gebhart/patrepeval huggingface dataset:
Feature Selection for SVMs (2000)

We introduce a method of feature selection for Support Vector Machines. The method is based upon finding those features which minimize bounds on the leave-one-out error, which can be efficiently computed via gradient descent. The resulting algorithms are shown to be superior to some standard feature selection algorithms on both toy data and real-life problems of face recognition, pedestrian detection and analyzing DNA microarray data. 1 Introduction In many supervised learning problems 1 feature selection is important for a variety of reasons: generalization performance, running time requirements, and constraints and interpretational issues imposed by the problem itself. In classification problems we are given ` data points x i 2 R n labeled y 2 \\Sigma1 drawn i.i.d from a probability distribution P (x; y). We would like to select a subset of features while preserving or improving the discriminative ability of a classifier. A brute force search of all possible subsets is kn...
Break in the BCL1 locus is closely associated with intermediate lymphocytic lymphoma subtype (1990)

The t(11;14)(q13;q32) is a recurring translocation associated with some chronic B-cell lymphocytic malignancies; the putative protooncogene BCL1, located at the chromosome band 11q13, can be involved during the translocation process. In order to determine if BCL1 rearrangement is associated with a particular subtype of lymphoma, we analysed 131 B-cell non-Hodgkin's lymphoma samples by Southern blot analysis, using a BCL1 probe. The BCL1 locus was rearranged in 9 out of 25 (36%) cases of intermediate lymphocytic cell lymphomas (ILL), in 1 out of 8 cases of diffuse small cleaved cell lymphoma, in 1 out of 12 cases of diffuse mixed cell lymphoma, and in 1 out of 21 cases of diffuse large cell lymphoma. In contrast, BCL1 was never found rearranged in any of the 46 follicular lymphomas analysed. The BCL2 gene was in germ-line configuration in all ILL. Sequential hybridization of Southern blots with JH, C mu, and BCLI probes identified comigrating fragments in only one case of ILL, which suggests that, in all the other cases, either the rearrangement of BCL1 did not result from a t(11;14) translocation or the break on chromosome 14 occurred outside the JH or C mu regions. These results indicate that rearrangement of the BCL1 locus may be closely associated with ILL and could be considered as a genotypic marker of this lymphoma subtype.
Heritability of nociception. III. Genetic relationships among commonly used assays of nociception and hypersensitivity (2002)

We and others have previously demonstrated that nociception in the mouse is heritable. A genetic correlation analysis of 12 common measures of nociception among a common set of inbred strains revealed three major clusters (or 'types') of nociception in this species. In the present study, we re-evaluated the major types of nociception and their interrelatedness using ten additional assays of nociception and hypersensitivity, including: three thermal assays (tail withdrawal from 47.5 degrees C water or -15 degrees C ethanol; tail flick from radiant heat), two chemical assays of spontaneous nociception (bee venom test; capsaicin test) and their subsequent thermal hypersensitivity states (including contralateral hypersensitivity in the bee venom test), a mechanical nociceptive assay (tail-clip test), and a mechanical hypersensitivity assay (intrathecal dynorphin). Confirming our earlier findings, the results demonstrate distinct thermal and chemical nociceptive types. It is now clear that mechanical hypersensitivity and thermal hypersensitivity are genetically dissociable phenomena. Furthermore, we now see at least two distinct types of thermal hypersensitivity: afferent-dependent, featuring a preceding significant period of spontaneous nociceptive behavior associated with afferent neural activity, and non-afferent-dependent. In conclusion, our latest analysis suggests that there are at least five fundamental types of nociception and hypersensitivity: (1) baseline thermal nociception; (2) spontaneous responses to noxious chemical stimuli; (3) thermal hypersensitivity; (4) mechanical hypersensitivity; and (5) afferent input-dependent hypersensitivity.
Inhibition of STAT3 Signaling Blocks the Anti-apoptotic Activity of IL-6 in Human Liver Cancer Cells (2010)

