gebhart/patrepeval huggingface dataset:
Immunoediting and Antigen Loss: Overcoming the Achilles Heel of Immunotherapy with Antigen Non-Specific Therapies (2013)

Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity.
MIMO Capacity Through Correlated Channels in the Presence of Correlated Interferers and Noise: A (Not So) Large N Analysis (2003)

The use of multiple-antenna arrays in both transmission and reception promises huge increases in the throughput of wireless communication systems. It is therefore important to analyze the capacities of such systems in realistic situations, which may include spatially correlated channels and correlated noise, as well as correlated interferers with known channel at the receiver. Here, we present an approach that provides analytic expressions for the statistics, i.e., the moments of the distribution, of the mutual information of multiple-antenna systems with arbitrary correlations, interferers, and noise. We assume that the channels of the signal and the interference are Gaussian with arbitrary covariance. Although this method is valid formally for large antenna numbers, it produces extremely accurate results even for arrays with as few as two or three antennas. We also develop a method to analytically optimize over the input signal covariance, which enables us to calculate analytic capacities when the transmitter has knowledge of the statistics of the channel (i.e., the channel covariance). In many cases of interest, this capacity is very close to the full closed-loop capacity, in which the transmitter has instantaneous channel knowledge. We apply this analytic approach to a number of examples and we compare our results with simulations to establish the validity of this approach. This method provides a simple tool to analyze the statistics of throughput for arrays of any size. The emphasis of this paper is on elucidating the novel mathematical methods used.
Isolation of the Human γ-Carboxylase and a γ-Carboxylase-Associated Protein from Factor IX-Expressing Mammalian Cells (1996)

A model system for the analysis of intracellular events governing the modification of individual vitamin K-dependent (VKD) proteins by the carboxylase has been developed using recombinant VKD protein-transfected cell lines. When untransfected 293 cells were analyzed by in vitro carboxylation followed by SDS-PAGE, endogenous VKD proteins were not detected. With 293 cells stably-transfected with recombinant native factor IX, most (> 95%) of the carboxylase was in complex with the factor IX, as assayed by adsorption of carboxylase activity to immobilized anti-factor IX antibody. In contrast, with 293 cells stably-transfected with recombinant factor IX deleted in the propeptide sequence (amino acids -18 to -4, delta pro factor IX), no association of factor IX with the carboxylase was observed. This observation was used to specifically isolate and identify the human carboxylase, and carboxylase-associated protein. When the carboxylase was purified from solubilized microsomes from either native factor IX, or delta pro factor IX, stably-transfected 293 cells, a single 98 kDa band was specifically obtained from native factor IX microsomes, but not from delta pro factor IX microsomes. This band was subsequently shown by Western and microsequencing analysis to comprise both the carboxylase and carboxylase-associated protein. This isolation, which represents the first isolation to near homogeneity of both the human carboxylase and the carboxylase from cell lines, will be valuable in isolating enzymatically active recombinant carboxylase, which has been refractile to other purification attempts. This system was also used to show that the human carboxylase in 293 cells is capable of binding and modifying two different liver-derived proteins. Protein C-producing 293 cells were generated from the same 293 progenitor cell line used to created the factor IX-expressing cells. With both factor IX- and protein C-transfected 293 cells, the secreted proteins were almost completely carboxylated, and in microsomes from each cell line the carboxylase was found in near quantitative complex with the two different VKD proteins. Thus the carboxylase modifies both VKD proteins. The approach described here for the analysis of the carboxylase from recombinant VKD protein-transfected cell lines should provide an important new system for studying protein carboxylation and VKD protein-carboxylase interaction.
Evaluation of human MSCs cell cycle, viability and differentiation in micromass culture (2006)

Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissue cells. They are easy to expand while maintaining their undifferentiated state, which suggests that these cells could be an attractive cell source for tissue engineering of cartilage. In vitro high density micromass culture has been widely used for chondrogenesis induction. Our objective was to investigate human MSCs cell cycle, viability and differentiation in these conditions. Therefore, to induce human MSCs chondrogenesis, micromasses were cultured in the presence of transforming growth factor-beta1 in serum free medium for 21 days. Cell cycle, cell viability and cell phenotype were analyzed by flow cytometry. From day 0 to 7, the G0/G1 phase increased, whereas the S phase decreased gradually, but cell cycle phases (S, G0/G1 and G2/M) did not significantly change after day 7. Less than 10% of cells were apoptotic, but no necrosis was observed, even at day 21. We observed a decrease in CD90 and CD105 expression, from day 0 to 21. In conclusion, our results demonstrate a good viability of human MSCs in micromass culture during the whole period of culture. Moreover, micromass culture allowed human MSCs to be synchronized at the G0/G1 phase, while their phenotype suggested some degree of differentiation.
Attending to All Mention Pairs for Full Abstract Biological Relation Extraction (2017)

