gebhart/patrepeval huggingface dataset:
Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer (2010)

Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
Nickel to the Fore (2001)

Nickel was long thought not to be important in biology, but now several enzymes are known to depend on nickel for activity. In his Perspective, [Thauer][1] highlights the report by [ Dobbek et al .][2], whose high-resolution crystal structure of a nickel enzyme reveals a novel nickel cluster in the active site. The structure offers surprising insights into the active site and the likely mechanism through which the enzyme harvests electrons from carbon monoxide.

 [1]: http://www.sciencemag.org/cgi/content/full/293/5533/1264
 [2]: http://www.sciencemag.org/cgi/content/short/293/5533/1281
Texture Analysis for Automatic Segmentation of Intervertebral Disks of Scoliotic Spines From MR Images (2009)

This paper presents a unified framework for automatic segmentation of intervertebral disks of scoliotic spines from different types of magnetic resonance (MR) image sequences. The method exploits a combination of statistical and spectral texture features to discriminate closed regions representing intervertebral disks from background in MR images of the spine. Specific texture features are evaluated for three types of MR sequences acquired in the sagittal plane: 2-D spin echo, 3-D multiecho data image combination, and 3-D fast imaging with steady state precession. A total of 22 texture features (18 statistical and 4 spectral) are extracted from every closed region obtained from an automatic segmentation procedure based on the watershed approach. The feature selection step based on principal component analysis and clustering process permit to decide among all the extracted features which ones resulted in the highest rate of good classification. The proposed method is validated using a supervised k-nearest-neighbor classifier on 505 MR images coming from three different scoliotic patients and three different MR acquisition protocols. Results suggest that the selected texture features and classification can contribute to solve the problem of oversegmentation inherent to existing automatic segmentation methods by successfully discriminating intervertebral disks from the background on MRI of scoliotic spines.
Cloning and analysis of the promoter region of CCR5, a coreceptor for HIV-1 entry (1997)

The chemokine receptor CCR5 is a cofactor for cellular entry of macrophage-tropic strains of HIV-1. Expression of CCR5 is restricted to T cells, macrophages, and certain cell lines; however, the mechanisms controlling its expression remain largely unknown. To delineate these mechanisms, approximately 1.0 kb of DNA from the immediate 5' upstream region of CCR5 was cloned and characterized. CCR5 promoter activity was up-regulated by PMA, and a region spanning -417 to +61 relative to the transcription start site was sufficient for the basal and induced activity. DNase I footprinting assays demonstrated several protected areas within this region, and gel shift assays determined binding sites for transcriptional factors Oct-1, Oct-2, T cell factor 1alpha, and GATA1. CCR5 promoter activity was also induced by IL-2 or anti-CD3 Ab, while stimulation with anti-CD28 Ab markedly reduced CD3-mediated up-regulation of the CCR5 promoter. Flow cytometry confirmed the findings at the level of cell surface expression. Further delineation of the regulation of the CCR5 promoter will be important for a more comprehensive understanding of the pathogenesis of HIV disease.
Cloning and expression of cDNA for the luciferase from the marine ostracod Vargula hilgendorfii. (1989)

The marine ostracod Vargula hilgendorfii ejects luciferin and luciferase into seawater to produce a bright luminous cloud. The light is due to the oxidation of luciferin, an imidazopyrazine compound, by molecular oxygen, catalyzed by luciferase. The mechanism of the reaction has been studied extensively and the 60 kcal/mol required for the blue emission have been shown to be derived from the oxidation of luciferin via a dioxetanone intermediate, in which the excited state oxyluciferin bound to luciferase is the emitter. However, only limited information is available regarding the properties of the enzyme. This paper reports the cloning and sequence analysis of the cDNA for Vargula luciferase and the expression of the cDNA in a mammalian cell system. The primary structure, deduced from the nucleotide sequence, consists of 555 amino acid residues in a single polypeptide chain with a molecular weight of 62,171. Two regions of the enzyme show significant amino acid sequence homology with an N-terminal segment of the photoprotein aequorin. The Vargula luciferase gene, which contains a signal sequence for secretion, should be well suited as a reporter in studies of gene expression.
Multiphase Complementary Codes (1978)

A new class of complementary codes, similar to the complementary series of Golay but having multiphase elements, have been found to exist with specific complementary aperiodic complex autocorrelation functions. These new codes, called multiphase complementary codes, form a class of generalized complementary codes, of which the Golay complementary series can be considered to be a particular biphase subclass. Unlike Golay pairs, kernels of the new codes exist for odd length and can be synthesized. These new codes, like Golay pairs, are characterized by mathematical symmetries that may not be initially obvious because of apparent disorder. Multiphase complementary codes can be recursively expanded and used to form orthogonal or complementary sets of sequences. These complementary sets are not constrained to have even length or even cardinality. In addition, certain generalized Barker codes can also be utilized to form complementary sets with unique properties.
Dual Roles of Histone Deacetylases in the Control of Cardiac Growth (2004)

Diverse aetiological factors, including myocardial infarction, hypertension and contractile abnormalities, trigger a cardiac remodelling process in which the heart becomes abnormally enlarged with a consequent decline in cardiac function and eventual heart failure. Pathological cardiac hypertrophy is accompanied by the activation of a fetal cardiac gene programme, which contributes to maladaptive changes in contractility and calcium handling. Traditional treatment for heart failure involves administration of drugs that antagonize early signalling events at or near the cell membrane (e.g. cell surface receptor or ion channels). Given the complexity and redundant nature of the signalling networks that drive cardiac pathogenesis, a potentially more efficacious therapeutic strategy for disrupting the disease process would be to target common downstream elements in pathological signalling cascades. We have shown that class II histone deacetylases (HDACs) suppress cardiac hypertrophy, and mice lacking class II HDACs are sensitized to hypertrophic signals. Paradoxically, HDAC inhibitors also block cardiac hypertrophy and fetal gene activation. Based on these findings, we propose that distinct HDACs play positive or negative roles in the control of cardiac growth by regulating opposing sets of target genes via their interactions with different sets of transcription factors.
Sulfamoylbenzamide Derivatives Inhibit the Assembly of Hepatitis B Virus Nucleocapsids (2013)

Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B.
Expression of E1A in Terminally Differentiated Muscle Cells Reactivates the Cell Cycle and Suppresses Tissue-Specific Genes by Separable Mechanisms† (1996)

Terminally differentiated cells are characterized by permanent withdrawal from the cell cycle; they do not enter S phase even when stimulated by growth factors or retroviral oncogenes. We have shown, however, that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. In this report, we describe the molecular events triggered by E1A in terminally differentiated skeletal muscle cells. We found that in myotubes infected with the adenovirus mutant dl520, 12S E1A bypasses the early G1 phase and activates the expression of late-G1 genes, such as the cyclin E and cyclin A genes, cdk2, PCNA, and B-myb. Of these, the cyclin E gene and cdk2 were significantly overexpressed in comparison with levels in proliferating, undifferentiated myoblasts. p130 and pRb were phosphorylated before the infected myotubes entered S phase, despite the high expression of the cyclin-dependent kinase inhibitor p21, and E2F was released. Our results suggest that one of the mechanisms that E1A uses to overcome the proliferative block of terminally differentiated cells involves coordinated overexpression of cyclin E and cdk2. Following E1A expression, the myogenic transcription factors MyoD and myogenin and the muscle-specific structural genes encoding muscle creatine kinase and myosin heavy chain were downregulated. The muscle regulatory factors were also silenced in myotubes infected with adenovirus E1A mutants incapable of reactivating the cell cycle in terminally differentiated muscle cells. Thus, the suppression of the differentiation program is not a consequence of cell cycle reactivation in myotubes, and it is induced by an independent mechanism. Our results show that E1A reactivates the cell cycle and suppresses tissue-specific gene expression in terminally differentiated muscle cells, thus causing dedifferentiation.
Genome Sequence of Aeromonas hydrophila ATCC 7966 T : Jack of All Trades (2006)

The complete genome of Aeromonas hydrophila ATCC 7966(T) was sequenced. Aeromonas, a ubiquitous waterborne bacterium, has been placed by the Environmental Protection Agency on the Contaminant Candidate List because of its potential to cause human disease. The 4.7-Mb genome of this emerging pathogen shows a physiologically adroit organism with broad metabolic capabilities and considerable virulence potential. A large array of virulence genes, including some identified in clinical isolates of Aeromonas spp. or Vibrio spp., may confer upon this organism the ability to infect a wide range of hosts. However, two recognized virulence markers, a type III secretion system and a lateral flagellum, that are reported in other A. hydrophila strains are not identified in the sequenced isolate, ATCC 7966(T). Given the ubiquity and free-living lifestyle of this organism, there is relatively little evidence of fluidity in terms of mobile elements in the genome of this particular strain. Notable aspects of the metabolic repertoire of A. hydrophila include dissimilatory sulfate reduction and resistance mechanisms (such as thiopurine reductase, arsenate reductase, and phosphonate degradation enzymes) against toxic compounds encountered in polluted waters. These enzymes may have bioremediative as well as industrial potential. Thus, the A. hydrophila genome sequence provides valuable insights into its ability to flourish in both aquatic and host environments.
Autoregulation of Enzymes by Pseudosubstrate Prototopes: Myosin Light Chain Kinase (1988)

The myosin light chain kinase requires calmodulin for activation. Tryptic cleavage of the enzyme generates an inactive 64-kilodalton (kD) fragment that can be further cleaved to form a constitutively active, calmodulin-independent, 61-kD fragment. Microsequencing and amino acid analysis of purified peptides after proteolysis of the 61- and 64-kD fragments were used to determine the amino-terminal and carboxyl-terminal sequences of the 64-kD fragment. Cleavage within the calmodulin-binding region at Arg505 generates the catalytically inactive 64-kD fragment, which is incapable of binding calmodulin. Further digestion removes a carboxyl-terminal fragment, including the pseudosubstrate sequence Ser484-Lys-Asp-Arg-Met-Lys-Lys-Tyr-Met- Ala-Arg-Arg-Lys-Trp-Gln-Lys-Thr-Gly-His-Ala-Val-Arg505 and results in a calmodulin-independent 61-kD fragment. Both the 61- and 64-kD fragments have the same primary amino-terminal sequences. These results provide direct support for the concept that the pseudosubstrate structure binds the active site and that the role of calmodulin is to modulate this interaction. Pseudosubstrates may be utilized in analogous ways by other allosterically regulated enzymes.
Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation (2006)

The Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/b(DeltaN/DeltaN) mice). We have now reanalyzed lymphoid development in Stat5a/b(null/null) mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/b(null/null) mice lacked CD8(+) T lymphocytes. A massive reduction of CD8(+) T cells was also found in Stat5a/b(fl/fl) lck-cre transgenic animals. While gammadelta T-cell receptor-positive (gammadeltaTCR(+)) cells were expressed at normal levels in Stat5a/b(DeltaN/DeltaN) mice, they were completely absent in Stat5a/b(null/null) animals. Moreover, B-cell maturation was abrogated at the pre-pro-B-cell stage in Stat5a/b(null/null) mice, whereas Stat5a/b(DeltaN/DeltaN) B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/b(null/null) cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/b(DeltaN/DeltaN)-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/b(DeltaN/DeltaN) and Stat5a/b(null/null) mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation.
The biofilm mode of life : mechanisms and adaptations (2007)

1. Introduction 2. The Biofilm Mode of Life 3. Do Not Fear Commitment: The Initial Transition to a Surface Lifestyle by Pseudomonads 4. The Biofilm Matrix: A Sticky Framework 5. Cyclic di-GMP as an Intracellular Signal Regulating Bacterial Biofilm Formation 6. N-Acylhomoserine Lactones, Quorum Sensing and Biofilm Development in Gram-Negative Bacteria 7. Signaling in Escherichia coli Biofilms 8. Peptide Signaling 9. Differentiation and Dispersal in Biofilms 10. Human Oral Multi-Species Biofilms: Bacterial Communities in Health and Disease 11. Biofilms as Refuge Against Predation 12. Biofilms on Plant Surfaces 13. Bacterial Biofilms on Fungal Surfaces
Extensive Halogen Scrambling and Buttressing Effects Encountered upon Treatment of Oligobromoarenes with Bases (2001)

As a rule, tri-, tetra- and pentahaloarenes readily undergo ortho-lithiation when treated with amide-type bases. However, halogen migration occurs whenever the substrate contains three or more contiguous halogen atoms, provided that at least one of them is bromine or iodine. Dismutation and reduction processes often take place concomitantly. In this manner, a variety of organometallic intermediates may be formed, the driving force always being a decrease in basicity. When no such energy gain can be achieved, a sterically crowded substrate may just turn out to be inert; this was found to be the case with 1,5-dibromo-3-fluoro-2-(trimethylsilyl)benzene, 1,5-dibromo-3-fluoro-2,4-bis(trimethylsilyl)benzene, and 1,5-dibromo-3-fluoro-2,4-diiodobenzene. Buttressing effects are apparently strong enough to prevent expedient deprotonation of those substrates.
Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients (2005)