Interleukin-6 (IL-6) is a multifunctional cytokine, which may block apoptosis during inflammation to protect cells under very toxic conditions. However, IL-6 also activates STAT3 in many types of human cancer. Recent studies demonstrate that high levels of IL-6 are associated with hepatocellular carcinoma, the most common type of liver cancer. Here we reported that IL-6 promoted survival of human liver cancer cells through activating STAT3 in response to doxorubicin treatment. Endogenous IL-6 levels in SNU-449 cells were higher than in Hep3B cells. Meanwhile, SNU-449 cells were more resistant to doxorubicin than Hep3B cells. Addition of IL-6 induced STAT3 activation in Hep3B cells and led to protection against doxorubicin. In contrast, neutralizing IL-6 with anti-IL-6 antibody decreased survival of SNU-449 cells in response to doxorubicin. To elucidate the mechanism of the anti-apoptotic function of IL-6, we investigated if STAT3 mediated this drug resistance. Targeting STAT3 with STAT3 siRNA reduced the protection of IL-6 against doxorubicin-induced apoptosis, indicating that STAT3 signaling contributed to the anti-apoptotic effect of IL-6. Moreover, we further explored if a STAT3 small molecule inhibitor could abolish this anti-apoptotic effect. LLL12, a STAT3 small molecule inhibitor, blocked IL-6-induced STAT3 phosphorylation, resulting in attenuation of the anti-apoptotic activity of IL-6. Finally, neutralization of endogenous IL-6 with anti-IL-6 antibody or blockade of STAT3 with LLL12 lowered the recovery in SNU-449 cells after doxorubicin treatment. Therefore, our results demonstrated that targeting STAT3 signaling could interrupt the anti-apoptotic function of IL-6 in human liver cancer cells.
New monoclonal antibodies to the T cell antigens CD4 and CD8. Production and characterization in formalin-fixed paraffin-embedded tissue. (1998)

We have generated a recombinant protein representing part of the CD4 molecule and a peptide representing an epitope of predicted high antigenicity on the CD8 molecule and employed these to generate mouse monoclonal antibodies using standard hybridoma protocols. The extracellular domain of the CD4 molecule was obtained by reverse transcription of mRNA from peripheral blood lymphocytes followed by polymerase chain reaction. The amplified gene fragment was cloned into an expression vector to allow a histidine-tagged fusion protein to be produced in Escherichia coli. Purified fusion protein was used to immunize mice. The CD8 monoclonal antibody was raised against a peptide consisting of 13 amino acids within the carboxyl-terminal region of the CD8 cytoplasmic domain. The antibodies showed appropriate reactivity on Western blotting. By heat pretreatment, these antibodies have been shown to be highly effective on paraffin-embedded tissue. In normal lymphoid tissue, the expected distribution of CD4 and CD8 lymphocytes was observed. In a series of 16 T cell lymphomas and B cell lymphomas, immunostaining results were compared with those obtained using reagents effective only in frozen tissue. A high degree of correlation was observed. These results suggest that NCL-CD4 and NCL-CD8 may be of value in the characterization of T cell disorders.
Schizotypal Symptoms and Signs in the Roscommon Family Study (1995)

"Schizotypy" is a complex, multidimensional clinical construct, whose various dimensions differ widely both in the degree and specificity with which they reflect the familial liability to schizophrenia. Subpsychotic thought disorder; negative schizotypal signs, such as poor rapport and odd behavior; deficient occupational functioning; and social isolation/avoidance best characterized relatives of schizophrenic probands compared with relatives of matched controls.
Characteristics of the influenza virus-specific CD8+ T cell response in mice homozygous for disruption of the H-2lAb gene (1995)

The development of influenza virus-specific CD8+ cytotoxic T lymphocyte precursors (CTLp) is diminished in H-2b mice that are homozygous (-/-) for disruption of the H-2lAb gene. Virus clearance was not obviously delayed when compared with the congenic H-2lAb (+/+) controls, and evidence of CTL activity was apparent for inflammatory cells recovered from the respiratory tract in both cases. However, the virus-specific CTLp that are normally present in the regional lymph nodes and in the infected lung were evidently being consumed at the peak of the host response to give the terminally differentiated CTL effectors. Even so, any exhaustion of the CTLp pool was apparently transitory with this localized infection as, though the frequencies were consistently lower than those found for the (+/+) controls, CTLp could be detected reproducibly in both lymph nodes and spleen through 14 mo after infection. Analysis of cytokine profiles during the acute response showed a substantial defect in the (-/-) mice, indicating that cytokine production is largely dependent on the influenza-specific CD4+ set.
Identifying determinants of folding and activity for a protein of unknown structure. (1989)

We have generated an extensive genetic map of functionally allowed and/or structurally allowed amino acid substitutions in Arc repressor, a DNA binding protein of unknown structure. Analysis of the allowed substitution patterns identifies residues that are likely to be involved in protein function and identifies side chains that play important structural roles, including residues likely to form the hydrophobic core. The identities of approximately one-third of the residues in Arc repressor are functionally important, about one-half are structurally important, and the remainder are unimportant for either structure or function. The patterns of obligatory hydrophobic positions permit strong predictions of secondary structure.
Tetracycline-regulated cardiac gene expression in vivo. (1994)

Tight regulation of foreign genes expressed in vivo would facilitate studies of many biologic processes and would be useful for gene transfer-based therapies. To test the ability of a tetracycline-regulated gene expression system to function in vivo, we directly injected chimeric tet repressor-VP16 transactivator expression plasmids and luciferase target genes into the hearts of adult rats. Cardiac luciferase activity increased over two orders of magnitude in response to small changes in input tetracycline-controlled transactivator DNA. Transactivation was repressed to background levels by subtherapeutic concentrations of tetracycline in a dose-dependent manner. Target gene expression could be rapidly and reversibly controlled by manipulating antibiotic administration. This system may be particularly useful for in vivo studies of gene function or gene therapies where the timing or extent of expression are critical variables.
Transmission of the Hepatitis B Virus-Associated Delta Antigen to Chimpanzees (1980)

Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (delta) into chimpanzees susceptible to infection with hepatitis B virus (HBV) resulted in type B hepatitis and delta markers (delta antigen and antibody to delta) in recipient animals. A dilution (10(-8)) of serum induced type B hepatitis without delta markers in another HBV-susceptible animal. HBV infection and delta markers did not develop in animals with preexisting titers of antibody of HBsAg. In chimpanzees with circulating HBsAg at the time of inoculation, synthesis of delta occurred earlier and its extent and duration were greater than in animals previously unexposed to HBV; coincident with synthesis of delta, hepatitis occurred in chronic HBsAg carriers, and synthesis of preexisting HBV gene products (HBsAg and hepatitis B core antigen) was diminished. Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.
Use of macroporous polymeric high-performance liquid chromatographic columns in pharmaceutical analysis (1987)

One of the advantages of polymeric HPLC packings over silica-based packings is chemical stability, particularly at elevated pH levels. This paper describes the application of polymeric (PLRP-S) columns to four typical pharmaceutical studies: the separation of Vigabatrin (4-aminohex-5-enoic acid), a novel GABA transaminase inhibitor, from its related compounds; the separation of Vigabatrin from a degradation product in a liquid formulation containing benzoic acid as a preservative; the determination of aminophylline in a tablet formulation; and the determination of sodium camphorsulphonate in a liquid formulation.This paper compares PLRP-S columns with silica-based columns and considers some theoretical parameters affecting chromatographic performance. The column efficiency of PLRP-S is shown to increase with temperature. Graphs of In k′ versus reciprocal temperature for LiChrosorb RP-18 and PLRP-S columns deviate slightly from linearity using methanol-water mobile phases. Graphs of reciprocal k′ versus reciprocal root ionic strength are linear for PLRP-S columns. The adsorption mechanism proposed to explain this phenomenon is the Stern-Gouy-Chapman theory of the electrical double layer.
Concise Review: Lessons from Naïve Human Pluripotent Cells (2016)

The naïve state of pluripotency is actively being explored by a number of labs. There is some controversy in the field as to the true identity of naïve human pluripotent cells as they are not exact mirrors of the mouse. The various reports published, although in basic agreement, present discrepancies in the characterization of the various lines, which likely reflect the etiology of these lines. The primary lesson learned from these contributions is that a human naïve state reflecting the preimplantation human is likely to exist. The essential factors that will universally maintain the naïve state in human cells in vitro are not yet fully understood. These first need to be identified in order to describe the definitive characteristics of this state. Comparisons of naïve and primed human pluripotent cells have also highlighted consistencies between states and broadened our understanding of embryonic metabolism, epigenetic change required for development, embryonic DNA repair strategies and embryonic expression dynamics. Stem Cells 2017;35:35-41.
A reversible functional defect of CD8+ T lymphocytes involving loss of tetramer labeling (2002)

We have observed that human CTL clones lose their specific cytolytic activity and cytokine production under certain stimulation conditions, while retaining an antigen-dependent growth pattern. These inactive CTL simultaneously lose their labeling by an HLA-peptide tetramer, even though the amount of TCR-CD3 at their surface is not reduced. The tetramer-negative cells recover tetramer staining and cytolytic activity after stimulation with tumor cells in the presence of a supernatant of activated lymphocytes. Our results suggest the existence of a new type of functional defect of CTL. They also indicate that tetramers may fail to reveal some CTL bearing the relevant TCR, even when such functionally arrested CTL retain the potential to participate in immune responses because their defect is reversible.
Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis (2002)

