gebhart/patrepeval huggingface dataset:
Common active site architecture and binding strategy of four phenylpropanoid P450s from Arabidopsis thaliana as revealed by molecular modeling (2003)

Despite extensive primary sequence diversity, crystal structures of several bacterial cytochrome P450 monooxygenases (P450s) and a single eukaryotic P450 indicate that these enzymes share a structural core of alpha-helices and beta-sheets and vary in the loop regions contacting individual substrates. To determine the extent to which individual structural features are conserved among divergent P450s existing in a single biosynthetic pathway, we have modeled the structures of four highly divergent P450s (CYP73A5, CYP84A1, CYP75B1, CYP98A3) in the Arabidopsis phenylpropanoid pathway synthesizing lignins, flavonoids and anthocyanins. Analysis of these models has indicated that, despite primary sequence identities as low as 13%, the structural cores and several loop regions of these P450s are highly conserved. Substrate docking indicated that all four enzymes employ a common strategy to identify their substrates in that their cinnamate-derived substrates align along helix I with their aromatic ring positioned towards the C-terminus of this helix and their aliphatic tails positioned towards the N-terminus. Further similarity was observed in the way the substrates contact the consensus P450 substrate recognition sites (SRS). Residues predicted to contact the aromatic ring region exist in SRS5, SRS6 and the C-terminal portion of SRS4 and residues contacting the distal end of each substrate exist in SRS1, SRS2 and the N-terminal portion of SRS4. Alignments of the regions contacting the aromatic ring region indicate that SRS4, SRS5 and SRS6 share higher degrees of sequence conservation than found in SRS1, SRS2 or the full-length protein.
Up-regulation of CC chemokine ligand 20 and its receptor CCR6 in the lesional skin of early systemic sclerosis (2011)

Mononuclear cell (MNC) infiltrate is one of the earliest pathological changes in systemic sclerosis (SSc) skin. However, little is known about the recruitment of these cells into skin lesions. Recently, the role of chemokines has been suggested in the pathogenesis of SSc. Here we studied the expressions and distributions of CC chemokine CCL20 and its receptor CCR6 in early SSc skin lesions and the difference in CCL20 expressions and ability to recruite MNCs of normal dermal fibroblast (NDF) and scleroderma dermal fibroblast (SSDF). We found that the expressions of CCL20 and its receptor CCR6 were obviously up-regulated in SSc in contrast to normal human skin. mRNA levels were significantly expressed in SSc lesional skins vs normal skin tissues. SSDF displayed increased constitutive expressions of CCL20 mRNA and protein. In addition, Th1 cytokines (TNF-α and IL-1β) remarkably increased the expression of CCL20 in both NDF and SSDF in a dose- and time-dependent manner. Supernatants from SSDF showed stronger chemotactic activity to PBMCs than those from NDF. Thus our findings suggest that CCL20 released from cytokine-activated SSDF plays an important role in the induction of SSc by further recruiting more MNCs to the skin.
Adjuvant bacillus Calmette-Guérin therapy in non-Hodgkin's malignant lymphomas: long-term results of a randomized trial in a single institution. (1990)

Between 1973 and 1977, 48 patients less than 65 years old with non-Hodgkin's malignant lymphoma (NHML) of poor prognosis (+/- high grade malignancy, +/- clinical stages III or IV, +/- first or repeated relapse) were included in a prospective clinical trial. After complete remission (CR), obtained with chemotherapy and radiotherapy, patients were randomized to receive bacillus Calmette-Guérin (BCG) or no further therapy. BCG was administered in weekly scarifications up to 3 years. Forty-three patients are assessable. Twenty-four patients have relapsed: nine out of 21 in the BCG group, and 15 out of 22 in the control group. There is a significant difference in favor of the BCG group in disease-free survival (P = .03). Twenty-one patients have died, 18 from NHML: seven in the BCG group, and 11 in the control group. There is a significant difference in favor of the BCG group for overall survival at 10 years (P = .05). A multivariate analysis points out BCG as a significant prognostic factor. Adjuvant BCG may improve particularly disease-free survival and overall survival for patients with clinical stages I and II or intermediate- and high-grade malignancy. These results suggest that in patients less than 65 years old with NHML of poor prognosis, BCG may significantly increase disease-free survival and overall survival.
The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing (1999)

To study gene expression in differentiated adult motoneuron subtypes, we used fluorescent dextrans for both anterograde and retrograde axonal tracing in adult rat and mouse. Application of these dyes to the cut distal and proximal ends of small extramuscular nerve branches revealed both the peripheral ramifications and the cell bodies of subsets of motoneurons. We show that the soleus muscle is innervated by two nerve branches, one of which contains gamma motor and sensory axons but no alpha motor axons. By retrograde tracing of this branch, we selectively labelled gamma motoneurons. In adult rat, the nerves innervating the soleus and extensor digitorum longus muscles contain almost exclusively axons innervating slow (type I) and fast (type 2) muscle fibres, respectively. We selectively labelled slow and fast type motoneurons by retrograde tracing of these nerves. With immunocytochemistry we show that adult motoneurons express several homeodomain genes that are associated with motoneuron differentiation during early embryonic development. Combining selective retrograde labelling with immunocytochemistry we compared the expression patterns in alpha and gamma motoneurons. The homeodomain transcription factors Islet 1 and HB9 were expressed in slow and fast alpha motoneurons and in soleus gamma motoneurons. Motoneurons in each population varied in their intensity of the immunostaining, but no factor or combination of factors was unique to any one population.
Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody (2016)

Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.
Salmonella typhimurium aroA recombinants and immune-stimulating complexes as vaccine candidates for feline immunodeficiency virus. (1997)

Two experimental feline immunodeficiency virus (FIV) vaccines were tested, either alone or in combination, in four groups of cats (A-D). One vaccine (SL3261-FIV) was composed of live attenuated Salmonella typhimurium aroA (SL3261) strains expressing the capsid (Gag) and part of the envelope (Env) proteins of FIV. The other was composed of FIV Gag and Env proteins incorporated into immune-stimulating complexes (iscom-FIV). Cats of group A were immunized four times with SL3261-FIV. Cats of group B were immunized twice with SL3261-FIV and then twice with iscom-FIV. Cats of group C were immunized twice with SL3261 expressing the B subunit of cholera toxin (SL3261-CtxB) and then twice with iscom-FIV. Cats of group D, which served as negative controls, were immunized twice with SL3261-CtxB and then twice with iscom into which the Gag and Env proteins of simian immunodeficiency virus (SIV) had been incorporated (iscom-SIV). Two weeks after the last immunization, all cats were challenged with FIV. At this time, cats immunized with iscom-FIV (groups B and C) showed strong plasma antibody responses to Gag and Env, whilst these responses were weak or undetectable in the cats immunized four times with SL3261-FIV (group A). Seven weeks after FIV challenge, Env-specific antibody responses had increased considerably in cats of all groups except group A. The mean virus loads in the cats of this group proved to be lower than those of the other groups at all time points, indicating partial protection.
Cytotoxicity of N<sup>6</sup>-Cycloalkylated Adenine and Adenosine Analogs to Mouse Hepatoma Cells (1989)

Cytotoxic effect(s) of N6-cycloalkylated adenine and adenosine derivatives, upon the viability of mouse hepatoma cells, were studied in vitro. N6-Cyclopropyl- and N6-cyclobutyladenine and adenosine derivatives (33 micrograms/ml; 24-48 h) exerted significant cytotoxic effects upon the cells. N6-Cyclopentyl- and N6-cyclohexyladenines exerted similar effects under different experimental conditions (133-166 micrograms/ml; 48-72 h), while no significant cytotoxic effect(s) were observed with the corresponding adenosine derivatives under these conditions. Observed physical changes in the treated cells included cell elongation, short stubby filaments, wide intracellular spaces and ruptured cell membranes. N6-Cycloalkylated nucleosides were usually more cytotoxic than the cycloalkylated bases.
Potential antidepressant activity of sigma ligands. (2004)

Despite many years' studies of antidepressant drugs (ADs), their mechanism of action still remains unclear. Recently, it has been postulated that substances capable of reducing neurotransmission at the NMDA complex may represent a new class of ADs. Since several ADs have a high affinity for sigma receptors, the sigma binding site may be a relevant mechanism in antidepressant action. Moreover, sigma ligands are able to modulate the activity of the central neurotransmitter systems, including noradrenergic, serotonergic, dopaminergic and glutamatergic (NMDA) ones, which are seemingly important for the mechanism of action of known ADs. The existence of at least two different subtypes of sigma receptors, denoted sigma1 and sigma2 is now widely accepted. The selective agonists of both sigma receptor subtypes are available at present. In particular, a potential antidepressant activity of sigma1 receptor agonists has been postulated, since the antidepressive-like actions of these compounds have been shown in animal models. This article reviews the findings related to potential antidepressant activity of new, selective sigma ligands.
NFV Service Density Benchmarking (2019)

Network Function Virtualization (NFV) system designers and operators
continuously grapple with the problem of qualifying performance of
network services realised with software Network Functions (NF) running
on Commercial-Off-The-Shelf (COTS) servers. One of the main challenges
is getting repeatable and portable benchmarking results and using them
to derive deterministic operating range that is production deployment
worthy. This document specifies benchmarking methodology for NFV
services that aims to address this problem space. It defines a way for
measuring performance of multiple NFV service instances, each composed
of multiple software NFs, and running them at a varied service
packing density on a single server. The aim is to discover
deterministic usage range of NFV system. In addition specified
methodology can be used to compare and contrast different NFV
virtualization technologies.
Poética del café (1994)

K-sam, also designated fibroblast growth factor receptor 2/BEK, was originally cloned from a stomach cancer cell line KATO-III. The gene is amplified and overexpressed preferentially in poorly differentiated types of stomach cancers. The major K-sam transcript in KATO-III cells encodes a receptor protein with a truncated carboxyl terminus and with a high-affinity binding site for keratinocyte growth factor. This truncated type is produced by an alternative splicing mechanism, and in normal tissues, the truncated type is far less prevalent than the untruncated form. The variant K-sam complementary DNA lacks tyrosine 769, which is a putative phospholipase C gamma 1 association site, and showed a higher transforming activity to NIH3T3 cells than the untruncated form, which is identical with the keratinocyte growth factor receptor.
Up-Regulation of MUC18 in Airway Epithelial Cells by IL-13 (2011)

Airway bacterial infections are a major problem in lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Increased Th2 cytokines, such as IL-13, are observed in lung diseases and may contribute to bacterial infections. How Th2 cytokines affect bacterial infection remains unknown. MUC18, an adhesion molecule shown to be involved in the pathogenesis of malignant melanoma, has been recently identified in airway epithelial cells of patients with COPD. We investigated MUC18 regulation by IL-13 and the role of MUC18 in bacterial adherence to epithelial cells. Human airway tissues, brushed bronchial epithelial cells from normal subjects and subjects with asthma, and epithelial cell lines (e.g., HEK293 cells) were used to study the regulation of MUC18 by IL-13 and the involvement of MUC18 in bacterial (e.g., Mycoplasma pneumoniae [Mp] and nontypeable Haemophilus influenzae [NTHi]) adherence to epithelial cells. Asthmatic bronchial epithelium expressed higher levels of MUC18 than normal bronchial epithelium. IL-13 increased MUC18 in cultured bronchial epithelial cells from normal subjects and particularly from subjects with asthma. IL-13-induced MUC18 expression may be modulated in part through transcription factor specificity protein 1. Overexpression of human MUC18 in HEK293 cells increased cell-associated Mp and NTHi levels. Moreover, MUC18 was shown to directly interact with Mp and NTHi. These results for the first time show that an allergic airway milieu (e.g., IL-13) increases MUC18 expression, which may contribute to increased bacterial infection/colonization in asthma and other lung diseases.
Sequence and structural requirements of a mitochondrial protein import signal defined by saturation cassette mutagenesis. (1989)

The Saccharomyces cerevisiae F1-ATPase beta subunit precursor contains redundant mitochondrial protein import information at its NH2 terminus (D. M. Bedwell, D. J. Klionsky, and S. D. Emr, Mol. Cell. Biol. 7:4038-4047, 1987). To define the critical sequence and structural features contained within this topogenic signal, one of the redundant regions (representing a minimal targeting sequence) was subjected to saturation cassette mutagenesis. Each of 97 different mutant oligonucleotide isolates containing single (32 isolates), double (45 isolates), or triple (20 isolates) point mutations was inserted in front of a beta-subunit gene lacking the coding sequence for its normal import signal (codons 1 through 34 were deleted). The phenotypic and biochemical consequences of these mutations were then evaluated in a yeast strain deleted for its normal beta-subunit gene (delta atp2). Consistent with the lack of an obvious consensus sequence for mitochondrial protein import signals, many mutations occurring throughout the minimal targeting sequence did not significantly affect its import competence. However, some mutations did result in severe import defects. In these mutants, beta-subunit precursor accumulated in the cytoplasm, and the yeast cells exhibited a respiration defective phenotype. Although point mutations have previously been identified that block mitochondrial protein import in vitro, a subset of the mutations reported here represents the first single missense mutations that have been demonstrated to significantly block mitochondrial protein import in vivo. The previous lack of such mutations in the beta-subunit precursor apparently relates to the presence of redundant import information in this import signal. Together, our mutants define a set of constraints that appear to be critical for normal activity of this (and possibly other) import signals. These include the following: (i) mutant signals that exhibit a hydrophobic moment greater than 5.5 for the predicted amphiphilic alpha-helical conformation of this sequence direct near normal levels of beta-subunit import (ii) at least two basic residues are necessary for efficient signal function, (iii) acidic amino acids actively interfere with import competence, and (iv) helix-destabilizing residues also interfere with signal function. These experimental observations provide support for mitochondrial protein import models in which both the structure and charge of the import signal play a critical role in directing mitochondrial protein targeting and import.
Regulatory T cells: prospective for clinical application in hematopoietic stem cell transplantation (2005)

Better understanding of the mechanisms of suppression mediated by regulatory T cells might enable their use to modulate specific immune responses. Moreover, the recent development of methods allowing the ex-vivo expansion of regulatory T cells, to provide sufficient number of cells for in-vivo infusion, represents the first step toward the use of these cells as cellular therapy for the treatment of immunologic and hematological diseases.
Scarecrow Plays a Role in Establishing Kranz Anatomy in Maize Leaves (2012)

More than a quarter of the primary productivity on land, and a large fraction of the food that humans consume, is contributed by plants that fix atmospheric CO(2) by C(4) photosynthesis. It has been estimated that transferring the C(4) pathway to C(3) crops could boost yield by 50% and also increase water use efficiency and reduce the need for fertilizer, particularly in dry, hot environments. The high productivity of maize (Zea mays), sugarcane (Saccharum spp.) and several emerging bioenergy grasses is due largely to C(4) photosynthesis, which is enabled by the orderly arrangement, in concentric rings, of specialized bundle sheath and mesophyll cells in leaves in a pattern known as Kranz anatomy. Here we show that PIN, the auxin efflux protein, is present in the end walls of maize bundle sheath cells, as it is in the endodermis of the root. Since this marker suggests the expression of endodermal genetic programs in bundle sheath cells, we determined whether the transcription factor SCARECROW, which regulates structural differentiation of the root endodermis, also plays a role in the development of Kranz anatomy in maize. Mutations in the Scarecrow gene result in proliferation of bundle sheath cells, abnormal differentiation of bundle sheath chloroplasts, vein disorientation, loss of minor veins and reduction of vein density. Further characterization of this signal transduction pathway should facilitate the transfer of the C(4) trait into C(3) crop species, including rice.
Influenza virus-like particle vaccines (2009)

Enveloped virus-like particle (VLP) vaccines containing influenza hemagglutinin (HA) and neuraminidase (NA) antigens are produced easily in insect or mammalian cells via the simultaneous expression of HA and NA along with a viral core protein, such as influenza matrix (M1) or a retroviral Gag protein. The size and shape of the resulting particles are dictated by the choice of the core component, but M1- and Gag-based VLPs are strongly immunogenic and protective in seasonal and highly pathogenic influenza challenge models. Current data are consistent with the hypothesis that influenza VLP vaccine efficacy is related to the particulate, multivalent composition coupled with the presence of correctly folded antigens with intact biological activities. This new influenza vaccine paradigm offers potential advantages over the conventional egg-based, split-vaccine platform in terms of enhanced immunogenicity and better breadth of protection.
Learning Deep Context-aware Features over Body and Latent Parts for Person Re-identification (2017)

Person Re-identification (ReID) is to identify the same person across different cameras. It is a challenging task due to the large variations in person pose, occlusion, background clutter, etc How to extract powerful features is a fundamental problem in ReID and is still an open problem today. In this paper, we design a Multi-Scale Context-Aware Network (MSCAN) to learn powerful features over full body and body parts, which can well capture the local context knowledge by stacking multi-scale convolutions in each layer. Moreover, instead of using predefined rigid parts, we propose to learn and localize deformable pedestrian parts using Spatial Transformer Networks (STN) with novel spatial constraints. The learned body parts can release some difficulties, eg pose variations and background clutters, in part-based representation. Finally, we integrate the representation learning processes of full body and body parts into a unified framework for person ReID through multi-class person identification tasks. Extensive evaluations on current challenging large-scale person ReID datasets, including the image-based Market1501, CUHK03 and sequence-based MARS datasets, show that the proposed method achieves the state-of-the-art results.
The Effect of Osteoclastic Activity on Tendon-to-Bone Healing (2007)

Osteoprotegerin significantly improves bone formation around the grafted tendon and improves the stiffness at the healing tendon-bone junction in a rabbit model.
Gene Expression Profiles in Formalin-Fixed, Paraffin-Embedded Tissues Obtained with a Novel Assay for Microarray Analysis (2004)

Gene expression profiling using microarrays has revolutionized the analysis of biological samples. In clinical applications, microarray data have been used to successfully distinguish among patients exhibiting similar symptoms (1)(2). Early demonstrations of this power were in the diagnosis of subtypes of acute leukemia (3) and diffuse large B-cell lymphomas (4), and such analyses are gradually gaining acceptance for diagnostic and prognostic applications (5)(6)(7). Investigators are currently accumulating microarray data for a broad assortment of such studies but are limited by the requirement of fresh/frozen tissues for sample preparation and labeling (8). This limitation requires the accumulation of fresh samples throughout the course of the disease, which may involve years of monitoring. However, formalin-fixed, paraffin-embedded (FFPE) tissues are widely available and have the advantage of a known patient outcome and drug response history. RNAs derived from these samples are commonly badly degraded and have not been useful for conventional microarray studies (9)(10). We applied a novel expression assay to simultaneously monitor 502 cancer-related genes in RNAs derived from FFPE samples, using microarrays assembled on fiber optic bundles. Our results suggest that this approach can be used for extending microarray analyses to RNAs derived from archival tissue samples.

We have recently developed a gene expression method called the DASL™ assay (cDNA-mediated annealing, selection, extension, and ligation) (11). This assay targets gene-specific sequences, using pools of chimeric query oligonucleotides. The oligonucleotides all share common primer landing sites so that once the upstream oligonucleotide is extended and ligated to the downstream oligonucleotide, an amplifiable product is generated. One PCR primer pair is used to amplify all of the amplifiable templates and generate amplicons of similar size (∼100 bp). This uniformity minimizes potential bias during amplification of many different targets. Currently, the DASL assay can be multiplexed …