gebhart/patrepeval huggingface dataset:
Analysis of antibodies of known structure suggests a lack of correspondence between the residues in contact with the antigen and those modified by somatic hypermutation (2001)

Forty unique murine antibody-antigen complexes determined at 2.5 A or less resolution are analyzed to determine whether the residues in direct contact with the antigen are modified by somatic hypermutation. This was done by taking advantage of the recent characterization of the pool of Vkappa germline genes of the mouse. The average number of residues in contact with the antigen in the V(L) gene, which contains the CDRL-1, CDRL-2, and all but one residue of CDRL-3, was six. The average number of somatic mutations was similar (around five). However, as many as 53% of the antibodies did not show somatic replacements of residues in contact with the antigen. Another 28% had only one. Overall, the frequency of antibodies with increasing number of somatic replacements in residues in contact with the antigen decreased exponentially. A possible explanation of this finding is that mutations in the contacting residues have an adverse effect on the antigen-antibody interaction. This implies that most of the observed mutations are those remaining after negative (purifying) selection. Therefore, efficient strategies of site-directed mutagenesis to improve the affinity of antibodies should be focused on residues other than those directly interacting with the antigen.
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma (2011)

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.
Generalized Regression Neural Network and Radial Basis Function for Heart Disease Diagnosis (2010)

In this paper, two types of Artificial Neural Network (ANNs), Generalized Regression Neural Network (GRNN) and Radial Basis Function (RBF) have been used for heart disease to prescribe the medicine. Diagnosing the heart disease and prescribing the medicine on the basis of symptoms is a very challenging task to improve the ability of the physicians. The training capacity and medicines provided by these two techniques are compared with the original medicines provided by the heart specialist. About 300 patients data are collected from Sahara Hospital, Aurangabad under the supervision of doctor. This study includes the detailed information about patient and preprocessing was done. The GRNN and RBF have been applied over this patient data for the outcome the medicine. The result of these evaluation show that the overall performance of RBF can be applied successfully for prescribing the medicine for the heart disease patient.
Factor XSt. Louis II (1996)

A molecular defect in factor X (fX) results from a point mutation that causes glycine substitution for gamma-carboxylated glutamic acid at position 7. The variant (fXSt. Louis II) and wild type (fXWT) proteins were produced in a mammalian expression system and characterized. fXSt. Louis II has <1% and approximately 3% of normal clotting activity in modified prothrombin time and partial thromboplastin time assays, respectively. The rate of activation of fXSt. Louis II by factor VIIa and tissue factor is undetectable under conditions that result in complete activation of fXWT; activation by factors VIIIa and IXa is approximately 30% of normal activation. The X-activating protein from Russell's viper venom activates fXSt. Louis II completely but at a reduced rate. Thrombin generation on phoshopolipid vesicles or activated platelets is approximately 30% or approximately 5%, respectively. Membrane-dependent autolysis is markedly reduced for fXSt. Louis II. In reactions that are not surface-dependent, fXSt. Louis II is nearly identical to that of fXWT. The rate of inhibition by antithrombin is indistiguishable, as is the rate of thrombin formation in the absence of phospholipid, with or without factor Va.
Disruption of iron homeostasis in Saccharomyces cerevisiae by high zinc levels: a genome‐wide study (2007)

Zinc is an essential metal that, when in excess, can be deleterious to the cell. Therefore, homeostatic mechanisms for this cation must be finely tuned. To better understand the response of yeast in front of an excess of zinc, we screened a systematic deletion mutant library for altered growth in the presence of 6 mM zinc. Eighty-nine mutants exhibited increased zinc sensitivity, including many genes involved in vacuolar assembling and biogenesis. Interestingly, a mutant lacking the Aft1 transcription factor, required for the transcriptional response to iron starvation, was found to be highly sensitive to zinc. Genome-wide transcriptional profiling revealed that exposure to 5 mM ZnCl(2) results in rapid increase in the expression of numerous chaperones required for proper protein folding or targeting to vacuole and mitochondria, as well as genes involved in stress response (mainly oxidative), sulphur metabolism and some components of the iron regulon. The effect of the lack of Aft1 both in the absence and in the presence of zinc overload was also investigated. Exposure to high zinc generated reactive oxygen species and markedly decreased glutathione content. Interestingly, zinc excess results in decreased intracellular iron content and aconitase and cytochrome c activities in stationary-phase cultures. These findings suggest that high zinc levels may alter the assembly and/or function of iron-sulphur-containing proteins, as well as the biosynthesis of haem groups, thus establishing a link between zinc, iron and sulphur metabolism.
Search for Cancer Markers from Endometrial Tissues Using Differentially Labeled Tags iTRAQ and cICAT with Multidimensional Liquid Chromatography and Tandem Mass Spectrometry (2005)