Multimarker qRT can detect circulating melanoma cells in blood. Measurement of the studied molecular markers in blood may be useful in detection of metastasis and monitoring treatment response of melanoma patients.
CELP coding at 4.0 kb/sec and below: improvements to FS-1016 (1992)

While code excited linear prediction (CELP) speech coders can produce high levels of output speech quality at rates near 4 kb/s, they may not be suitable for toll quality communications. The authors propose several modifications to improve the quality of the standard CELP algorithm while simultaneously reducing its transmission rate. The modifications include a multimode excitation that increases the convergence rate of the adaptive (pitch) codebook. A low-complexity spectral vector quantization algorithm is also developed that reduces the coding rate and decreases the spectral distortion. SNR improvements of 2 dB and a significant reduction in perceptual artifacts have been observed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A soft-input soft-output maximum a posteriori (MAP) module to decode parallel and serial concatenated codes (1996)

Concatenated coding schemes with interleavers consist of a combination of two simple constituent encoders and an interleaver. The parallel concatenation known as “turbo code” has been shown to yield remarkable coding gains close to theoretical limits, yet admitting a relatively simple iterative decoding technique. The recently proposed serial concatenation of interleaved codes may offer performance superior to that of turbo codes. In both coding schemes, the core of the iterative decoding structure is a soft-input soft-output (SISO) module. In this article, we describe the SISO module in a form that continuously updates the maximum a posteriori (MAP) probabilities of input and output code symbols and show how to embed it into iterative decoders for parallel and serially concatenated codes. Results are focused on codes yielding very high coding gain for space applications.
Review of Disaster Backup and Recovery Technology of Information System (2010)

Disaster backup and recovery is an important approach for system security and reliability,which can be used as an important support for information assurance in the development policy of China informationization.The measurements used for assessing the performance of disaster-tolerant systems are introduced firstly.The key technologies and realization methods of data-level disaster tolerance,system-level disaster tolerance,and application-level disaster tolerance are then summarized.Three future directions of disaster backup and recovery techniques are presented,which is the service-model shift from the data-storage-center to application-service-center,the architecture shift from a centralized structure to a shared mode based on the combination of distribution and virtualization,and the application mode shift from an isolate and specified system to a comprehensive service system,respectively.
LOW CURIE TEMPERATURE IN Fe-Cr-Ni-Mn ALLOYS (2011)

Studiile si cercetarile experimentale se axeaza pe realizarea unor aliaje cu temperatura Curie scazuta care sa fie utilizate in aplicaţii industriale. Cercetarile au avut la baza studii asupra structurii si proprietaţilor magnetice ale sistemului de aliaje Fe-Ni-Cr si influenţa Mn asupra temperaturii Curie in aceste aliaje. The study and experimental researches focus on the development of alloys with low Curie temperature that can be use in industry applications. Researches were based on studies of the structure and magnetic properties of Fe-Ni-Cr system alloys and the influence of Mn to Curie temperature in these alloys.
Combined effects of phase sweeping transmitter diversity and channel coding (1992)

A novel transmitter diversity scheme that generates forced fading to improve the performance of channel coding is proposed and investigated. Since the required phase sweeping frequency is much smaller than the transmission bit rate, bandwidth expansion is negligible. A sinusoidal phase sweeping function Delta Theta sin(2 pi f/sub H/t) is employed in laboratory experiments using 32 kbit/s quarternary differential phase shift keying (QDPSK) with differential detection and BCH(23,12) code. It is shown that Delta Theta =200 degrees and f/sub H/=67 Hz can be used when m (interleaving depth)=10 b. Hence, excessively long interleaving is not required by the use of transmitter diversity. Under very slow Rayleigh fading (f/sub D/=1 Hz), a measured improvement of 4.8 dB is obtained at a word error rate of 10/sup -2/ without receiver diversity. Applications include paging systems that require very simple receivers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Differential Calculus on Quantum Lorentz Group (1997)

In this paper, we discuss the bicovariant differential calculus on quantum Lorentz group, and provide corresponding de Rham complex and Maurer–Cartan formulae.