gebhart/patrepeval huggingface dataset:
eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences (2015)

eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de.
Leveraging Enzyme Structure−Function Relationships for Functional Inference and Experimental Design:  The Structure−Function Linkage Database (2006)

The study of mechanistically diverse enzyme superfamilies-collections of enzymes that perform different overall reactions but share both a common fold and a distinct mechanistic step performed by key conserved residues-helps elucidate the structure-function relationships of enzymes. We have developed a resource, the structure-function linkage database (SFLD), to analyze these structure-function relationships. Unique to the SFLD is its hierarchical classification scheme based on linking the specific partial reactions (or other chemical capabilities) that are conserved at the superfamily, subgroup, and family levels with the conserved structural elements that mediate them. We present the results of analyses using the SFLD in correcting misannotations, guiding protein engineering experiments, and elucidating the function of recently solved enzyme structures from the structural genomics initiative. The SFLD is freely accessible at http://sfld.rbvi.ucsf.edu.
Enzyme-Therapy Approaches for the Treatment of Drug Overdose and Addiction (2010)

“Recent progress in the study of cocaine-metabolizing enzymes demonstrates that enzyme-therapy approaches using appropriately designed enzymes show promise for the treatment of drug overdose and addiction.”
Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning (2019)

ABSTRACT Nanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5’ and 3’ ends of reads, which complicates sequence-based barcode demultiplexing. Here, we propose a novel strategy to barcode and demultiplex direct RNA sequencing nanopore data, which does not rely on base-calling or additional library preparation steps. Specifically, custom DNA oligonucleotides are ligated to RNA transcripts during library preparation. Then, raw current signal corresponding to the DNA barcode is extracted and transformed into an array of pixels, which is used to determine the underlying barcode using a deep convolutional neural network classifier. Our method, DeePlexiCon , implements a 20-layer residual neural network model that can demultiplex 93% of the reads with 95.1% specificity, or 60% of reads with 99.9% specificity. The availability of an efficient and simple barcoding strategy for native RNA sequencing will enhance the use of direct RNA sequencing by making it more cost-effective to the entire community. Moreover, it will facilitate the applicability of direct RNA sequencing to samples where the RNA amounts are limited, such as patient-derived samples.
Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology (2000)

Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate-putamen (striatum). In a clinical trial of human fetal striatal tissue transplantation, one patient died 18 months after transplantation from cardiovascular disease, and postmortem histological analysis demonstrated surviving transplanted cells with typical morphology of the developing striatum. Selective markers of both striatal projection and interneurons such as dopamine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, choline acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and substance P showed positive transplant regions clearly innervated by host tyrosine hydroxylase fibers. There was no histological evidence of immune rejection including microglia and macrophages. Notably, neuronal protein aggregates of mutated huntingtin, which is typical HD neuropathology, were not found within the transplanted fetal tissue. Thus, although there is a genetically predetermined process causing neuronal death within the HD striatum, implanted fetal neural cells lacking the mutant HD gene may be able to replace damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue can survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD.
Conversion of lysine 91 to methionine or glutamic acid in human choriogonadotropin alpha results in the loss of cAMP inducibility. (1991)

Human choriogonadotropin (hCG) is a heterodimeric glycoprotein hormone. The alpha subunit comprises 92 amino acids, of which 6 are Lys residues (Morgan, F.G., Birken, S., and Canfield, R.E. (1975) J. Biol. Chem. 250, 5247-5258). Our photoaffinity-labeling studies indicate that several of these Lys residues make contact with the lutropin receptor and are covalently cross-linked to the receptor. Lys-91 of the alpha subunit is of interest because deletion of the two alpha C-terminal residues, Lys-91 and Ser-92, results in a significant reduction in the bioactivity of lutropin and thyrotropin (Cheng, K.-W., Glazer, A.N., and Pierce, J.G. (1973) J. Biol. Chem. 248, 7930-7937). To determine the importance of Lys-alpha 91, we substituted it with Arg, Met, or Glu. The resulting mutant alpha cDNA constructs were co-transfected into CHO cells with the wild type hCG beta cDNA construct. Secreted hCG dimers were assayed for binding to receptors on porcine granulosa cells and stimulation of cAMP synthesis in a murine Leydig tumor cell line. The natural hCG, wild type hCG, and all mutant hCGs recognized the receptor, although with somewhat divergent affinities. However, there was a striking difference in the ability of cAMP induction. The natural hCG, wild type hCG, and Lys-91----Arg mutant hCG induced cAMP synthesis, whereas the Lys-91----Met and Lys-91----Glu mutants did not. These results demonstrate that Lys-91 is important for receptor modulation in the stimulation of cAMP synthesis.
CD28-independent, TRAF2-dependent Costimulation of Resting T Cells by 4-1BB Ligand (1998)