A total of nine potential markers for endometrial cancer (EmCa) have been discovered and identified from endometrial tissue homogenates using a combination of differentially labeled tags, iTRAQ and cICAT, with multidimensional liquid chromatography and tandem mass spectrometry. The tissues were snap frozen in liquid nitrogen within 15-20 min after devitalization. Samples for proteomic analysis were treated with protease inhibitors before processing. Marker proteins that were overexpressed in EmCa are chaperonin 10, pyruvate kinase M1 or M2 isozyme, calgizzarin, heterogeneous nuclear ribonucleoprotein D0, macrophage migratory inhibitory factor, and polymeric immunoglobulin receptor precursor; those that were underexpressed are alpha-1-antitrypsin precursor, creatine kinase B, and transgelin. The chaperonin 10 result confirms our earlier observation of overexpression in EmCa tissues using surface-enhanced laser desorption/ionization mass spectrometry, verified by Western analysis and immunohistochemistry [Yang, E. C. C. et al. J. Proteome Res. 2004, 3, 636-643]. Pyruvate kinase was observed to be overexpressed using both iTRAQ and cICAT labeling. All nine markers have been found to be associated with various forms of cancer. A panel of these plus other markers may confer sufficient selectivity for diagnosing and screening of EmCa. The use of cICAT led to identification of a higher proportion of lower-abundance signaling proteins; conversely, iTRAQ resulted in a higher percentage of the more abundant ribosomal proteins and transcription factors.
Principles of crop improvement (1979)

The first edition of this higly regarded text was published in 1979 to provide a general introduction to the principles of plant breeding. It has been out of print since late 1993 and a new edition is long overdue as there are no up to date and comprehensive single volumes on the subject in print. The original text has been amended and enhanced where there have been advances in plant breeding to provide coverage of recent developments relevant to crop improvement which as intellectual property rights, biotechnology and the use and conservation of genetic resources. The emphasis of the text will be, as it was for the first edition, on the principles of plant breeding and the expanded range of techniques now available for effective crop improvement.
Nonribosomal peptides: from genes to products (2003)

The ability to synthesize nonribosomally small bioactive peptides that find application in modern medicine is widely spread among microorganisms. As broad as the spectrum of biological activities is the structural diversity of these peptides, which are mostly cyclic or branched cyclic compounds containing non-proteinogenic amino acids, small heterocyclic rings and other unusual modifications in the peptide backbone. They are synthesized by multimodular enzymes, the so-called nonribosomal peptide synthetases (NRPSs), from simple building blocks. Biochemical and genetic studies have unveiled the key principles of nonribosomal peptide syntheses, as well as the realization of many structural features of these peptides. This review focuses on recent results in NRPS research and highlights how this knowledge can be exploited for biotechnological purposes. In addition, possibilities and limitations for prediction of structural features of uncharacterized NRPSs and approaches for their engineering are discussed.
X‐ray scatter removal by deconvolution (1988)

The distribution of scattered x rays detected in a two-dimensional projection radiograph at diagnostic x-ray energies is measured as a function of field size and object thickness at a fixed x-ray potential and air gap. An image intensifier-TV based imaging system is used for image acquisition, manipulation, and analysis. A scatter point spread function (PSF) with an assumed linear, spatially invariant response is modeled as a modified Gaussian distribution, and is characterized by two parameters describing the width of the distribution and the fraction of scattered events detected. The PSF parameters are determined from analysis of images obtained with radio-opaque lead disks centrally placed on the source side of a homogeneous phantom. Analytical methods are used to convert the PSF into the frequency domain. Numerical inversion provides an inverse filter that operates on frequency transformed, scatter degraded images. Resultant inverse transformed images demonstrate the nonarbitrary removal of scatter, increased radiographic contrast, and improved quantitative accuracy. The use of the deconvolution method appears to be clinically applicable to a variety of digital projection images.
Generalized iterative spectrum balancing and grouped vectoring for maximal throughput of digital subscriber lines (2005)

