gebhart/patrepeval huggingface dataset:
Unified Kinematics and Singularity Analysis of a Metamorphic Parallel Mechanism With Bifurcated Motion (2013)

This paper introduces a new metamorphic parallel mechanism consisting of four reconfigurable rTPS limbs. Based on the reconfigurability of the reconfigurable Hooke (rT) joint, the rTPS limb has two phases while in one phase the limb has no constraint to the platform, in the other it constrains the spherical joint center to lie on a plane. This results in the mechanism to have ability of reconfiguration between different topologies with variable mobility. Geometric constraint equations of the platform rotation matrix and translation vector are set up based on the point-plane constraint, which reveals the bifurcated motion property in the topology with mobility 2 and the geometric condition with mobility change in altering to other mechanism topologies. Following this, a unified kinematics limb modeling is proposed considering the difference between the two phases of the reconfigurable rTPS limb. This is further applied for the mechanism modeling and both the inverse and forward kinematics is analytically solved by combining phases of the four limbs covering all the mechanism topologies. Based on these, a unified singularity modeling is proposed by defining the geometric constraint forces and actuation forces in the Jacobian matrix with their change in the variable topologies in terms of constraint screws. Analysis of workspace with singularity distribution is carried out using this model and corresponding singularity loci are obtained with special singular configurations illustrated.
Role of Na/K/Cl cotransport in astrocytes (1992)

The kinetic characterization of the Na/K/Cl cotransport of cultured astrocytes and evidence for its involvement in volume regulation and K+ net uptake during K+ clearance are reviewed. Emphasis is put on experimental evidence for a proposed sodium cycle in astrocytes; this cycle involves a Na(+)-K+ ATPase that is stimulated by both a high external K+ and intracellular Na+. Elevated external K+ also stimulates the Na/K/Cl carrier, transporting these ions inward. As a result Na+ is cycled across the membrane, carried inward by the Na/K/Cl carrier, and returned by the Na(+)-K+ ATPase. Both functionally coupled mechanisms lead to intracellular KCl accumulation and inward movements of water to compensate for increased osmolarity. The combined cycle is expected to play a major role in the regulation of physiological K+ levels in the brain.
Targeting KIT on innate immune cells enhances the antitumor activity of checkpoint inhibitors in vivo (2015)

Meeting abstracts Mast cell infiltrates are associated with tumors, though their role in the tumor microenvironment remains unclear. Mast cells express high levels of KIT throughout differentiation and as mature cells. Mast cells in tumors have been shown to release proinflammatory cytokines and
A Biomimetic pH-Responsive Polymer Directs Endosomal Release and Intracellular Delivery of an Endocytosed Antibody Complex (2002)

Poly(propylacrylic acid) (PPAAc) is a synthetic pH-responsive polymer that has been shown to disrupt cell membranes at low pH values typical of the endosome, but not at physiological pH, suggesting its use as an endosomal-releasing agent [Murthy et al. J. Controlled Release 61, 137-43]. We have constructed an antibody-targeted biotherapeutic model to investigate whether PPAAc can enhance intracellular trafficking of proteins to the cytoplasm. A ternary complex composed of a biotinylated anti-CD3 antibody, streptavidin, and biotinylated PPAAc was fluorescently labeled, and its intracellular fate was analyzed by confocal microscopy, flow cytometry, and quantitative western blotting of cell fractionates. The 64.1 anti-CD3 antibody was previously shown to direct receptor-mediated endocytosis in the Jurkat T-cell lymphoma cell line and was rapidly trafficked from the endosome to the lysosomal compartment. The antibody-streptavidin complex was also rapidly internalized to the endosomal/lysosomal compartment and retained there, as evidenced by punctate regions of fluorescence observed by confocal fluorescence microscopy. In samples containing the ternary complex of antibody, streptavidin, and PPAAc-biotin, diffuse fluorescence in the cytoplasm was observed, indicating that PPAAc enhanced translocation to the cytoplasm. This was confirmed by western blotting analysis of the isolated cytoplasm. Flow cytometry results demonstrated that neither streptavidin nor PPAAc caused nonspecific uptake of the complex, nor did they inhibit antibody-mediated endocytosis. The striking enhancement of protein delivery to the cytoplasm by complexed PPAAc suggests that this polymer could provide a new delivery agent for therapeutic, vaccine, and diagnostics development.
Human neural tube defects: Genetic causes and prevention (2011)

