gebhart/patrepeval huggingface dataset:
714 PD1 x TGFβR2 bispecifics selectively block TGFβR2 on PD1-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors (2020)

<h3>Background</h3> TGFβ production by solid tumors and their microenvironment is a major mechanism used by tumors to avoid immunosurveillance. Blockade of TGFβ has been shown to promote an anti-tumor response; however, systemic blockade of TGFβ has also been associated with toxicity. We hypothesized that a PD1 x TGFβR2 bispecific antibody could selectively block the suppressive activity of TGFβ on tumor T cells and enhance their anti-tumor activity while avoiding the toxicity associated with systemic blockade. <h3>Methods</h3> We engineered bispecific antibodies that simultaneously engage PD1 and TGFβR2 using Xencor’s XmAb platform. The anti-TGFβR2 arm was tuned for optimal activity by introducing affinity-modulating amino acid substitutions. The activity of PD1 x TGFβR2 bispecifics was evaluated in vitro using a signaling assay to measure phosphorylated SMAD (pSMAD) by flow cytometry with exogenous TGFβ in unactivated and activated PBMC. In vivo activity was evaluated by monitoring the engraftment of human PBMC in NSG mice (huPBMC-NSG). Anti-tumor activity was assessed in huPBMC-NSG mice engrafted with established human cancer cell lines. Antibodies against other T cell targets were also incorporated into TGFβR2 bispecifics, and similarly evaluated in vitro and in vivo. <h3>Results</h3> PD1 x TGFβR2 bispecifics were confirmed to bind PD1 and block binding of TGFβ to TGFβR2. In vitro, we found that T cells from activated, serum-deprived PBMC exhibited robust induction of pSMAD in response to TGFβ, and PD1 x TGFβR2 bispecifics selectively inhibited pSMAD induction in PD1-positive T cells as demonstrated by over a 100-fold potency increase compared to an untargeted anti-TGFβR2 control. Additionally, we saw an enhancement of potency when evaluating blocking activity in activated (PD1-high) vs. unactivated (PD1-low) T cells. Similar selectivity was measured when comparing inhibition of pSMAD induction for activated T cells versus other PD1-negative, TGFβ-responsive immune cells. Intriguingly, TGFβR2 bispecifics incorporating antibodies against other T cell targets allowed for the targeting of a broader population of T cells while still conferring potent selectivity against target-negative cells. In vivo, treatment of huPBMC-NSG mice with TGFβR2 bispecifics promoted superior T cell engraftment and combined additively with PD1 blockade. Furthermore, TGFβR2 bispecific treatment of huPBMC-NSG mice containing established MDA-MB-231 triple-negative breast cancer tumors promoted an anti-tumor response that was also augmented with PD1 blockade. <h3>Conclusions</h3> Multiple PD1 x TGFβR2 bispecifics were engineered to selectively block TGFβR2 on PD1-positive T cells and evaluated in vitro and in vivo. Compelling activity, including additivity with PD1 blockade, suggests that clinical development is warranted for the treatment of human malignancies.
Treatments for Wasting in Patients with the Acquired Immunodeficiency Syndrome (1999)

Wasting was an early identifying characteristic of human immunodeficiency virus (HIV) infection, originally termed “slim disease” in Africa.1 As defined by the Centers for Disease Control and Prevention (CDC), wasting in patients with the acquired immunodeficiency syndrome (AIDS) is the involuntary loss of more than 10 percent of base-line body weight in combination with diarrhea, weakness, or fever.2 Wasting is considered an AIDS-defining condition. However, there is considerable controversy about the appropriate definition of AIDS wasting (whether it should be defined as the loss of 5 or 10 percent of usual weight) and whether changes in body composition, rather than . . .
Collisional stabilization of negative ions produced by a monoenergetic electron beam (1999)

The effect of different buffer gases on the intensity of negative ions was studied using a gas chromatography/electron monochromator mass spectrometer (GC/EM-MS). The buffer gas was introduced into the ion source not to moderate the electron energies, but specifically to investigate the process of collisional stabilization of negative ions. Three different designs of ion source were tested to study this phenomenon. It was found that collisional stabilization has a profound effect on the intensity of molecular radical anions and begins to play an important role at buffer gas pressures in the order of 10 mTorr. By using a partitioned ion-forming chamber, it was shown that for optimum stabilization to take place the buffer gas should be present in the region of negative ion formation. The gases possessing internal degrees of freedom which are capable of accommodating the excess energy of short-lived excited molecular anion states showed the largest increase in molecular radical anion intensities. At the same time helium, a widely used GC carrier gas, showed sufficient stabilization properties to allow detection of the molecular radical anions of typical electron-capturing molecules with positive electron affinities.
View-based and modular eigenspaces for face recognition (1994)

We describe experiments with eigenfaces for recognition and interactive search in a large-scale face database. Accurate visual recognition is demonstrated using a database of O(10/sup 3/) faces. The problem of recognition under general viewing orientation is also examined. A view-based multiple-observer eigenspace technique is proposed for use in face recognition under variable pose. In addition, a modular eigenspace description technique is used which incorporates salient features such as the eyes, nose and mouth, in an eigenfeature layer. This modular representation yields higher recognition rates as well as a more robust framework for face recognition. An automatic feature extraction technique using feature eigentemplates is also demonstrated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries (2015)

Loss of retinal ganglion cells (RGCs) occurs in retinal degenerative diseases, such as glaucoma, age-related macular degeneration, diabetic retinopathy, central retinal artery occlusion and ischemic central retinal vein thrombosis in adults and in retinopathy of prematurity in infants. A critical role of hypoxia, which underlies most of the above disorders, has been reported in causing RGC death. Disruption of blood-retinal barrier (BRB) occurs due to increased production of vascular endothelial growth factor and nitric oxide in response to hypoxia resulting in extravasation of serum derived substances and retinal edema and this may be one of important factors mediating RGC death. Activation of microglial cells in response to hypoxia and subsequent increased release of proinflammatory cytokines by them such as tumor-necrosis factor- (TNF-) and interleukin-1 (IL-1) target the TNF-receptor 1 and IL-receptor 1 on RGCs. Excess release of glutamate in retinal tissue under hypoxia activates the ionotropic glutamate receptors causing excitotoxicity through increased influx of calcium into the RGCs. Increased production of TNF-, IL-1 and enhanced intracellular calcium results in RGC death through activating several pathways such as caspase signaling, mitochondrial dysfunction and oxidative stress. In our investigations, melatonin, an antioxidant, was shown to reduce RGC death in the adult and neonatal hypoxic retina, through suppression of TNF-, IL-1 and glutamate levels as well as oxidative stress. Moreover, the function and structure of BRB was well preserved in these animals along with reduction in retinal edema. In view of our observations, we suggest that melatonin could be considered as a therapeutic agent to reduce RGC death in various retinal pathologies, in addition to other potential drugs/molecules of therapeutic interest that could render protection to RGCs. However, future in-depth research on the effects of melatonin on the retina under hypoxic conditions needs to be undertaken to explore its full potential in preventing/ameliorating RGC death.
Using microbial desalination cells to reduce water salinity prior to reverse osmosis (2010)

A microbial desalination cell (MDC) is a new method to reduce the salinity of one solution while generating electrical power from organic matter and bacteria in another (anode) solution. Substantial reductions in the salinity can require much larger volumes of the anode solution than the saline water, but any reduction of salinity will benefit the energy efficiency of a downstream reverse osmosis (RO) desalination system. We investigated here the use of an MDC as an RO pre-treatment method using a new type of air-cathode MDC containing three equally sized chambers. A single cycle of operation using a 1 g L−1 acetate solution reduced the conductivity of salt water (5 g L−1 NaCl) by 43 ± 6%, and produced a maximum power density of 480 mW m−2 with a coulombic efficiency of 68 ± 11%. A higher concentration of acetate (2 g L−1) reduced solution conductivity by 60 ± 7%, and a higher salt concentration (20 g L−1 NaCl) reduced solution conductivity by 50 ± 7%. The use of membranes with increased ion exchange capacities further decreased the solution conductivity by 63 ± 2% (20 g L−1 NaCl). These results demonstrate substantial (43–67%) desalination of water is possible using equal volumes of anode solution and salt water. These results show that MDC treatment could be used to substantially reduce salt concentrations and thus energy demands for downstream RO processing, while at the same time producing electrical power.
Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1 (2014)

This is the first study to systematically search for mutations in the tyrosine kinome in clear cell endometrial tumors. Our findings indicate that high-frequency somatic mutations in the catalytic domains of the tyrosine kinome are rare in clear cell ECs. We uncovered ten new mutations in TNK2 and DDR1 within serous and endometrioid ECs, thus providing novel insights into the mutation spectrum of each gene in EC.
Thermal, mechanical, and rheological behavior of blends of ultrahigh and normal‐molecular‐weight linear polyethylenes (1983)

Abstract Physical Blends of ultrahigh‐molecular‐weight linear polyethylene (UHMW LPE) and normal‐molecular‐weight linear polyethylene (NMW LPE) have been evaluated in terms of melt flow rate, tensile stress‐strain behavior, heat of fusion, melting temperature, and crystallinity. The behavior of the blends is intermediate between that of the parent polymers; no synergistic effects are observed. The addition of small quantities of NMW LPE does not improve the flow behavior of UHMW LPE sufficiently to render it amenable to conventional melt processing.
Nonviral Transfer of the Gene Encoding Coagulation Factor VIII in Patients with Severe Hemophilia A (2001)

