to eat and talk regularly.
Do Dentures Replace All My Teeth?
Not necessarily. We will do a thorough examination of the state of each tooth to determine if it needs to be removed. Once the determination is made, we will construct a set of dentures that will be just right for your mouth.
At Salt Lake Dental Care in Murray, UT, we also offer denture implants. This is often a wonderful alternative to traditional dentures and solves many of the most common problems. Implant-supported dentures are a type of overdenture that is actually attached to dental implants. Having dentures anchored to your mouth means that they will not slip or slide around. This sturdier attachment makes eating much easier, giving you triple the biting power of traditional denture and allowing you to eat more of the foods you could eat with your natural teeth. The sturdy fit also makes it easier to speak and most importantly, the denture implants promote a healthy jaw bone which will dramatically slow bone loss!
That depends. Due to major advances in cosmetic dental technology, restoration work can often be done on individual teeth instead of using full dentures. However, in many cases, dentures still are the right answer.Dr. Blackwood can consult with you to help you make the right decision if you are in the Salt Lake City area. In order to set up an appointment to talk with him about dentures, please call us at 801-938-8855, or, fill out the contact form on the right, and we'll call you as soon as possible! We work with patients from all over the area, including Murray and Sandy, Utah!


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In Diversity, Gender•June 14, 2012•5 Minutes
Women and Work Life Management in China
Recently Catalyst published a series of reports on talent management in Asia. Its study, "Expanding Work-Life Perspectives: Talent Management in China," revealed that women and men in China have high expectations when it comes to their careers.
Laura Sabattini, author of the report, says that Western companies operating in an Asian context need to get a better understanding of the cultural issues in the global localities in which they operate. She writes, "Implementing work-life programs requires the thoughtful integration of a global approach with local customs to ensure the strategies make sense in employees' day-to-day lives."
For example, China's one-child policy has had a considerable impact on the career ambitions of women, as well as the childcare needs of parents.
Ambition and Work Life
Based on the input of 300 high potentials working in European and US companies in China, Sabattini found that most individuals hope to move to the next level in the next five years (92% of women and 90% of men).
While the majority of respondents, both men and women, said they were more focused on the work side of the work life equation, considerably more men said they felt this way (69% of women and 81% of men). More women than men said they had a dual focus on work and family (23% of women and 13% of men).
Sabattini continued, "About half of respondents were satisfied with the level of flexibility their company afforded. However, women were less satisfied than men, i.e., they were less likely than men to agree that their workplace provided enough flexibility to manage work and family demands."
Half of women surveyed were dissatisfied with the flexibility provided at their companies, while only 37% of men said they were not satisfied with their company's flexibility offerings.
Professional Women in China
Catalyst explained that women are increasingly prevalent in the Chinese workplace.
"With women representing nearly 50 percent of the workforce, China has the highest rate of women's employment participation among Asian countries. Recent benchmarking data among Asian multinational companies shows that the representation of women at the middle and senior leadership levels has increased considerably since 2009."
Part of this change is due to China's one child policy enacted in the 1979. In the Center for Diversity Innovation's study The Battle for Female Talent in China [PDF], Sylvia Ann Hewlett and Ripa Rashid explain that parents of daughters have raised them to be increasingly ambitious.
They write:
"Introduced in 1979 as a strict population control measure, the policy has had important ramifications for the status of women, in particular in the urban areas where it was most heavily enforced. Women in their twenties and thirties today, as only children and hence the "one hope in the family," recall being pushed as hard as their male counterparts to achieve academically and economically."
Hewlett and Rashid suggest that one positive outcome of the policy is that work-life pressures are decreased insofar as parents have fewer children, and grandparents usually become caretakers.
Sabattini explains further:
"The accessibility of low-cost childcare and extended family networks provide resources for both mothers and fathers to manage work and family responsibilities. Part-time arrangements are not very popular or available as a work option in this region. Some have argued that concepts such as 'work-life balance' or 'work-family conflict' are somewhat foreign to the Chinese work culture; and managing work and personal life assumes a very different meaning than it does in other cultural contexts and requires different approaches."
Nevertheless, the Catalyst study showed that women were much more likely than men to report work-life challenges, which suggests that there are still many cultural and familial expectations about which gender handles family responsibilities, despite the commensurate levels of ambition between the genders. Companies looking to get the most out of their high potential female employees should work to find ways to ease these unique challenges.


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A Celebration of St. Monica
Lawrence S. Cunningham
Monica (or, spelled more accurately, Monnica) was born in 332 in the North African city of Thagaste in what is now Algeria. Most of what we know of her we learn from her son, Augustine, who gives ample space to her life in his classic work, Confessions.
Educated by a household servant, Monica cared for her father and siblings until she married Patricius, a pagan landowner and minor Roman official of the same town. Patricius seems to have been an arrogant man who was not always faithful to his wife but, as Augustine says, unlike other husbands of the time, never beat her, despite his volatile temper.
Patricius was unhappy that his wife raised Augustine as a Christian but, as an ambitious father, invested in his son's education. Before his early death, Patricius was baptized due to the good example of his wife. She was a widow at 40.
Her Famous Son
Monica was 23 when Augustine was born (she had another son and a daughter). She doted on him though she was unhappy with his lifestyle and lack of maturity. When Augustine left for Rome after his studies in Carthage (without telling his mother, who was quite wounded by his secret departure), she followed him and lived in his household.
Augustine praised her deep piety and prayerful life. After Augustine was baptized by St. Ambrose in Milan, Monica and her son lived a quiet life in nearby Cassiciacum where she figures as one of the characters in her son's dialogues On the Blessed Life (De Vita Beata) and On Order (De Ordine).
At this time, Augustine decided never to marry formally, which freed Monica from the onerous task of finding him a suitable bride. She was quite close to Augustine's son, Adeodatus ("gift from God"), born to him from a common-law marriage.
While waiting at the port of Ostia—near Rome—for a ship to Africa, she and her son had a conversation which Augustine famously describes in Book IX of the Confessions. This exchange between mother and son about the ascent to God was done in a fashion that some have described as mystical.
Before their ship departed, Monica became sick and died in the year 387 at the age of 55. She was buried in Ostia. In 1945, a fragment of an inscription from her gravesite was discovered.
In the 15th century, her remains were reburied in the Church of Sant'Agostino in Rome, where she is venerated today. Her feast is observed, fittingly enough, a day before the feast of her son, Augustine, on August 28.
Mother and Muse
In the closing part of Book IX of the Confessions, Augustine has a moving tribute to both mother and father in a text where, for the first and only time, he uses his mother's name.
Monica told her son that the only thing she wanted from life was to see her son "a Catholic and a child of heaven." She had seen him through his tumultuous adolescence, his flirtation with the religion of the Manichees, his irregular sexual life and his long search to find the faith which she had never doubted.
Monica was a North African. Her very name echoes the paganism that had once been part of Numidian history, since Mon was a Libyan god. Quite likely, Monica was of Berber origin although she was a Christian from birth. Her son Navigius was with her in her last illness and her daughter Perpetua (named for the great Carthaginian martyr) was head of a monastery near Augustine's own church in Hippo. Navigius's son, Monica's grandson, was a deacon in the North African Church.
That ancient land was thoroughly Christian in the fourth century and its rich agricultural output made it the breadbasket of Rome. Monica and Augustine were Africans who belonged to a Christian church which not only produced powerful theologians like Tertullian and Augustine himself but also great martyrs like Cyprian of Carthage and Sts. Perpetua and Felicity. It is crucial to keep those facts in mind to counteract the impression that white Europeans had a monopoly on Christianity.
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All Excursions in the Center of Lanzarote
Discover the Center of Lanzarote
The central area of Lanzarote is strongly influenced by the volcanic activity on the island. From the satellite perspective, this barren area is visually comparable to the lunar surface. As countless craters of extinguished fire chimneys rise up on an almost black background in this area. Therefore, the visitors of these surroundings think they are on another planet. If you plan to explore the center of the island, a visit to the Timanfaya National Park is a must. It undoubtedly is the glowing heart of the island. On the southwestern boundary of the park you will also find the green seawater lagoon "El Golfo", which is probably one of the most famous natural attractions in the center of Lanzarote.
If you spend your vacation in Puerto del Carmen, you should definitely go to the nearby La Geria. The vines grow in the island-typical holes here, in the middle of a breathtaking black backdrop. This is the right place for you to go, especially if you want to try the Lanzarote wine. Also visit Yaiza, a beautiful quite village on the edge of the Timanfaya, which has retained its typical Canarian charm to this day. You can find out which excursions you can take in the center of Lanzarote and which sights await you below.
Photo by: Pixabay
Things to Do in the Center of Lanzarote
Things to See in the Center of Lanzarote
Interesting Facts About the Center of Lanzarote
The Weather in the Center of Lanzarote
Special Beaches in the Center of Lanzarote
Hotels in the Center of Lanzarote
Our Tours and Excursions in the Center of Lanzarote
Excursions in the Center
Many of the organized excursions include the Timanfaya National Park. For wine lovers who would like to embark on this adventure, we recommend the Fire & Wine bus tour. On this tour you will be accompanied by a professional guide who will initially provide you with all the information about the volcano park. He afterwards brings you to a winery in La Geria where you can taste delicious wines from Lanzarote. If you spend your vacation in the towns of Puerto del Carmen or Puerto Calero, you can choose from most excursions in Lanzarote. Almost every operator offers hotel transfers from your region, due to its central location. At the end of this article you will find all excursions that take place in your area or for which you will be picked up at the hotel.
Selection of Excursions in the Center of Lanzarote
In the center of Lanzarote, tourism concentrates on the coastal towns of Puerto del Carmen and Puerto Calero. If you are accommodated there, you should be able to take part in any excursion without further ado. As both, operators from the south and from the north pick you up from there. Some of the operators are even located in the immediate vicinity of your resort. Holidaymakers in the less touristy places like Yaiza or Tías unfortunately have to consider not being able to enjoy the hotel transfer. This means that you would have to travel to the starting points of the excursions yourself. When choosing your desired excursion it is therefore important that you make sure whether pickup is offered. You can find out all details in our tour descriptions in the menu item "Services & Prices".
In the center of Lanzarote you can admire some of the most beautiful and famous sights of the island. You should definitely visit these four:
La Geria
The area around La Geria emerged during the volcanic eruptions in the 18th century. At that time, large fields were covered with a high layer of black volcanic ash. It was soon recognized that this created excellent conditions for wine growing. The vines grow here in holes of up to three meters depth, which are surrounded by natural stones in the shape of a half moon. The plants are protected in this way, but still get enough sunlight and the particularly fertile volcanic ash supplies them with all important substances. These trough fields have now reached considerable dimensions and give the areas between the volcanoes their extraordinary landscape. By the way, the result is particularly delicious white and sweet wines. You can even visit one or the other bodega and of course try the delicious wines on the occasion.
Photo by: andrew_j_w on VisualHunt / CC BY-SA
Yaiza is one of the villages that were almost completely destroyed by the severe eruptions in the 18th century. The reconstruction was complex, but gave the place its charming character of today. Countless palm trees line the streets between the white-painted Canarian houses with green shutters. In the village square, Plaza de los Remedios, you can watch the hustle and bustle of the residents in the shade of the palm trees. No wonder that Yaiza has been recognized as one of the most beautiful villages in Spain several times.
Montaña de Guardilama
At 603 meters, the Montaña de Guardilama is the fourth highest mountain in Lanzarote. At its foot you will find the La Geria wine region. Climbing this mountain is definitely worth it. As you have one of the most spectacular views of all of Lanzarote from its top. No higher elevation blocks your 360 degree panoramic view from here. You can see most of the island. In the northwest you can see the Timanfaya, to the southeast is Puerto del Carmen off the coast and to the south is the volcano Atalalya de Femès.
Rancho Texas Lanzarote Park
This extraordinary park is a zoo and water park in one. The locals jokingly call it "the enclosure in the water". On the extensive area you will find a pool area with water features same as large and small slides. After the water fun, you can admire the wild animals and the kids can even ride ponies in the Wild West Village. It will be an unforgettable day for the whole family.
More sights in the center of Lanzarote can be found here. You can also find detailed information about the Timanfaya National Park and the coastal towns of Puerto del Carmen and Puerto Calero. Just click.
Photo by: Alessandro Caproni on Visualhunt / CC BY
The weather in the coastal towns of central Lanzarote is considered the mildest and most balanced of the entire island. However, when you get away from the coast to the highlands and mountains from the center of the island, you will notice a few temperature differences. In summer it gets much hotter at high altitudes, while in winter it is significantly cooler, this is because the air masses of the Atlantic cannot get there. In general, the rain hardly has any importance to the weather in the center of Lanzarote. There are, on average, only 16 rainy days throughout the year, and all of them occur in the winter half year. Therefore, you can basically expect a sun guarantee on your vacation at any time of the year. After all, the sun shines on the Canary Island about 2,500 hours a year.
Playa El Golfo
Photo by: kanbron on Visualhunt.com / CC BY-SA
This natural beach is right next to the famous green lagoon "El Golfo". It is bordered by a horseshoe-shaped rock formation. A number of brightly colored wooden boats are on land here and make wonderful photo motifs. However, waves and currents should not be underestimated on this beach. It is therefore rather not recommended with children. You can experience the most beautiful sunsets from here.
Playa del Cochino
This natural beach is located on the west side of Timanfaya National Park. It is about 700 meters long and 70 wide and is made of dark sand. Waves and wind are strong here, which makes this beach absolutely unsuitable for children. However, it is an insider tip among nudists. Access to the beach is quite difficult. The best way to get there is by boat.
Playa Montaña Bermeja
This natural gray-black sandy beach is easy to reach by car. Due to the great view of the reddish mountain Montaña Bermeja, this beach is very suitable as a photo opportunity. However, it is less good as a bathing beach because the waves and currents are too strong. You will also be very impressed by the large crabs that populate the stones by the water.
Photo by: Jose Luis Garcia de los Salmones on VisualHunt / CC BY
In the immediate vicinity of the beach you will find some very nice hotels in Puerto del Carmen and Puerto Calero. They can be found in each star category and are designed for different needs. If you prefer something more active, check in at a fitness or wellness hotel. In the center of Lanzarote you can also find adults-only hotels and facilities that specialize in families. Popular hotels include: the Secrets Lanzarote Resort & Spa (Adults Only and 5 stars), the RIU Paraiso and the Suite Hotel Fariones (both 4 stars). We created this list after researching it on the Internet. We therefore do not give any guarantees.
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Bus and Jeep Tours
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Center of Lanzarote BOAT TRIPS
1,5 h Dolphin Tour Puerto del Carmen Lanzarote
2,5 h Dolphin Tour Sunset Lanzarote
5,0 h Dolphin Tour Los Lobos Lanzarote
4,0 h Catamaran We Love Papagayo Lanzarote
5,0 h Catamaran We Love La Graciosa Lanzarote
Center of Lanzarote BUGGY TOURS
3,0 h Quad Tour to La Geria in Lanzarote
2,0 h Quad Tour to Papagayo Beaches
2,0 h Quad Tour XT Outlander Lanzarote
2,0 h Polaris Slingshot Tour Lanzarote
2,0 h Adventure Trike Tour Lanzarote
3,0 h Buggy Tour 1000 Turbo 175 HP Lanzarote
3,0 h Extreme Buggy Tour Lanzarote
3,0 h Buggy Tour Lanzarote Island Hopping
Center of Lanzarote BUS & JEEP TOURS
Bus Tour Teguise Market & La Graciosa
Bus Tour Around The Island Lanzarote
César Manrique Bus Tour Lanzarote
Bus Tour Lanzarote to Fuerteventura
Bus Tour Fire & Wine Lanzarote
Bus Tour Lanzarote to Corralejo & the Dunes
Jeep Bus Tour The North of Lanzarote
Jeep Bus Safari The South of Lanzarote
Minibus Tour The Real Lanzarote
Minibus Tour The Flavours of Lanzarote
Center of Lanzarote CYCLING TOURS
2,5 h Segway Off-road Tour Playa Blanca
Center of Lanzarote DIVING & SNORKELLING
Introductory Scuba Diving in Lanzarote
Sea Trek Underwater Walk Lanzarote
Center of Lanzarote DOLPHINS & WHALES
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Center of Lanzarote HORSES & CAMELS
Center of Lanzarote QUAD BIKING
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Center of Lanzarote WALKING & HIKING TOURS
Walking on the Moonscape of Lanzarote
Hiking Tour to the Volcano La Corona Lanzarote
Center of Lanzarote WATER SPORTS
Parasailing Puerto del Carmen Lanzarote
Jet Ski Tour Puerto del Carmen Lanzarote
Jet Ski Safari Arrecife Lanzarote
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Top 10 Most Overrated Video Game Characters
Sick of hearing about a certain character over and over again? Tired of people yelling in your ear how awesome this or that character is? If so then I feel your pain. I've comprised a list of characters in desperate need of being shelved for a bit so we can have a little breathing room from the many ranks of the overrated.
10. Tim (Braid)
Obsessive psychopath or passionate, worried boyfriend? However you interpret Braid's story, it's hard to argue that Tim is actually any sort of viable character. Without real, direct input from Tim himself, he's hard enough to relate to, and as the game was full of annoyances on its own, I struggle to see how Tim to this day still receives so much praise. I can get down with the indie developer support, but be real here -- he's really no more of a character than the silhouetted boy of Limbo.
9. Talim (Soulcalibur)
Never before has a Soulcalibur character annoyed me to the point of not wanting to play online matches because opponents love little, innocent Talim. Not only is she similar to an RPG protagonist's helpless, cherubic little sister, but she speaks in the third person. Unless you're playing with a button-masher, every match faced against this pure little girl is nerve-wracking. She's a speedy little cuss, and dual-blades don't make matters much better. She grates on the nerves with her angelic personality and "never give up" spirit. Now, Taki on the other hand...
8. (Miranda Lawson, Mass Effect 2)
I'm unsure why so much buzz surrounds this femme fatale. She may be the "perfect woman," but in reality she's quite dull. Sure, she's got a killer figure, but while you're busy drinking it in, it's easy to overlook her behavior -- that of, in many instances, an ice queen. Let's not forget her involvement with Cerberus, which is in my mind similar to notorious xenophobe Ashley Williams. Frigid, arrogant, and filled with sarcastic remarks, it's difficult to transform her into a likeable (or interesting) character in my book, pre-relationship or otherwise. When you've got Tali, Morinth, Thane, Jack, or any of the rest of the crew waiting for you to unlock their secrets, this human vixen simply pales in comparison. Despite a fantastic performance from Yvonne Strahovsky, Miranda continued to bore me throughout my journey to the galaxy's furthest reaches. And you better believe I took Jack's side in that momentous argument. Miranda won't be seeing the light of day in my Mass Effect 3 playthrough.
7. Sonic the Hedgehog (Sonic the Hedgehog series)
Though I'm a huge Sonic fan, the 'fastest thing alive' hit his stride years ago. Sonic Colors was a workable comeback, but poor old Sonic's been rode hard and put up wet. He may have been all that years ago, but now he's a tired old rodent who needs to kick off his trademark red kicks and have a bit of a rest. The cheesy, peppy, do-gooder attitude, and the speed has been doing him a lot of damage, and I think we all know it's time for a break.
6. Kratos (God of War series)
Don't get me wrong -- I like to cleave through baddies as the newest fledgling God of War, but Kratos is, well, kind of a jerk. He may be responsible for some truly heinous crimes, and we see hints at true repentance and guilt for his wrongdoing, but...he never truly gets it, does he? All I really know of Kratos beyond his past sins is that he likes orgies, bloodshed, and being angry. Okay, honestly, I know a little more than that, but as much as I like the Ghost of Sparta, he's not the action hero he's cracked up to be.


Ben McAdams was sworn into office as Salt Lake County Mayor on Jan. 7, 2013. Mayor McAdams pledged to work collaboratively, across party lines, to find efficiencies in County government and to be open and accountable to citizens.
During his tenure as County Mayor, he has championed education, helping the county become the first in the country to partner with the private sector to offer greater access to high-quality preschool for low-income children. Mayor McAdams has also emphasized economic development and job growth, partnering with cities to attract business while being a careful steward of taxpayer dollars. He has also supported greater access for businesses and residents to transit, trails, and open space.


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Q: How can I get valgrind to tell me the address of each non-freed block of memory? Valgrind tells me function xxx allocated memory which was not freed. Fine. It's proving more difficult than usual to trace however.
To this end I have created numerous:
#ifdef DEBUG
fprintf(stderr, "something happening:%lx\n", (unsigned long)ptr);
#endif

So I just need to match these ptr addresses that are displayed with the addresses of non-freed memory.
How can I get valgrind to tell me the address of each non-freed block of memory?

A: I don't believe Memcheck's leak checker supports printing addresses, unfortunately. This is due to the fact it's willing to merge multiple unallocated blocks into one "loss report" if they're similar.
If you don't mind poking around in Memcheck, this functionality should be abled to be added  in memcheck/mc_leakcheck.c in the Valgrind source. I'll take a look at it when I get home and post a more detailed location.

A: Thanks to Falaina for the code location.
For valgrind-3.2.3, location that worked for me was in memcheck/mc_leakcheck.c, lc_scan_memory_WRK function.
Added this after lc_markstack_push_WRK(addr, clique); on line # 472
if (clique != -1) { VG_(printf)("clique %d: %p\n", clique, ptr); }

A: Here we are twelve years later and this still hasn't been added. The following patch is @Chaim's suggestion to valgrind-3.18.1
diff -uir valgrind-3.18.1/memcheck/mc_leakcheck.c valgrind-3.18.1-new/memcheck/mc_leakcheck.c
--- valgrind-3.18.1/memcheck/mc_leakcheck.c     2021-01-21 15:09:33.000000000 +0000
+++ valgrind-3.18.1-new/memcheck/mc_leakcheck.c 2022-03-08 18:55:24.323996739 +0000
@@ -1166,6 +1166,7 @@
             }
          } else {
             lc_push_if_a_chunk_ptr(addr, clique, cur_clique, is_prior_definite);
+            if (clique != -1) { VG_(printf)("clique %d: %p\n", clique, (void*)ptr); }
          }
       } else if (0 && VG_DEBUG_LEAKCHECK) {
          VG_(printf)("%#lx not valid\n", ptr);

redpajama_set_name: RedPajamaStackExchange


Today is one of the biggest hurdles for bills making their way through the California State Legislature, House of Origin Deadline. All bills must be out of the chamber in which they were introduced. So, both houses have had very long floor sessions to wade through thousands of measures legislators have introduced this year. Below is a summary of some of the key measures.


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https://www.sfgate.com/opinion/saunders/article/On-Michele-Bachmann-s-migraines-2353905.php
On Michele Bachmann's migraines
By Debra J. Saunders
Published 4:00 am PDT, Thursday, July 21, 2011
Republican presidential candidate Rep. Michele Bachmann, R-Minn., speaks about balancing the budget prior to signing the Cut Cap Balance Pledge during a news conference in Columbia, S.C., Monday, July 18, 2011.
Photo: Brett Flashnick, AP
I've been plagued with migraines for years. So when the Daily Caller reported that GOP presidential hopeful Michele Bachmann has had severe migraines, it took my colleagues but minutes to propose that I write on the controversy.
I resisted, but this story is a big talker. I've got a personal angle. I'm a columnist. What else could I do?
Some people give migraines; some people get them. We, the chosen few, do both.
According to the Daily Caller's anonymous sources, the Republican congresswoman from Minnesota takes medication to control her migraines - which, she confirms, sometimes have been "incapacitating" and which her campaign denies. The unnamed sources leaked the story, they said, because they worried that Bachmann's migraines could affect her performance in office, as well as present a winning opposition issue for President Obama if she garners the GOP nomination.
Do they have a point? I suppose. I've had days when I was in so much pain that I could not write. I wouldn't trust myself to pilot a plane.
Then again, with or without a migraine, I would have trouble keeping up with Bachmann's nonstop schedule.
This controversy takes care of itself. Bachmann faces months under the pressure cooker of high-stakes hardball presidential politics - the mother of all migraine triggers. She's at a disadvantage. When you're running for president, you can't ask town-hall sponsors to turn down the bright lights and ask participants to speak really softly.
Migraine argument recycles cheap shot about women candidates
If she can tough out the campaign despite the headaches, then she can tough out a lot. If she can't, then she loses.
Me? I am more concerned about Bachmann's promise to vote against any bill that raises the debt ceiling. Congress bought the car years ago, and put some miles on it; now Bachmann argues that it is moral to avoid the car payments - that's what scares me.
Meanwhile, this brouhaha could win Bachmann, if not support, at least sympathy.
Women are more likely to get migraines than men. Many women develop migraines as they approach perimenopause. (Bachmann's doctor son said that his 55-year-old mother started getting migraines 15 years ago.) Do not think that women will read the anonymous leakers' fears about Bachmann buckling under the stress and not smell a rat.
Remember that old argument that a woman could not be president because she would have trouble keeping her cool during "that time of the month"? Brace yourself. In 2012, that mothballed idea has morphed into migraines and menopause.
The old menstrual-cycle argument was based on the notion that women are too emotional for high office, but men do not lose their cool. (It helps if you don't know any men.)
Now comes the migraine argument. As former Minnesota Gov. Tim Pawlenty, also a GOP White House hopeful, told reporters, "There's no real time off in that job."
Apparently Western civilization would crumble if a female president spent an afternoon on a couch with a cold washcloth on her forehead. Because then she wouldn't be able to play golf, pose for a photo opportunity or campaign for re-election. Like your usual president.
Oh, and Gov. Pawlenty, if you're worried about a candidate not being able to govern 24-7, don't play hockey.
E-mail: dsaunders@sfchronicle.com.


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Skjervøya (en sami septentrional: Skiervá) es una isla del municipio de Skjervøy en la provincia de Troms, Noruega. Se ubica entre las islas de Kågen al este y Laukøya al sur. El fiordo de Kvænangen se extiende por el este de la isla. La localidad de Skjervøy es el principal núcleo urbano del lugar, que posee un área de 11,7 km². La pesca es la principal industria económica de Skjervøya. Las principales rutas para llegar son el puente Skjervøy, que conecta con Kågen y el túnel Maursund que une Kågen al continente.

Referencias

Skjervøy
Archipiélagos e islas del condado de Troms og Finnmark (mar de Noruega)

redpajama_set_name: RedPajamaWikipedia


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Board index Sports Talk RealGM Basketball More Boards Wiretap Discussion
City Council Vote For Major Defeat Of Downtown Seattle Arena
Moderators: BombsquadSammy, Domejandro, bwgood77
RealGM Wiretap
And1: 179
Post#1 » by RealGM Wiretap » Tue May 3, 2016 3:49 pm
In a 5-4 decision, the Seattle City Council voted against giving up part of Occidental Avenue South to entrepreneur Chris Hansen for his arena in hopes of bringing an NBA team back to the city.
Though a Memorandum of Understanding between Hansen, the city and King County runs through November 2017, odds of a new deal being struck by then seem remote.
In a statement put out on Hansen's SonicsArena.com website, he said, "Today's City Council vote was disappointing but we don't believe it is the end of the road in our quest to bring the NBA and NHL back to Seattle."
Mayor Ed Murray put out a statement shortly after the vote saying: "Today's council vote makes it less likely that the NBA will return to the city of Seattle."
He said he remains committed to exploring options for bringing the NBA and NHL to the region.
Via Geoff Baker/Seattle Times
Re: City Council Vote For Major Defeat Of Downtown Seattle Arena
BeGreezy
Post#2 » by BeGreezy » Tue May 3, 2016 4:54 pm
This really sucks man... I really miss Seattle. Loved that city and their team
arasu
Pro Prospect
Post#3 » by arasu » Tue May 3, 2016 6:49 pm
It's interesting how the Sustainability and Transportation Committee worked on the issue for months before voting 4-1 in favor of vacating the street, then the full council came on and ruined all of that work (wasted) in short order. It is also interesting that the voting breakdown was men vs women, in a town that appears to have been going through a long-term gender-culture war. Certain council members clearly are highly risk-averse, which is an attitude that often prevents short-term disasters at the expense of long-term growth.
On Monday, council members, including Sally Bagshaw and Debora Juarez, noted the importance of supporting the Port of Seattle, rather than the unknown future that comes with a third arena. Kshama Sawant said she hated voting jobs vs. jobs, but that she couldn't get past the threat of undermining working-class, waterfront jobs.
The vote was split along gender lines, with council members Sawant, Juarez, Bagshaw, Lisa Herbold and Lorena Gonzalez voting no; Tim Burgess, Mike O'Brien, Bruce Harrel and Rob Johnson voted yes.
http://mynorthwest.com/282523/seattle-city-council-votes/
anatomicbomb
Post#4 » by anatomicbomb » Tue May 3, 2016 8:15 pm
Until franchises find another way to pay for their fancy new stadia, or provide more direct lines of financial incentive for the cities from whom they want hundreds of millions of dollars in support, I expect we'll see more small-market cities rejecting these proposals than we have in the past.
Everything is practice.
bselig
Post#5 » by bselig » Wed May 4, 2016 1:22 am
anatomicbomb wrote: Until franchises find another way to pay for their fancy new stadia, or provide more direct lines of financial incentive for the cities from whom they want hundreds of millions of dollars in support, I expect we'll see more small-market cities rejecting these proposals than we have in the past.
It's the big market cities that typically reject such proposals (when they're event put forth in big markets) and small market teams often see them and accept them. And Seattle is a big market city
Post#6 » by arasu » Wed May 4, 2016 1:01 pm
In the case of Seattle, it is not about financial incentive or asking the city to contribute, it is about clearing a section of the city for development, a thing that occurs in every city from time to time. Unfortunately this city council lacks the courage to commit to change. Avoidance of change is a recipe for stagnation, which it appears is the future of that city.
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