Most work in relation extraction forms a prediction by looking at a short span of text within a single sentence containing a single entity pair mention. However, many relation types, particularly in biomedical text, are expressed across sentences or require a large context to disambiguate. We propose a model to consider all mention and entity pairs simultaneously in order to make a prediction. We encode full paper abstracts using an efficient self-attention encoder and form pairwise predictions between all mentions with a bi-affine operation. An entity-pair wise pooling aggregates mention pair scores to make a final prediction while alleviating training noise by performing within document multi-instance learning. We improve our model's performance by jointly training the model to predict named entities and adding an additional corpus of weakly labeled data. We demonstrate our model's effectiveness by achieving the state of the art on the Biocreative V Chemical Disease Relation dataset for models without KB resources, outperforming ensembles of models which use hand-crafted features and additional linguistic resources.
Serum Glial Fibrillary Acidic Protein Is a Highly Specific Biomarker for Traumatic Brain Injury in Humans Compared With S-100B and Neuron-Specific Enolase (2010)

Serum GFAP has remarkable diagnostic value for TBI, defined by abnormal head CT findings, in prehospital-triaged patients with severe trauma.
Effects of GDNF on Axotomized Sensory and Motor Neurons in Adult Rats (1997)

Glial cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor shown to rescue developing and adult motoneurons in vitro and in vivo from programmed and injury-induced cell death. To test whether GDNF would rescue adult mammalian sensory and motor neurons from physiological consequences of injury, the tibial nerve of rats was axotomized and, after a 10 day delay to permit injury processes to proceed, vehicle or GDNF was supplied directly to the nerve for 2 or 4 weeks or GDNF intrathecally for 2 weeks. Conduction velocity (CV) of both sensory and motor axons declined during the initial 10 days, and even more so if then treated with vehicle. Treatment with GDNF resulted in marginal improvement of sensory axon CV. CV of motor axons recovered significantly in a dose- and time-dependent manner. The results suggest that GDNF may have therapeutic potential in the treatment of peripheral neuropathies.
Adult Kidney Tubular Cell Population Showing Phenotypic Plasticity, Tubulogenic Capacity, and Integration Capability into Developing Kidney (2005)

Using in vivo bromodeoxyuridine (BrdU) labeling, a tubular cell population (label-retaining tubular cells [LRTC]) was identified recently in normal adult kidneys, which contributes actively to the regeneration process of the kidney after injury. Here, these LRTC are characterized in vitro. The LRTC population was isolated from BrdU-treated rat kidney by FACS. Both LRTC and non-LRTC underwent proliferation and maintained an epithelial phenotype in the presence of tubulogenic growth factors such as EGF, TGF-alpha, IGF-I, and hepatocyte growth factor. It is interesting that LRTC also proliferated without epithelial markers expression in the presence of soluble factors derived from an embryonic kidney metanephric mesenchyme cell line. The type of extracellular matrix strongly influenced the phenotype of LRTC. Furthermore, in three-dimensional collagen gel culture, LRTC formed tubule-like or tubulocystic structures in response to growth factors (hepatocyte growth factor and fibroblast growth factor) that are known to induce kidney cell tubulogenesis in vitro and/or participate in renal regeneration in vivo. In contrast, non-LRTC did not form these structures. When transplanted into the metanephric kidney, LRTC but not non-LRTC were integrated into epithelial components of nephron, including the proximal tubular cells and the ureteric bud. They also differentiated into fibroblast-like cells. Collectively, these findings suggest that LRTC are an adult kidney tubular cell population that shows phenotypic plasticity, tubulogenic capacity, and integration capability into the developing kidney.
Spanner: Google's globally-distributed database (2012)

Spanner is Google's scalable, multi-version, globally-distributed, and synchronously-replicated database. It is the first system to distribute data at global scale and support externally-consistent distributed transactions. This paper describes how Spanner is structured, its feature set, the rationale underlying various design decisions, and a novel time API that exposes clock uncertainty. This API and its implementation are critical to supporting external consistency and a variety of powerful features: nonblocking reads in the past, lock-free read-only transactions, and atomic schema changes, across all of Spanner.
Non-coding RNA: what is functional and what is junk? (2015)

