gebhart/patrepeval huggingface dataset:
Anatomy of a hash-based long read sequence mapping algorithm for next generation DNA sequencing (2010)

Abstract Motivation: Recently, a number of programs have been proposed for mapping short reads to a reference genome. Many of them are heavily optimized for short-read mapping and hence are very efficient for shorter queries, but that makes them inefficient or not applicable for reads longer than 200 bp. However, many sequencers are already generating longer reads and more are expected to follow. For long read sequence mapping, there are limited options; BLAT, SSAHA2, FANGS and BWA-SW are among the popular ones. However, resequencing and personalized medicine need much faster software to map these long sequencing reads to a reference genome to identify SNPs or rare transcripts. Results: We present AGILE (AliGnIng Long rEads), a hash table based high-throughput sequence mapping algorithm for longer 454 reads that uses diagonal multiple seed-match criteria, customized q-gram filtering and a dynamic incremental search approach among other heuristics to optimize every step of the mapping process. In our experiments, we observe that AGILE is more accurate than BLAT, and comparable to BWA-SW and SSAHA2. For practical error rates (&amp;lt; 5%) and read lengths (200–1000 bp), AGILE is significantly faster than BLAT, SSAHA2 and BWA-SW. Even for the other cases, AGILE is comparable to BWA-SW and several times faster than BLAT and SSAHA2. Availability: http://www.ece.northwestern.edu/~smi539/agile.html. Contact: smi539@eecs.northwestern.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Conventional and Kilohertz-frequency Spinal Cord Stimulation Produces Intensity- and Frequency-dependent Inhibition of Mechanical Hypersensitivity in a Rat Model of Neuropathic Pain (2013)

Kilohertz SCS attenuated mechanical hypersensitivity in a time course and amplitude that differed from conventional 50 Hz SCS, and may involve different peripheral and spinal segmental mechanisms.
Advancing Molecular Therapies through In Vivo Bioluminescent Imaging (2003)

Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI) is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLi is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.
Immune Pathogenesis of Hepatocellular Carcinoma (1998)

Hepatocellular carcinoma (HCC) is a common complication of chronic hepatitis B virus (HBV) infection. The pathogenetic mechanisms potentially responsible for HCC during chronic HBV infection are not well defined. This study demonstrates that chronic immune-mediated liver cell injury triggers the development of HCC in the absence of viral transactivation, insertional mutagenesis, and genotoxic chemicals. These results strongly suggest that the immune response to HBV is both necessary and sufficient to cause liver cancer during chronic HBV infection, and that all other procarcinogenic events associated with HCC are probably dependent on this process.
Purification of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans. An iron-sulfur protein (1987)

1. The (R)-2-hydroxyglutaryl-CoA dehydratase system from Acidaminococcus fermentans was separated by chromatography of cell-free extracts on Q-Sepharose into two components, an activator and the actual dehydratase. The latter enzyme was further purified to homogeneity by chromatography on blue-Sepharose. It is an iron-sulfur protein (Mr 210,000) consisting of two different polypeptides (alpha, Mr 55,000, and beta, Mr 42,000) in an alpha 2 beta 2 structure with probably two [4Fe-4S] centers. After activation this purified enzyme catalysed the dehydration of (R)-2-hydroxyglutarate only in the presence of acetyl-CoA and glutaconate CoA-transferase, demonstrating that the thiol ester and not the free acid is the substrate of the dehydration. The result led to a modification of the hydroxyglutarate pathway of glutamate fermentation. 2. The activation of the dehydratase by the flow-through from Q-Sepharose concentrated by ultrafiltration required NADH, MgCl2, ATP and strict anaerobic conditions. This fraction was designated as Ao. Later when the concentration was performed by chromatography on phenyl-Sepharose, an NADH-independent form of the activator, designated as A*, was obtained. This enzyme, which required only ATP for activation of the dehydratase, was purified further by affinity chromatography on ATP-agarose. It contains neither iron nor inorganic sulfur. A*, as well as the activated dehydratase, were irreversibly inactivated by exposure to air within less than 15 min. The activated dehydratase but not A* was also inactivated by 1 mM hydroxylamine or by 0.1 mM 2,4-dinitrophenol. 3. The (R)-2-hydroxyglutaryl-CoA dehydratase system is closely related the that of (R)-lactoyl-CoA dehydratase from Clostridium propionicum as described by R. D. Kuchta and R. H. Abeles [(1985) J. Biol. Chem. 260, 13,181-13,189].
Alexandrite-pumped alexandrite regenerative amplifier seeded by a frequency-doubled erbium-doped fiber laser (1995)

The main benefit of chirped pulse amplification is that very-high-peak power lasers have become laboratory tools. The emphasis in this area has continued to be higher peak power in a more compact form. One major improvement has been the use of tunable solid-state materials for amplifying shorter pulses which was first demonstrated in flashlamp-pumped alexandrite.1 Another decrease in size and improvement in stability has been achieved by going to laser pumping which was first demonstrated in Ti:sapphire pumped by frequency-doubled Nd:YAG.2 Further dramatic improvement in peak power has recently been accomplished by amplifying shorter pulses in this type of system.3
THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic Functions (1999)

Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.
Inhibitor of hematopoietic pluripotent stem cell proliferation: purification and determination of its structure. (1989)

We report here a five-step purification procedure that led to the isolation from fetal calf bone marrow extract of a tetrapeptide, Ac-Ser-Asp-Lys-Pro (Mr 487), exerting a high inhibitory activity on the proliferation of hematopoietic pluripotent stem cells [defined here as spleen colony-forming units (CFU-S)]. The structure of this molecule was established from amino acid analysis, fast atom bombardment mass spectrometry, and 1H nuclear magnetic resonance spectral data. This structure was confirmed by comparison with the corresponding synthetic molecule, which presents identical physiochemical characteristics and biological properties. Natural and synthetic peptides administered to mice (at a dose of 100 ng per mouse) after one injection of cytosine arabinonucleoside prevent CFU-S recruitment into DNA synthesis.
Recursive estimation of generative models of video (2006)

In this paper we present a generative model and learning procedure for unsupervised video clustering into scenes. The work addresses two important problems: realistic modeling of the sources of variability in the video and fast transformation invariant frame clustering. We suggest a solution to the problem of computationally intensive learning in this model by combining the recursive model estimation, fast inference, and on-line learning. Thus, we achieve real time frame clustering performance. Novel aspects of this method include an algorithm for the clustering of Gaussian mixtures, and the fast computation of the KL divergence between two mixtures of Gaussians. The efficiency and the performance of clustering and KL approximation methods are demonstrated. We also present novel video browsing tool based on the visualization of the variables in the generative model.
Arabidopsis H + -PPase AVP1 Regulates Auxin-Mediated Organ Development (2005)

The transport of auxin controls developmental events in plants. Here, we report that in addition to maintaining vacuolar pH, the H+-pyrophosphatase, AVP1, controls auxin transport and consequently auxin-dependent development. AVP1 overexpression results in increased cell division at the onset of organ formation, hyperplasia, and increased auxin transport. In contrast, avp1-1 null mutants have severely disrupted root and shoot development and reduced auxin transport. Changes in the expression of AVP1 affect the distribution and abundance of the P-adenosine triphosphatase and Pinformed 1 auxin efflux facilitator, two proteins implicated in auxin distribution. Thus, AVP1 facilitates the auxin fluxes that regulate organogenesis.
A plasmocyte selective monoclonal antibody (B‐B4) recognizes syndecan‐1 (1996)

We developed a new monoclonal antibody. B-B4, which specifically identifies human plasma cells. It strongly reacts with all multiple myeloma cell lines and with malignant plasma cells of all tumour samples of the multiple myeloma patients tested. B-B4 does not react with any peripheral blood, bone marrow or tonsil cells. Cloning of the B-B4 antigen reveals that the monoclonal antibody recognizes syndecan-1. It appears that the monoclonal antibody B-B4 is a suitable marker for human plasmocyte identification among haemopoietic cells and a useful probe for the diagnosis of haematological malignancies. Furthermore, this monoclonal antibody can be used for depletions prior to CD34 grafting.
DNA-binding Proteins of Chick Embryo Lethal Orphan Virus: Lack of Complementation between Early Proteins of Avian and Human Adenoviruses (1984)

Chick cells infected by chick embryo lethal orphan (CELO) virus (fowl adenovirus type 1) contained four prominent virus-specific, structurally related DNA-binding proteins with mol. wt. of 74K, 64K, 56K, 52K, and two minor forms. The CELO virus DNA-binding proteins were phosphorylated, delayed-early nuclear proteins. CELO virus early proteins were expressed in BHK cells, but did not complement human adenovirus type 5 mutants with lesions E1A, E2A or E2B. Moreover, CELO virus DNA-binding proteins were not produced in 293 cells, which express human adenovirus E1 genes. These results suggest that activation of transcription by adenovirus E1A genes involves specific interactions between the E1A gene products and viral early promoters.
Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. (1992)

The immunosuppressive agents cyclosporin A (CsA) and FK 506 bind to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK 506-binding proteins (FKBPs). Recently, it has been shown that, in vitro, the complexes of CsA-cyclophilin and FK 506-FKBP-12 bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase. We have investigated the effects of drug treatment on phosphatase activity in T lymphocytes. Calcineurin is expressed in T cells, and its activity can be measured in cell lysates. Both CsA and FK 506 specifically inhibit cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. Rapamycin, which binds to FKBPs but exhibits different biological activities than FK 506, has no effect on calcineurin activity. Furthermore, excess concentrations of rapamycin prevent the effects of FK 506, apparently by displacing FK 506 from FKBPs. These results show that calcineurin is a target of drug-immunophilin complexes in vivo and establish a physiological role for calcineurin in T-cell activation.
Elevated Mitochondrial Reactive Oxygen Species Generation Affects the Immune Response via Hypoxia-Inducible Factor-1α in Long-Lived Mclk1 +/− Mouse Mutants (2009)

Mitochondrial reactive oxygen species (ROS) are believed to stabilize hypoxia-inducible factor (HIF)-1alpha, a transcriptional regulator of the immune response. Mclk1 encodes a mitochondrial protein that is necessary for ubiquinone biosynthesis. Heterozygote Mclk1(+/-) mutant mice are long-lived despite increased mitochondrial ROS and decreased energy metabolism. In this study, Mclk1(+/-) mutant mice in the C57BL/6J background displayed increased basal and induced expression of HIF-1alpha in liver and macrophages in association with elevated expression of inflammatory cytokines, in particular TNF-alpha. Mutant macrophages showed increased classical and decreased alternative activation, and mutant mice were hypersensitive to LPS. Consistent with these observations in vivo, knock-down of Mclk1 in murine RAW264.7 macrophage-like cells induced increased mitochondrial ROS as well as elevated expression of HIF-1alpha and secretion of TNF-alpha. We used an antioxidant peptide targeted to mitochondria to show that altered ROS metabolism is necessary for the enhanced expression of HIF-1alpha, which, in turn, is necessary for increased TNF-alpha secretion. These findings provide in vivo evidence for the action of mitochondrial ROS on HIF-1alpha activity and demonstrate that changes in mitochondrial function within physiologically tolerable limits modulate the immune response. Our results further suggest that altered immune function through a limited increase in HIF-1alpha expression can positively impact animal longevity.
Diagnosis and Management of Thyroid Disease and the Critically Ill Patient (2004)

Abnormal thyroid function tests are commonly found in the critically ill patient and do not require treatment. However, hypothyroid and hyperthyroid states may present with acute cardiorespiratory failure and require careful and specific management strategies to resolve the thyroid disorder.
Interleukin-18 (2003)

Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-gamma (IFN-gamma)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-gamma production by murine splenocytes [(1) ]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [(2) ]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [(3) ] and showed that both contain an unusual leader sequence consisting of 35 amino acids at their N terminus.
Treatment with controlled-release lovastatin decreases serum concentrations of human β-amyloid (Aβ) peptide (2001)

The deposition of beta-amyloid (A beta) in neuronal plaques is believed to be crucial for the initiation and progression of Alzheimer's disease (AD). Studies in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or its active metabolite lovastatin acid, lowers A beta production. To examine the effects of lovastatin on A beta in vivo, human subjects who had elevated low-density lipoprotein cholesterol were treated during a double-blind, randomized, placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a controlled-release formulation of lovastatin, or matching placebo. Serum A beta concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum A beta concentrations showed a dose-dependent decrease, and analysis of variance indicated that treatment was statistically significant (p < 0.0348). Differences between the 40- and 60-mg dose groups and placebo were statistically significant (Dunnett's p < or = 0.05).
Purification of a pituitary receptor for somatostatin. The utility of biotinylated somatostatin analogs. (1992)

A somatostatin (SRIF) receptor and its associated Gi regulatory proteins was purified from GH4C1 rat pituitary cells by: 1) saturation of the membrane-bound receptor with biotinyl-NH-[Leu8,D-Trp22,Tyr25] SRIF28 (bio-S28); 2) solubilization of receptor-ligand (R.L) complex with deoxycholate-lysophosphatidylcholine (D.L); 3) adsorption of solubilized receptor-ligand complex to immobilized streptavidin; and 4) elution of receptor and G-protein by GTP. The receptor, a glycoprotein with an average M(r) of 85,000, was then purified to substantial homogeneity on immobilized wheat germ agglutinin. The 85-kDa glycoprotein was identified as a SRIF receptor by several criteria. (a) It had the same size as the chemically cross-linked R.[125I]L complex. (b) Yield of the purified protein increased and plateaued in the same range of bio-S28 concentrations where specific high affinity binding reached saturation. (c) It was copurified with appropriate G-protein subunits. The 85-kDa receptor and two other proteins with M(r) values of 35,000 and 40,000, the sizes of G beta and G alpha, did not appear in eluates from control streptavidin columns done with SRIF receptors loaded with nonbiotinylated S14. The 40-kDa protein was identified as a Gi alpha by ADP-ribosylation from [32P]NAD catalyzed by pertussis toxin. (d) Both the chemically cross-linked R.[125I]L complex and SRIF receptor purified from [35S]methionine-labeled GH4C1 cells were reduced in size to about 38 kDa by endoglycosidase F. (e) Amino acid sequence from the purified receptor was nearly identical with that of a recently cloned SRIF receptor subtype.
Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord (2007)

Spina bifida, which results from failure of fusion in the spinal region of neural tube, is among the most common birth defects associated with diabetic pregnancy. However, the mechanism underlying maternal diabetes-induced congenital malformations including spina bifida is not fully understood. It was hypothesized that hyperglycemic conditions affect the proliferation and apoptosis of neural progenitor cells in the developing spinal neural tube, leading to abnormal neurodevelopment. In the present study, biological processes such as proliferation and apoptosis were investigated in the neuroepithelial cells of the developing spinal neural tube of embryos from diabetic mice, and in embryonic spinal neural tube derived neural progenitor cell cultures exposed to high glucose in vitro. Maternal diabetes caused decreased proliferation and increased apoptosis of the neuroepithelial cells in the developing spinal cord of embryos from diabetic mouse. Decreased proliferation and increased apoptosis were also found in neural progenitor cells exposed to high glucose. In addition, high glucose-induced apoptosis in neural progenitor cells was associated with activation of caspase-3. Thus, high glucose disturbs both proliferation and cell death of neural progenitors in the developing spinal neural tube. This could provide a cellular mechanism by which maternal hyperglycemia induces spina bifida in embryos from diabetic pregnancy.
Synthesis and electrochemical behaviors of layered Na0.67[Mn0.65Co0.2Ni0.15]O2 microflakes as a stable cathode material for sodium-ion batteries (2013)

Stable Na+ ion storage cathodes with adequate reversible capacity are now greatly needed for enabling Na-ion battery technology for large scale and low cost electric storage applications. In light of the superior Li+ ion storage performance of layered oxides, pure P2-phase Na0.67[Mn0.65Ni0.15Co0.2]O2 microflakes are synthesized by a simple sol–gel method and tested as a Na+ ion storage cathode. These layered microflakes exhibit a considerably high reversible capacity of 141 mA h g−1 and a slow capacity decay to 125 mA h g−1 after 50 cycles, showing much better cyclability than previous NaMnO2 compounds. To further enhance the structural and cycling stability, we partially substituted Co3+ by Al3+ ions in the transition-metal layer to synthesize Na0.67[Mn0.65Ni0.15Co0.15Al0.05]O2. As expected, the Al-substituted material demonstrates a greatly improved cycling stability with a 95.4% capacity retention over 50 cycles, possibly serving as a high capacity and stable cathode for Na-ion battery applications.