Implantation of genetically altered fibroblasts that produce factor VIII is safe and well tolerated. This form of gene therapy is feasible in patients with severe hemophilia A.
Imaging of hard- and soft-tissue structure in the oral cavity by optical coherence tomography (1998)

We have developed a prototype optical coherence tomography (OCT) system for the imaging of hard and soft tissue in the oral cavity. High-resolution images of in vitro porcine periodontal tissues have been obtained with this system. The images clearly show the enamel-cementum and the gingiva-tooth interfaces, indicating OCT is a potentially useful technique for diagnosis of periodontal diseases. To our knowledge, this is the first application of OCT for imaging biologic hard tissue.
Online Processing Redux. (1997)

The term &amp;quot;online&amp;quot; has become an all-too-common addendum to database system names of the day. In this article we reexamine the notion of processing queries online. We distinguish between online processing and preprocessing, and argue that online processing for large queries requires redesigning major portions of a database system. We highlight pressing applications for truly online processing, and sketch ongoing research in these applications at Berkeley. We also outline basic techniques for running long queries online. We close by reevaluating the typical measurements of cost/performance for online systems, and propose a mass-market approach for designing and measuring data-intensive processing. 1 Introduction In the parlance of today&amp;apos;s database systems, &amp;quot;online&amp;quot; signifies &amp;quot;interactive&amp;quot;, &amp;quot;within the bounds of patience.&amp;quot; Online processing is the opposite of &amp;quot;batch&amp;quot; processing. In the dark days of computing, all serious work was done in batch mode --- the COBOL or FORTRAN programmer sub...
Development of Human Genome Editing Tools for the Study of Genetic Variations and Gene Therapies (2013)

The human genome encodes information that instructs human development, physiology, medicine, and evolution. Massive amount of genomic data has generated an ever-growing pool of hypothesis. Genome editing, broadly defined as targeted changes to the genome, posits to deliver the promise of genomic revolution to transform basic science and personalized medicine. This thesis aims to contribute to this scientific endeavor with a particular focus on the development of effective human genome engineering tools.
Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure (2005)

The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.
Implementation of mixed precision in solving systems of linear equations on the Cell processor (2007)

Abstract This paper describes the design concepts behind implementations of mixed‐precision linear algebra routines targeted for the Cell processor. It describes in detail the implementation of code to solve linear system of equations using Gaussian elimination in single precision with iterative refinement of the solution to the full double‐precision accuracy. By utilizing this approach the algorithm achieves close to an order of magnitude higher performance on the Cell processor than the performance offered by the standard double‐precision algorithm. The code is effectively an implementation of the high‐performance LINPACK benchmark, as it meets all of the requirements concerning the problem being solved and the numerical properties of the solution. Copyright © 2007 John Wiley &amp; Sons, Ltd.
A simple fabrication route to a highly transparent super-hydrophobic surface with a poly(dimethylsiloxane) coated flexible mold (2007)

A super-hydrophobic and highly transparent nanostructured film was fabricated via imprinting and conformally uniform chemical anchoring of poly(dimethylsiloxane) on a controlled nanoscopic dimension.
Migration by haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin. (1983)

Laminin is a large (greater than 850-kdalton) glycoprotein that is localized within basement membranes. Recent work has indicated that this protein is present within the endoneurium of mouse sciatic nerve. Furthermore, it has been shown that a rat Schwannoma cell line, RN22F, produced laminin and that laminin promoted the attachment of these cells to bacterial plastic. This report presents evidence that RN22F cells migrate in vitro to laminin in a concentration-dependent fashion. Laminin was extracted from the mouse EHS tumor and purified by molecular sieve and heparin-agarose affinity chromatography. The migration of Schwannoma cells to laminin, as assessed in a microwell modified Boyden chamber, was inhibited in a dose-dependent manner by affinity-purified antilaminin antibody. Zigmond-Hirsch checkerboard analysis experiments indicated that laminin stimulated both random and directed movement of RN22F cells. Additionally, reversal of the laminin gradient in the chambers also stimulated RN22F migration in a concentration-dependent manner, suggesting that directed migration of RN22F cells was due to a substratum-bound laminin (haptotaxis) as opposed to cell movement in response to fluid-phase laminin (chemotaxis). Binding studies using [3H]laminin demonstrated that laminin bound to the filter surface under the assay conditions used, and support the contention that cells are migrating to substrate-bound material. Furthermore, RN22F cells were shown to migrate on filters coated with laminin in the absence of additional fluid-phase laminin. The magnitude of this response could be altered by changing the relative density of bound laminin. In contrast, fibronectin promoted only marginal migration of RN22F cells. Collectively, these observations indicate that haptotaxis may be a mechanism by which laminin may guide cells during development and raise the possibility that it may be involved in peripheral nervous system myelination.
Crystal structure of macrophage migration inhibitory factor (MIF), a glucocorticoid-induced regulator of cytokine production, reveals a unique architecture. (1996)