The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as "intergenic RNA," "long non-coding RNAs" etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.
Multifunctional Dendrimer‐Templated Antibody Presentation on Biosensor Surfaces for Improved Biomarker Detection (2010)

Dendrimers, with their well-defined globular shape and a high density of functional groups, are ideal nanoscale materials for templating sensor surfaces. This work exploits dendrimers as a versatile platform for capturing biomarkers with improved sensitivity and specificity. Synthesis, characterization, fabrication, and functional validation of the dendrimer-based assay platform are described. Bifunctional hydroxyl/thiol functionalized G4-polyamidoamine (PAMAM) dendrimer is synthesized and immobilized on to the polyethylene-glycol (PEG)-functionalized assay plate by coupling PEG-maleimide and dendrimer thiol groups. Simultaneously, part of the dendrimer thiol groups are converted to hydrazide functionalities. The resulting dendrimer-modified surface is coupled to the capture antibody in the Fc region of the oxidized antibody. This preserves the orientation flexibility of the antigen binding region (Fv) of the antibody. To validate the approach, the fabricated plates are further used as a solid phase for developing a sandwich type ELISA to detect IL-6 and IL-1β, important biomarkers for early stages of chorioamnionitis. The dendrimer-modified plate provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg ml<sup>-1</sup> for IL-6 luminol detection and 1.15 pg ml<sup>-1</sup> for IL-1β TMB detection, which are significantly better than those for the traditional ELISA. The assays were validated in human serum samples from normal (non-pregnant) woman and pregnant women with pyelonephritis. The specificity and the improved sensitivity of the dendrimer-based capture strategy could have significant implications for the detection of a wide range of cytokines and biomarkers since the capture strategy could be applied to multiplex microbead assays, conductometric immunosensors and field effect biosensors.
Development of a Method for Analyzing the Volatile Thiols Involved in the Characteristic Aroma of Wines Made fromVitis viniferaL. Cv. Sauvignon Blanc (1998)

Volatile thiols were purified from a dichloromethane extract of Sauvignon blanc wine by the reversible combination of the thiols with p-hydroxymercuribenzoate, fixation of the resulting complex in an anion exchange column, and finally release of the thiols with cysteine. By analyzing the purified thiol extract from 500 mL of wine, using gas chromatography coupled with mass spectrometry, it was possible to measure the concentrations of five volatile compounds at once: 4-mercapto-4-methylpentan-2-one, 3-mercaptohexyl acetate, 3-mercaptohexan-1-ol, 4-mercapto-4-methylpentan-2-ol, and 3-mercapto-3-methylbutan-1-ol. Analysis of 10 typical Sauvignon Blanc wines (Bordeaux, Sancerre) showed that the first three compounds listed above are expected to be involved in varietal aroma, as they may be present at concentrations greatly in excess of their respective perception thresholds. Keywords: Volatile thiol; aroma; Sauvignon blanc wine; Vitis vinifera; p-hydroxymercuribenzoate
Cellular-Automata Supercomputers for Fluid-Dynamics Modeling (1986)

We report recent developments in the modeling of fluid dynamics, and give experimental results (including dynamical exponents) obtained with cellular automata machines. Because of their locality and uniformity, cellular automata lend themselves to an extremely efficient physical realization; with a suitable architecture, an amount of hardware resources comparable to that of a home computer can achieve (in the simulation of cellular automata) the performance of a conventional supercomputer.
Facile deoxygenation of phenols and enols using sodium borohydride–nickel chloride (1992)

A facile deoxygenation reaction of phenol and 1,3-dicarbonyl compounds was investigated. Phenols, enolizable 1,3-diketones and 3-ketoesters were converted into the toluene-p-sulfonates which were reduced by a sodium borohydride–nickel chloride system to give the deoxygenated aromatic compounds, alcohols and esters, respectively.
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus) (2017)

Standard dose P can be safely combined with G, G+NP, G+V, I and LD. Efficacy was observed in multiple tumour types and evaluation to determine if response and duration of response are more robust than what would be expected for chemotherapy or immunotherapy alone requires further validation.
Iron accumulation in Alzheimer disease is a source of redox-generated free radicals (1997)

Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease. In this study, we investigated whether iron, a potent source of the highly reactive hydroxyl radical that is generated by the Fenton reaction with H2O2, might contribute to the source of radicals in Alzheimer disease. We found, using a modified histochemical technique that relies on the formation of mixed valence iron complexes, that redox-active iron is associated with the senile plaques and neurofibrillary tangles-the pathological hallmark lesions of this disease. This lesion-associated iron is able to participate in in situ oxidation and readily catalyzes an H2O2-dependent oxidation. Furthermore, removal of iron was completely effected using deferoxamine, after which iron could be rebound to the lesions. Characterization of the iron-binding site suggests that binding is dependent on available histidine residues and on protein conformation. Taken together, these findings indicate that iron accumulation could be an important contributor toward the oxidative damage of Alzheimer disease.
Advances in understanding and treatment of immune‐mediated disorders of the peripheral nervous system (2004)

During recent years, novel insights in basic immunology and advances in biotechnology have contributed to an increased understanding of the pathogenetic mechanisms of immune-mediated disorders of the peripheral nervous system. This increased knowledge has an impact on the management of patients with this class of disorders. Current advances are outlined and their implication for therapeutic approaches addressed. As a prototypic immune-mediated neuropathy, special emphasis is placed on the pathogenesis and treatment of the Guillain-Barré syndrome and its variants. Moreover, neuropathies of the chronic inflammatory demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed. This review summarizes recent progress with currently available therapies and--on the basis of present immunopathogenetic concepts--outlines future treatment strategies.
C-Reactive Protein Binding to Murine Leukocytes Requires Fcγ Receptors (2000)

Human C-reactive protein (CRP) is an acute phase protein that binds to receptors on human and mouse leukocytes. We have recently determined that the high and low affinity receptors for CRP on human leukocytes are Fc gamma RIIa and Fc gamma RI, respectively. Previous work by others suggested that CRP receptors on mouse macrophages are distinct from Fc gamma R. We have taken advantage of the availability of mice deficient in one or more Fc gamma R to reexamine the role of Fc gamma R in CRP binding to mouse leukocytes. Three strains of Fc gamma R-deficient mice were examined: gamma-chain-deficient mice that lack Fc gamma RI and Fc gamma RIII, Fc gamma RII-deficient mice, and mice deficient in both gamma-chain and Fc gamma RII that lack all Fc gamma R. No binding of CRP was detected to leukocytes from double-deficient mice, indicating that Fc gamma R are required for CRP binding. CRP binding to leukocytes from gamma-chain-deficient and Fc gamma RII-deficient mice was reduced compared with binding to leukocytes from wild-type mice. Further analysis of CRP binding to macrophages, neutrophils, and lymphocytes provides direct evidence that Fc gamma RIIb1, Fc gamma RIIb2, and Fc gamma RI are the receptors for CRP on mouse leukocytes. These findings may have important implications in understanding the physiological function of CRP.
Parallel Tempering for Training of Restricted Boltzmann Machines (2010)

Alternating Gibbs sampling between visible and latent units is the most common scheme used for sampling from Restricted Boltzmann Machines (RBM), a crucial component in deep architectures such as Deep Belief Networks (DBN). However, we find that it often does a very poor job of rendering the diversity of modes captured by the trained model. We suspect that this property hinders RBM training methods such as the Contrastive Divergence and Persistent Contrastive Divergence algorithm that rely on Gibbs sampling to approximate the likelihood gradient. To alleviate this problem, we explore the use of tempered Markov Chain Monte-Carlo for sampling in RBMs. We find both through visualization of samples and measures of likelihood on a toy dataset that it helps both sampling and learning.
LynIs a Target Gene for Prostate Cancer (2004)

The Src-related protein kinase Lyn plays an important role in B-cell activation. However, several lines of evidence suggest that it is also involved in the control of cellular proliferation and the inhibition of apoptosis. We have discovered that Lyn is expressed in normal prostate epithelia, in 95% of primary human prostate cancer (PC) specimens examined, and in all of the PC cell lines that we assayed. Moreover, Lyn knockout mice display abnormal prostate gland morphogenesis, which suggests that Lyn plays an important role in prostate epithelium development and implies that Lyn is a candidate target for specific therapy for PC. Using a drug-design strategy to construct sequence-based peptide inhibitors, a Lyn-specific inhibitor, KRX-123, targeting a unique interaction site within Lyn, was synthesized. KRX-123 was found to inhibit cellular proliferation in three hormone-refractory PC cell lines, DU145, PC3, and TSU-Pr1 with IC(50) values of 2-4 micro M. In vivo, tumor volume of DU145 explants in nude mice was significantly reduced after once-a-week injections of KRX-123, at a dose of 10 mg/kg, for a period of 5 weeks. Histological analyses of the treated tumors indicated extensive apoptosis. Thus, we suggest that Lyn inhibition may serve as a prime target for the treatment of hormone-refractory PC.