The present study emphasizes the importance of cell surface expression and secretion of heparanase (endo-beta-D-glucuronidase) in tumor angiogenesis and metastasis. For this purpose, nonmetastatic Eb mouse lymphoma cells were transfected with the predominantly intracellular human heparanase or with a readily secreted chimeric construct composed of the human enzyme and the chicken heparanase signal peptide. Eb cells overexpressing the secreted heparanase invaded a reconstituted basement membrane to a much higher extent than cells overexpressing the intracellular enzyme. Cell invasion was inhibited in the presence of laminaran sulfate, a potent inhibitor of heparanase activity and experimental metastasis. The increased invasiveness in vitro was reflected in vivo by rapid and massive liver colonization and accelerated mortality. In fact, mice inoculated with cells expressing the secreted enzyme succumb because of liver metastasis and dysfunction, as early as 10 days after s.c. inoculation of the cells, when their tumor burden did not exceed 1% of body weight. Cell surface localization and secretion of heparanase markedly stimulated tumor angiogenesis, as demonstrated by a 4-6-fold increase in vessel density and functionality evaluated by MRI of tumors produced by cells expressing the secreted vs. the nonsecreted heparanase, consistent with actual counting of blood vessels. Altogether, our results indicate that the potent proangoigenic and prometastatic properties of heparanase are tightly regulated by its cellular localization and secretion. The increased potency of the secreted enzyme makes it a promising target for anticancer drug development.
Clinical Experience with the 22-MeV Microtron at the National Cancer Center Hospital (1984)

Experience with the 22-MeV microtron is presented. The maintenance and ease of operability of the system are satisfactory. The physical characteristics showed many clinical advantages. Fundamental measurement of dose distribution and depth dose curves were performed and clinically applied. The two-gantry system is very satisfactory and effective for irradiation by photons and electrons to treat many patients per day. The facility for intraoperative radiotherapy and the physical conditions for total body irradiation are also sufficient because of the well-designed building layout and the systematized facility with the microtron system.
Biochemical properties of a high fidelity DNA ligase from Thermus species AK16D (1999)

NAD+-dependent DNA ligases from thermophilic bacteria Thermus species are highly homologous with amino acid sequence identities ranging from 85 to 98%. Thermus species AK16D ligase, the most divergent of the seven Thermus isolates collected worldwide, was cloned, expressed in Escherichia coli and purified to homogeneity. This Thermus ligase is similar to Thermus thermophilus HB8 ligase with respect to pH, salt, NAD+, divalent cation profiles and steady-state kinetics.However, the former is more discriminative toward T/G mismatches at the 3'-side of the ligation junction, as judged by the ratios of initial ligation rates of matched and mismatched substrates. The two wild-type Thermus ligases and a Tth ligase mutant (K294R) demonstrate 1-2 orders of magnitude higher fidelity than viral T4 DNA ligase. Both Thermus ligases are active with either the metal cofactor Mg2+, Mn2+or Ca2+but not with Co2+, Ni2+, Cu2+or Zn2+. While the nick closure step with Ca2+becomes rate-limiting which results in the accumulation of DNA-adenylate intermediate, Ni2+only supports intermediate formation to a limited extent. Both Thermus ligases exhibit enhanced mismatch ligation when Mn2+is substituted for Mg2+, but the Tsp. AK16D ligase remains more specific toward perfectly matched substrate.
Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis (2007)

Angiostatic therapies designed to inhibit neovascularization associated with multiple pathological conditions have only been partially successful; complete inhibition has not been achieved. We demonstrate synergistic effects of combining angiostatic molecules that target distinct aspects of the angiogenic process, resulting in the complete inhibition of neovascular growth associated with development, ischemic retinopathy, and tumor growth, with little or no effect on normal, mature tissue vasculature. Tumor vascular obliteration using combination angiostatic therapy was associated with reduced tumor mass and increased survival in a rat 9L gliosarcoma model, whereas individual monotherapies were ineffective. Significant compensatory up-regulation of several proangiogenic factors was observed after treatment with a single angiostatic agent. In contrast, treatment with combination angiostatic therapy significantly reduced compensatory up-regulation. Therapies that combine angiostatic molecules targeting multiple, distinct aspects of the angiogenic process may represent a previously uncharacterized paradigm for the treatment of many devastating diseases with associated pathological neovascularization.
Identification of a Novel Human Rho Protein with Unusual Properties: GTPase Deficiency and In Vivo Farnesylation (1996)

We have identified a human Rho protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Replacing all three positions in RhoE with conventional amino acids completely restores GTPase activity. In vivo, RhoE is found exclusively in the GTP-bound form, suggesting that unlike previously characterized small GTPases, RhoE may be normally maintained in an activated state. Thus, amino acid changes in Ras that are selected during tumorigenesis have evolved naturally in this Rho protein and have similar consequences for catalytic function. All previously described Rho family proteins are modified by geranylgeranylation, a lipid attachment required for proper membrane localization. In contrast, the carboxy-terminal sequence of RhoE predicts that, like Ras proteins, RhoE is normally farnesylated. Indeed, we have found that RhoE in farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion. Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases.