gebhart/patrepeval huggingface dataset:
The Carboxyl-terminal Domain(111–165) of Vascular Endothelial Growth Factor Is Critical for Its Mitogenic Potency (1996)

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for endothelial cells. VEGF is synthesized and secreted by many differentiated cells in response to a variety of stimuli including hypoxia. VEGF is expressed in a variety of tissues as multiple homodimeric forms (121, 165, 189, and 206 amino acids/monomer) resulting from alternative RNA splicing. VEGF121 is a soluble mitogen that does not bind heparin; the longer forms of VEGF bind heparin with progressively higher affinity. The higher molecular weight forms of VEGF can be cleaved by plasmin to release a diffusible form(s) of VEGF. We characterized the proteolysis of VEGF by plasmin and other proteases. Thrombin, elastase, and collagenase did not cleave VEGF, whereas trypsin generated a series of smaller fragments. The isolated plasmin fragments of VEGF were compared with respect to heparin binding, interaction with soluble VEGF receptors, and ability to promote endothelial cell mitogenesis. Plasmin yields two fragments of VEGF as indicated by reverse phase high performance liquid chromatography and SDS-polyacrylamide gel electrophoresis: an amino-terminal homodimeric protein containing receptor binding determinants and a carboxyl-terminal polypeptide which bound heparin. Amino-terminal sequencing of the carboxyl-terminal peptide identified the plasmin cleavage site as Arg110-Ala111. A heterodimeric form of VEGF165/110, was isolated from partial plasmin digests of VEGF165. The carboxyl-terminal polypeptide (111-165) displayed no affinity for soluble kinase domain region (KDR) or Fms-like tyrosine kinase (FLT-1) receptors. The various isoforms of VEGF (165, 165/110, and 121) bound soluble kinase domain region receptor with similar affinity (approximately 30 pM). In contrast, soluble FLT-1 receptor differentiated VEGF isoforms (165, 165/110, 110, and 121) with apparent affinities of 10, 30, 120, and 200 pM, respectively. Endothelial cell mitogenic potencies of VEGF110 and VEGF121 were decreased more than 100-fold compared to that of VEGF165. The present findings indicate that removal of the carboxyl-terminal domain, whether it is due to alternative splicing of mRNA or to proteolysis, is associated with a significant loss in bioactivity.
Experimental transplantation of autologous iris pigment epithelial cells to the subretinal space (2001)

Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodelling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration.
Regulation of Extracellular Protease Production in Bacillus cereus T: Characterization of Mutants Producing Altered Amounts of Protease (1971)

Twenty-nine mutants of Bacillus cereus T were selected on casein agar for their inability to produce large amounts of extracellular protease. They all formed spores, and 27 were also auxotrophs for purines or pyrimidines. Upon reversion to prototrophy, a large fraction regained the capacity to produce protease. Conversely, reversion to normal protease production resulted in loss of the purine or pyrimidine requirement in a large fraction of the revertants. One spontaneous low-protease-producing pyrimidine auxotroph studied in detail grew as well as the wild type and produced spores which were identical to those produced by the wild type on the basis of heat resistance, dipicolinic acid content, density, and appearance in the electron microscope. The rate of protein turnover in the mutant was the same as the wild type. The mutant did grow poorly, however, when casein was the principal carbon source. A mutant excreting 5 to 10 times as much protease as the wild type was isolated as a secondary mutation from the hypoproducer discussed above. Loss of the pyrimidine requirement in this case did not alter the regulation of protease production. Although the secondary mutant grew somewhat faster in most media than the wild type, the final cell yield was lower. The spores of this mutant appeared to have excess coat on the basis of both electron microscopic and chemical studies. There appear to be closely related but distinct catabolic controls for both extracellular protease and spore formation. These controls can be dissociated as for the hypoproducers but can also appear integrated as for the hyperprotease producer.
Pulmonary Delivery of Antiarrhythmic Drugs for Rapid Conversion of New-Onset Atrial Fibrillation (2020)

Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.
Current Distribution in a Tubular Electrode under Laminar Flow: One Electrode Reaction (1977)

The reaction rate distribution along a tubular electrode was measured directly with a sectioned electrode during steady laminar flow of electrolyte through the electrode. The Fe(III)/Fe(II) redox reaction was studied at the limiting current, and the Cu(II) deposition reaction was studied at all fractions of the limiting current, The experimental conditions were systematically varied in order to determine the effect of counterelectrode placement, tube radius and length, reactant concentration, flow rate, and current density. Experimental polarization curves, limiting current, and current distribution data were compared with a theoretical model of the electrochemical system, and agreement was obtained over a wide range of parameter space. Theoretical calculations were carried out in order to make additional predictions of tubular electrode behavior at and below the limiting current.
Analysis of the role of glycosylation of the human fibronectin receptor (1989)

1-Deoxymannojirimycin (MNJ), an inhibitor of Golgi alpha-mannosidase IA and IB, was used to assess the possible roles of asparagine-linked oligosaccharides in the structure and function of the integrin fibronectin receptor from cultured human fibroblasts. These cells normally attach well to fibronectin substrates and have only mature forms of the fibronectin receptor on their surfaces. MNJ inhibits the intracellular trimming of high mannose oligosaccharides, and cells treated with 0.2 mg/ml MNJ synthesize only immature precursor forms of both the alpha and beta subunits of the fibronectin receptor. The immature receptor polypeptides were found to be nonfunctional by two criteria: 1) cells treated with MNJ attached poorly to fibronectin substrates; and 2) receptor from the treated cells was defective in binding to fibronectin affinity columns. The precursor forms of the fibronectin receptor subunits were found on the surfaces of cells treated with MNJ, demonstrating that processing of receptor carbohydrates to mature forms was not necessary for receptor insertion into the plasma membrane. A monoclonal antibody that specifically bound the alpha subunit of the fibronectin receptor immunoprecipitated both alpha and beta subunit polypeptides from both control cells and cells treated with MNJ. Similarly, a monoclonal antibody that specifically bound only the beta subunit also immunoprecipitated both alpha and beta subunit polypeptides of the receptor from extracts of both control and MNJ-treated cells. These results indicate that receptor assembly can occur in the absence of complete oligosaccharide processing. Thus, oligosaccharide processing to the mature form of the fibronectin receptor is important for its binding function but not for receptor assembly or insertion into the plasma membrane.
Answer-focused and Position-aware Neural Question Generation (2018)

In this paper, we focus on the problem of question generation (QG). Recent neural networkbased approaches employ the sequence-tosequence model which takes an answer and its context as input and generates a relevant question as output. However, we observe two major issues with these approaches: (1) The generated interrogative words (or question words) do not match the answer type. (2) The model copies the context words that are far from and irrelevant to the answer, instead of the words that are close and relevant to the answer. To address these two issues, we propose an answer-focused and position-aware neural question generation model. ( (2) By position-aware, we mean that we model the relative distance between the context words and the answer. Hence the model can be aware of the position of the context words when copying them to generate a question. We conduct extensive experiments to examine the effectiveness of our model. The experimental results show that our model significantly improves the baseline and outperforms the state-of-the-art system.
The significance of Her2 on androgen receptor protein stability in the transition of androgen requirement in prostate cancer cells (2011)

Androgen ablation therapy is the most common strategy for suppressing prostate cancer progression; however, tumor cells eventually escape androgen dependence and progress to an androgen-independent phase. The androgen receptor (AR) plays a pivotal role in this transition. To address this transition mystery in prostate cancer, we established an androgen-independent prostate cancer cell line (LNCaPdcc), by long-term screening of LNCaP cells in androgen-deprived conditions, to investigate changes of molecular mechanisms before and after androgen withdrawal. We found that LNCaPdcc cells displayed a neuroendocrine morphology, less aggressive growth, and lower expression levels of cell cycle-related factors, although the cell cycle distribution was similar to parental LNCaP cells. Notably, higher protein expression of AR, phospho-Ser(81)-AR, and PSA in LNCaPdcc cells were observed. The nuclear distribution and protein stability of AR increased in LNCaPdcc cells. In addition, cell proliferation results exhibited the biphasic nature of the androgen (R1881) effect in two cell lines. On the other hand, LNCaPdcc cells expressed higher levels of Her2, phospho-Tyr(1221/1222)-Her2, ErbB3, and ErbB4 proteins than parental LNCaP cells. These two cell lines exhibited distinct responses to Her2 activation (by heregulin treatment) on Her2 phosphorylation and Her2 inhibition (by AG825 or Herceptin treatments) on proliferation. In addition, the Her2 inhibitor more effectively caused AR degradation and diminished AR Ser(81) phosphorylation in LNCaPdcc cells. Taken together, our data demonstrate that Her2 plays an important role in the support of AR protein stability in the transition of androgen requirement in prostate cancer cells. We hope these findings will provide novel insight into the treatment of hormone-refractory prostate cancer.
Th1 to Th2 Cytokine Shifts in Nonobese Diabetic Mice: Sometimes an Outcome, Rather Than the Cause, of Diabetes Resistance Elicited by Immunostimulation (2001)

Numerous immunostimulatory protocols inhibit the development of T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse model. Many of these protocols, including treatment with the nonspecific immunostimulatory agents CFA or bacillus Calmette-Guérin (BCG) vaccine, have been reported to mediate protection by skewing the pattern of cytokines produced by pancreatic beta-cell autoreactive T cells from a Th1 (IFN-gamma) to a Th2 (IL-4 and IL-10) profile. However, most of these studies have documented associations between such cytokine shifts and disease protection rather than a cause/effect relationship. To partially address this issue we produced NOD mice genetically deficient in IFN-gamma, IL-4, or IL-10. Elimination of any of these cytokines did not significantly alter the rate of spontaneous IDDM development. Additional experiments using these mice confirmed that CFA- or BCG-elicited diabetes protection is associated with a decreased IFN-gamma to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but this is a secondary consequence rather than the cause of disease resistance. Unexpectedly, we also found that the ability of BCG and, to a lesser extent, CFA to inhibit IDDM development in standard NOD mice is actually dependent upon the presence of the Th1 cytokine, IFN-gamma. Collectively, our studies demonstrate that while Th1 and Th2 cytokine shifts may occur among beta-cell autoreactive T cells of NOD mice protected from overt IDDM by various immunomodulatory therapies, it cannot automatically be assumed that this is the cause of their disease resistance.
Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. (1992)

A standardised inventory of stressful life events and a bowel symptom questionnaire were administered at three month intervals for one year to 383 women who were unselected with respect to bowel symptoms. A NEO Personality Inventory was given initially to assess neuroticism. Subjects who satisfied restrictive diagnostic criteria for irritable bowel syndrome were compared with those who complained of abdominal pain plus altered bowel habits but who did not meet restrictive diagnostic criteria (functional bowel disorder) and with controls without bowel dysfunction. The irritable bowel group showed significantly higher levels of stress than the other two groups even when the confounding effects of neuroticism were statistically controlled for. Time lagged correlations showed that stress in one three month interval was significantly correlated with bowel symptoms in the subsequent three month interval for all groups. The slope of the regression line relating stress to bowel symptoms was significantly steeper for the irritable bowel group than for the other two groups at three and six months, suggesting that subjects with irritable bowel syndrome show a greater reactivity to stress. Stress scores were also significantly correlated with the number of disability days and the number of medical clinic visits for bowel symptoms.
Labeling DNA with Stable Isotopes: Economical and Practical Considerations (2001)

Labeling DNA with stable isotopes to measure cell proliferation can be a technique as effective as 3H-thymidine labeling without the limitations imposed by using radioisotopes. Here, we investigated the relative efficiency of four nonradioactive precursors to DNA: [1-13C]-glycine, [1,2-13C2]-glycine, [U-13C]-glucose, and [U-13C, 15N]-thymidine. The efficiency of incorporation for each of these labeled precursors in HEP G2 cells in culture has been studied. When considering the actual costs of in vivo experiments in which large doses of labeled material are needed, economical constraints may play an important role in defining a practical method. Therefore, the economics of this process were also considered. Using the enrichment per dollar for whichever nucleoside had the highest incorporation in a given experiment, glycine is about five times more economical as a label than thymidine and eight times more economical than glucose in these cells.
Human Papillomaviruses and the Interferon Response (2009)

Human papillomaviruses (HPV) are small DNA viruses that target stratified keratinocytes for infection. A subset of HPV types infect epithelia in the genital tract and are the causative agents of cervical as well as other anogenital cancers. Interferon treatment of existing genital HPV lesions has had mixed results. While HPV proteins down-regulate the expression of interferon-inducible genes, interferon treatment ultimately induces their high-level transcription after a delay. Cells containing complete HPV genomes that are able to undergo productive replication upon differentiation are sensitive to interferon-induced growth arrest, while cells from high-grade cancers that only express E6 and E7 are resistant. Recent studies indicate this sensitivity is dependent upon the binding of the interferon-inducible factor, p56, to the E1 replication protein. The response to interferon by HPV proteins is complex and results from the action of multiple viral proteins.
Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis (2004)

Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific IL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection. Surprisingly, however, although the thymi of IL-7Ralpha Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DN cells, increased DN apoptosis, and decreased DN cell number. Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells.
Age and Third Molar Extraction as Risk Factors for Temporomandibular Disorder (2008)

This study investigated third molar removal as a risk factor for temporomandibular disorder (TMD) in all age groups. We compared 2217 Kaiser Permanente Northwest health plan enrollees with a history of third molar extraction with 2217 age-and gender-matched enrollees with radiographic confirmation of no lifetime third molar removal. Common Dental Terminology codes were used to identify information on third molar removal, and International Classification of Disease codes were used to identify TMD. Relative risks were calculated overall, and by each decade of life, in univariate and multivariate analyses. The incidence of TMD in subjects with and without third molar removal were 7 and 5 per thousand person-years, respectively. Third molar removal among subjects of all ages resulted in a statistically insignificant increased relative risk for TMD (1.4, 95% confidence interval (CI): 0.9-2.2). The relative risk was slightly higher in those under 21, but was also not statistically significant (1.6, CI: 0.8-3.1).
Monocular 3D pose estimation and tracking by detection (2010)

Automatic recovery of 3D human pose from monocular image sequences is a challenging and important research topic with numerous applications. Although current methods are able to recover 3D pose for a single person in controlled environments, they are severely challenged by real-world scenarios, such as crowded street scenes. To address this problem, we propose a three-stage process building on a number of recent advances. The first stage obtains an initial estimate of the 2D articulation and viewpoint of the person from single frames. The second stage allows early data association across frames based on tracking-by-detection. These two stages successfully accumulate the available 2D image evidence into robust estimates of 2D limb positions over short image sequences (= tracklets). The third and final stage uses those tracklet-based estimates as robust image observations to reliably recover 3D pose. We demonstrate state-of-the-art performance on the HumanEva II benchmark, and also show the applicability of our approach to articulated 3D tracking in realistic street conditions.
Propagation effects in apertureless near-field optical antennas (2004)

We report a direct observation of the electromagnetic wave propagation on optical antennas. A free-space broadband terahertz pulse is coupled into a propagating mode along the shaft of an optical antenna acting as an apertureless near-field probe. We determine the spatial extent of this guided mode and its velocity. In addition, we consider the possibility of multiply reflected modes propagating along the near-field probe, an effect which will be significant in near-field spectroscopic measurements.
Embryonic lethality inDeargene-deficient mice: new player in angiogenesis (2005)

The dual endothelin-1/angiotensin II receptor (Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JRHS rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear(-/-) deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JRHS rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear(+/-)/C57BL6BC10 mice, but not in males (age 3.5 mo), and in 127Cs radiation-induced orthotopic mammary tumors in Sprague-Dawley female rats (age range 3-6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.
Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy (2012)

Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).