gebhart/patrepeval huggingface dataset:
Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues. (1988)

During early fetal development, T cell precursors home from fetal yolk sac and liver to the epithelial thymic rudiment. From cells that initially colonize the thymus arise mature T cells that populate T cell zones of the peripheral lymphoid system. Whereas colonization of the thymus occurs late in the final third of gestation in the mouse, in birds and humans the thymus is colonized by hematopoietic stem cell precursors during the first third of gestation. Using a large series of early human fetal tissues and a panel of monoclonal antibodies that includes markers of early T cells (CD7, CD45), we have studied the immunohistologic location and differentiation capacity of CD45+, CD7+ cells in human fetal tissues. We found that before T cell precursor colonization of the thymus (7-8 wk of gestation), CD7+ cells were present in yolk sac, neck, upper thorax, and fetal liver, and were concentrated in mesenchyme throughout the upper thorax and neck areas. By 9.5 wk of gestation, CD7+ cells were no longer present in upper thorax mesenchyme but rather were localized in the lymphoid thymus and scattered throughout fetal liver. CD7+, CD2-, CD3-, CD8-, CD4-, WT31- cells in thorax and fetal liver, when stimulated for 10-15 d with T cell-conditioned media and rIL-2, expressed CD2, CD3, CD4, CD8, and WT31 markers of the T cell lineage. Moreover, CD7+ cells isolated from fetal liver contained all cells in this tissue capable of forming CFU-T colonies in vitro. These data demonstrate that T cell precursors in early human fetal tissues can be identified using a mAb against the CD7 antigen. Moreover, the localization of CD7+ T cell precursors to fetal upper thorax and neck areas at 7-8.5 wk of fetal gestation provides strong evidence for a developmentally regulated period in man in which T cell precursors migrate to the epithelial thymic rudiment.
STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast. (1990)

The STE11 gene of Saccharomyces cerevisiae is one of several genes required for mating between two haploid cell types of this yeast. Its product is required for response to a signal that causes arrest of the mitotic cell cycle in the G1 phase and induction of mating-type-specific genes. The nucleotide sequence of the STE11 gene was determined. The predicted amino acid sequence shows homology to the protein kinase family. We demonstrate that the STE11 product has kinase catalytic activity and that this activity is required for its in vivo functions.
Epidemiologic and Molecular Prognostic Review of Glioblastoma (2014)

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value.
Long wavelength waveguide multiple quantum well optical modulators (1987)

The first measurements of large anisotropic modulation of long-wavelength light with a large on/off ratio and low driving voltage propagating along the plane of InGaAs/InAlAs multiple quantum well (MQW) structures grown by molecular beam epitaxy (MBE) are reported. Photocurrent response and optical modulation of waveguide pin diodes is measured for incident light polarization parallel and perpendicular to the MQW layers emitting from a color center laser. The incident-light power and wavelength dependence of on/off ratio are also determined.
Contragestion and Other Clinical Applications of RU 486, an Antiprogesterone at the Receptor (1989)

RU 486, a steroid with high affinity for the progesterone receptor, is the first available active antiprogesterone. It has been used successfully as a medical alternative for early pregnancy interruption, and it also has other potential applications in medicine and for biochemical and pathophysiological endocrine research.
Robust inference of baseline optical properties of the human head with three-dimensional segmentation from magnetic resonance imaging (2003)

We model the capability of a small (6-optode) time-resolved diffuse optical tomography (DOT) system to infer baseline absorption and reduced scattering coefficients of the tissues of the human head (scalp, skull, and brain). Our heterogeneous three-dimensional diffusion forward model uses tissue geometry from segmented magnetic resonance (MR) data. Handling the inverse problem by use of Bayesian inference and introducing a realistic noise model, we predict coefficient error bars in terms of detected photon number and assumed model error. We demonstrate the large improvement that a MR-segmented model can provide: 2-10% error in brain coefficients (for 2 x 10(6) photons, 5% model error). We sample from the exact posterior and show robustness to numerical model error. This opens up the possibility of simultaneous DOT and MR for quantitative cortically constrained functional neuroimaging.
Electrophysiological Control of Ventricular Rate During Atrial Fibrillation (2000)

Thirteen anesthetized canine subjects (17-29 kg) were used to demonstrate that mild cervical left vagal stimulation could control ventricular rate effectively during atrial fibrillation (AF). Two studies are presented. The first study used six subjects to demonstrate the inverse relationship between (manually applied) left vagal stimulation and ventricular excitation (R wave) rate during AF. As left vagal stimulation frequency was increased, ventricular excitation rate decreased. In these studies, a left vagal stimulus frequency of 0-10 per second reduced the ventricular excitation rate from > 200/min to < 50/min. The decreasing ventricular excitation rate with increasing left vagal stimulation frequency was universal, occurring in all 26 trials with the six subjects. This fundamental principle was used to construct an automatic controller for use in the second study, in which seven subjects were used to demonstrate that ventricular rate can be brought to and maintained within a targeted range with the use of an automatic (closed-loop) controller. A 45-minute record of automatic ventricular rate control is presented. Similar records were obtained in all seven subjects.
Feature selection based on mutual information criteria of max-dependency, max-relevance, and min-redundancy (2005)

Feature selection is an important problem for pattern classification systems. We study how to select good features according to the maximal statistical dependency criterion based on mutual information. Because of the difficulty in directly implementing the maximal dependency condition, we first derive an equivalent form, called minimal-redundancy-maximal-relevance criterion (mRMR), for first-order incremental feature selection. Then, we present a two-stage feature selection algorithm by combining mRMR and other more sophisticated feature selectors (e.g., wrappers). This allows us to select a compact set of superior features at very low cost. We perform extensive experimental comparison of our algorithm and other methods using three different classifiers (naive Bayes, support vector machine, and linear discriminate analysis) and four different data sets (handwritten digits, arrhythmia, NCI cancer cell lines, and lymphoma tissues). The results confirm that mRMR leads to promising improvement on feature selection and classification accuracy.
Expression of cytoplasmic and nuclear Survivin in primary and secondary human glioblastoma (2005)

Clinically, human glioblastoma (GBM) may develop de novo or from a low-grade glioma (secondary GBM), and molecular alterations in the two pathways may differ. This study examined the status of Survivin expression and apoptosis in 30 primary and 26 secondary GBMs. Our results show that cytoplasmic Survivin positivity was significantly (P<0.001) more frequent in primary GBMs (83%) than that in secondary GBMs (46%). In addition, an inverse correlation of cytoplasmc Survivin positivity with GBM apoptotic index, and a positive association between cytoplasmic Survivin and size of the tumours were observed. These results suggest that cytoplasmic Survivin, via its antiapoptotic function, may be involved in the tumorigenesis of many primary GBMs, but only in a small fraction of secondary GBMs. Furthermore, the overall progression times from low-grade precursor lesions to secondary GBMs were significantly shorter (P<0.05) in cytoplasmic Survivin-positive cases (mean, 15.6 months) than those in Survivin-negative cases (mean, 23.8 moths), and the positive expression level of Survivin in cytoplasm was upregulated in most secondary GBMs when compared to matched pre-existing low-graded lesions. These results suggest that the increased accumulation of Survivin in the cytoplasm of more malignant glioma cells may prove to be a selective advantage, thus accelerating progression to a more aggressive phenotype.
Use of the most JH-proximal human Ig H chain V region gene, VH6, in the expressed immune repertoire (1993)

VH6, the most 3' human H chain V region gene, is preferentially expressed in the preimmune repertoire of the developing human fetus. To determine whether VH6 contributes to the immune repertoire, we amplified and sequenced from human spleen RNA VH6 rearrangements that were isotype-switched to IgG. Eighteen distinct in-frame VH6 clones were sequenced. Definitive assignment to C gamma 1 could be made in the majority of clones, and all had undergone extensive somatic hypermutation in the V region with an average of 14 (range, 2 to 25) mutations/281 bp in the VH6 segment. The overall frequency of somatic mutation was 5.2% of the total nucleotides sequenced. Replacement somatic mutations were targeted to the complementarity determining region, and the complementarity determining region had higher replacement to silent mutation ratios, consistent with antigenic selection. Silent somatic mutations were also significantly more frequent in the complementarity determining region compared to the framework region. Five clones were derived from the same VH6Dxp'1JH6 rearrangement, each containing unique and shared mutations. All DH segments used by independently arising clones were unique, and all DH reading frames were seen. N segments were lacking at either the 5'DH-JH junction or the 3'DH-JH junction in 7 of 13 independent rearrangements. DH-DH recombinations were frequently observed, and there was biased usage of JH3b and JH4b in the clones. The data imply that a high degree of diversity arises from use of this 3'-VH gene in the immune repertoire.
Structure Guided Design of Potent and Selective Ponatinib-Based Hybrid Inhibitors for RIPK1 (2015)

RIPK1 and RIPK3, two closely related RIPK family members, have emerged as important regulators of pathologic cell death and inflammation. In the current work, we report that the Bcr-Abl inhibitor and anti-leukemia agent ponatinib is also a first-in-class dual inhibitor of RIPK1 and RIPK3. Ponatinib potently inhibited multiple paradigms of RIPK1- and RIPK3-dependent cell death and inflammatory tumor necrosis factor alpha (TNF-α) gene transcription. We further describe design strategies that utilize the ponatinib scaffold to develop two classes of inhibitors (CS and PN series), each with greatly improved selectivity for RIPK1. In particular, we detail the development of PN10, a highly potent and selective "hybrid" RIPK1 inhibitor, capturing the best properties of two different allosteric RIPK1 inhibitors, ponatinib and necrostatin-1. Finally, we show that RIPK1 inhibitors from both classes are powerful blockers of TNF-induced injury in vivo. Altogether, these findings outline promising candidate molecules and design approaches for targeting RIPK1- and RIPK3-driven inflammatory pathologies.
Using SeDuMi 1.02, A Matlab toolbox for optimization over symmetric cones (1999)

Abstract SeDuMi is an add-on for MATLAB, which lets you solve optimization problems with linear, quadratic and semidefiniteness constraints. It is possible to have complex valued data and variables in SeDuMi. Moreover, large scale optimization problems are solved efficiently, by exploiting sparsity. This paper describes how to work with this toolbox. Keywords: Symmetric conesemidefinite programmingsecond order cone programmingself-dualityMATLABSeDuMi *MATLAB is a registered trademark of the The Mathworks, Inc. *MATLAB is a registered trademark of the The Mathworks, Inc. Notes *MATLAB is a registered trademark of the The Mathworks, Inc.
Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (2014)

The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1-7 and 15-21, 25 mg lenalidomide on days 1-21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed.
Vemurafenib Synergizes with Nutlin-3 to Deplete Survivin and Suppresses Melanoma Viability and Tumor Growth (2013)

These results show preclinical feasibility for overcoming primary vemurafenib resistance by restoring p53 function. Moreover, it identifies survivin as one downstream mediator of the observed synergism and a potential secondary target.
Surface-reflection elimination in polarization imaging of superficial tissue (2003)

A major drawback in polarization gating of light backscattered from tissue is that surface reflections dominate the image. An optically flat plate and matching fluid applied to the tissue surface, combined with off-axis detection, were previously used to address this problem. This approach is often inappropriate or inconvenient for practical use and more importantly can affect the tissue's optical properties. A method is demonstrated that combines images obtained with linearly and circularly polarized light to produce a polarization-gated image that is free from surface reflections and does not require optically flat plates or matching fluid.
A single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment) from incorporating ribonucleotides (1998)

Although nucleic acid polymerases from different families show striking similarities in structure, they maintain stringent specificity for the sugar structure of the incoming nucleoside triphosphate. The Klenow fragment of E. coli DNA polymerase I selects its natural substrates, deoxynucleotides, over ribonucleotides by several thousand fold. Analysis of mutant Klenow fragment derivatives indicates that discrimination is provided by the Glu-710 side chain which sterically blocks the 2'-OH of an incoming rNTP. A nearby aromatic side chain, at position 762, plays an important role in constraining the nucleotide so that the Glu-710 "steric gate" can be fully effective. Even with the E710A mutation, which is extremely permissive for addition of a single ribonucleotide to a DNA primer, Klenow fragment does not efficiently synthesize pure RNA, indicating that additional barriers prevent the incorporation of successive ribonucleotides.
Zn2+-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors (2003)

Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC(50) in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn(2+)-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic omega-amino acid linkers. This strategy has led to a novel class of Zn(2+)-chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIP1) expression, which are hallmark features associated with intracellular HDAC inhibition.
VISUAL ACUITY AND CONTRAST SENSITIVITY IN MULTIPLE SCLEROSIS—HIDDEN VISUAL LOSS (1977)

In 48 patients with multiple sclerosis sine-wave gratings were used to test visual sensitivity for coarse, medium, and fine detail rather than measuring visual acuity for fine detail only, as in conventional clinical tests. In 20/48 patients the test revealed a visual defect of neural origin, qualitatively different from that caused by refractive error. In 11 of these 20 patients, visual sensitivity to detail of medium coarseness was markedly degraded, even though sensitivity to both coarse and fine detail was unimpaired. In 3 of these 20 patients visual sensitivity to coarse detail was selectively degraded. These visual defects could not be detected by the Snellen test, yet the patient might experience visual problems in everyday life and also experience distorted visual perception. Possible neural bases for these visual impairments are discussed. Since 8 of the 14 patients with selective loss showed no clinical evidence of visual involvement, the test can aid the earlier diagnosis of multiple sclerosis.
Enzymatic reduction of disulfide bonds in lysosomes: Characterization of a Gamma-interferon-inducible lysosomal thiol reductase (GILT) (2000)

Proteins internalized into the endocytic pathway are usually degraded. Efficient proteolysis requires denaturation, induced by acidic conditions within lysosomes, and reduction of inter- and intrachain disulfide bonds. Cytosolic reduction is mediated enzymatically by thioredoxin, but the mechanism of lysosomal reduction is unknown. We describe here a lysosomal thiol reductase optimally active at low pH and capable of catalyzing disulfide bond reduction both in vivo and in vitro. The active site, determined by mutagenesis, consists of a pair of cysteine residues separated by two amino acids, similar to other enzymes of the thioredoxin family. The enzyme is a soluble glycoprotein that is synthesized as a precursor. After delivery into the endosomal/lysosomal system by the mannose 6-phosphate receptor, N- and C-terminal prosequences are removed. The enzyme is expressed constitutively in antigen-presenting cells and induced by IFN-gamma in other cell types, suggesting a potentially important role in antigen processing.
Improved Left Ventricular Aneurysm Repair With Bioengineered Vascular Smooth Muscle Grafts (2003)

Surgical repair with muscle-cell seeded grafts reduced abnormal chamber distensibility and improved LV function after myocardial infarction as compared with unseeded grafts. Bioengineered muscle grafts may be superior to synthetic materials for the surgical repair of LV scar.
The pulmonary vascular bed as a site for implantation of isolated liver cells in inbred rats. (1984)

Experiences sur rats. Des cellules hepatiques separees peuvent etre introduites dans le poumon, au moyen d'une introduction dans la veine jugulaire. La presence de cellules hepatiques dans le poumon est verifiee ensuite histologiquement, et l'activite biologique specifique peut etre mise en evidence. Interet possible de cette technique pour le traitement de l'insuffisance hepatique grave
A pulsed corona discharge switchable high resolution ion mobility spectrometer-mass spectrometer (2002)

A pulsed corona discharge ionisation source, a candidate replacement for 63Ni ionisation sources for ion mobility spectrometry, is described along with a new design of ion mobility spectrometer-mass spectrometer. Preliminary research on the characterisation of the reactant ion peaks associated with the use of this ionisation source was undertaken by assembling a pulsed corona discharge ionisation switchable high-resolution ion mobility spectrometer-mass spectrometer to enable the mobility spectra, atmospheric chemical ionisation mass spectra and selected-mass mobility spectra to be obtained. With ammonia doping at 2.39 mg m(-3) in air and a water content of approximately 80 mg m(-3) in the positive mode the observed response was attributable to the formation of 1(H2O)(n)NH4]+ and [(H2O)n(NH3)NH4]+ in the reaction region. The observed responses in the negative mode were more complex with evidence for the formation [(H2O)(n)O2]-, [(H2O)(n)CO3]-, [(H2O)(n)HCO3]-, [(H2O)(n)CO4]- and [(H2O)(n)NO3]-. The responses due to these species were clearly discernible in the resultant mobility spectra, with enough oxygen-based species formed to support analytically useful responses.
Golgi nucleotide sugar transport and leukocyte adhesion deficiency II (2001)

nFigure 1n
Immune Responses and Antibody Decay after Immunization of Adolescents and Adults with an Acellular Pertussis Vaccine: The APERT Study (2004)

As part of a prospective acellular pertussis (ACP) vaccine efficacy trial, 5 serum samples were obtained, over an 18-month period, from 101 ACP-vaccine recipients and 99 control subjects, to assess ACP antibody response and decay. Immunoglobulin (Ig) G and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2/3 (FIM) were measured by enzyme-linked immunosorbant assay, and titers of agglutinin were determined. Of the subjects, 16%-19% had preimmunization values of antibodies to PT that were above the assay's limit of quantitation (LOQ); in contrast, 36%-63% of the subjects had preimmunization values of antibodies to FHA, PRN, or FIM that were above the LOQ. Substantial increases in titers of IgG and IgA antibodies to the 3 ACP antigens (PT, FHA, and PRN) were observed. Over the 18-months, the percent decay in IgG and IgA antibodies ranged from 56% to 73% and from 57% to 70%, respectively; the IgG antibody response and decay suggests that geometric mean titers likely remain above the LOQ for 2-9 years and above the threshold of detection for 4-13 years. These findings support the use of ACP booster immunizations for adolescents and adults, to provide sustained levels of antibody.