The mediator originally described as a macrophage migration inhibitory factor (MIF) has been identified recently to be a novel anterior pituitary hormone and the first protein to be released from immune cells upon stimulation with glucocorticoids. Once released, MIF acts to override or counter-regulate the immunosuppressive effects of glucocorticoids on cytokine production in vitro and on LPS lethality in vivo. MIF also has been described to catalyze a tautomerization reaction, suggesting that an enzymatic activity may underlie certain of its biological properties. The three-dimensional crystal structure of human MIF has been solved at 2.6A resolution. The X-ray crystal structure reveals MIF to be a trimer of identical subunits. Each monomer contains two antiparallel alpha-helices that pack against a four-stranded beta-sheet. The monomer has an additional two beta-strands that interact with the beta-sheets of adjacent subunits to form the interface between monomers. The three beta-sheets are arranged to form a barrel containing a solvent-accessible channel that runs through the center of the protein along a molecular three-fold axis. Electrostatic potential maps reveal that the channel has a positive potential, suggesting that it binds negatively charged molecules. The elucidated structure for MIF is unique among cytokines or hormones and suggests that this glucocorticoid-induced counter-regulatory hormone has a novel mechanism of action.
Optical waveguides in oxygen-implanted buried-oxide silicon-on-insulator structures (1988)

We analyze the waveguiding properties of the oxygen-implanted, buried-oxide, silicon-on-insulator structures currently being developed for use in microelectronics. We find that in spite of the fact that the buried-oxide layer is only a few tenths of a micrometer thick, the single-crystal overlayer can support TE0 guided-wave propagation, at subbandgap wavelengths, with losses due to substrate radiation leakage at or below the benchmark level of 1 dB/cm.
Mast Cells Are Essential for Early Onset and Severe Disease in a Murine Model of Multiple Sclerosis (2000)

In addition to their well characterized role in allergic inflammation, recent data confirm that mast cells play a more extensive role in a variety of immune responses. However, their contribution to autoimmune and neurologic disease processes has not been investigated. Experimental allergic encephalomyelitis (EAE) and its human disease counterpart, multiple sclerosis, are considered to be CD4(+) T cell-mediated autoimmune diseases affecting the central nervous system. Several lines of indirect evidence suggest that mast cells could also play a role in the pathogenesis of both the human and murine disease. Using a myelin oligodendrocyte glycoprotein (MOG)-induced model of acute EAE, we show that mast cell-deficient W/W(v) mice exhibit significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores when compared with their wild-type congenic littermates. No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals. Reconstitution of the mast cell population in W/W(v) mice restores induction of early and severe disease to wild-type levels, suggesting that mast cells are critical for the full manifestation of disease. These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation.
Prognostic value of TrkA protein detection by monoclonal antibody 5C3 in neuroblastoma. (1996)

The effects of nerve growth factor, a neurotrophin mediating growth and differentiation of neural crest-derived cells, are mediated by the receptor TrkA. TrkA mRNA expression has been associated with a good prognosis in human neuroblastoma (NB). We describe the use of monoclonal antibody 5C3 in detecting TrkA expression by immunohistochemistry in NB and other malignant tumors. A murine anti-TrkA IgG1 monoclonal antibody, 5C3, was generated against the extracellular domain of human p140(TrkA). 5C3 detected a 140-kDa band on Western blots. 5C3 was optimized for immunostaining and used to detect p140(TrkA) on 113 frozen NB samples and 42 samples from nine other malignancies. MOPC21 IgG1 antibody was used as a control. Results by immunohistochemistry were compared to TrkA expression assessed by reverse transcription-PCR and Western analysis. The prognostic value of TrkA expression by these methods was evaluated and compared to other known prognostic variables, including stage, age, and MYCN copy number. TrkA expression was detected by immunohistochemistry in 73 of the 113 NB tumor specimens and strongly correlated with nonmetastatic disease. TrkA expression was specific for NB among small round blue cell tumors. Both TrkA expression by immunohistochemistry and localized/4s disease correlated with survival. Tumors from 55 of 60 patients with localized/4s NB exhibited homogeneous or a mixed pattern of TrkA immunohistochemistry, whereas only 18 of 53 patients with stage 4 NB were immunoreactive. Detection of TrkA by reverse transcription-PCR and Western analysis was much more sensitive and no longer correlated with survival. 5C3 enables rapid detection of p140(TrkA) by immuno-histochemistry and identifies patients more likely to have localized NB with a favorable clinical outcome. Lack of TrkA expression is correlated with metastatic, malignant NB. A subset of patients with NB, however, died of aggressive metastatic disease despite TrkA expression. As a mimic of nerve growth factor, 5C3 may be useful in the study of TrkA-expressing tumors.