Loop loss and crosstalk are the main impairments in DSL. Recently, novel crosstalk rejection and reduction techniques have been proposed to achieve the maximum capacity of the DSL channel. The performance of these techniques depends strongly on the degree of coordination among the users. In this paper, we consider maximizing the throughput of DSL when the users are coordinated at different levels. Moreover, we propose a novel centralized power allocation algorithm by generalizing a recently proposed iterative spectrum balancing (ISB) algorithm. Our generalized ISB (GISB) algorithm provides a superior performance to the ISB with polynomial complexity in the number of users. This complexity is much lower than that of the optimal spectral balancing (OSB) algorithm. Moreover, it can be selected adaptively based on the available processing power
Prognostic significance of allelic imbalance of chromosome arms 7q, 8p, 16q, and 18q in stage T3N0M0 prostate cancer. (1998)

Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.
Automatic Web Page Categorization by Link and Context Analysis (1999)

Assistance in retrieving documents on the World Wide Web is provided either by search engines, through keyword-based queries, or by catalogues, which organize documents into hierarchical collections. Maintaining catalogues manually is becoming increasingly difficult, due to the sheer amount of material on the Web; it is thus becoming necessary to resort to techniques for the automatic classification of documents. Automatic classification is traditionally performed by extracting the information for representing a document (``indexing&amp;apos;&amp;apos;) from the document itself. The paper describes the novel technique of categorization by context, which instead extracts useful information for classifying a document from the context where a URL referring to it appears. We present the results of experimenting with Theseus, a classifier that exploits this technique.
Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo (1998)

These results demonstrate that inhibition of the key regulatory paracrine growth factor for endothelial cells, VEGF, results in complete suppression of prostate cancer induced angiogenesis and prevents tumor growth beyond the initial prevascular growth phase.
Lysosomal high molecular weight multienzyme complex. (2003)

Three acidic glycosidases: beta-galactosidase (beta-GAL, EC 3.2.1.23), alpha-neuraminidase (NEUR, sialidase, EC 3.2.1.18), N-acetylaminogalacto-6-sulfate sulfatase (GALNS, EC 3.1.6.4) and serine carboxypepidase cathepsin A (EC 3.4.16.1) form a functional high molecular weight complex in the lysosomes. The major constituent of this complex is cathepsin A, the so-called "lysosomal protective protein" (PPCA). By forming a multienzyme complex, it protects the glycosidases from rapid intralysosomal proteolysis, and it is also required for the intracellular sorting and proteolytic processing of their precursors. In man, a deficiency of cathepsin A leads to a combined deficiency of beta-GAL and NEUR activities, called "galactosialidosis". Multiple mutations identified in the cathepsin A gene are the molecular basis of this lysosomal storage disease. This review describes the structural organization of the lysosomal high molecular weight multienzyme complex and the importance of the protective protein/cathepsin A in physiology and pathology.
Origins of DNA replication in metazoan chromosomes. (1993)

In metazoan chromosomes, initiation of DNA replication occurs primarily at specific sites (0.5-3 kb; the OBR) using the same replication fork mechanism favored by simple genomes. Nucleosome segregation is distributive. However, initiation events also occur at other sites randomly distributed throughout a larger initiation zone (8-55 kb). These nonspecific initiation events presumably occur at a lower frequency than those at the OBR. Although origins in native chromosomes appear to be genetically determined, ori sequences have been convincingly demonstrated only during programmed gene amplification. It seems likely that metazoan origins include both specific DNA sequences as well as chromatin structure and nuclear organization, something that may be difficult to reproduce with plasmid DNA. Definitive answers will come only with a functional assay for initiation that exhibits the sequence-specific characteristics observed in vivo.
The Complete Genome of Comamonas testosteroni Reveals Its Genetic Adaptations to Changing Environments (2009)

