gebhart/patrepeval huggingface dataset:
DeepSplice: Deep classification of novel splice junctions revealed by RNA-seq (2016)

Alternative splicing (AS) is a regulated process that enables the production of multiple mRNA transcripts from a single multi-exon gene. The availability of large-scale RNA-seq datasets has made it possible to predict splice junctions, as well as splice sites through spliced alignment to the reference genome. This greatly enhances the capability to decipher gene structures and explore the diversity of splicing variants. However, existing ab initio aligners are vulnerable to false positive spliced alignments as a result of sequence errors and random sequence matches. These spurious alignments can lead to a significant set of false positive splice junction predictions, confusing downstream analyses of splice variant detection and abundance estimation. In this work, we illustrate that splice junction sequence characteristics can be ascertained from experimental data with deep learning techniques. We employ deep convolutional neural networks for a novel splice junction classification tool named DeepSplice that (i) outperforms state-of-the-art methods for predicting splice sites, (ii) shows high computational efficiency and (iii) can be applied to self-defined training data by users.
Evidence for an Intracellular ADP-ribosyl Cyclase/NAD+-glycohydrolase in Brain from CD38-deficient Mice (2003)

Cyclic ADP-ribose, a metabolite of NAD+, is known to modulate intracellular calcium levels and signaling in various cell types, including neural cells. The enzymes responsible for producing cyclic ADP-ribose in the cytoplasm of mammalian cells remain unknown; however, two mammalian enzymes that are capable of producing cyclic ADP-ribose extracellularly have been identified, CD38 and CD157. The present study investigated whether an ADP-ribosyl cyclase/NAD+-glycohydrolase independent of CD38 is present in brain tissue. To address this question, NAD+ metabolizing activities were accurately examined in developing and adult Cd38-/- mouse brain protein extracts and cells. Low ADP-ribosyl cyclase and NAD+-glycohydrolase activities (in the range of pmol of product formed/mg of protein/min) were detected in Cd38-/- brain at all developmental stages studied. Both activities were found to be associated with cell membranes. The activities were significantly higher in Triton X-100-treated neural cells compared with intact cells, suggesting an intracellular location of the novel cyclase. The cyclase and glycohydrolase activities were optimal at pH 6.0 and were inhibited by zinc, properties which are distinct from those of CD157. Both activities were enhanced by guanosine 5'-O-(3-thiotriphosphate), a result suggesting that the novel enzyme may be regulated by a G protein-dependent mechanism. Altogether our results indicate the presence of an intracellular membrane-bound ADP-ribosyl cyclase/NAD+-glycohydrolase distinct from CD38 and from CD157 in mouse brain. This novel enzyme, which is more active in the developing brain than in the adult tissue, may play an important role in cyclic ADP-ribose-mediated calcium signaling during brain development as well as in adult tissue.
SPRINT: A Scalable Parallel Classifier for Data Mining (1996)

Classification is an important data mining problem. Although classification is a well-studied problem, most of the current classification algorithms require that all or a portion of the the entire dataset remain permanently in memory. This limits their suitability for mining over large databases. We present a new decision-tree-based classification algorithm, called SPRINT that removes all of the memory restrictions, and is fast and scalable. The algorithm has also been designed to be easily parallelized, allowing many processors to work together to build a single consistent model. This parallelization, also presented here, exhibits excellent scalability as well. The combination of these characteristics makes the proposed algorithm an ideal tool for data mining.
A Plasmid Encoding Murine Granulocyte-Macrophage Colony-Stimulating Factor Increases Protection Conferred by a Malaria DNA Vaccine (1998)

Using the murine parasite Plasmodium yoelii (Py) as a model for malaria vaccine development, we have previously shown that a DNA plasmid encoding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP1012 with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) increases protection against malaria, and we have characterized in detail the increased immune responses due to GM-CSF. PyCSP1012 plasmid alone protected 28% of mice, and protection increased to 58% when GM-CSF was added (p < 0.0001). GM-CSF plasmid alone did not protect, and control plasmid expressing inactive GM-CSF did not enhance protection. GM-CSF plasmid increased Abs to PyCSP of IgG1, IgG2a, and IgG2b isotypes, but not IgG3 or IgM. IFN-gamma responses of CD8+ T cells to the PyCSP 280-288 amino acid epitope increased but CTL activity did not change. The most dramatic changes after adding GM-CSF plasmid were increases in Ag-specific IL-2 production and CD4+ T cell proliferation. We hypothesize that GM-CSF may act on dendritic cells to enhance presentation of the PyCSP Ag, with enhanced IL-2 production and CD4+ T cell activation driving the increases in Abs and CD8+ T cell function. Recombinant GM-CSF is already used in humans for medical purposes, and GM-CSF protein or plasmids may be useful as enhancers of DNA vaccines.
Fabrication of an Optoelectrochemical Microring Array (2002)

