Transformation of follicular lymphoma most typically occurs as diffuse large B-cell lymphoma, however other forms of transformation such as classic Hodgkin lymphoma and lymphoblastic transformation can occur. Secondary malignant histiocytosis also represents a rare form of transformation, which is thought to occur due to a process of transdifferentiation whereby the lymphoma cells exhibit lineage plasticity and lose all evidence of B-cell phenotype and instead acquire the phenotype of a histiocytic neoplasm. Little is known about the underlying genetic alterations that occur during this unusual process. Comparative genetic analysis of pre- and post-transformation/transdifferentiation would be one tool by which we could better understand how this phenomenon occurs.
Here we report the clinical, immunophenotypic and genetic features of a rare case of secondary malignant histiocytosis, Langerhans cell-type (Langerhans cell sarcoma) arising from a previous low grade follicular lymphoma. FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. Comparative whole exome sequencing was then performed, which identified a KRAS p.G13D mutation in the LCS that was not present in the FL.
This report highlights genetic alterations, in particular an acquired somatic KRAS mutation, that may occur during transdifferentiation, with additional significance of KRAS mutation as a possible therapeutic target in cases which otherwise would have limited treatment options.
Follicular lymphoma (FL) is an indolent B-cell lymphoma composed of follicle center B cells . While generally regarded as a manageable disease with a long survival rate, it can also progress to more aggressive forms of lymphoma, such as diffuse large B-cell lymphoma. Another rare and distinct form of disease progression is transdifferentiation from a B cell neoplasm to a neoplasm of another cell lineage [2–9]. In these instances, the neoplastic cells demonstrate lineage plasticity, manifested as an apparent shift in cellular phenotype from one lineage to another while still carrying shared underlying clonal genetic abnormalities. Most reported cases have involved transdifferentiation of chronic lymphocytic leukemia to histiocytic neoplasms [2–4, 6, 8, 9]. Transdifferentiation is an elusive process, and the exact pathogenic mechanisms remain unknown. Comprehensive genetic analysis could provide a useful tool by which to identify genetic alterations that occur during transdifferentiation and may provide clues to the underlying pathogenesis of this process. Furthermore, as this form of transformation heralds a very poor prognosis, identification of targetable genetic mutations could offer therapeutic options in cases where there are few alternatives. Here, we described a rare occurrence of a low grade FL transdifferentiating into a Langerhans cell sarcoma (LCS) with acquisition of KRAS mutation. As comparative whole exome sequencing of pre- and post-transdifferentiation lymphoma samples has not yet been reported in the literature, this report will contribute to the presently limited understanding of this rare phenomenon.
Our patient had a long history of follicular lymphoma which initially presented as a localized neck mass. A biopsy of the mass showed low grade follicular lymphoma. The patient was treated with radiation therapy, but 3 years later, was diagnosed with diffuse large B cell lymphoma involving lung with discordant low grade follicular lymphoma in the marrow. After eight cycles of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient went into remission. Unfortunately, 6 years later, the patient presented with skin and breast lesions as well as increased adenopathy, and was treated with rituximab, with some improvement of adenopathy. The skin nodules on the left arm were noted enlarging, a subsequent biopsy revealed low-grade follicular lymphoma, which responded to rituximab and bendamustine therapy. A few months later, the patient noted an enlarged inguinal lymph node, a biopsy of which showed Langerhans cell sarcoma. Despite 4 cycles of ICE chemotherapy and 8 weeks of ibrutinib, a PET/CT showed evidence of disease progression with diffuse intensely hypermetabolic soft tissue nodules and lymph nodes. Biopsy of one of the lymph nodes was consistent with diffuse large B cell lymphoma. The patient received palliative radiation therapy and passed away in a hospice facility. The patient's clinical history and treatment was summarized in Table 1.
The initial biopsy of the mass at presentation showed complete architectural effacement by a nodular lymphoid proliferation of small lymphocytes with elongated and cleaved nuclei (Fig. 1). Flow cytometric analysis identified a surface lambda light chain-restricted B-cell population that was CD10+ and CD5-. Diagnosis of a low grade follicular lymphoma was made.
Three years later, a transbronchial biopsy showed atypical mononuclear cell infiltrate composed of large cells with large nuclei and prominent nucleoli associated with frequent apoptotic bodies (Fig. 2). Immunohistochemical staining showed the large cells were positive for CD20 and CD10, and exhibited a moderate proliferation rate based on Ki-67 staining (40–50%). These findings were consistent with diffuse large B-cell lymphoma. A concurrent bone marrow biopsy showed a paratrabecular lymphoid infiltrate composed of small centrocytes consistent with involvement by follicular lymphoma (Fig. 2). Flow cytometric analysis identified a monotypic, surface lambda light chain-restricted B-cell population that was dim CD10+ and CD5-, supporting involvement by follicular lymphoma.
The breast biopsy showed an abnormal lymphoid infiltrate composed predominantly of small lymphocytes with elongated nuclei and condensed chromatin. The abnormal lymphocytes were CD20+, CD10+, BCL-6+ and BCL-2+, consistent with recurrent follicular lymphoma (Fig. 3). A few months later, an enlarged inguinal lymph node showed effacement of architecture by an abnormal polymorphous infiltrate composed of many highly atypical large cells with admixed histiocytes, small lymphocytes, neutrophils, eosinophils and rare plasma cells (Fig. 4). The large pleomorphic cells had deeply convoluted nuclei and abundant cytoplasm. Immunohistochemical stains showed the large cells were positive for CD45, CD43, CD1a, and S-100. CD20 and PAX5 immunostains showed virtually no B cells present in the lesion. Flow cytometric analysis did not identify a distinct CD19+ B-cell population. The findings were consistent with Langerhans cell sarcoma.
To establish the genetic relationship between the LCS and the patient's prior FL, FISH analysis for t(14;18) BCL2/IgH was performed on the touch imprints of the recurrent breast follicular lymphoma and LCS. FISH analysis revealed the presence of t(14;18) BCL2/IgH fusion signals in 62% and 21% of the 200 cells analyzed in follicular lymphoma and LCS respectively (Fig. 3 and Fig. 5). In LCS, the fusion signal is only present within the sarcoma cells identified by their enlarged size and bizarre nuclear morphology, but not in any background inflammatory cells. And almost all the sarcoma cells harbor this translocation. Interestingly, the sarcoma cells displayed 4–5 copies of IgH/BCL2, indicating amplification of fusion signals from t(14:18) (Fig. 5). Using MYC break apart probes, both FL and Langerhans cell sarcoma sample were negative for MYC rearrangement; however, extra MYC signals were seen in 21% and 22% of the 200 cells analyzed in FL and LCS respectively, and in latter only present in the sarcoma cells. Molecular analysis was performed on the bone marrow aspirate with involvement of follicular lymphoma. The result was positive for clonal IGH gene rearrangement with 334 bp, 273 bp and 133 bp clonal bands by FR1, FR2 and FR3 biomed primers. Molecular analysis was also performed on the LCS and was negative for clonal immunoglobulin heavy chain rearrangement.
Additional molecular analysis for BRAF V600E mutation, which has been reported in 38–57% of Langerhans cell histiocytosis but not as of yet in any cases of Langerhans cell sarcoma [1, 10, 11], and was negative for this mutation.
Comparative whole exome sequencing was performed on paraffin-embedded tissue sections from the breast low-grade follicular lymphoma sample and Langerhans cell sarcoma sample. The tumor burden was estimated at 90% and 20–30% with median depth of read of 140 and 92 for the follicular lymphoma and Langerhans cell sarcoma samples, respectively. After filtering, there were 12 variants including 10 nonsynonymous SNVs and two inframe mutations shared by both the FL and LCS. The majority of SNVs, which had a variant allele frequency (VAF) close to 0.5 in both samples or had alternative allele frequency above or close to 0.01 in the 1000 g or ExAC database, may represent germline polymorphisms (Table 2, Additional file 1: Table S1). The shared CREBBP mutation (NM_001079846:exon29:c.4920_4922del:p.1640_1641del) has a VAF lower than other shared variants (0.31 in FL and 0.23 in LCS), and may represent a shared somatically acquired driver mutation. CREBBP is a histone modifier that is frequently mutated in FL [12, 13].
Twelve variants were present in the FL but not in the LCS. After filtering, there were 4 remaining nonsynonymous SNVs, 1 stopgain, and 3 inframe deletions (Table 2, Additional file 2: Table S2). Included among these variants were KMT2D p.R5097* and BCL2 p.S203 N, which have been previously identified in FL [14, 15].
Although copy number alterations were not covered in this assay, analysis of allele frequency of commonly occurring SNVs can be a useful indicator of loss of heterozygosity (LOH). There were 14 nonsynonymous single nucleotide variants demonstrating potential LOH (i.e. heterozygous in the FL and homozygous in the LCS). None of the variants were considered deleterious (Table 2, Additional file 3: Table S3).
Thirty variants were identified in the LCS sample that were not present in the FL sample including 26 nonsynonymous SNVs, 2 frameshift insertions and 2 inframe deletions. After filtering out of benign or likely benign variants, the remaining variants included 11 nonsynonymous SNVs, 2 frameshift insertions and 2 inframe deletions (Table 2, Additional file 4: Table S4). Most of the variants were of unknown significance, except KRAS p.G13D (Fig. 6), which is a well-known pathogenic variant in a variety of malignancies including carcinoma and hematopoietic neoplasms [16–18]. To confirm the presence of KRAS mutation, a real-time PCR analysis was also performed in both the FL and LCS. The results confirmed the presence of KRAS p.G13D in the LCS but not in the FL (data not shown).
Multiple chromosomal abnormalities were identified in the follicular lymphoma sample which include 6p CN-LOH, 6q deletion, small gain at 7p, 9p21.3 deletion (CDKN2A/2B genes included), small deletion at 10q, small deletion at 12q (distal breakpoint within BCL7A gene), 16p deletion, small 16p gain, 2 CN-LOHs on 20p and some gains involving 20p, a homozygous loss involving chromosome 22q11.22 involving the IGL gene and likely related to gene rearrangements in the tumor, a CNV gain involving chromosome 22q11.23 and gain of entire chromosome X (Table 3). However, there were no significant abnormalities identified in the Langerhans cell sarcoma sample with the exception of KRAS p. G13D and a CNV gain on chromosome 22q11.23, which was also observed in the follicular lymphoma sample (Table 3).
Classification of hematopoietic neoplasms is predicated on the assumption that the phenotype of a neoplastic cell is intrinsically linked to a predefined lineage and that this lineage determines the type and nature of the neoplasm. However, as demonstrated in cases of transdifferentiation, these associations are not hard and fast rules, as cells, both physiologic and neoplastic, can demonstrate lineage plasticity [3–9, 19–21]. Our patient's pathologic studies include a wide range of morphologic variation in the neoplastic clone, ranging from low grade FL to DLBCL to later on, LCS.
The mechanisms by which transdifferentiation occurs are largely unknown and previously described cases have relied upon molecular clonality or other genetic markers to establish a clonal relationship between what otherwise would appear as two phenotypically distinct neoplasms. Clonal IgH rearrangements have been reported in 39% of sporadic cases of histiocytic/dendritic cell sarcomas  which may reflect the close relationship and possible common precursor between neoplasms of histiocytic differentiation and lymphoid differentiation [4, 6, 7, 9, 19, 23–25]. In our case, while a clonal IgH rearrangement was detected in the FL from the fresh bone marrow sample, PCR analysis failed to identify a clonal IgH rearrangement in LCS. The reason for the absence of clonal IgH rearrangement in the LCS sample is not entirely clear, but could be due to additional genetic alterations affecting the specific binding of the PCR primers or decreased assay sensitivity in formalin fixed tissue. However, the clonal relationship between FL and LCS was definitively confirmed by FISH analysis, which able to readily identify the t(14;18), IgH/BCL2 within morphologically-apparent sarcoma cells. The shared t(14;18), IGH/BCL2 translocation in both the follicular lymphoma and LCS by FISH provided strong evidence of their clonal relationship, as this translocation is considered very specific for follicular lymphoma and has not been reported in any de novo sarcoma.
The shared CREBBP mutation (NM_001079846:exon29:c.4920_4922del:p.1640_1641del) is an interesting finding. CREBBP mutations, particularly mutations of the acetyltransferase domain, has been implicated as an early driver event in follicular lymphoma [26, 27]. Although the specific CREBBP mutation that we have detected in this case has not been previously reported in COSMIC database, it does occur within this functional acetyltransferase domain (p.1342-p.1649) [28, 29]. Thus, it could potentially represent a shared acquired somatic driver mutation and further support a model of direct transdifferentiation of LCS from antecedent follicular lymphoma rather than, for example, evolution from a common precursor neoplastic cell harboring an early translocation t(14;18) event.
The additional SNP microarray results also suggest that the LCS likely originated from an earlier follicular lymphoma with t(14;18). As the LCS does not share the other complex genetic alterations with the exception of the shared CNV gain involving 22q11.23. However, it is worth pointing out that the LCS sample contains relatively low tumor burden (20–30% by visual estimation) with a dense background of inflammatory cells, whereas the follicular lymphoma contains almost 100% tumor cells. Therefore, other more subtle genetic alterations in the sarcoma cells may not be identified by the OncoScan SNP microarray which requires at least 25% tumor content.
The most intriguing finding in this case is the detection of KRAS p. G13D, a known pathogenic mutation, detected solely in the LCS sample. RAS mutations have been implicated in a number of hematologic malignancies, with NRAS mutations being more prevalent than KRAS mutations, particularly in myeloid neoplasms . RAS-MAPK alterations have also been frequently described in hairy cell leukemia and multiple myeloma, but are more rarely seen in other lymphoproliferative disorders, such as diffuse large B-cell lymphoma [31, 32]. In studies analyzing mutational profiles of follicular lymphoma, a pathogenic role for RAS mutation in the development of follicular lymphoma has not been described [33, 34], although it has been reported as a rare event in cases of histologic transformation . In a study of 55 primary DLBCL samples, KRAS p.G13D mutation was identified in 2 cases, thus is it possible that RAS mutations could drive the pathogenesis of a relatively rare subset of primary and secondary DLBCL . A separate study described differential gene expression of genes in the MAPK signaling pathway, including NRAS, in cases of follicular lymphoma compared with transformed follicular lymphoma, suggesting activation of this pathway could be important in disease transformation . In our case, the KRAS p.G13D may have arisen during the transformation process. Further studies to completely delineate clonal derivation were desired but precluded by the absence of material from original FL and subsequent DLBCL for additional testing. Nonetheless, the high prevalence of KRAS p.G13D mutation in the sarcoma cells, inferred from a variant allele frequency similar to the sarcoma tumor burden, suggests that it is a predominant mutation within the sarcoma cells.
Our finding raises a couple of important questions. What is the significance of KRAS mutation in histiocytic neoplasms? Could this mutation potentially drive transdifferentiation process itself? A recent abstract presentation  retrospectively reviewed cases of histiocytic sarcomas and discovered RAS/MAPK mutations in 44% (n = 8) of cases. KRAS p.G13D was present in 3 of the cases. Some of the cases of histiocytic sarcoma also possessed mutations that are common in B-cell lymphoma (such as MYD88, SOCS1, KMT2D, ARID1A) and furthermore, a subset of patients with histiocytic sarcoma had concurrent or prior history of B-cell lymphoma, including follicular lymphoma, which raised the possibility of transdifferentiation. This suggests that RAS/MAPK mutations are actually quite common in histiocytic neoplasms, even some that may be secondary to B-cell lymphoma, and that given their prevalence, may actively participate in driving this disease process.
In terms of Langerhans cell neoplasms, the RAS/MAPK signaling pathway has been strongly implicated as a pathogenic driver. Recent mouse models have demonstrated that expression of KRAS p.G12D mutation in lung myeloid cells induce the development of pulmonary Langerhans cell histiocytosis (LCH) . NRAS p.Q61K mutations have also been reported at higher frequency in cases of pulmonary LCH , but have not thus far been seen in non-pulmonary cases. A study of 61 cases of non-pulmonary LCH reported BRAF V600E mutations in half of cases, also detected several other point mutations including TP53 p.R175H, KRAS p.G13D and MET p.E168D . BRAF is an essential component of the RAS-RAF-MEK-ERK signaling cascade, which is triggered by binding of extracellular growth factor or cytokines to surface tyrosine kinase receptors, eventually leading to the modulation of downstream gene expression . The activation of this pathway in LCH is further supported by the fact that MEK and ERK phosphorylation could be detected by immunohistochemistry in all cases of LCH, regardless of BRAF mutational status . Activating mutations in BRAF other than V600E have also been detected in LCH [42–44]. Furthermore, cases without BRAF V600E mutation have demonstrated a high prevalence of somatic MAP2K1 mutation, which are mutually exclusive with BRAF mutations [43, 45]. Thus, there is a substantial amount of evidence to suggest that the RAS-RAF-MEK-ERK signaling pathways is important to the evolution of LCH.
LCS is an extremely rare malignancy thought to be derived from Langerhans histiocytes, and because of the scarcity of reported cases, the molecular pathogenesis of this entity is mostly unknown. However, it is not unreasonable to infer that some of the same pathways that drive LCH could also drive LCS. Interestingly, a recent report of histiocytic sarcoma transdifferentiation from B-lymphoblastic leukemia demonstrated NRAS p.G12D mutation, further suggesting RAS pathway alterations may be important in the transdifferentiation process . It is also possible that other genetic or epigenetic changes which are as yet uncharacterized may contribute to lineage conversion and phenotypic switch seen during transdifferentiation.
Because of its prevalent role in neoplasms of multiple different organ systems, the RAS-RAF-MEK-ERK signaling pathway is also a target for novel therapeutics, including monoclonal antibodies and small molecule inhibitors, for example BRAF and MEK inhibitors in melanoma [47–49]. KRAS is one integral component of the RAS-RAF-MEK-ERK signaling pathway that acts upstream of BRAF . Detection of KRAS mutation is now recommended in colorectal carcinoma, since its presence indicates resistance to targeted therapy against upstream signaling proteins (i.e. EGFR) . Recent studies have shown specific efficacy of cetuximab in colorectal cancer patients with KRAS p.G13D mutations (the same mutation detected in our patient) and not other KRAS mutations [52, 53]. Ongoing studies in a variety of neoplasms examining RAS proteins and other downstream mediators, such as BRAF and MEK, as druggable targets offer additional therapeutic possibilities in patients with applicable genetic alterations, such as the current case [54–56].
It is important to recognize that while the results of whole exome sequencing in this case suggest complex genetic reprogramming may occur during the transdifferentiation process, this method may fail to identify all possible genetic abnormalities, including splice variants or chromosomal gains/losses. As such, additional genetic events may play a cooperative role in developing this aggressive disease. However, the detection of an activating KRAS mutation, which is not typically associated with B-cell lymphoma, combined with the growing body of evidence that this signaling pathway is essential to the development of Langerhans cell neoplasms, suggests that acquisition of this mutation could potentially drive or influence transdifferentiation.
In summary, this case describes transformation/transdifferentiation of a low grade FL into a LCS with detection of KRAS p.G13D mutation in the transformed sample. Our findings demonstrate characterize genetic events that may occur during transdifferentiation and further emphasizes the role of alterations of RAS-RAF-MEK-ERK signaling in the pathogenesis of Langerhans cell neoplasms. Importantly, the discovery of acquired KRAS mutation raises the possibility of targeted therapies (e.g. small molecule inhibitors) [50, 57] in the treatment of patients with these neoplasms who otherwise have limited therapeutic options.
H&E sections from the patient's previous biopsies were retrieved from the Department of Pathology at Northwestern Memorial Hospital. The available archival materials were reviewed, along with associated ancillary studies, including immunohistochemical stains performed at the time of diagnosis, flow cytometric analysis and molecular analysis. Additional immunohistochemical stains, molecular and fluorescence in situ hybridization (FISH) analysis were performed in this study and are further described.
Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue. Antigen retrieval and immunohistochemical stain were performed on an automated immunostainer following the manufacturer's protocol (Ventana Medical Systems, Tuczon, AZ). The following predilute antibodies were used: CD3 (Ventana), BCL-2 (Cell Marque, Rocklin, CA), BCL-6 (Cell Marque), Ki-67 (Ventana), CD43 (Ventana), CD1a (Beckman Coulter, Miami, FL), S-100 (Ventana). The following antibodies were also used: CD20 (Dako, Carpinteria, CA), Pax-5 (1:10, Cell Marque), CD10 (1:30, Leica, Buffalo Grove, IL), CD45 (1:300, Dako). Positive and negative controls were performed with all cases and showed appropriate staining.
Interphase FISH with Vysis dual color break-apart MYC (8q24), and dual color break-apart BCL2 (18q21) probes (Abbott Molecular Inc., Des Plaines, IL) were performed on paraffin-embedded tissue sections. The 5′ and 3′ portions of the MYC and BCL2 probes are labeled with SpectrumOrange and SpectrumGreen, respectively. Interphase FISH analysis with Vysis dual color dual fusion IGH (14q32) and BCL2 (18q21) probes were performed on the lymph node touch imprints. Negative and positive control slides were performed in parallel with the patient sample in the same hybridization process. A total of 100 interphase cells were evaluated for MYC and BCL2 rearrangement independently by two laboratory technologists. An abnormal result was determined if the percentage of cells with abnormal FISH signals (i.e. separation of the 5′ and 3' MYC and BCL2 probes due to a translocation or abnormal FISH signal patterns due to fusions) was above the relevant cut-off values at 95% confidence.
Molecular analyses were performed to assess for the presence of clonal IGH rearrangements. DNA was extracted from fresh bone marrow aspirate or formalin-fixed, paraffin-embedded tissue sections. DNA extraction and purification was performed on automated nucleic extraction instrument QIAsymphony SP using QIAsymphony DNA Mini Kit (Qiagen, Valencia, CA). Multiplex PCR-based clonality assays were performed following manufacturers' protocols (Invivoscribe, San Diego, CA, USA). The PCR products are detected by capillary gel electrophoresis on an ABI 3130XL genetic analyzer (Applied Biosystems, Foster City, CA, USA). An amplification band was considered clonal if the height of the peak was more than 3 times the height of the third highest peak in a given range of DNA sizes.
Analysis of BRAF V600E mutation was performed using COBAS 4800 BRAF Mutation assay according to the manufacturer's protocol (Roche Molecular Diagnostics). The results were reported as follows: i) V600E mutation detected, ii) V600E mutation not detected, or iii) invalid (ie, no result was obtained on the COBAS test). The COBAS BRAF Mutation assay can detect the BRAF V600E mutation at greater than 5% mutation level.
Whole exome sequencing was performed at the UCLA Technology Center for Genomics & Bioinformatics. DNA was extracted from the formalin fixed paraffin embedded tissue sections from both the breast biopsy and inguinal lymph node. The library construction was performed using the SeqCap EZ System from NimbleGen (Roche NimbleGen, Inc. Madison, WI) according to the manufacturer's instructions. Briefly, genomic DNA was sheared, size selected to roughly 300 base pairs, and the ends were repaired and ligated to specific adapters and multiplexing indexes. Fragments were then incubated with SeqCap biotinylated DNA baits after LM-PCR and the hybrids were purified using streptavidin-coated magnetic beads. After amplification of 18 or less PCR cycles, the libraries were then sequenced on the HiSeq 3000 platform from Illumina, using 100-bp pair-ended reads.
The sequence data were aligned to the GRCh37 human reference genome using BWA v0.7.7-r411. PCR duplicates were marked using MarkDuplicates program in Picard-tools-1.115 tool set. GATK v3.2–2 was used for INDEL (insertions and deletions) realignment and base quality recalibration. Exome coverage was calculated using the bedtools. Samtools was used to call the SNVs (single nucleotide variants) and small INDELs. Varscan2 was used to call the somatic SNVs. All variants were annotated using the Annovar program. Copy number alterations and structural variants were not covered in this assay. The variants were ranked by SIFT and PolyPhen scores. A variant with SIFT score < 0.05 is predicted as deleterious (D), otherwise is tolerated (T). A variant with Polyphen score > 0.9 is predicted probably damaging, < 0.45 is predicted benign, between 0.45 and 0.9 is predicted possibly damaging. Variants were filtered out based on allele frequency of > 1% reported in 1000Genome, exAC (The Exome Aggregation Consortium); minimum read-depth of 30; any variants that were in the UTR or upstream/downstream of the gene; variants with a synonymous coding effect and variants within intronic region, unless they result in splice site mutations. Variants of 100% allele frequency in both tissues were considered germline and not included.
Evaluation of KRAS mutational status was performed using the KRAS Mutation real-time PCR Analysis Kit (EntroGen, Tarzana, CA, USA) following the manufacturer's protocol. This assay employs allele-specific primers that are complementary to mutant variants of the KRAS genes. Detection of the amplification products was performed with the use of fluorescent hydrolysis probes. Probes tagged with the FAM fluorophore were complementary to the targets of KRAS genes. This assay identifies the following mutations in codon 12: G12S, G12D, G12V, G12C, G12A, G12R; in codon 13: G13D; and in codon 61: Q61H (61CAA > CAT), Q61L, Q61R, Q61H (61CAA > CAC).
SNP microarray analysis was performed using the OncoScan FFPE Express 3.0 assay kit (Affymetrix, Santa Clara, CA) as per manufacturer's recommendation. The assay utilizes Molecular Inversion Probe (MIP) technology, which is optimized for highly degraded FFPE samples (probe interrogation site of just 40 base pairs) (1–3). The assay employs 220,000 SNP MIP probes which ensure a resolution of 50–100 kb in selected genomic regions covering 900 cancer genes and of 300 kb outside of these regions. Briefly, 10 unstained FFPE tissue sections cut at 10 μM were obtained and tumor was macrodissected using a hematoxylin and eosin -stained slide as a guide. DNA was extracted and purified from the samples using the QIAmp DNA FFPE Tissue Kit (Qiagen, Dusseldorf, Germany) according to the manufacturer's protocols. Extracted DNA was quantified using the Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen, Carlsbad, CA, USA) following the manufacturer's protocol. A total of 80 ng of DNA from each sample was annealed to the MIP probe panel. Annealed MIPs were circularized, followed by enzymatic removal of any un-ligated probe and template DNA. Remaining MIPs were linearized, amplified, enzymatically fragmented, and hybridized to oligonucleotide microarrays. The arrays were washed, scanned, and the results were analyzed and interpreted using OncoScan Console and Nexus Express for OncoScan 3 software (BioDiscovery, El Segundo, CA, USA) as previously described [58–60].
SC, AA, MW, and JG collected the data, created the figures, and wrote the manuscript. AB and YC provided critical review. XL and YZ performed the FISH analysis. DD and JC performed molecular studies and analysis. AA and MW performed the SNP microarray studies and analysis. All authors read and approved the final manuscript.
Exemption was received from the Northwestern University Institutional Review Board.


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Home end times Iran sees current unrest as signal the Islamic Messiah is about to...
Iran sees current unrest as signal the Islamic Messiah is about to appear
Erick Stakelbeck, CBN News terrorism analyst is reporting evidence the Iranian government sees the current unrest in the Middle East as a signal that the Mahdi–or Islamic messiah–is about to appear.
CBN News has obtained a never-before-seen video produced by the Iranian regime that says all the signs are moving into place — and that Iran will soon help usher in the end times.
the basij
While the revolutionary movements gripping the Middle East have created uncertainty throughout the region, the video shows that the Iranian regime believes the chaos is divine proof that their ultimate victory is at hand.
"The Coming is Near"
According to Stakelbeck, the propaganda footage was approved at the highest levels of the Iranian government.
It's called "The Coming is Near" and it describes current events in the Middle East as a prelude to the arrival of the tweflth Imam or Mahdi — a messiah figure whom Islamic scriptures say will lead the armies of Islam to victory over all non-Muslims in the last days.
The Basij, an Iranian paramilitary force that is a branch of the Islamic Revolutionary Guard Corps, enforces Iran's Islamic social codes, and have a branch in almost every Iranian mosque.
"This video has been produced by a group called the Conductors of the Coming, in connection with the Basij — the Iranian paramilitary force, and in collaboration with the Iranian president's office," said Reza Kahlil, a former member of Iran's Revolutionary Guards who shared the video with CBN News.
Kahlil, author of the book, "A Time to Betray," worked as a double agent for the CIA inside the Iranian regime.
"Just a few weeks ago, Ahmadenijad's office screened this movie with much excitement for the clerics," Kahlili told CBN News. "The target audience is Muslims in the Middle East and around the world."
The video claims that Iran is destined to rise as a great power in the last days to help defeat America and Israel and usher in the return of the Mahdi. And it makes clear the Iranians believe that time is fast approaching.
"The Hadith have clearly described the events and the various transformations of countries in the Middle East and also that of Iran in the age of the coming," said a narrator, who went on to say that America's invasion of Iraq was foretold by Islamic scripture–and that the Mahdi will one day soon rule the world from Iraq.
The ongoing upheavals in other Middle Eastern countries like Yemen and Egypt–including the rise of the Muslim Brotherood — are also analyzed as prophetic signs that the Mahdi is near — so is the current poor health of the king of Saudi Arabia, an Iranian rival.
"Isn't the presence of Abdullah, his illness, and his uncertain condition, great news for those anxious for the coming?" asks the narrator.
Iran's supreme leader, Ayatollah Khameini, and Hassan Nasrallah, leader of Iran's terrorist proxy Hezbollah, are hailed as pivotal end times players, whose rise was predicted in Islamic scriptures.
The same goes for Iran's President Mahmoud Ahmadenijad, who the video says will conquer Jerusalem prior to the Mahdi's coming.
"I think it's a very grave development," Mideast expert Joel Rosenberg, author of The Twelfth Imam, told CBN News, "because it gives you a window into the thinking of the Iranian leadership: that they believe the time for war with Israel may be even sooner than others had imagined."
Kahlili says "The Coming is Near" will soon be distributed by the Iranian regime throughout the Middle East. He explained that their goal is to instigate further uprisings in Arab countries.
In Sunni and Shia eschatology, the Mahdi is the prophesied redeemer of Islam who will stay on Earth for seven, nine or nineteen years (according to various interpretations) before the Day of Judgment, literally, the Day of Resurrection) and, alongside Jesus, will rid the world of wrongdoing, injustice and tyranny.
In Shia Islam, the belief in the Mahdi is a "powerful and central religious idea" and closely related to the Twelfth Imam, Muhammad al-Mahdi, whose return from occultation is deemed analogous with the coming of the Mahdi. In Sunni traditions, there are several hadiths referring to the Mahdi. — Dan Wooding, founder of ASSIST News
To watch the video report from CBN by Erick Stakelbeck, go to: www.cbn.com/cbnnews/world/2011/March/Iranian-Regime-Video-Says-Mahdi-is-Near-/
Ahmadenijad
Islamic messiah
Reza Khalil
Twelfth Imam
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Iran sees current unrest as signal the Islamic Messiah is about to appear | markellis4 March 30, 2011 at 4:52 am
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redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Ajax data not getting into controller I am using an ajax request to show some information, on my local development version it works perfectly, but on the production server (Ubuntu 16.04 LEMP) it fails in validation, because there is no data in the request.
Checks

*

*The url is correctly showing (e.g. example.com/employeeInfo?employeeId=1)

*Ajax itself is working: when I hard-code the controller's response everything is fine.

I cannot figure out why this happens in production, but not on the local version... Huge thanks for any clues!
View

Route
Route::get('/employeeInfo', 'EmployeeController@getInfo');

Controller
public function getInfo(Request $request) {

    if($request->ajax()) {

        $this->validate($request, [
            'employeeId' => 'required|integer',
        ]);

        $employee = Employee::find($request->employeeId);
        $output_linkedin = 'linkedIn.'"class="linkedin" target="blank">';

        $data = array("output_resume"=>$employee->resume,"output_linkedin"=>$output_linkedin, "output_name"=>$employee->name, "output_role"=>$employee->role);
        echo json_encode($data);

    }
}

A: If you want to pass a get data employeeId you have to pass a slug through your route either you should pass the data by POST method.
Route::get('/employeeInfo/{slug}', 'EmployeeController@getInfo');

And Get the slug on your function on controller .
public function getInfo($employeeId)

redpajama_set_name: RedPajamaStackExchange


Watercolours – "St Paul's Cathedral #1". Kevin Derbyshire – Artist.
St. Paul's is something of an obsession for me. Its perfect proportions, the mix of square (male) and round (female) shapes, the colours and beauty of the materials and its historical significance combine to make it endlessly fascinating.
There have been many attempts, but this one, painted over a couple of days standing in the churchyard, is the most successful observational painting of St. Paul's that I have managed.


Network Marketing – What Is Your Most Wanted Response?
The first article in our Network Marketing series discussed why so many network marketers struggle online… because they don't have the right tools and strategies to win new leads and sales.
What Is the Right Way to Success?
It's been interesting watching the Network Marketing industry try to figure out the Net. You'd think that if any industry could figure out the networking power of the Net fast, it would be this one.


family | Nauval Yazid & His Words.
I am writing this entry as I am still reeling from the atmosphere of my little sister's somewhat big wedding.
For the past two days, we had nothing but this wedding in our mind.
For some, such as my family and those who help organizing it, the wedding had been on their minds for the past few weeks and months.
For the bride and the groom, the wedding had also been on their minds for the past year when they decided to tie the knot.
For me, the wedding has been lingering on my conscience, meaning that I had been made aware of the wedding for some time. But not only in the past few minutes ago I realize that a wedding like this is a big deal.
Not exactly a fan of big wedding myself, I made my way into it by benefitting from the obvious, natural status as a member of the hosting family. Once stepped in, I felt lost. Everyone was busy, but me. Eventually I was made busy as well, but only to a miniscule portion of what others had done greatly.
The awareness started kicking in when the wedding ceremony happened. I was made to sit next to dad before he gave his daughter to the hand of marriage.
Awkward, yes, but the uncomfortable position also made me realize that a son has to learn being a good guardian to his family in every small step. As I get to witness my sister signed the note of marriage legally from a very close sight, it is clear that she also signs an approval note that part of my duty being a brother to her has now been taken over by someone else.
Someone whom she is expected to spend the rest of this lifetime with. Someone who will be her first immediate contact in any given circumstances.
The adjustment period did not even start yet when we had to prepare for the wedding reception the next day, a day after the ceremony. The aforementioned status as a family member only prompted organizers to point me as one of ushers to bring the newlyweds to the stage, and to welcome guests who came to greet the couple. As guests walked past me, I struggled to recall names and faces from distant relatives, neighbors, old family friends, to which I mostly failed. My other sister helped me to memorize the names to an already forgotten effect by now.
But what I won't forget is the joyful faces of aunts, uncles, nephews, nieces and cousins who cheered the wedding from their smiles.
Coming from different cities and islands, they reunited in this wedding, albeit briefly.
"Your belated aunt must be proud seeing her children gather again today, unexpectedly," my other aunt pointed out. I could not agree more.
When we posed for a group photo, my mind flew briefly to big Lebaran gatherings we always did years ago, back when the elders were still around. As one by one departed, the tradition slowly fades out, but apparently, the memory is not.
The price for embracing the nostalgia is the intrusion of privacy we often get. But then the more I thought about it, the more I realize that it may take a while for both our ability to convey our choice, and for them to accept what we have chosen.
Then again, this note is made as I am still reeling from the euphoria of a wedding.
It may not make me wanting to do the same for myself, but it is the exuberant joy of seeing our present family members, both close and extended ones, that make such event sticks to our mind as long as we live.


text:
Android Instant Apps – A How-To Guide
February 13, 2017 Will ClausenAndroid, Blog, Instant AppsNo Comments
It's no secret that everyone on the Cartogram team is a big fan of Google's new Android feature, Instant Apps. Since mobile browsers are always a few years behind in terms of their ability to programmatically access smartphone sensors and features, users have been forced to install apps to get the most cutting-edge functionality. Google's initiative with Android's Instant Apps aims to buck the trend and enable your mobile browser to leverage the same powerful user experience as a native app, without actually installing the app. Kind of.
Actually, Google DOES install an app, but the duration of the install is supposedly limited to the time it's being used. The difference is really in the user experience of how this app gets onto your phone. Instead of downloading an app on Google Play, the app is presented to you in your Google search results similar to the way that current apps are displayed.
It's still pretty early and Google hasn't provided much in the way of details in terms of how to use the new feature (which is currently in beta).
This post isn't meant to be a thorough explanation of how Instant Apps works. It's also not a developer guide (still waiting for Google to share this). Instead, it's meant as a how-to guide for those who would like to try out Instant Apps today. Here are a few notes:
At the time of writing, Google has indicated that Android Instant Apps is a feature which is available for a few apps which have partnered with Google to test the feature. These include Viki, Buzzfeed, Periscope, and Wish.
There is no official list of support devices at this time. This guide was created using a Google Pixel (which happens to be one of the Cartogram team's favorite devices for testing inertial indoor positioning).
Google has noted a 4 MB limitation on the APK size, but I suspect that this may change over time. They're probably limiting the size to improve responsiveness on first launch of the app, but 4 MB seems pretty low. We would like to see it increased to 15 MB.
The first step is to trigger Instant Apps to download and install on your device. Instant Apps is presumably a system app that manages the persistent app data stored on your phone and the permissions associated with each of the instant apps. You'll know whether Instant Apps is installed by going to Settings->Google and checking if there is an element titled "Instant Apps". If not, then you'll likely have to upgrade your OS and/or security patch. The update that triggered the Instant Apps installation for me was an update that installed security patch level February 5, 2017. Also note the Android version of 7.1.1, but it's unclear what the minimum required Android version is.
Once your system has the prerequisites for Instant Apps, you'll trigger something like the following screenshot:
Then, head over to your Settings and toggle Instant Apps. You'll get a dialogue like this:
Even though there are four apps being listed by Google as Instant Apps compatible, I was only able to make "Wish" work, despite running searches on the other three apps. To trigger Instant Apps, open your Chrome browser and search for "Wish Shopping Made Fun". You should notice something slightly different about your search results:
See how there is an "Instant" tag next to this particular listing? You may have to scroll through a few app options before you get to it. After you click on it, the Instant Apps system app (which you enabled earlier) will engage and ask you if you want to open the Wish website, of if you want to use the Instant App. To use the Instant App, tap on "Open App".
This will open up the app, which looks and feels like the regular Wish app. Pretty cool. The same user experience without the clunky Google Play installation.
I was curious about how the data and user permissions were being managed. It would be a poor user experience if the user had to explicitly enable permissions (like those required for BLE positioning or your camera) every time they used the Instant App. This is why Google stores settings, permissions, and maybe even the apk on the device. Here's what that looks like:
Why are we so excited about Instant Apps at Cartogram? Really, it's about covering as much ground as we can in terms of providing optimal value and experience for our customers and their visitors. Cartogram provides several platforms to help visitors find their way indoors and our native app SDK is only one of them.
For instance, one of Cartogram's new services is an SMS chatbot, which enables anyone to send a simple text message in the format "Where is <X>?" to a phone number or short code displayed throughout the building. Cartogram will respond intelligently with details about where the search element is inside of the building, and even provide a link to an indoor map which can be opened in the user's mobile browser – no app required.
We see Instant Apps as a natural evolution of these core technologies we've built at Cartogram. Android Instant Apps may enable the Cartogram team to take this experience to the next level and redirect our customers' users to the native Cartogram experience.


