gebhart/patrepeval huggingface dataset:
A Critical Role of CaBP4 in the Cone Synapse (2005)

Results indicate that the cone synaptic function in Cabp4(-/-)Gnat1(-/-) mice was severely disrupted, whereas the morphologic defects observed in Cabp4(-/-)Gnat1(-/-) mice were similar to those of single Cabp4(-/-) knockout mice. This and a previous study reveal that CaBP4 is critical for signal transmission from rods and cones to second-order neurons.
An Open, Controlled, Randomized Comparison of Cyclosporine and Azathioprine in the Treatment of Rheumatoid Arthritis: A Preliminary Report (1987)

Cyclosporine (10 mg/kg/day) and azathioprine (2.5-3 mg/kg/day) were compared for 26 weeks in an open, controlled, randomized study of 24 patients with rheumatoid arthritis. Each treatment group consisted of 12 patients. Those patients who took cyclosporine improved significantly in the 50-foot walk time, circumferences of proximal interphalangeal joints, Ritchie articular index, global assessment by investigator, and grip strength, when compared with baseline findings. In the azathioprine group, there was improvement only in grip strength.
Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide (2015)

The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the 'personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.
Inhibition of hepatitis delta virus (HDV) replication by lymphoblastoid human alpha interferon. (1987)

Lymphoblastoid interferon inhibited hepatitis delta virus (HDV) replication in four out of five HDV carriers with chronic active liver disease. Serum HDV-RNA was undetectable in three patients, but in one of these evidence of continuing intrahepatic HDV replication was present on biopsy one year after treatment. In the four cases which showed total or partial inhibition of HDV replication, there was a transient increase in transaminases during treatment, and in three this was followed by improvement. These effects lasted for longer than one year. The lysis of hepatocytes occurring on exposure to interferon may be related to the induction of 2-5A oligosynthetase which, in the presence of the dsRNA of HDV, activates endonucleases which destroy the rRNA of the infected cells.
Monoclonal antibodies against vascular endothelial growth factor 165 (VEGF165): Neutralization of biological activity and recognition of the epitope (1999)

Five antibodies against vascular endothelial growth factor 165 (VEGF165) were obtained. These antibodies, Ab-2, Ab-20, Ab-153, Ab-309, Ab-342, were able to recognize not only native VEGF165, but also reducing VEGF165. Three of the antibodies, Ab-153, Ab-309, Ab-342, were identified as VEGF165 neutralizing antibody on the basis of its ability to inhibit the proliferation of human umbilical vein endothelial cells (HUVEC) induced by VEGF165 and the binding of [125I]-VEGF165 to receptors on HUVEC. The fragments of E1 (VEGF120-135) and E2 (VEGF46-60) recognized by neutralizing antibodies may be related the receptor binding domain of VEGF.
Stem cell options for kidney disease (2008)

Chronic kidney disease (CKD) is increasing at the rate of 6-8% per annum in the US alone. At present, dialysis and transplantation remain the only treatment options. However, there is hope that stem cells and regenerative medicine may provide additional regenerative options for kidney disease. Such new treatments might involve induction of repair using endogenous or exogenous stem cells or the reprogramming of the organ to reinitiate development. This review addresses the current state of understanding with respect to the ability of non-renal stem cell sources to influence renal repair, the existence of endogenous renal stem cells and the biology of normal renal repair in response to damage. It also examines the remaining challenges and asks the question of whether there is one solution for all forms of renal disease.
M-CSF mediates TNF-induced inflammatory osteolysis (2005)

TNF-alpha is the dominant cytokine in inflammatory osteolysis. Using mice whose BM stromal cells and osteoclast precursors are chimeric for the presence of TNF receptors, we found that both cell types mediated the cytokine's osteoclastogenic properties. The greater contribution was made, however, by stromal cells that express the osteoclastogenic cytokine M-CSF. TNF-alpha stimulated M-CSF gene expression, in vivo, only in the presence of TNF-responsive stromal cells. M-CSF, in turn, induced the key osteoclastogenic cytokine receptor, receptor activator of NF-kappaB (RANK), in osteoclast precursors. In keeping with the proproliferative and survival properties of M-CSF, TNF-alpha enhanced osteoclast precursor number only in the presence of stromal cells bearing TNF receptors. To determine the clinical relevance of these observations, we induced inflammatory arthritis in wild-type mice and treated them with a mAb directed against the M-CSF receptor, c-Fms. Anti-c-Fms mAb selectively and completely arrested the profound pathological osteoclastogenesis attending this condition, the significance of which is reflected by similar blunting of the in vivo bone resorption marker tartrate-resistant acid phosphatase 5b (TRACP 5b). Confirming that inhibition of the M-CSF signaling pathway targets TNF-alpha, anti-c-Fms also completely arrested osteolysis in TNF-injected mice with nominal effect on macrophage number. M-CSF and its receptor, c-Fms, therefore present as candidate therapeutic targets in states of inflammatory bone erosion.
Effects of Ciclosporin and Protein Synthesis Inhibitors on Cutaneous Inflammation in Mouse Skin (1989)

Ciclosporin is clinically effective in a variety of inflammatory skin diseases. We have therefore studied the effects of the drug on cutaneous inflammation in mice. Ciclosporin inhibited the inflammatory response to 12-O-tetradecanoylphorbol-13-acetate (TPA) and to the contact sensitising agent oxazolone when applied topically to mouse skin. The drug had no effect on arachidonic acid-induced inflammation. The protein synthesis inhibitor cycloheximide showed a similar profile of activity. Ciclosporin, like actinomycin D but unlike cycloheximide, was only effective in inhibiting the inflammatory response to TPA if given 0.5 h before, but not 2 h, after TPA. These results suggest that the anti-inflammatory activity of ciclosporin in the skin is due to an effect on the production of proinflammatory proteins.
Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. (1991)

The t(14; 18)(q32;q21) chromosomal translocation, characteristic of follicular lymphoma, couples the bcl-2 protooncogene on chromosome 18 to the immunoglobulin heavy-chain joining region (JH). This results in a deregulated transcription rate of bcl-2, suggesting a major role of the t(14;18) translocation in lymphomagenesis. By using a sensitive polymerase chain reaction technique specific for the major breakpoint region t(14;18), we now demonstrate the presence of bcl-2/JH rearrangements in lymph nodes and tonsils with follicular hyperplasia in 13 of 24 cases (54%). The approximate frequency was one translocation-positive cell in 10(5) cells. No bcl-2/JH rearrangements were detected in reactive lymph nodes without follicular hyperplasia or in bone marrow cells. Sequence analysis showed the amplified bcl-2/JH fragments to be unique to each individual sample and distinct from 24 sequenced follicular lymphoma-derived t(14;18) junctions, thus excluding contamination artifacts. The presence of random nucleotide insertions at the breakpoint junctions suggests a pre-B-cell origin of the t(14;18) translocation, in analogy with follicular lymphomas. We conclude that the t(14;18) translocation can occur in non-malignant tissue and will not, on its own, lead to malignancy.
Determination of the ligands of the low spin heme of the cytochrome o ubiquinol oxidase complex using site-directed mutagenesis. (1992)

The cytochrome o complex of Escherichia coli is a ubiquinol oxidase which is the predominant respiratory terminal oxidase when the bacteria are grown under high oxygen tension. The amino acid sequences of three of the subunits of this quinol oxidase reveal a substantial relationship to the aa3-type cytochrome c oxidases. The two cytochrome components (b563.5 and o) and the single copper (CuB) present in the E. coli quinol oxidase appear to be equivalent to cytochrome a, cytochrome a3, and CuB of the aa3-type cytochrome c oxidases, respectively. These three prosthetic groups are all located within subunit I of the oxidase. Sequence alignments indicate only six totally conserved histidine residues among all known sequences of subunit I of the cytochrome c oxidases of various species plus the E. coli quinol oxidase. Site-directed mutagenesis has been used to change each of these totally conserved histidines with the presumption that two of these six must ligate to the low spin cytochrome center of the E. coli oxidase. The presence of the low spin cytochrome b563.5 component of the oxidase can be evaluated both by visible absorbance properties and by its EPR spectrum. The results unambiguously indicate that His-106 and His-421 are the ligands of the six-coordinate low spin cytochrome b563.5. Although the data are not definitive in making additional metal ligation assignments of the remaining four totally conserved histidines, a reasonable model is suggested for the structure of the catalytic core of the cytochrome o complex and, by extrapolation, of cytochrome c oxidase.
Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor (2009)

GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic beta-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand binding domain. Exendin-4 and GLP-1 are 50% identical, and exendin-4 is a full agonist with similar affinity and potency for the GLP-1 receptor. We recently solved the crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4(9-39). Interestingly, the isolated extracellular domain binds exendin-4 with much higher affinity than the endogenous agonist GLP-1. Here, we have solved the crystal structure of the extracellular domain in complex with GLP-1 to 2.1 Aresolution. The structure shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extracellular domain, but certain residues in the ligand-binding site adopt a GLP-1-specific conformation. GLP-1 is a kinked but continuous alpha-helix from Thr(13) to Val(33) when bound to the extracellular domain. We supplemented the crystal structure with site-directed mutagenesis to link the structural information of the isolated extracellular domain with the binding properties of the full-length receptor. The data support the existence of differences in the binding modes of GLP-1 and exendin-4 on the full-length GLP-1 receptor.
Islet assessment for transplantation (2009)

More sensitive and reliable islet viability and potency tests have been recently developed and tested. Those evaluating mitochondrial function are most promising, correlate with transplant outcomes in mice, and are currently being evaluated in the clinical setting.
Klaus: A System for Managing Information and Computational Resources (1980)

This report presents a broad-brush description of the basic goals and philosophy of a research program at SRI International (SRI) aimed at developing the technology needed to support systems that can be tutored in English about new subject areas, and that can thereafter aid the user in filing and retrieving information and in conveniently applying to the new subject area other computer software, such as data-base management systems (DBMS), planners, schedulers, report generators, and simulators. These systems, which the authors call Knowledge Learning and Using Systems (KLAUS), are intended to act as brokers between the user's needs, as expressed in the user's terms, and the resources available in a rich computational environment. In a nutshell, the core concept of a KLAUS is that of an interactive system preprogrammed with essential skills for readily learning the concepts and vocabulary of new subject domains, and with expertise for applying acquired knowledge in problem-solving situations. A KLAUS is tutored about new domains in English (perhaps also using tables, menus, and domain-specific formalisms). While being taught, a KLAUS does not play a passive role, but actively looks for gaps and inconsistencies in its knowledge, asking its tutor pointed clarification questions. In this manner, the KLAUS aids the user in formalizing, organizing, and clarifying his or her ideas. After tutoring, a KLAUS can aid its tutor and other users in performing tasks that require combining knowledge of the new domain with knowledge of how to use sophisticated computer systems.
Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis (2002)

A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus.
Estrogen modulates the recruitment of myelopoietic cell progenitors in rat through a stromal cell-independent mechanism involving apoptosis (1996)

Loss of ovarian function leads to a significant increase in the number of bone-resorbing osteoclasts. Estrogen replacement is known to manifest bone protective effects in the treatment of postmenopausal osteoporosis. In the present study, we used ovariectomized rats to examine the effects of estrogen loss at the osteoclast progenitor colony forming unit-granulocyte macrophage (CFU-GM) level. A significant increase in CFU-GM number was observed as early as 7 days following ovariectomy, and correlated directly with an increase in the number of osteoclast-like cells generated in marrow cultures. The increase in CFU-GM following ovariectomy was abrogated in animals that received estrogen treatment in vivo. A similar suppressive effect was observed on CFU-GM number when ovariectomized rat marrow was treated with estrogen in vitro. This effect was blocked in the presence of the estrogen antihormone ICI 164,384. Thus, the data suggest the possibility that estrogen exerts a direct effect on osteoclast progenitors, and does so through the estrogen receptor-mediated mechanism. Ovariectomy also led to an increase in the early hematopoietic stem/progenitor cell population (Thy 1.1+ cells) as determined by FLOW cytometry methods. Morphological changes as well as terminal deoxynucleotidyl transferase assays revealed that estrogen treatment negated growth factor-induced proliferation of these early progenitors by promoting apoptosis. The cellular effects of estrogen in vitro together with the immunocytochemical detection of the estrogen receptor in these cells, strongly support the contention that in addition to osteoclast progenitors such as CFU-GM, earlier hematopoietic progenitors are also unique cellular targets for estrogen action.
Alloantigen priming induces a state of unresponsiveness in human umbilical cord blood T cells. (1995)

Induction of alloreactivity in human adult and umbilical cord blood T cells was evaluated in mixed leukocyte culture by exposure to an allogeneic lymphoblastoid line that expresses known costimulatory molecules. Initial exposure to alloantigen-presenting cells (allo-APC) induced strong proliferative responses in both adult and cord blood T cells. However, in contrast to adult T cells, cord blood T cells exhibited little proliferation after restimulation with donor APC. Primed cord blood T cells could respond to interleukin 2 (IL-2), but unresponsiveness to alloantigen was not overcome by addition of exogenous IL-2. Unresponsiveness was long-lasting and appeared to be maintained by a combination of induction of anergy and activity of CD8+ suppressor cells. This information may contribute to use of human cord blood as an allogeneic source of transplantable stem cells.
Electrical Stimulation of Bone Growth with Direct Current (1986)

A Publication of The Association of Bone and Joint Surgeons® | CORR® Clinical Orthopaedics and Related Research is a leading peer-reviewed orthopaedic journal and a publication of The Association of Bone and Joint Surgeons®. Learn more!
Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response (2017)

Our previous screening of 50 240 structurally diverse compounds led to the identification of 39 influenza A virus infection inhibitors (Kao R.Y., Yang D., Lau L.S., Tsui W.H., Hu L. et al. Nat Biotechnol 2010;28:600-605). Further screening of these compounds against common respiratory viruses led to the discovery of compound FA-613. This inhibitor exhibited low micromolar antiviral activity against various influenza A and B virus strains, including the highly pathogenic influenza A strains H5N1 and H7N9, enterovirus A71, respiratory syncytial virus, human rhinovirus A, SARS- and MERS-coronavirus. No significant cellular toxicity was observed at the effective concentrations. Animal studies showed an improved survival rate in BALB/c mice that received intranasal FA-613 treatments against a lethal dose infection of A/HK/415742Md/2009 (H1N1). Further cell-based assays indicated that FA-613 interfer with the de novo pyrimidine biosynthesis pathway by targeting the dihydroorotate dehydrogenase. Surprisingly, FA-613 lost its antiviral potency in the interferon-deficient Vero cell line, while maintaining its inhibitory activity in an interferon-competent cell line which showed elevated expression of host antiviral genes when infected in the presence of FA-613. Further investigation of the specific connection between pyrimidine synthesis inhibition and the induction of host innate immunity might aid clinical development of this type of drug in antiviral therapies. Therefore, in acute cases of respiratory tract infections, when rapid diagnostics of the causative agent are not readily available, an antiviral drug with properties like FA-613 could prove to be very valuable.
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma (2016)

In this study, acquired resistance to PD-1 blockade immunotherapy in patients with melanoma was associated with defects in the pathways involved in interferon-receptor signaling and in antigen presentation. (Funded by the National Institutes of Health and others.).
Scrambled Coded Multiple Access (2011)

The advantages of Interleave Division Multiple Access (IDMA) are taken one step further by Scrambled Coded Multiple Access (SCMA) where user specific, long interleave tables are replaced by a common scrambling sequence that can be used for all users with a simple shift.
Janus and Minerva: Essays in the Theory and Practice of International Politics (1987)

In these essays, one of the most eminent political scientists of our time examines international relations from a variety of perspectives connected by timeless and common themes: the conflict between die ever-present risk of violence and the quest for international order, the tensions between the imperatives of power and those of morality, the ties that bind domestic and foreign policy, the ambiguities of the nuclear revolution, the break between prenuclear and post-1945 politics, and the dangers created by the competition between the nuclear superpowers. Assessing the development of the discipline of international relations, the author presents both a summary of the field's significant findings and a critical discussion of its most representative traditions of realism and liberalism. Written between 1960 and 1985, many of these essays have not been previously published in English. They reflect the author's own intellectual evolution and represent a complete picture of his approach to the study of world politics.
[Synthesis and preliminary pharmacological characteristics of various derivatives of 1,2,5-oxadiazole (furazan)]. (1977)

The synthesis, the chemical properties, the acute toxicity, the action of frog flexor reflex of 4-methylfurazan-3-N-methylcarboxamide (II), 4-methylfurazan-3-N-isopropylcarboxamide (III), 3-methyl-4-morpholinocarbonylfurazan (IV), 3-methyl-4-pyrrolidinocarbonylfurazan (V), 3-amino-4-methylfurazan (VI), 3-acetylamino-4-methylfurazan (VII), are reported. LD50 decrease in the following order: (VI), (II), (IV), (III), (VII), (V). All compounds, except (VII), depressed frog flexor reflexes.
Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism (1992)

The hemocompatibility of a polymer containing a phospholipid polar group, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate(BMA)), with human whole blood was evaluated. When human whole blood without an anticoagulant was contacted with polymers, the blood cell adhesion and aggregation on the polymer without the MPC moiety was extensive, and considerable fibrin deposition was observed. This phenomenon was suppressed with an increase in the polymer MPC composition. Thus, the MPC moiety in the copolymer plays an important role in the nonthrombogenic behavior of the copolymer. These results were also confirmed by the whole blood coagulation time on the polymer surface which was determined by Lee-White method. The adsorption of phospholipids and proteins from human plasma on poly(MPC-co-BMA) was investigated to clarify the mechanism of the nonthrombogenicity observed with the polymer. The amount of phospholipids was increased; whereas, adsorbed proteins were decreased with an increase in the MPC composition. From these results, we concluded that the phospholipids adsorbed on poly(MPC-co-BMA) play the most important role in the nonthrombogenicity of the MPC copolymer.
Identification of two genes, cpsX and cpsY, with putative regulatory function on capsule expression in group B streptococci (1998)

Two divergently transcribed open reading frames: cpsX and cpsY separated by a common regulatory region was identified upstream of the cpsA–D genes involved in polysaccharide capsule biosynthesis in group B streptococci (GBS). We suggest that these genes are involved in the regulation of capsule expression in GBS, since the CpsX protein shares sequence similarities with LytR of Bacillus subtilis, an attenuator of transcription while CpsY has similarity to a wide variety of members of the LysR family of transcriptional regulators. No deletions, insertions, DNA rearrangements, or apparent differences were discovered in the postulated regulatory genes when the gene region was compared in GBS with different capsule phenotypes. Thus, other yet unidentified gene loci may control capsule phase variation in GBS.