In this paper, we describe a novel approach for fabricating an optoelectrochemical microring array. The array was fabricated by coating individual optical fibers of 25-microm diameter with a 1-microm layer of gold nanoparticles via electroless gold deposition. A SAM layer around the individual gold-coated imaging fibers prevented electrical contact with neighboring ring electrodes. To achieve better mechanical stability and to make the device more practical, the electrode/fiber bundle comprising approximately 600 individual gold-coated optical fibers was dipped into epoxy. By polishing the ends of such a device, a ring microelectrode array comprising 600 individual and insulated ring electrodes was formed. To limit diffusional overlap of current, only 20-30% of the microring fiber/electrodes were wired. The inner diameter of the ring electrode is fixed by the diameter of the individual optical fibers (25 microm), while the outer radius is determined by the thickness of the deposited gold. The array was characterized using ferrocyanide in aqueous solution as a model electroactive species to demonstrate that this microelectrode array format exhibits steady-state currents at short response times. In addition, cyclic voltammetry experiments were performed using conventional potentiostats due to the amplification of current inherent in the array format. Finally, electrochemiluminescence at the ring electrode array was demonstrated through the oxidation of Ru(bpy)3(2+) in tri-n-propylamide in a pH 7 phosphate buffer solution, where the light generated was collected and detected via the fiber bundle.
Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression. (1994)

Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor and a member of the steroid hormone receptor superfamily. HNF-4 is required for the hepatoma-specific expression of HNF-1 alpha, another liver-enriched transcription factor, suggesting the early participation of HNF-4 in development. To prepare for further study of HNF-4 in development, the tissue-specific expression of the mouse HNF-4 gene was studied by analyzing the promoter region for required DNA elements. DNase-hypersensitive sites in the gene in liver and kidney tissues were found in regions both distal and proximal to the RNA start that were absent in tissues in which HNF-4 expression did not occur. By use of reporter constructs in transient-transfection assays and with transgenic mice, a region sufficient to drive liver-specific expression of HNF-4 was identified. While an HNF-1 binding site between bp -98 and -68 played an important role in the hepatoma-specific promoter activity of HNF-4 in transient-transfection assays, it was not sufficient for the liver-specific expression of a reporter gene in transgenic mice. Distal enhancer elements indicated by the presence of DNase I-hypersensitive sites at kb -5.5 and -6.5, while not functional in transient-transfection assays, were required for the correct expression of the mouse HNF-4 gene in animals.
Congestion control for best-effort service: why we need a new paradigm (1996)

The current congestion control paradigm assumes that end users will use a single mandated algorithm. While the work done in this area has proven to be of great value, we need to recognize as a community that this paradigm is clearly inappropriate for future public networks. The reformulation of congestion control for best-effort service is discussed. We are not attempting to design specific new congestion control algorithms. Instead, we are merely trying to articulate the design principles. Many of these principles have been discussed before; however, with ATM currently designing a best-effort service under the name available bit rate (ABR) and the increasing commercialization of the Internet, these issues warrant revisiting. We outline the service model for best-effort service, describe the set of mechanisms available to implement this service model and contrast their various roles. The implications of our findings for future network design are discussed including some well-known examples of congestion control mechanisms.
Exploiting fine-grain thread level parallelism on the MIT multi-ALU processor (1998)

Much of the improvement in computer performance over the last twenty years has come from faster transistors and architectural advances that increase parallelism. Historically, parallelism has been exploited either at the instruction level with a grain-size of a single instruction or by partitioning applications into coarse threads with grain-sizes of thousands of instructions. Fine-grain threads fill the parallelism gap between these extremes by enabling tasks with run lengths as small as 20 cycles. As this fine-grain parallelism is orthogonal to ILP and coarse threads, it complements both methods and provides an opportunity for greater speedup. This paper describes the efficient communication and synchronization mechanisms implemented in the Multi-ALU Processor (MAP) chip, including a thread creation instruction, register communication, and a hardware barrier. These register-based mechanisms provide 10 times faster communication and 60 times faster synchronization than mechanisms that operate via a shared on chip cache. With a three-processor implementation of the MAP, fine-grain speedups of 1.2-2.1 are demonstrated on a suite of applications.
Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance (2016)

Genetic, epigenetic, and gene expression alterations often fail to explain adaptive drug resistance in cancer. This work presents a novel post-translational mechanism of such resistance: Kinase inhibitors, particularly targeting MAPK signaling, increase tumor cell surface receptor levels due to widely reduced proteolysis, allowing tumor signaling to circumvent intended drug action.
Granulocyte-macrophage colony-stimulating factor enhances 5-lipoxygenase levels in human polymorphonuclear leukocytes. (1994)

Stimulation of human polymorphonuclear leukocytes (PMNL) with granulocyte-macrophage CSF (GM-CSF) results in the enhanced expression of several genes, including some coding for cytokines and enzymes. In this study, we investigated the ability of GM-CSF to up-regulate the human neutrophil 5-lipoxygenase (5-LO), a key enzyme in the leukotriene synthetic pathway. GM-CSF induced a dose- and time-dependent de novo synthesis of the 5-LO in PMNL, as determined by immunoprecipitation of 35S-methionine-labeled 5-LO. This up-regulation occurred within 30 min of treatment with GM-CSF and was observed using concentrations of GM-CSF as low as 30 pM. Prior treatment of the cells with the protein synthesis inhibitor cycloheximide abolished this effect of GM-CSF. Western blot analyses demonstrated that levels of 5-LO did not vary over a 6-h period in unstimulated PMNL treated with CX, and that GM-CSF induced a rapid increase in the total cellular level of 5-LO protein; taken together these results indicated a translational effect of GM-CSF on the expression of the 5-LO. However, GM-CSF did not significantly affect the level of 5-LO mRNA in neutrophils, as determined by Northern blot analysis. Furthermore GM-CSF did not alter the stability of 5-LO mRNA, in agreement with a posttranscriptional effect of GM-CSF on 5-LO expression in PMNL. These results show that human PMNL are capable of up-regulating the expression of the 5-LO in response to physiologic activation.
Presence of Phosphorylated Hepatocyte Growth Factor Receptor/c-Met Is Associated with Tumor Progression and Survival in Patients with Conventional Renal Cell Carcinoma (2006)

Phosphorylated HGFR/c-Met may be important in the tumor progression of RCC. Expression of pY1349 HGFR/c-Met is a useful predictor for metastasis and survival of conventional RCC patients.
A noninvasive method to assess skin irritation and compromised skin conditions using simple tape adsorption of molecular markers of inflammation (2001)

Our results demonstrate that this method is a useful noninvasive technique for assessing skin inflammatory events. In addition, the method is simple and easily applied in a clinical setting, whether on infants or adults.
Longevity, Genes, and Aging (1996)

Until recently, biogerontology was a backwater of biology, but progress in the qualitative and quantitative genetic analysis of longevity has led to a revolution in aging research. This research has revealed that extended longevity is frequently associated with enhanced metabolic capacity and response to stress. Moreover, it suggests that there are multiple mechanisms of aging. Because of its complexity, the aging process takes us into the realm of integrative biology, and thus, biogerontology should prove instrumental in deciphering the functional and regulatory circuitry of the sequenced genome.
Retinoic Acid Stimulates the Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Human Choriocarcinoma JEG-3 Cells1 (1999)

The syncytiotrophoblasts of the human placenta express high levels of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme responsible for the inactivation of glucocorticoids. It has been proposed that the placental 11beta-HSD2 serves as a barrier to protect the fetus from high levels of maternal cortisol. To examine the hypothesis that nutritional signals regulate the expression of 11beta-HSD2 in placental syncytiotrophoblasts, we investigated the effects of retinoic acids (RAs), the major metabolites of vitamin A, on the expression of 11beta-HSD2 using human choriocarcinoma JEG-3 cells as a model. This trophoblast-like cell line displays a number of functional similarities to the syncytiotrophoblast. Treatment for 24 h with all-trans RA (1-1000 nM) resulted in a dose-dependent increase in 11beta-HSD2 activity with a maximal effect (increase to 3-fold) at 100 nM. The effect of all-trans RA (100 nM) was also time-dependent in that the effect was detectable at 6 h and reached its maximum by 48 h. Similar increases in 11beta-HSD2 activity were observed when the cells were treated with 9-cis RA. Results from semi-quantitative reverse transcription-polymerase chain reaction demonstrated that there was a corresponding increase in 11beta-HSD2 mRNA after RA treatment. Moreover, treatment with actinomycin D (100 ng/ml) abrogated the increase in 11beta-HSD2 mRNA induced by RA, indicating an effect on transcription. In conclusion, the present study has demonstrated for the first time that RA, at physiological concentrations, induces 11beta-HSD2 gene expression and enzyme activity in JEG-3 cells. If this occurs in vivo, the present finding suggests that high expression of 11beta-HSD2 in the human placenta may be maintained, at least in part, by dietary intake of vitamin A.
Iterative Optimization of High-Affinity Protease Inhibitors Using Phage Display. 1. Plasmin (1996)

We generated a series of libraries having variants of the first Kunitz domain of human lipoprotein-associated coagulation inhibitor (LACI-D1, also known as tissue-factor pathway inhibitor-I) displayed on bacteriophage M13 as pIII-fusions. We varied LACI-DI iteratively in two regions: the P1 region (positions 10-21) and the "second loop", (positions 31-39), which together form one end of the domain. Display-phage library Lib#1 allows 31 200 amino-acid sequences in P1 region (residues 13, 16-19). Preliminary, we screened Lib#1 against human plasmin (PLA, EC 3.4.21.7) immobolized on agarose to enrich for phage displaying variants with PLA affinity. We introduced a 1600-fold increase in second-loop diversity (residues 31, 32, 34, 39) into the population of selectants from Lib#1, yielding Lib#2. Lib#2 (allowing approximately 50 million amino-acid sequences) was screened against PLA-agarose to isolate highest affinity binders. Protein EPI-P211, derived from the best isolate of Lib#2, inhibits PLA with Ki = 2 nM (at least 500-fold better than LACI-D1) and with high specificity. We used amino-acid sequences of PLA-binding selectants to design a PLA-biased library (Lib#3) which we screened against PLA. The protein EPI-P302 (derived from the best binder obtained from Lib#3) has Ki for PLA inhibition of 87 pM, which is 25-fold better than the first-round best binder and > or = 12 500-fold better than LACI-D1. EPI-P302 also shows very high specificity for PLA vs other human proteases and is resistant to inactivation by oxidants and extremes of temperature or pH. Thus, one can use selectants from one library to design target-tailored combinatorial libraries and obtain quite stable, highly specific, very high-affinity binding molecules while maintaining an essentially human framework.
Flux: an adaptive partitioning operator for continuous query systems (2004)

The long-running nature of continuous queries poses new scalability challenges for dataflow processing. CQ systems execute pipelined dataflows that may be shared across multiple queries. The scalability of these dataflows is limited by their constituent, stateful operators - e.g. windowed joins or grouping operators. To scale such operators, a natural solution is to partition them across a shared-nothing platform. But in the CQ context, traditional, static techniques for partitioned parallelism can exhibit detrimental imbalances as workload and runtime conditions evolve. Long-running CQ dataflows must continue to function robustly in the face of these imbalances. To address this challenge, we introduce a dataflow operator called flux that encapsulates adaptive state partitioning and dataflow routing. Flux is placed between producer-consumer stages in a dataflow pipeline to repartition stateful operators while the pipeline is still executing. We present the flux architecture, along with repartitioning policies that can be used for CQ operators under shifting processing and memory loads. We show that the flux mechanism and these policies can provide several factors improvement in throughput and orders of magnitude improvement in average latency over the static case.
Factors Associated With Low Body Mass Index and Weight Loss in Nursing Home Residents (1995)

Undernutrition in nursing home residents is a multifactorial syndrome. Improved oral feeding methods and treatment of depression are potentially important ways to counteract undernutrition in nursing home residents by targeting reversible features.
Cavity Quantum Acoustic Device in the Multimode Strong Coupling Regime (2018)

We demonstrate an acoustical analog of a circuit quantum electrodynamics system that leverages acoustic properties to enable strong multimode coupling in the dispersive regime while suppressing spontaneous emission to unconfined modes. Specifically, we fabricate and characterize a device that comprises a flux tunable transmon coupled to a 300 μm long surface acoustic wave resonator. For some modes, the qubit-cavity coupling reaches 6.5 MHz, exceeding the cavity loss rate (200 kHz), qubit linewidth (1.1 MHz), and the cavity free spectral range (4.8 MHz), placing the device in both the strong coupling and strong multimode regimes. With the qubit detuned from the confined modes of the cavity, we observe that the qubit linewidth strongly depends on its frequency, as expected for spontaneous emission of phonons, and we identify operating frequencies where this emission rate is suppressed.
Characterizing the Self-Sensing Properties of Photoactive P3H T-Based Nanocomposites (2013)

In this study, the strain sensing properties of poly(3-hexylthiophene) (P3HT)- based films were characterized using absorption spectroscopy and photocurrent generation. In particular, the objective was to reveal how photocurrent generation and bulk film strain sensitivity were influenced by morphological changes of the bulk heterojunction (BHJ) layer, which consisted of P3HT and fullerene-based [6,6]-phenyl C61 butyric acid methyl ester (PCBM) polymers. Eight different P3HT:PCBM sets were prepared, each with a unique P3HT:PCBM concentration ratio. The absorption spectra of the eight different sample sets were measured, and their sensitivity to strain was characterized. Then, their optoelectronic properties were investigated by measuring their photocurrent generation under light on/off conditions. Lastly, the films’ photocurrent time histories were measured as strain was applied to them. It was found that strain-sensitive photocurrent was observed as a result of strain-induced changes in the light absorption properties of the P3HT:PCBM BHJ layer.
Identification of the Binding Site for Fibrinogen Recognition Peptide γ383–395 within the αMI-Domain of Integrin αMβ2 (2001)

The leukocyte integrin alpha(M)beta(2) (Mac-1, CD11b/CD18) is a cell surface adhesion receptor for fibrinogen. The interaction between fibrinogen and alpha(M)beta(2) mediates a range of adhesive reactions during the immune-inflammatory response. The sequence gamma(383)TMKIIPFNRLTIG(395), P2-C, within the gamma-module of the D-domain of fibrinogen, is a recognition site for alpha(M)beta(2) and alpha(X)beta(2). We have now identified the complementary sequences within the alpha(M)I-domain of the receptor responsible for recognition of P2-C. The strategy to localize the binding site for P2-C was based on distinct P2-C binding properties of the three structurally similar I-domains of alpha(M)beta(2), alpha(X)beta(2), and alpha(L)beta(2), i.e. the alpha(M)I- and alpha(X)I-domains bind P2-C, and the alpha(L)I-domain did not bind this ligand. The Lys(245)-Arg(261) sequence, which forms a loop betaD-alpha5 and an adjacent helix alpha5 in the three-dimensional structure of the alpha(M)I-domain, was identified as the binding site for P2-C. This conclusion is supported by the following data: 1) mutant cell lines in which the alpha(M)I-domain segments (245)KFG and Glu(253)-Arg(261) were switched to the homologous alpha(L)I-domain segments failed to support adhesion to P2-C; 2) synthetic peptides duplicating the Lys(245)-Tyr(252) and Glu(253)-Arg(261) sequences directly bound the D fragment and P2-C derivative, gamma384-402, and this interaction was blocked efficiently by the P2-C peptide; 3) mutation of three amino acid residues within the Lys(245)-Arg(261) segment, Phe(246), Asp(254), and Pro(257), resulted in the loss of the binding function of the recombinant alpha(M)I-domains; and 4) grafting the alpha(M)(Lys(245)-Arg(261)) segment into the alpha(L)I-domain converted it to a P2-C-binding protein. These results demonstrate that the alpha(M)(Lys(245)-Arg(261)) segment, a site of the major sequence and structure difference among alpha(M)I-, alpha(X)I-, and alpha(L)I-domains, is responsible for recognition of a small segment of fibrinogen, gammaThr(383)-Gly(395), by serving as ligand binding site.