On linux once downloaded the linux version of the launcher: -right click the file technic-launcher-latest.jar, go to properties then on the open window go to the tab permissions and check the box allowing execution of the file as a program. -then right click if java is already installed click open with java -if java isn't installed right click and got to open with other applications. Then... Fill in the unique name of your pack, the version of minecraft it is for, whether it's publicly visible, and a short description. Now after agreeing to the submission guidelines hit Create Modpack.
Technic Support; Download the Launcher; Technic Forums; Minecraft Subreddit; Apex Gaming. Rules and Guidelines; Be kind to everyone and try to help out as best you can. Do not spam. That means you ggggggggggggggg. Only post content relating to Technic or content on the Technic Platform. Keep "Drama" posts at a minimum. NO SERVER OR MODPACK ADS! Feel free to share your favorite �... Select the Minecraft version that Technic is currently running and name it as you wish. From memory, Technic is running 1.6.4 . Allow it to install Minecraft, or skip this step completely.
Fill in the unique name of your pack, the version of minecraft it is for, whether it's publicly visible, and a short description. Now after agreeing to the submission guidelines hit Create Modpack.... 24/10/2015�� Decided to make a custom modpack, combining the elements my friends and I wanted a lot of which came from Crazy Craft. It lets you download all the mods just fine, but when you click "play" it simply opens the vanilla version of minecraft without any mods.
Select the Minecraft version that Technic is currently running and name it as you wish. From memory, Technic is running 1.6.4 . Allow it to install Minecraft, or skip this step completely.
24/10/2015�� Decided to make a custom modpack, combining the elements my friends and I wanted a lot of which came from Crazy Craft. It lets you download all the mods just fine, but when you click "play" it simply opens the vanilla version of minecraft without any mods.
Technic Launcher 4.0 - this launcher is designed for easy operation and install all sorts of mods. This launcher number of mods more than all other launchers combined. After starting the launcher, go to the modpacks tab and in the search line to drive we are interested in the mod, such as lucky block and install.


The Recommended computer chairs should have a 5-point chair base with casters. Such a base provides maximum stability and allows you move and turn quickly.
It is also suggested that the base of a computer chair be at least 27 inches in diameter for ultimate stability. Consider hard or soft casters depending on the type of flooring.
This feature adjusts the tilt of the computer chair to give users more naturals sitting position. A good chair can be adjusted to allow your legs sit at a 90 degrees angle. Many reclining seats will also include a knee tilt so that the seat is also adjusted when reclining. Note that proper positioning of your legs while sitting allows for correct blood flow and prevents cramps and pains associated with poor posture.
Gas lifts can be used to adjust the height of the seat about the computer desk for extra comfort and ergonomic benefits. This means that you can move your chair closer to your desk to achieve the right angle about your computer screen, thus reducing tension on your eyes.
These allow you adjust the seat of your computer chair, back or forth on a horizontal plane. A seat with this feature can be set up to the right angle for ultra-comfort.
A spring tilt allows you change your position on the seat and transfer some of the upper body weight, the chair's backrest. This way you do not have to seat at one position all day and can keep shifting weight to different parts of the body.
When typing, the neck and shoulders are often strained. With an adjustable arm rest, you can move closer to the workstation and even level your arms with the keyboard to relieve the neck and shoulders of any tension.
It is important to note that the presence of these features may not necessarily translate to a good computer chair. It is, therefore, to take into consideration other factors like the quality of construction, the materials used, and the overall style and design of the chair.


text:
STORY: Location: Los Angeles
This 'mega pizza' will dish out 68,000 slices once it is completed
Pizza Hut is hoping it will become the world's largest pizza ever made
[David Graves, President / Pizza Hut]
"Yeah. So, it's a big team, as you can see. Look, I mean, look at the size of it. It's a giant pizza. It's about 14,000 square feet. So, if you think about that, it's going to be like 68,000 slices of pizza when we're all done. And the great thing is none of it's going to waste. We can actually donate it to some local food banks here in the Los Angeles community. So, we're really excited about that."
To make the pizza, rectangular slices of pizza dough are laid along the base
Pizza sauce is then painted on to the dough before cheese and pepperoni are added
A cooking device then hovers over the pizza to cook it
"You know, Pizza Hut has a history of making firsts, right? We were the first to deliver a pizza. We're the first to take an order over the Internet. We've always done big, exciting things. And so, breaking the world record for the world's largest pizza just felt like the right thing to do to celebrate bringing back our largest pizza. So, that's why we did it."
Refuting Noh, Khaled says decision to fire and suspend members made by disciplinary board
KUALA LUMPUR, Jan 27 — Umno vice-president Datuk Seri Mohamed Khaled Nordin insisted tonight that the decision to fire a...


Type and handwrite math notation in your HTML editor and your Textarea.
WIRIS plugin for a generic editor enhances your text editor with new icons to edit math equations and chemical formulas with WIRIS EDITOR.
WIRIS tools can also be integrated with a Textarea.
Before starting any development, please ensure that there is no plugin already available for your needs. See the list of available SPECIFIC PLUGINS .
Just click on the new MathType and ChemType icons that appear in your rich text editor toolbar. Create a scientific expressions with the classical interface or handwrite it.
When you click on Accept, your expression will be converted into an image and displayed along with your other content.
Escritura manuscrita para dispositivos móviles. Funciona con iPad y otras tabletas.


text:
<title>C and C++ Trees - GNU Compiler Collection (GCC) Internals</title>
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10.10 C and C++ Trees

This section documents the internal representation used by GCC to
represent C and C++ source programs.  When presented with a C or C++
source program, GCC parses the program, performs semantic analysis
(including the generation of error messages), and then produces the
internal representation described here.  This representation contains a
complete representation for the entire translation unit provided as
input to the front end.  This representation is then typically processed
by a code-generator in order to produce machine code, but could also be
used in the creation of source browsers, intelligent editors, automatic
documentation generators, interpreters, and any other programs needing
the ability to process C or C++ code.

This section explains the internal representation.  In particular, it
documents the internal representation for C and C++ source
constructs, and the macros, functions, and variables that can be used to
access these constructs.  The C++ representation is largely a superset
of the representation used in the C front end.  There is only one
construct used in C that does not appear in the C++ front end and that
is the GNU “nested function” extension.  Many of the macros documented
here do not apply in C because the corresponding language constructs do
not appear in C.

The C and C++ front ends generate a mix of GENERIC trees and ones
specific to C and C++.  These language-specific trees are higher-level
constructs than the ones in GENERIC to make the parser's job easier.
This section describes those trees that aren't part of GENERIC as well
as aspects of GENERIC trees that are treated in a language-specific
manner.

If you are developing a “back end”, be it is a code-generator or some
other tool, that uses this representation, you may occasionally find
that you need to ask questions not easily answered by the functions and
macros available here.  If that situation occurs, it is quite likely
that GCC already supports the functionality you desire, but that the
interface is simply not documented here.  In that case, you should ask
the GCC maintainers (via mail to gcc@gcc.gnu.org) about
documenting the functionality you require.  Similarly, if you find
yourself writing functions that do not deal directly with your back end,
but instead might be useful to other people using the GCC front end, you
should submit your patches for inclusion in GCC.

Types for C++:                Fundamental and aggregate types.

Namespaces:                   Namespaces.

Classes:                      Classes.

Functions for C++:            Overloading and accessors for C++.

Statements for C++:           Statements specific to C and C++.

C++ Expressions:     From typeid to throw.

redpajama_set_name: RedPajamaGithub


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At present, the high quality IWC Portofino replica watches is sold in our website. So, you can buy IWC Portofino replica watches with a wet finger. And that, you will not regret on account of it.


text:
Soc Cogn Affect Neurosci. 2014 Sep;9(9):1281-8. doi: 10.1093/scan/nst110. Epub 2013 Jul 24.
The suggestible brain: posthypnotic effects on value-based decision-making.
Ludwig VU1, Stelzel C1, Krutiak H2, Magrabi A1, Steimke R1, Paschke LM1, Kathmann N2, Walter H3.
Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnother
Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany.
Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany Department of Psychiatry & Psychotherapy, Division of Mind and Brain Research, Charité Universitätsmedizin Berlin, 10117 Berlin, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, 10117 Berlin, Department of Psychology, Humboldt-Universität zu Berlin, 12489 Berlin, Berlin Center for Advanced Neuroimaging, 10119 Berlin, Fortbildungszentrum OST der Deutschen Gesellschaft für Hypnose und Hypnotherapie e.V., 10777 Berlin, and Institute of Cognitive Science, Universität Osnabrück, 49069 Osnabrück, Germany.
Hypnosis can affect perception, motor function and memory. However, so far no study using neuroimaging has investigated whether hypnosis can influence reward processing and decision-making. Here, we assessed whether posthypnotic suggestions can diminish the attractiveness of unhealthy food and whether this is more effective than diminishing attractiveness by one's own effort via autosuggestion. In total, 16 participants were hypnotized and 16 others were instructed to associate a color cue (blue or green) with disgust regarding specific snacks (sweet or salty). Afterwards, participants bid for snack items shown on an either blue or green background during functional magnetic resonance imaging measurement. Both hypnosis and autosuggestion successfully devalued snacks. This was indicated by participants' decision-making, their self-report and by decreased blood oxygen level-dependent signal in the ventromedial prefrontal cortex (vmPFC), a region known to represent value. Different vmPFC subregions coded for cue and snack type. The cue had significantly stronger effects on vmPFC after hypnosis than after autosuggestion, indicating that hypnosis was more effective in genuinely reducing value. Supporting previous findings, the precuneus was involved in the hypnotic effects by encoding whether a snack was sweet or salty during hypnotic cue presentation. Our results demonstrate that posthypnotic suggestions can influence valuation and decision-making.
© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
hypnosis; precuneus; self-control; value-based decision-making; ventromedial prefrontal cortex
10.1093/scan/nst110
Methods. (A) Procedure: hungry participants were either hypnotized or they used autosuggestion in order to feel disgust regarding either sweet or salty snacks upon seeing either a blue or a green color cue. Afterwards, they carried out an auction on sweet and salty snacks shown on an either blue or green background in the fMRI scanner. They could buy a real snack at the auction. (B) Experimental auction. (C) Overview of the trial types. Note that in this figure, example stimuli have been modified so that the brands of the snacks are not recognizable.
The suggestible brain: posthypnotic effects on value-based decision-making
Soc Cogn Affect Neurosci. 2014 Sep;9(9):1281-1288.
Behavior and self-report. (A) Bids. (B) Postexperimental disgust ratings. (C) Postexperimentally reported degree of physicality of disgust, experience of self-control (as opposed to automaticity) regarding the feeling of disgust, pretending of disgust and conscious recall of suggestion/instruction during the experiment. Ninety-five percent confidence interval (CI) of the mean are shown, adjusted for within-subject designs where appropriate . T: target snacks (sweet or salty). NT: non-target snacks. CueON: cue color shown in the background. CueOFF: neutral background color. ME: Main effect. IE: Interaction effect. ***P < 0.001, **P < 0.01, *P < 0.05; n.s., not significant.
Correlation with bids independent of condition for participants of both groups analyzed together (n = 32; peak: − 6, 35, − 2, t = 5.09). Results are masked by the a priori defined vmPFC ROI (Supplementary Figure S1A). For visualization purpose, activations are shown at P < 0.005, k = 10. The beta-plot visualizes the results (mean beta ± 1 s.e.). The plot was constructed using a procedure that ensures independency from the main analysis (see Supplementary Data; ).
Effect of the cue (yellow), of snack type (cyan) and of the interaction of cue × snack type (red) in vmPFC for participants of both groups analyzed together (n = 32; peaks within ROI for cue: −6, 35, −2, t = 4.01; snack type: 6, 26, −17, t = 4.29; cue × snack type: 0, 32, −2, t = 3.63). Results are masked by the vmPFC ROI. For visualization, activations are shown at P < 0.005, k = 10. beta-plots visualize the results (mean beta ± 1 s.e.) and were constructed in a way that ensures independency from the main analysis (see Supplementary Data). T: target snacks (sweet or salty). NT: non-target snacks. CueON: cue color shown in the background. CueOFF: neutral background color.
Group differences. (A) There was a stronger effect of the cue on vmPFC activation in the hypnosis group (peak: 3, 32, 4, t = 4.73). (B). There was also a stronger interaction effect of cue × snack type on the precuneus in the hypnosis group (peak: 9, −58, 46, t = 4.00). Results are masked by the vmPFC ROI in panel A and by the precuneus ROI in panel B (Supplementary Figure S1 gives a depiction of the ROIs). For visualization, activations are shown at P < 0.005, k = 10. beta-plots visualize the results (mean beta ± 1 s.e.) and were constructed in a way that ensures independency from the main analysis (see Supplementary Data). T: target snacks (sweet or salty); NT: non-target snacks. CueON: cue color shown in the background. CueOFF: neutral background color.
Acrosome Reaction
Brain/blood supply
Brain/physiology*
Decision Making/physiology*
Hypnosis*
Image Processing, Computer-Assisted
Oxygen/blood
Reward*
Suggestion*
OXYGEN - Hazardous Substances Data Bank


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text:
Welcome to Wakaliwood
Bill Jones, Jr. / 02 February 2017
We've all heard of Hollywood, that western Los Angeles bastion of film, fantasy, and phoniness. Hollywood didn't invent the movies. nor did they perfect them, but they sure as heck added to movies' worldwide popularity. Of course, California has hardly been the sole home of the movie industry: there has always been a burgeoning trade in the UK, in Europe, in Japan, in Hong Kong / China, and in developed countries worldwide. With economic growth in India, Bollywood films emerged, their industry's partly a homage to Hollywood, but also giving a bowing reference to their distinct, local feel.
Not to be outdone, Nigeria, home to over 100 million Africans, grew their own home-grown industry, labeled, cleverly, Nollywood. Well now, all of them can take a step back. Uganda is in the house, and Wakaliwood is where it's at.
The genius behind this pop-up industry is Isaac Nabwana, 45, head of Ramon Productions and dedicated, imaginative, if non-traditional filmmaker. Nabwana has made some 40 films, each of which he estimates to have had a budget of around $200.
That's not $200 million. That's two hundred dollars — around 130 quid, give or take. He manages this insanely low cost by having "amateur" actors who double as film crew and prop makers, all while juggling real jobs. The actors and crew aren't paid, but get to sell copies of the films door to door and pocket half of the profits (before the bootleggers go black market and kill the trade).
With the help of American fan and film buff, Alan Hofmanis, Bruce U, stuntman and kung fu coordinator, and his crew of Wakaliwood filmmakers, Ramon Studios has begun to get noticed, both via winning awards like the Best Director (action genre) and Audience Award at FANTASTIC FEST 2016, in Austin Texas, and via a 2015 Kickstarter campaign that brought them in some $13,181 when they were try to raise $160 to make a film.
Of course, as a BBC profile points out, if Hollywood gets hold of the story it'll likely star Alan Hofmanis instead of the Wakaliga, Uganda ghetto residents that comprise Ramon Film Productions ( and perhaps rightly so, since Hofmanis abandoned his life in New York to live and work with Nabwana in their film adventures). But make no bones about it, this is the product of imagination, wit, creativity, and a green screen made of cloth purchased from a local store.
Bosa, the official dead body dummy, now more famous than Mythbusters' Buster.
As a sampling of their product, below is the eight-minute opening scene (as trailer) for their film Bad Black. I'm hoping Bruce U did the fight scenes in the flick.
Bruce U
Are you hooked yet? If so, enjoy Wakaliwood's first action movie, Who Killed Captain Alex, FREE on YouTube. Also, feel free to check out the Wakaliwood website where you can watch of download the film or become a patron of the arts via Wakaliwood's Patreon page. Check it out! You won't even need a Ugandan Key!
02 February 2017 in Movies. Tags: filmmaking, movies, Ramon Productions, Uganda, Wakaliwood
Gojira! A Review from a lifelong fan
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3 thoughts on "Welcome to Wakaliwood"
I knew this would appeal to you. It's a great story. Thanks for doing a post on this. 🙂
Thanks for finding it. It's awesome. I wish them riches (that the government will then steal from them, but still…)
It looks as if they have a lot of fun making the films, despite the lack of money. I too hope they make it big.
I stumbled across them all because my dream…


Roblox The CrusheR Gameplay! Loving the New Revolving Lobby! Loud Warning!
0:01:15 Office Tower! We made it!
0:02:19 Fortress! I made it!
0:04:51 Quarry! We made it!
0:05:42 Frosted Aurora! No one survived because we didn't know where to go!
0:06:42 Prehistoric Lands! I made it!
0:07:59 Lava Facility! I MADE IT!
0:14:45 Climate Change! We made it!
0:16:53 Himalayas! I made it!
0:19:11 Autumn Grove! I DID IT!
0:22:33 Chocolate Land! We made it and I owe Chocolate lots of Chocolate bars XD!
0:23:38 Climate Change! I made it!
Can you survive the crusher? Find holes in the floors of the 115 maps to avoid being crushed. Level up and earn coins by surviving rounds, and spend those coins on gear, effects, and other cool stuff that will make your character more awesome.


Product prices and availability are accurate as of 2019-04-03 21:08:09 EDT and are subject to change. Any price and availability information displayed on http://www.amazon.com/ at the time of purchase will apply to the purchase of this product.
The Canon PIXMA MX300 Office All-in-One Inkjet Printer lets you scan, fax, copy, and print photographs and documents with one easy machine. This all-in-one printer features a compact, streamlined design that can scan vivid images with color resolutions up to 4800 by 1200 dpi, copy images and documents, or print bold, laser-quality text or photos directly from memory cards, cameras, DV camcorders, or camera phones in seconds. The printer's Easy Scroll Wheel makes operation a breeze, and the Auto-Image Fix feature ensures that every photo is clear and vivid. With this PIXMA, you can even fax at Super G3 fax speed in color and black-and-white, and its memory can store 20 speed-dial codes and receive 50 incoming pages.
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Pixma MX300 all-in-one printer, cross sell sheet, easy setup instructions, quick start guide, setup software and user's guide CD-ROM, PG-40 black cartridge, CL-41 color cartridge, power cord, and telephone line cable.


text:
World Travel Guide > Guides > North America > United States of America > Louisiana > New Orleans
Local time New Orleans
Introducing New Orleans
Images of New Orleans
Travel to New Orleans
United States of America Information
About United States of America
the IDs5140New Orleans Louis Armstrong International Airport
Places in New Orleans
New Orleans Louis Armstrong International Airport
New Orleans Nightlife
New Orleans has a nightlife that is as diverse as it is abundant. It draws people from around the world, in some measure because the bars and clubs are permitted to remain open 24 hours and it is one of the few places in the USA where you can consume alcohol on the street provided it is in a plastic container.
The French Quarter (known locally as 'The Quarter') is the main hub, with Bourbon Street at its centre. Bourbon is a brash, neon-lit street full of bars, restaurants and (towards the west side) strip clubs. The locals are more likely to go to neighbourhood bars on Decatur Street.
Jazz is generally considered to be a New Orleans' creation and the city is constantly buzzing with music. There are dozens of live venues, as well as numerous jazz trumpeters and other buskers on the streets. Those in the know head to Frenchman Street, where some of the city's best musicians play informal bars and clubs, often for a small cover.
Listings are available from the daily newspaper Times-Picayune (www.nola.com/entertainment), the free monthly publication OffBeat (www.offbeat.com), as well as from free weekly Gambit and the monthly New Orleans Magazine (www.neworleansmagazine.com). Gambit's affiliated online outfit (www.bestofneworleans.com) also posts weekly cultural events and performances. In preparation for your trip, listen to the live stream of WWOZ (www.wwoz.org) to get to know the local music scene.
Tickets are available from the venues or from Ticketmaster (www.ticketmaster.com), which levies a surcharge per ticket.
Bars in New Orleans
This uptown bar attracts many accolades for its inventive cocktails and laid-back vibe. Using fresh juices and innovative techniques, the friendly, unpretentious staff serve a young, sophisticated clientele. It is housed in a converted fire station and is more New York in style than traditional New Orleans. Give the bar staff dealer's choice for a tasty surprise.
Address: Uptown, 4905 Freret Street, New Orleans, 70115
Telephone: +1 504 302 2357.
Website: http://www.curenola.com
The Old Absinthe House
Opened in 1806, this is one of the oldest bars in town, but is youthful for a historical artefact. It's also one of the few bars on Bourbon Street that isn't completely touristy, and if you want to avoid weirdly coloured daiquiris, then it's a step up on the scale. Go on a Friday afternoon to watch New Orleans high society file in from their boozy lunches at neighbouring Galatoires.
Address: French Quarter, 240 Bourbon Street, New Orleans, 70130
Website: http://www.oldabsinthehouse.com
A compact cocktail bar located on the edge of the Quarter, Tonique gets good foot traffic thanks to its position and inventive drinks menus. The bartenders here serve up classic local cocktails as well as their own contemporary creations, and many of the ingredients (the tonic, for example) are made in-house fresh each day.
Address: French Quarter, 820 North Rampart Street, New Orleans, 70116
Website: http://www.bartonique.com
Clubs in New Orleans
This Bourbon Street institution is regularly voted the city's best dance club and attracts a mostly gay clientele. During Mardi Gras, it is one of the most popular spots in the city, and to get on the balcony there is considered a major achievement. As well as a dance floor, there are paid (male) dancers on the bar tops.
Website: http://www.ozneworleans.com
Live music in New Orleans
The city's largest regular music venue (stadium acts play at the Superdome) covers many musical genres, from blues and funk to rock and country. It is now one in a chain of restaurant-clubs, owned in part by comedian Dan Aykroyd. Headline acts are usually nationally touring names or at least local legends.
Address: French Quarter, 225 Decatur Street, New Orleans, 70130
Website: http://www.houseofblues.com
Held as one of the most authentic venues in the city, 'Prez Hall' attracts music fans in some number. Come early and queue for entrance to the legendary hall itself, where guests sit on the floor, if they must, to catch musicians trained in the 'Louis Armstrong school'. The Preservation Hall band is a collection of the city's fine musicians.
Address: French Quarter, 726 St Peter Street, New Orleans, 70116
Website: http://www.preservationhall.com
Set in a converted storefront dating from the 1800s, this jazz venue has three rooms: a wood-and-brick bar, a restaurant serving Creole food and an intimate performance space with mezzanine seating. Book in advance to hear top-notch jazz in an enthusiastic backroom of aficionados.
Address: Marigny, 626 Frenchmen Street, New Orleans, 70119
Website: http://www.snugjazz.com
Classical music in New Orleans
Dance in New Orleans
Theatres in New Orleans
Music and Dance in New Orleans
Culture in New Orleans
Formerly a 1903 'skyscraper' office building, the Hampton Inn is just two blocks from the French Quarter. Every Monday to Thursday 1730-1900, the lavish lobby is the scene for the complimentary manager's reception. Rooms are large and comfortable with high-speed Internet and king-size or two double beds. The hotel also has a gym, concierge, coffee shop and parking for a fee, along with access to Spa Atlantis, directly across the street. The daily hot breakfast buffet is included.
La Quinta Inn and Suites Downtown
This hotel has great facilities for bargain prices, such as guestrooms with either king-size or two double beds and large bathrooms, and some have microwaves. In-room business facilities include data ports, oversized desks, free high-speed Internet access and local calls. Add to that, cocktail lounge, business centre, a heated pool, and fitness centre, plus a free breakfast. The location is convenient for the French Quarter, Superdome, downtown, and the convention center.
Hotel Monteleone
One of the classic New Orleans luxury hotels, the Monteleone has been wowing visitors since 1886. Rooms are decked out with plush curtains, high-thread-count sheets and large flat-screen TVs. The lobby is suitably grand, and the Carousel Bar is something of a local haunt for cocktails and people watching.
Melrose Mansion
A tasteful, small property on the edge of the French Quarter, this luxury Victorian-era mansion dates back to the late 19th century. The interiors are suitably plush, with antique furniture, original artwork and all the mod cons you'd expect (iPod dock, LCD TV, Wi-Fi and minifridge). There's also a fairly large outdoor swimming pool.
Soniat House
Old books, fine artwork, Oriental rugs, American and European antiques: it is the little touches like these that make this hotel unique. The two restored 1830s townhouses have spiral staircases, balconies and patios. Sweet olive, magnolia, guava and ginger grow in the courtyards. Each of the 19 rooms and 14 suites are furnished with antiques that are accompanied by Frette Egyptian cotton bed linen, Wi-Fi, data ports and two phones.
Dauphine Orleans Hotel
This unassuming building on a quiet stretch of the French Quarter is recorded back as far as 1775, almost to the city's own beginnings. A former bordello site, the hotel now has 111 modern rooms and a host of old, atmospheric cottages. The pool and courtyard are nicely secluded and the hotel bar, May Baily's Place, also harks back to those hedonistic times.


FORMER Manchester United great Denis Irwin sees something of David Beckham in £25m new-boy Memphis Depay.
The former PSV Eindhoven star was profilic for the Dutch side last term and has already opened his United account after netting in a pre-season game against San Jose Earthquakes recently.
Depay is a dead-ball specialist and scored a number of stunning free-kicks during his time in Holland.
Irwin, United's full-back throughout the 1990s, believes Depay can match his former team-mate and Old Trafford legend Beckham in set-piece situations.
He told United's official website: "I think Memphis could match Becks. I saw him score a few goals last year for PSV and I think he will be a big addition to our team.
"It's still early days yet, but there's no doubt that he has a lot of talent. He brings that unpredictability and we don't possess too many players like that.
"His records will tell you that, even though he's young, he's a goalscorer as well, having scored 28 goals last year in Holland.
"We've already seen how good he is at finishing, so I think he'll become a big player for us even though he's young."
Irwin also hailed boss Louis van Gaal's other big-money summer signings and can't wait to see them in action when the Premier League bursts back into life next weekend.
He added: "[Morgan] Schneiderlin has had a great few years at Southampton, he's very mobile, not afraid to put a tackle in and it was a bonus for him to get a goal on his tour debut. I think he'll be an important player for us.
"As for the other two – [Matteo] Darmian looks more than accomplished in the full-back position.
"I don't know an awful lot about him but he's done well in the games he's played in.
"And of course [Bastian] Schweinsteiger is obviously a serial winner - he's won several Bundesliga titles, the World Cup and made over 100 appearances for Germany and 500 for Bayern Munich, so he's a very experienced player.
"I think all the players have been great additions and I'm really looking forward to seeing them play in the new season."


Contrary to popular belief, the manufacturing industry in the United States is stronger than ever. In fact, it's the strongest in the world and is responsible for nearly 20% of all the world's goods. However, it is true that manufacturing has changed immensely in the past few decades and will continue to evolve in the future. Factors such as outsourcing, automation, and the leaps and bounds computer technology makes every year will drastically impact every facet of manufacturing. For those companies trying to keep up and maintain a competitive edge, it's critical to understand how the evolution of the manufacturing landscape affects spindle repair.
With outsourcing on the rise, many industries make the bulk of their products internationally in places like Asia, Africa, and Mexico. While this greatly reduces the labor costs for the OEM, it also increases the distance between them and where their products will be in use. As anyone who works in manufacturing knows, downtime is the death of productivity. Every minute a plant is shut down is money lost. The shipping and logistics required for OEMs to repair many of their own products adds enormously to the downtime costs for their customers as machines stay out of operation. For this reason, many OEMs partner with independent repair specialists to provide closer support. Independent repair technicians can also provide onsite repairs for many common spindle problems to get the production line up and running even faster.
Currently, the manufacturing industry is experiencing a severe labor shortage. As equipment evolves and U.S. machinery becomes more complex, the need for skilled labor has skyrocketed. Many companies are turning to high schools and creating outreach programs to encourage the next generation to pursue careers in manufacturing. However, recruiting the right talent isn't cheap. Some estimates place the cost of recruiting experienced, skilled labor at over 100% the annual salary cost. For this reason, it's often inefficient for manufacturers to rely on in-house technicians for all their spindle repair needs. Independent companies specialize in recruiting and training the best candidates, and with their broad customer base, these technicians typically have a much greater depth of knowledge – handling all kinds of repairs every single day.
It's long been said that computer technology makes significant advancements every 18-months, thanks to the technological exponential growth known as Moore's Law. Recently, researchers at MIT found that Moore's Law can be applied with similar accuracy to technological growth across many industries including manufacturing. With every new piece of equipment or accessory, there becomes a need to master a new skill set. In order to avoid falling behind, manufacturers rely on high-end independent repair companies to keep apprised of the latest advancements in their industry.
To learn how an independent spindle repair company can best serve your needs and keep your production line ahead during these changing times, contact the professionals at GTI Spindle Technology today!


The concept of party families is central to comparative party politics. Looking systematically at individual party families, their origins, development, ideology, policy positions, organizational structure, and/or sociological composition, this series investigates the nature of families of political parties. Themes are systematically developed through case studies and comparative chapters to consider key issues around: ¢Electoral performance and composition: the electoral fate of each party family, differences among national, sub-national and European elections, common patterns in the electoral development and the composition of the electorate of each party family. ¢Participation to power: how the relationship to power has evolved for each party family. How their origins affect their capacity to enter government. What type of governmental coalitions or alliances they favour and which policies they develop once in power. ¢Ideology and policy positions: how the ideological positioning of each party family evolved. How electoral performances, participation to power, or leadership change contribute or not to major programmatic evolutions. ¢Party organization: how the intra-party organizational feature of each party family has evolved. Are these features homogeneous within each family? Is each family unique in their organizational choices? Aimed at scholars and students of comparative politics, with a specific appeal for those interested in political parties and party systems, representation and elections, voting behaviour and public opinion the comparative nature of titles in the series will appeal to readers throughout the world. Bringing together expert authors, editors and contributors it renews and expands our knowledge of political parties and party families in Europe.


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Q: Double decay $\beta\beta$ observation and neutrino mass If the double decay $\beta\beta$ will be detected this means the neutrino is a Majorana particle coincident with its antiparticle. At the moment the half life of this decay is put to $\tau\ge10^{25}$years. The limit of the Majorana neutrino mass is about 0.2–0.4 eV. What is the relation between the probability of $\beta\beta$ decay and the neutrino mass? Thanks.

A: Your statement is wrong in one point:
Regular $\beta\beta$ decay happens in nature, even with dirac neutrinos. However, this shows the continuous electron (or positron) energy distribution one expects from just two (largely independent) $\beta$ decays (see image below).

What's interesting is that, if neturinos are marjorana particles indeed, a different decay channel opens up: neutrinoless double beta decay, also denoted $\beta\beta 0\nu$. This would in theory lead to a spike at the upper end of the combined electron energy spectrum, since no unobservable particles carry away part of the decay energy. The Feynman diagram looks like this

The internal fermion line (the one with $\nu_e$ on it) is only allowed for majorana particles, since they do not carry a well-defined fermion number and thus have no arrows.
Note that the image of the spectrum above laaaaargly exaggerates the expected spike. Double beta decay is rare as it is and the neutrinoless version is supressed w.r.t. the $2\nu$ version. What the experiments looking for $\beta\beta 0\nu$ expect, are single digit event numbers after years of observation.
Now, to your actual question: The smaller the neutrino majorana mass, the less likely neutrinoless double beta decay is. Therefore, in the limit of zero majorana mass (thus only dirac mass), we have no $\beta\beta 0\nu$. Note that this is for left-handed neutrinos, i.e. the neutrinos that are part of the $SU(2)_L$ doublet only. Right-handed majorana masses may be arbitrarily large without influencing the $\beta \beta 0 \nu$.
Still, if the small neutrino masses originate from a seesaw mechanism, the induced majorana mass qualifies for $\beta \beta 0 \nu$.

A: You can compare neutrinoless double-beta decay to the problem of
\begin{align}
\pi^+ &\to e^+ + \nu_e, & \text{with branching ratio} &\sim 10^{-4} \\
\pi^+ &\to \mu^+ + \nu_\mu, & \text{ branching ratio} &\sim 1
\end{align}
Here the pion has spin zero and is at rest in some reference frame; in that reference frame the neutrino and the charged lepton must have equal and opposite momentum and have opposite spins, which works out to having the same helicity. But the weak charged current $W^+$ couples to left-handed particles and right-handed antiparticles. A relativistic, polarized lepton can only couple to the $W$ if its spin goes the right way. The neutrinos are hyper-relativistic and come out entirely left-handed. The $\mu$ has pretty low energy, and so its handedness is not very strong. But the positron is also strongly relativistic, with $\gamma \approx 100$, and has to come out spinning the "wrong" way due to the spins of the neutrino and the pion.
You have the same sort of thing happening in neutrinoless $\beta\beta$ decay: one of the neutrinos has to have the "wrong" spin, and the probability goes roughly like $\gamma^2$.


Safety nets are made to EN 1263-1 and installed to EN standard 1263-2. EN 1263-1. Sicor are also a member of FASET who are a trade association and training body for safety net manufacturing and installation.


A team of 11 Nazarenes from Australia, Portugal, and Spain traveled across Greece for a vision prayer tour in March as the Church of the Nazarene attempts to establish a registered ministry there.
The Australia/New Zealand Field has long been connected to Greece.
Moore and his wife, Vicki, were joined on the trip by Satish Manmothe, Australia South district superintendent; Harry Malos, an Australia South District pastor; Steve Kasambalis, Melbourne team coordinator; Gretchen Freeman, a Global Serve partner working in Australia; Bruce McKellips, Western Mediterranean field strategy coordinator; Charlton and Christine Kerr, visiting Greek Australians, and Joshua and Shannon Herndon, missionaries to Spain who were recently appointed to start the work of the Church of the Nazarene in Greece.
During the visit, the team spent time in prayer and discussion with people and organizations who could help establish a registered Church of the Nazarene in Greece. They met with Evangelical leaders from various denominations and consulted with pastors, legal representatives, nongovernmental organizations, Christian humanitarian organizations, and a Orthodox humanitarian organization. They visited places of biblical and archeological significance, including Athens, Corinth, Thessaloniki, Philippi, and Mikri Volvi.
The team also visited Idomeni, where they assisted refugees trapped in "no man's land" located at the border of Former Yugoslavia Republic of Macedonia and Greece.
Greece's economy, political situation, and the influx of millions of refugees have caused the people to become fearful and despondent, making it a country of urgency for Nazarene mission work. A recent census showed 88.3 percent of the population are Christians, but during the team's visit they found that church attendance is low and it seems that the Greeks' personal relationship with God is not well understood.
The Church of the Nazarene, with its holistic message of Christ's salvation, compassionate and humanitarian assistance, is an ideal match to meet the needs of modern Greeks.
The city of Thessaloniki, as in the days of Apostle Paul, was selected for future Nazarene work because of its strategic position in the Balkans as a gateway city to Asia, Europe, and Africa.
This trip is only the beginning of a longterm partnership as the Australian church seeks to assist the blossoming efforts of the Herndons, their children, and the Church of the Nazarene in Greece.
The team members enjoyed witnessing how God is opening the doors for the Church of the Nazarene in Greece and would like to thank the people who partnered with them in prayer.


The Ambassador Extraordinary and Plenipotentiary of Belarus in Latvia Republic, Gerasimenko Alexander, came to Grodno.
He had the meeting with Grodno leadership, and other official and business representatives, where alot of questions of trade, economic and cultural co-operation between Latvia and region of Grodno were discussed.
On April 27th the Ambassador is going to meet with Shapiro Semion, the Chairman of Grodno Executive Committee. Also he is gong to visit some Grodno enterprises: Glove's factory "Aktsent", "Grodnokhimvolokhno", "Conte SPA", "Bigun", "Zov-Len-Euromebel".


This is Willow's favorite way to cozy up to people she likes, whether it's on the sofa, or as in this case, in the back of the car. I have no idea why she does it it, but she does. This photo was not provoked or arranged in any way.
Isaiah may be hiding it in this photo, but he was pretty flattered by her womanly charm.


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text:
Események
 A 32. olümpiai játékok
 Samas-sum-ukín babiloni király fellázad öccse, Assur-bán-apli ellen, amivel négyéves háború veszi kezdetét.

Születések

Halálozások

652

fr:652 av. J.-C.

redpajama_set_name: RedPajamaWikipedia