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.
Slow Breathing Increases Arterial Baroreflex Sensitivity in Patients With Chronic Heart Failure (2002)

These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.
Characterization of Natural and Technical Lignins using FTIR Spectroscopy (2008)

Characterization of lignins is an extremely difficult task because of their diversity in respect both to source and extraction method. In the present work, the possibility to use infrared spectroscopy instead of chemical analysis to characterize the changes in the functional groups of lignin during cooking was evaluated and a library of infrared spectra from different lignin samples was created. Lignin samples from different sources were obtained under different cooking conditions and the structure of the functional groups of the samples were determined by both chemical methods and infrared spectroscopy. Two different types of cooking procedures were carried out resulting in 24 lignin samples. The changes in the functional groups during cooking were determined and analysed and the results obtained with chemical- and spectroscopic methods were compared. The results of the work shows that, with the methods employed in the present work, it is not possible to use infrared-spectroscopy instead of chemical analysis to characterize the changes in the functional groups of lignin during cooking.
Hydrodynamic properties of rodlike and disklike particles in dilute solution (2003)

The hydrodynamic properties of cylindrical (rodlike and discoidal) particles in dilute solution have been computed using the bead-shell model treatment. Previous results [Tirado and Garcı́a de la Torre, J. Chem. Phys. 71, 2581 (1979); 73, 1993 (1980)] for rods with length-to-diameter ratio p&amp;gt;2 are now extended to short cylinders and disks down to p=0.1. The intrinsic viscosity is obtained for rods and disks, and results are presented for the three rotational relaxation times of a cylindrical particle. The hydrodynamic properties are expressed in forms that have a weak variation with p, and are therefore useful for the analysis of experimental values. We present examples of the determination of the length and diameter of the cylindrical particles, for DNA oligonucleotides and tobacco mosaic virus.
Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. (1998)

Angiogenesis is a crucial step in the growth and metastasis of cancers. Curcumin inhibits tumor initiation and growth. We analyzed the effect of curcumin on endothelial cell migration, attachment, and tube formation on Matrigel. Curcumin had no effect on endothelial cell migration or attachment to either plastic or Matrigel. Curcumin treatment resulted in a dose-dependent inhibition of tube formation when the cells were treated before plating or at the time of plating on Matrigel. Curcumin treatment also caused the preformed tubes to break down. Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice. The role of metalloproteinases has been shown to be important in angiogenesis; therefore, zymography was performed to determine whether curcumin affected protease activity. Zymographs of curcumin-treated culture supernatants showed a decrease in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases. Western and Northern analysis showed a dose-dependent decrease in the protein expression and transcript of 72 kDa, indicating that curcumin may be exerting its inhibitory effect at both the transcriptional and posttranscriptional level. These findings suggest that curcumin acts as an angiogenesis inhibitor by modulating protease activity during endothelial morphogenesis. Curcumin could be developed as an antiangiogenic drug.
Phase transition of liquid‐crystalline polyesters with biphenyl mesogen under high pressures (1993)

Abstract The structural and thermal behavior of liquid‐crystalline polyesters at hydrostatic pressure was investigated by using a high‐pressure DTA and a wide‐angle X‐ray scattering apparatus equipped with a high‐pressure sample vessel. The thermotropic polyesters (two homopolymers and the corresponding copolymer) are based upon 4,4′‐biphenyldiol as the mesogen and aliphatic dibasic acids containing 7 and 8 methylene groups as flexible spacer, which are labeled as PB‐7, PB‐8, and PB‐7,8 (30/70 mol‐%), respectively. The phase diagrams of the PB‐7, PB‐8 and PB‐7,8 samples were constructed for pressures up to 300 MPa. At room temperature both the PB‐7 and the PB‐8 crystals are compressed hydrostatically in the molecular chain and lateral packing directions. The d spacing of the low‐angle reflection of the PB‐8 crystal, corresponding to the layer spacing, decreases by about 2,6 ± 0,2 Å at the crystal (K)‐smectic H(S H ) transition under all pressures, while the crystal reflections of PB‐7 disappear at the K‐nematic (N) transition. The d spacings of the wide‐angle reflections of both crystals, corresponding to the lateral packing in the crystals, expand gradually with increasing temperature up to the K‐mesophase transition. The increase in lateral spacing of the PB‐8 crystal at the K‐S H transition changes slightly from ca. 0,29 Å at 0,1 MPa to 0,22 Å at 300 MPa. It is concluded that the transition mechanisms of the K‐S H transition of PB‐8 and the K‐N transition of PB‐7 are maintained at pressures up to 300 MPa.
Evaluating machine translation output with automatic sentence segmentation. (2005)

1. related work 2. motivation 3. state-of-the-art translation error measures 4. document-level vs. sentence-level evaluation 5. description of the algorithm 6. experimental results 7. summary
Inhibition of the conversion of 3T3 fibroblast clones to adipocytes by dehydroepiandrosterone and related anticarcinogenic steroids. (1986)

Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one; DHEA) and related steroids have widespread protective effects against spontaneous and chemically induced tumors, suppress weight gain without affecting food intake, and depress lipogenesis. We have observed that DHEA and 16 alpha-bromoepiandrosterone (16 alpha-bromo-3 beta-hydroxy-5 alpha-androstan-17-one) block the conversion to adipocytes of the 3T3-L1 and 3T3-F442A mouse embryo fibroblast clones. The arrest of lipogenic conversion was assessed by measurements of lipid biosynthesis and the specific activity of cytosolic glycerol-3-phosphate dehydrogenase. In the presence of 215 microM DHEA or 30 microM 16 alpha-bromoepiandrosterone, the increase in glycerol-3-phosphate activity was only 50% of that of fully differentiated control cells. The blocking effects were concentration dependent and were observed only if the differentiation stimuli and the blocking steroid were present simultaneously. Concentrations of these steroids that almost completely blocked conversion to adipocytes were not cytotoxic. Although the relation between structure and blocking activity of steroids is complicated by metabolism of DHEA in these cultures, a strong correlation exists between the structural requirements for blocking differentiation and for inhibition of glucose-6-phosphate dehydrogenase. The 3T3-L1 and 3T3-F442A preadipocyte clones are, therefore, appropriate and convenient model systems for the analysis of the mechanism of the anticarcinogenic effects of DHEA and related steroids.
Treatment with oral 4‐aminopyridine in disorders of neuromuscular transmission (1981)

Four patients with Eaton-Lambert syndrome, four patients with congenital myasthenia, and one patient with myasthenia gravis were treated with oral 4-aminopyridine for periods of up to 10 months, doses varying from 40 to 200 mg per day. Clinical and electrophysiologic assessment confirmed the effectiveness of the drug when given alone or in conjunction with anticholinesterases. At therapeutically effective doses, central side effects were frequent and unpredictable. Three patients had a generalized fit and one patient developed a confusional state. Adverse side effects must severely limit the place of 4-aminopyridine in the treatment of patients with these conditions.
Reaction of No With O2−. Implications for the Action of Endothelium-Derived Relaxing Factor (EDRF) (1990)