Members of the gram-negative, strictly aerobic genus Comamonas occur in various environments. Here we report the complete genome of Comamonas testosteroni strain CNB-2. Strain CNB-2 has a circular chromosome that is 5,373,643 bp long and has a G+C content of 61.4%. A total of 4,803 open reading frames (ORFs) were identified; 3,514 of these ORFs are functionally assigned to energy production, cell growth, signal transduction, or transportation, while 866 ORFs encode hypothetical proteins and 423 ORFs encode purely hypothetical proteins. The CNB-2 genome has many genes for transportation (22%) and signal transduction (6%), which allows the cells to respond and adapt to changing environments. Strain CNB-2 does not assimilate carbohydrates due to the lack of genes encoding proteins involved in glycolysis and pentose phosphate pathways, and it contains many genes encoding proteins involved in degradation of aromatic compounds. We identified 66 Tct and nine TRAP-T systems and a complete tricarboxylic acid cycle, which may allow CNB-2 to take up and metabolize a range of carboxylic acids. This nutritional bias for carboxylic acids and aromatic compounds enables strain CNB-2 to occupy unique niches in environments. Four different sets of terminal oxidases for the respiratory system were identified, and they putatively functioned at different oxygen concentrations. This study conclusively revealed at the genomic level that the genetic versatility of C. testosteroni is vital for competition with other bacteria in its special niches.
Production of Recombinant Human Trimeric CD137L (4-1BBL) (2005)

The interaction between 4-1BB ligand (CD137L), a member of the tumor necrosis factor superfamily, and its receptor 4-1BB provides a co-stimulatory signal for T lymphocyte proliferation and survival. However, the structure of 4-1BBL has not been thoroughly investigated, and none of the human recombinant 4-1BBL molecules available have been described as capable of co-stimulating T cells. The present work provides a model of the three-dimensional structure of the tumor necrosis factor homology domain of 4-1BBL and describes the production of a recombinant human soluble 4-1BBL whose originality lies in that it contains the whole extracellular tail preceding the tumor necrosis factor homology domain and an AviTag peptide (AviTag-4-1BBL) allowing enzymatic biotinylation and multimerization via streptavidin. We provide evidence that this chimeric protein exists as a homotrimer, whereas commercial FLAG-tagged 4-1BBL does not. This resulted in a much higher affinity for 4-1BB (1.2 nM) as compared with FLAG-4-1BBL (55.2 nM). We demonstrate that the single extracellular cysteine residue in the tail (Cys-51) could form a disulfide bond, both in our recombinant protein and in physiologically expressed 4-1BBL. The mutation of this cysteine residue exerted no effect on trimerization but increased the dissociation rate of AviTag-4-1BBL from 4-1BB. In its soluble form, AviTag-4-1BBL did not stimulate purified T cells but dramatically inhibited proliferation of peripheral blood mononuclear cells stimulated with anti-CD3 mAb. In contrast, a very significant co-stimulatory effect was observed on purified T cells once AviTag-4-1BBL was immobilized onto streptavidin beads. In addition, we show that the cross-linking of two trimeric AviTag-4-1BBL molecules was the minimum step required to elicit significant costimulatory activity.
Glycogen Synthase Kinase-3β Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium (2004)

Lithium is widely used to treat bipolar disorder, but its mechanism of action in this disorder is unknown. Several molecular targets of lithium have been identified, but these putative targets have not been shown to be responsible for the behavioral effects of lithium in vivo. A robust model for the effects of chronic lithium on behavior in mice would greatly facilitate the characterization of lithium action. We describe behaviors in mice that are robustly affected by chronic lithium. Remarkably, these lithium-sensitive behaviors are also observed in mice lacking one copy of the gene encoding glycogen synthase kinase-3beta (Gsk-3beta), a well established direct target of lithium. In addition, chronic lithium induces molecular changes consistent with inhibition of GSK-3 within regions of the brain that are paralleled in Gsk-3beta+/- heterozygous mice. We also show that lithium therapy activates Wnt signaling in vivo, as measured by increased Wnt-dependent gene expression in the amygdala, hippocampus, and hypothalamus. These observations support a central role for GSK-3beta in mediating behavioral responses to lithium.