Neural tube defects (NTDs) are severe congenital malformations affecting 1-2 in 1,000 live births, whose etiology is multifactorial, involving environmental and genetic factors. NTDs arise as consequence of the failure of fusion of the neural tube early during embryogenesis. NTDs' pathogenesis has been linked to genes involved in folate metabolism, consistent with an epidemiologic evidence that 70% of NTDs can be prevented by maternal periconceptional supplementation. However, polymorphisms in such genes are not linked in all populations, suggesting that other genetic factors and environmental factors could be involved. Animal models have provided crucial mechanistic information and possible candidate genes to explain susceptibility to NTDs. A crucial role has been assigned to the planar cell polarity (PCP) pathway, a highly conserved, non-canonical Wnt-frizzled-dishevelled signaling cascade that plays a key role in establishing and maintaining polarity in the plane of the epithelium and in the process of convergent extension during gastrulation and neurulation in vertebrates. The Loop-tail (Lp) mouse that develops craniorachischisis carry missense mutations in the PCP core gene Vangl2, that is the mammalian homolog of the Drosophila Strabismus/Van gogh (Stbm/Vang). The presence of mutations in human VANGL1 and VANGL2 genes encourages us to extend the investigation to other PCP genes that, with VANGL, play an essential role in neurulation during development.
Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. (2000)

We had previously shown that high gene expressions (mRNA levels) of thymidylate synthase (TS; Leichman et al., J. Clin. Oncol., 15: 3223-3229, 1997) and thymidine phosphorylase (TP; Metzger et al., Clin. Cancer Res., 4: 2371-2376, 1998) in pretreatment tumor biopsies could identify tumors that would be nonresponsive to 5-fluorouracil (5-FU)-based therapy. In this study, we investigated the association between intratumoral gene expression of the pyrimidine catabolism enzyme dihydropyrimidine dehydrogenase (DPD) and the response of colorectal tumors to the same 5-FU-based protocol. DPD expressions were measured by quantitative reverse transcription-PCR in 33 pretreatment biopsies of colorectal tumors from patients who went on to receive treatment with 5-FU and leucovorin (LV). The range of DPD gene expression in those tumors that were nonresponsive to 5-FU was much broader than that of the responding tumors. None of the tumors with basal-level DPD expressions above a DPD:beta-actin ratio of 2.5 x 10(-3) (14 of 33) were responders to 5-FU/LV therapy, whereas those tumors with DPD gene expressions below DPD: beta-actin ratio of 2.5 x 10(-3) had a response rate of 50%. There was no correlation among DPD, TS, and TP expression values in this set of colorectal tumors, which indicated that these gene expressions are independent variables. All of the tumors that responded to 5-FU therapy (11 of 33) had expression values of all three of the genes, TS, TP, and DPD, below their respective nonresponse cutoff values, whereas, in each of the nonresponding tumors, at least one of these gene expressions was high. The patients with low expression of all three of the genes had significantly longer survival than patients with a high value of any one of the gene expressions. The results of this study show that intratumoral gene expression level of DPD is associated with tumor response to 5-FU and that the use of more than one independent determinant of response permits the identification of a high percentage of responding patients.
Modeling as a Decision Support Tool for Bovine TB Control Programs in Wildlife (2018)

Computer modeling has a long history of association with epidemiology, and has improved our understanding of the theory of disease dynamics and provided insights into wildlife disease management. A summary of badger bovine TB models and their role in decision making is presented, from a simple initial SEI model, to SEIR (inclusion of a recovered category) and SEI<sub>1</sub>I<sub>2</sub> (inclusion of two stages of disease progression) variants, and subsequent spatially-explicit individual-based models used to assess historical badger management strategies. The integration of cattle into TB models allowed comparison of the predicted impacts of different badger management strategies on cattle herd breakdown rates, and provided an economic dimension to the outputs. Estimates of R<sub>0</sub> for bovine TB in cattle and badgers are little higher than unity implying that the disease should be relatively easy to control, which is at odds with practical experience. A cohort of recent models have suggested that combined strategies, involving management of both host species and including vaccination may be most effective. Future models of badger vaccination will need to accommodate the partial protection from infection and likely duration of immunity conferred by the currently available vaccine (BCG). Descriptions of how models could better represent the ecological and epidemiological complexities of the badger-cattle TB system are presented, along with a wider discussion of the utility of modeling for bovine TB management interventions. This includes consideration of the information required to maximize the utility of the next generation of models.
The case for cyber foraging (2002)

In this paper, we propose cyber foraging: a mechanism to augment the computational and storage capabilities of mobile devices. Cyber foraging uses opportunistically discovered servers in the environment to improve the performance of interactive applications and distributed file systems on mobile clients. We show how the performance of distributed file systems can be improved by staging data at these servers even though the servers are not trusted. We also show how the performance of interactive applications can be improved via remote execution. Finally, we present VERSUDS: a virtual interface to heteregeneous service discovery protocols that can be used to discover these servers.
Manipulation and flow of biological fluids in straight channels micromachined in silicon (1994)

Analysis of minute sample volumes is a major analytical challenge that requires an understanding of fluid flow in microstructures. Accordingly, flow dynamics of biological fluids and cell suspensions in straight glass-capped silicon microchannels (40 to 150 microns wide, 20 and 40 microns deep) were studied. We demonstrated that these microstructures are appropriate components for microfluidic analytical devices. Different fluids were easily manipulated in the microchannels, and measurements of flow rate as a function of pressure for whole human blood, serum, plasma, and cell suspensions revealed non-Newtonian behavior. By means of micromachined filters (5 microns) located in channels, blood cells and microparticles were effectively separated from nanoliter-sized samples, clearly indicating the future role of microstructures for a variety of analytical purposes.
Subcutaneous vs Intravenous Heparin in the Treatment of Deep Venous Thrombosis – A Randomized Clinical Trial (1990)

271 patients with acute symptomatic deep venous thrombosis of lower limbs, confirmed by strain-gauge plethysmography and/or venography, were randomly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6-10 days. Heparin dosage was adjusted to maintain activated partial thromboplastin time values (Thrombofax reagent) at 1.3-1.9 times the basal ones. Strain-gauge plethysmography was repeated at the end of heparin treatment, and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications. In the intravenous group, Maximal Venous Outflow (MVO) increased from 20.8 +/- 12.8 to 28.4 +/- 17.5 ml/min per 100 ml of tissue and Venous Capacitance (VC) from 1.39 +/- 0.92 to 1.94 +/- 1.0 ml/100 ml of tissue (mean +/- SD). In the subcutaneous group, MVO increased from 21.0 +/- 12.7 to 27.5 +/- 18.1 and VC from 1.60 +/- 0.86 to 2.06 +/- 1.0. The median improvement of MVO and VC were 22% and 36% respectively in the IV group and 20% and 24% in the SC group. Clinical pulmonary embolism occurred in 2 patients in the intravenous group (1 fatal) and in 4 in the subcutaneous group (1 fatal). 9 major bleeding complications occurred in the intravenous group (1 fatal) and 5 in the subcutaneous group (1 fatal). The differences were not significant at the statistical analysis. The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis. To the same conclusion points an overview of the seven randomized trials which compared these treatment modalities.
Improved Patency of Transjugular Intrahepatic Portosystemic Shunts in Humans: Creation and Revision with PTFE Stent-Grafts (1999)

PTFE stent-grafts can markedly prolong TIPS patency, potentially reducing the need for shunt follow-up and revision and the risk of recurrent symptoms associated with shunt stenosis or occlusion.
Comprehensive molecular characterization of urothelial bladder carcinoma (2019)

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomas to provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3–TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Osteo/Chondrocytic Transcription Factors and Their Target Genes Exhibit Distinct Patterns of Expression in Human Arterial Calcification (2003)

These observations suggest a sequence of molecular events in vascular calcification beginning with the loss of expression by VSMCs, of constitutive inhibitory proteins, and ending with expression by VSMCs and macrophages of chondrocytic, osteoblastic, and osteoclastic-associated proteins that orchestrate the calcification process.
Cloning and characterization of alternatively spliced isoforms of Dp71 (1995)

Dp71, a C-terminal isoform of dystrophin, has been identified as the major DMD gene product in many nonmuscle tissues. In this report, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to clone and characterize four alternatively spliced Dp71 transcripts from cultured human amniocytes. The cDNAs encoding these Dp71 transcripts were shown to be alternatively spliced for exons 71 and/or 78. RT-PCR analysis also revealed that Dp71 transcripts alternatively spliced for exons 71 and/or 78 were expressed at varying levels in a number of adult human tissues, including muscle, heart, brain, kidney, lung, testis and liver. To investigate size heterogeneity at the translational level, Dp71 cDNAs isolated from amniocytes were expressed in E.coli to generate recombinant Dp71 fusion proteins. These fusion proteins were identified on immunoblots using antibodies specific for the C-terminal sequences of dystrophin that either included (antibody 1461) or excluded exon 78 (antibody 462B). The molecular masses of the Dp71 fusion proteins ranged from 71-75 kDa on SDS-PAGE, consistent with their predicted values. Immunoblot analysis using antibodies 1461 and 462B identified multiple Dp71 isoforms of approximately 70-75 kDa on SDS-PAGE in total protein lysates from amniocytes and various adult human tissues. This variation in molecular mass is consistent with the expression of Dp71 isoforms derived from transcripts alternatively spliced for exons 71 and/or 78. Total protein lysates from normal skeletal muscle, DMD muscle, amniocytes and brain were shown to contain beta-dystroglycan, a component of the dystrophin-associated glycoprotein complex (DGC).(ABSTRACT TRUNCATED AT 250 WORDS)
Transformation and transactivation suppressor activity of the c-Jun leucine zipper fused to a bacterial repressor. (1992)

Transcription factor c-Jun appears to be a nuclear target of the Ras-induced signal transduction pathway. In fact, some experiments show that transforming forms of the Ras protein cooperate with Jun in transcriptional activation mediated by an AP-1 site and others indicate that the two oncoproteins cooperate in cellular transformation. Although it is likely that intracellular signaling systems activated by Ras might act directly on c-Jun by inducing specific phosphorylation, it is unclear how c-Jun participates in the transformation process. Here, we present results obtained with a LexA-Jun zipper fusion that lacks both the transcriptional activation domains and the basic region of the DNA-binding domain of c-Jun and contains only the intact leucine-zipper domain. This fusion product has a dominant negative effect on the transcriptional activation elicited by phorbol esters, c-Jun, c-Fos, Ras and E1A on an AP-1-responsive site. An analogous LexA-Fos zipper fusion has similar effects on transcriptional induction. The LexA-Jun zipper fusion acts further as a transformation suppressor, since it causes the generation of nontransformed revertants of ras-transformed cells. This effect is likely to be elicited by the dimerization potential of the Jun leucine zipper trapping cellular Jun and/or Fos in a protein complex unable to bind to DNA. These data implicate further that Ras-mediated transformation involves functional transcription factor AP-1 and that it is possible to interfere with cell transformation by interfering simply with the dimerization of transcription factors involved in the transformation process.
The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/degradative pathway. (1990)

The amyloid forming beta-peptide of Alzheimer's disease is synthesized as part of a larger integral membrane precursor protein (beta APP) of which three alternatively spliced versions of 695, 751, and 770 amino acids have been described. A fourth beta APP form of 563 amino acids does not contain the beta-peptide region. Recent experiments using transient expression in HeLa cells (Weidemann, A., Konig, G., Bunke, D., Fischer, P., Salbaum, J.M., Masters, C.L., and Beyreuther, K. (1989) Cell 57, 115-126) indicate that the beta APP undergoes several posttranslational modifications including the cleavage and secretion of a large portion of its extracellular domain. The nature and fate of the fragment that remains cell-associated following this cleavage has not heretofore been described. The metabolism of this fragment may have particular significance in Alzheimer's disease since it must contain at least part of the beta-peptide. To study the metabolic fate of this fragment, we have established cell lines overexpressing the 695- and 751-amino acid versions of beta APP. Pulse-chase studies show that this system is similar to the HeLa cell system in that both proteins are synthesized first as membrane-bound proteins of approximately 98 and 108 kDa carrying asparagine-linked sugar side chains and are subsequently processed into higher molecular mass forms by the attachment of sulfate, phosphate, and further sugar groups including sialic acid, adding approximately 20 kDa in apparent molecular mass. The mature form of beta APP is cleaved and rapidly secreted, leaving an 11.5-kDa fragment with the transmembrane region and the cytoplasmic domain behind in the cell. This fragment is stable with a half-life of at least 4 h.
Chronic Autoimmune Thyroiditis (1996)

In 1912, Hashimoto described four women in whom the thyroid gland was enlarged and appeared to have been transformed into lymphoid tissue (“struma lymphomatosa”).1 Although the patients were not initially hypothyroid, they became so after thyroid surgery. Over 40 years later, the presence of antithyroid antibodies was reported in patients with this disorder.2 Hashimoto's disease, or Hashimoto's thyroiditis, is now recognized as a form of chronic autoimmune thyroiditis.There is no internationally accepted classification of autoimmune thyroid diseases.3 Some investigators consider autoimmune thyroiditis a histologic diagnosis that can be subdivided into lymphocytic thyroiditis, if only lymphocytic infiltration is present, and . . .
Pro-angiogenesis action of thyroid hormone and analogs in a three-dimensional in vitro microvascular endothelial sprouting model. (2006)

T4, T3, and T4-agarose are pro-angiogenic in the three-dimensional human microvascular endothelial sprouting model, an action that is initiated at the plasma membrane, involves avb3 integrin receptors, and is MAPK-dependent.