Under physiological pH conditions (pH 7.2-7.4) the rate constant of the reaction NO + O2- yielding peroxonitrite (ONOO-) was determined as k = (3.7 +/- 1.1) x 10(7) M-1 s-1. The decay of peroxonitrite at this pH follows first order kinetics with a rate constant of 1.4 s 1. At alkaline pH peroxonitrite is practically stable. Possible consequences of these reactions for the biological lifetime of EDRF will be discussed.
Unchain my heart: the scientific foundations of cardiac repair (2005)

In humans, the biological limitations to cardiac regenerative growth create both a clinical imperative--to offset cell death in acute ischemic injury and chronic heart failure--and a clinical opportunity; that is, for using cells, genes, and proteins to rescue cardiac muscle cell number or in other ways promote more efficacious cardiac repair. Recent experimental studies and early-phase clinical trials lend credence to the visionary goal of enhancing cardiac repair as an achievable therapeutic target.
Efficacy of Lithium vs. Valproate in the Treatment of Mania in the Elderly (1999)

Results suggest that lithium may be more efficacious than valproate overall, but response rates for the 2 drugs were similar when "therapeutic" serum levels were achieved. For lithium, levels similar to those reported for younger adults were associated with response. For valproate, a "therapeutic window" different from that in younger adults was found. While the retrospective and naturalistic design of this study has limitations, these data may help direct further studies and treatment of mania in the elderly.
Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers (1990)

Indirect evidence is presented that free-standing Si quantum wires can be fabricated without the use of epitaxial deposition or lithography. The novel approach uses electrochemical and chemical dissolution steps to define networks of isolated wires out of bulk wafers. Mesoporous Si layers of high porosity exhibit visible (red) photoluminescence at room temperature, observable with the naked eye under &amp;lt;1 mW unfocused (&amp;lt;0.1 W cm−2) green or blue laser line excitation. This is attributed to dramatic two-dimensional quantum size effects which can produce emission far above the band gap of bulk crystalline Si.
Preparation and Characterisation of TiO<sub>2</sub>-Supported on the Surface of SiO<sub>2</sub> (2011)

A surface TiO 2 -supported of silica composite material was prepared by surface organometallic chemistry method and the structure was characterized by FTIR, EDAX and XRD. The results show the bonding interaction between TiO 2 and SiO 2 , linking by Si-O-Ti bond. Furthermore, the anatase phase crystal structure is observed by XRD analysis.
4-1BB Ligand-Mediated Costimulation of Human T Cells Induces CD4 and CD8 T Cell Expansion, Cytokine Production, and the Development of Cytolytic Effector Function (2002)

4-1BB (CD137) is a costimulatory member of the TNFR family expressed on activated T cells. Its ligand, 4-1BBL, is expressed on activated APC. In the mouse, CD8 T cells are preferentially activated by agonistic anti-murine 4-1BB Abs. However, murine 4-1BBL can stimulate both CD4 and CD8 T cells. To date, there are only limited data on the effects of 4-1BBL on human T cell responses. To further understand the role of 4-1BBL in human T cell responses, we compared human CD4 and CD8 T cell responses to transfected human 4-1BBL plus TCR-mediated stimulation. Both human CD4 and CD8 T cells responded to 4-1BBL. The presence of 4-1BBL on the APC led to increased expansion, cytokine production, and the development of cytolytic effector function by human T cells. In unfractionated T cell cultures, CD4 and CD8 T cells could expand to a similar extent in response to signals through the TCR and 4-1BB, as measured by CFSE labeling and by quantitating T cell numbers in the cultures. In contrast to the results with total T cells, isolated CD8 T cells produced less IL-2 and expanded to a lesser extent than isolated CD4 T cells responding to 4-1BBL. Thus, 4-1BBL is most effective when both CD4 and CD8 T cells are included in the cultures. CD28 and 4-1BB were found to synergize in the induction of IL-2 by human T cells, and CTLA-Ig partially blocked 4-1BBL-dependent IL-2 production. However, a portion of the 4-1BBL-mediated effects were independent of CD28-B7 interaction.
Multisite tyrosine phosphorylation of the N‐terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein (2016)

Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate β-amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild-type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease.