gebhart/patrepeval huggingface dataset:
Equine Follicle-Stimulating Hormone: Molecular Cloning of β Subunit and Biological Role of the Asparagine-Linked Oligosaccharide at Asparagine56 of α Subunit1 (2001)

Equine FSH (eFSH) and eCG are members of the glycoprotein hormone family. These proteins are heterodimeric, composed of noncovalently associated alpha and beta subunits. We have previously reported that recombinant eCG has potent LH- and FSH-like activities and that the oligosaccharide at Asn(56) of the alpha subunit plays an indispensable role in expressing LH- but not FSH-like activity. In the present study, we cloned eFSH beta subunit cDNA and expressed wild-type recombinant eFSH and a partially deglycosylated mutant FSH (eFSH alpha56/beta) to investigate the biological role of the oligosaccharide at Asn(56) in FSH activity. The wild-type eFSH and eCG stimulated estradiol production in a dose-dependent manner in the primary cultures of rat granulosa cells, indicating that these equine gonadotropins have FSH activity. Partially deglycosylated eCG (eCG alpha56/beta) also stimulated estradiol production, confirming that the FSH-like activity of eCG is resistant to the removal of the N-linked oligosaccharide. Partially deglycosylated eFSH (eFSH alpha56/beta), however, did not show any FSH activity, indicating that the oligosaccharide at Asn(56) was necessary for eFSH. Thus, FSH-like activities of two gonadotropins, eCG and eFSH, are evoked through the distinct molecular mechanisms regarding the biological role of oligosaccharide at Asn(56) of the alpha subunit.
Genome-wide scan for Parkinson's disease (2001)

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.
Intracerebral xenotransplantation of semipermeable membrane- encapsuled pancreatic islets (2005)

BSM xenotransplantation in combination with the privileged site can inhibit the rejection of implanted heterogeneous ICCs, and death of implanted heterogeneous B cells is associated with apoptosis.
CD34: structure, biology, and clinical utility [see comments] (1996)

A surface glycophosphoprotein expressed on developmentally early lymphohematopoietic stem and progenitor cells,"3 small-vessel endothelial and embryonic fibroblasts6 CD34+ bone marrow (BM) cells comprise only 1.5% of marrow mononuclear cells, but contain precursors for all lymphohematopoietic lineages, as evidenced by the finding that CD34+ cells purified from marrow can reconstitute hematopoiesis of primates, humans, or mice undergoing autologous marrow reinfusion after myeloablative therapy (BM tran~plant~-~.""). CD34+ hematopoietic cells obtained from marrow or blood are in clinical use in transplantation and gene therapy studies, including ongoing attempts to expand hematopoietic stedprogenitor cells ex vivo. Despite the importance of CD34 as a marker of early hematopoietic stedprogenitor cells in experimental and clinical hematopoiesis, the function of CD34 is not yet clear. Because of its potential role in such fundamental processes as hematopoietic stedprogenitor cell development and inflammation, studies on the regulation and function of CD34 are being pursued in several laboratories.
Receptor oligomerization and beyond: a case study in bone morphogenetic proteins (2009)

Binding of a ligand to a single high affinity receptor chain functioning as anchoring molecule and providing sufficient complex stability allows the subsequent formation of signaling competent complexes. Another receptor of the same subtype, and up to two receptors of the other subtype, can then be recruited. Thus, the resulting receptor arrangement can principally consist of four different receptors, which is consistent with our interaction analysis showing low ligand-receptor specificity within one subtype class. For BMP2, further complexity is added by the fact that heterooligomeric signaling complexes containing only one type I receptor chain can also be found. This indicates that despite prominent ligand receptor promiscuity a manifold of diverse signals might be generated in this receptor limited system.
Immunologic strategies for HIV-1 remission and eradication (2014)

Antiretroviral therapy (ART) is able to suppress HIV-1 replication indefinitely in individuals who have access to these medications, are able to tolerate these drugs, and are motivated to take them daily for life. However, ART is not curative. HIV-1 persists indefinitely during ART as quiescent integrated DNA within memory CD4(+) T cells and perhaps other long-lived cellular reservoirs. In this Review, we discuss the role of the immune system in the establishment and maintenance of the latent HIV-1 reservoir. A detailed understanding of how the host immune system shapes the size and distribution of the viral reservoir should lead to the development of a new generation of immune-based therapeutics, which may eventually contribute to a curative intervention.
Steroid Production from Plasma Cholesterol. II.In VivoConversion of Plasma Cholesterol to Ovarian Progesterone and Adrenal C19and C21Steroids in Humans (1974)

Tritiated cholesterol was injected intravenously into 3 ovulating women, 10, 14 and 23 days prior to tubal ligation. The specific activity of urinary pregnanediol (SA in dpm/μmole) was consistently lower than the SA of plasma free cholesterol of the corresponding day. This was observed in the luteal phase of 2 normal cycles and in 1 normal cycle prolonged with hCG from day 22 to day 31. This finding would suggest that the corpus luteum of a normal cycle as well as in early pregnancy produces progesterone from at least two sources, plasma cholesterol and probably newly formed cholesterol within the gland. The steroid production in the adrenal gland from plasma cholesterol was studied in a similar manner, by the determination of the SA of 2 C21 urinary metabolites, tetrahydrocortisone and tetrahydrocortisol and 3 C19 compounds, dehydroepiandrosterone, androsterone and etiocholanolone. The SA of all 5 compounds were similar to the SA of the corresponding plasma free cholesterol in the control periods of 3 subjects. With an increased endogenous ACTH production due to stress, the pattern was again similar (1 subject). Intramuscular injections of ACTH were given every 12 hr for at least 2 days in 2 subjects. The results were similar except for a slight decrease in the SA of all 5 compounds in one case where the tracer cholesterol had been administered only 6 days prior to the ACTH. These data suggest that hydrocortisone and adrenal C19 compounds are derived almost exclusively from plasma free cholesterol even under ACTH stimulation.
A fast segmental Viterbi algorithm for large vocabulary recognition (2002)

The paper presents a fast segmental Viterbi algorithm. A new search strategy particularly effective for very large vocabulary word recognition. It performs a tree based, time synchronous, left-to-right beam search that develops time-dependent acoustic and phonetic hypotheses. At any given time, it makes active a sub-word unit associated to an arc of a lexical tree only if that time is likely to be the boundary between the current and the next unit. This new technique, tested with a vocabulary of 188892 directory entries, achieves the same results obtained with the Viterbi algorithm, with a 35% speedup. Results are also presented for a 718 word, speaker independent continuous speech recognition task.
Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi‐mutated herpes simplex virus type‐1 (G207) (1999)

G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%-36.6%) and was proportional to response to G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 +/- 10 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases.
Electrospray ionization mass spectrometry as a mechanistic tool: Mass of human leukocyte elastase and a .beta.-lactam-derived E-I complex (1993)

We have utilized liquid chromatography electrospray ionization mass spectrometry (ESI-MS) to probe the nature of the covalent E-I complex of human leucocyte elastase (HLE) and a beta-lactam. The mass spectrum of HLE isozyme 4 displayed one major and two minor components with masses of 25,202, 25,043, and 24,522 Da, respectively. Isozyme 3 displayed three components, with masses of 25,180, 24,030, and 24,523 Da. These data suggest that the isozymes differ in the type and not the content of carbohydrate. The minor components represent decreases in carbohydrate content. Inactivation of isozyme 4 with trans-4-(ethoxycarbonyl)-3-ethyl-1-[(4-nitrophenyl)sulfonyl]-azetidin -3-one increased the mass of the three components by that of the parent compound. Similar results were obtained with the mixture of HLE isozymes. These observations demonstrate that HLE does not catalyze the beta-elimination of p-nitrophenylsulfinate as Firestone et al. [(1990) Tetrahedron 46, 2255) suggested. In addition, it suggests that a "double hit" of both the active-site serine and histidine is not required to form a stable acyl-enzyme. Noncovalent complexes between HLE and either the tight-binding secretory leucoprotease inhibitor (SLPI) or a slow tight-binding peptide difluoroketone inhibitor were not observed by ESI-MS. SLPI displayed a mass of 11,710 Da in the absence and presence of HLE. These data demonstrate the utility of ESI-MS to probe the mechanism of inhibition of enzymes by mechanism-based inhibitors.
Impaired Macrophage Function and Enhanced T Cell-Dependent Immune Response in Mice Lacking CCR5, the Mouse Homologue of the Major HIV-1 Coreceptor (1998)

The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the existence of many other HIV-1 coreceptors. To investigate the physiologic function of CCR5 and to understand the cellular mechanisms of these clinical observations, we generated a CCR5-deficient mouse model (ccr5[-/-]) by targeted deletion of the ccr5 gene. We found that although developed normally in a pathogen-free environment, CCR5-deficient mice showed reduced efficiency in clearance of Listeria infection and exert a protective effect against LPS-induced endotoxemia, reflecting a partial defect in macrophage function. In addition, CCR5-deficient mice had an enhanced delayed-type hypersensitivity reaction and increased humoral responses to T cell-dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating T cell-dependent immune response.
Escherichia coli thioredoxin stabilizes complexes of bacteriophage T7 DNA polymerase and primed templates. (1987)

The DNA polymerase activity induced after bacteriophage T7 infection of Escherichia coli is found in a complex of two proteins, the T7 gene 5 protein and a host protein, thioredoxin. Gene 5 protein is a DNA polymerase and a 3' to 5' exonuclease. Thioredoxin binds tightly to the gene 5 protein and increases the processivity of polymerization some 1000-fold. Gene 5 protein forms a short-lived complex with the primer-template, poly(dA).oligo(dT), in the absence of Mg2+ and nucleotides. Thioredoxin increases the half-life of the preformed primer-template-polymerase complex from less than a second to approximately 5 min. The dissociation is accelerated by excess single-stranded DNA in an apparent second order reaction, indicating direct transfer of polymerase between DNA fragments. Thioredoxin also reduces the equilibrium dissociation constant, Kd, of the gene 5 protein -poly(dA).oligo(dT) complex 20- to 80-fold. The salt dependence of Kd indicates that thioredoxin stabilizes the primer-template-polymerase complex mainly through additional charge-charge interactions, increasing the estimated number of interactions from 2 to 7. The affinity of gene 5 protein for single-stranded DNA is at least 1000-fold higher than for double-stranded DNA and is little affected by thioredoxin. Under conditions of steady state synthesis the effect of thioredoxin on the polymerization rate is determined by two competing factors, an increase in processivity and a decrease of the dissociation rate of polymerase and replicated template.
Optomechanical zipper cavity lasers: theoretical analysis of tuning range and stability (2010)

The design of highly wavelength tunable semiconductor laser structures is presented. The system is based on a one dimensional photonic crystal cavity consisting of two patterned, doubly-clamped nanobeams, otherwise known as a "zipper" cavity. Zipper cavities are highly dispersive with respect to the gap between nanobeams in which extremely strong radiation pressure forces exist. Schemes for controlling the zipper cavity wavelength both optically and electrically are presented. Tuning ranges as high as 75 nm are achieved for a nominal design wavelength of lambda = 1.3 microm. Sensitivity of the mechanically compliant laser structure to thermal noise is considered, and it is found that dynamic back-action of radiation pressure in the form of an optical or electrical spring can be used to stabilize the laser frequency. Fabrication of zipper cavity laser structures in GaAs material with embedded self-assembled InAs quantum dots is presented, along with measurements of photoluminescence spectroscopy of the zipper cavity modes.
Production, purification and analysis of an experimental DNA vaccine against rabies (2001)

This study demonstrates that the method developed for the purification of milligram amounts of plasmid delivers an endotoxin-free, experimental rabies DNA vaccine, with protective activity similar to that obtained with the vaccine purified using a commercial kit.
Preparation and Some Properties of Maleimido Acids and maleoyl derivatives of peptides (1975)

Abstract N‐Alkoxycarbonylmaleimides 3 have been prepared and used to convert amino acids to maleimido acids (6–8) in aqueous solution. The carboxyl group of maleimido acids can be activated for amide or peptide synthesis ( e.g. , in the N‐succinimidyl esters 10); t ‐butyl‐based protecting groups can be cleaved without damage to the maleimide moiety. Peptides carrying maleimide groups are accessible either from the maleimido acids ( e.g. , 11b, 15) or by direct maleoylation ( e.g. , 16b). The maleoyl group can be cleaved off by successive mild alkaline and acid hydrolysis or by hydrazinolysis. The reactivity of maleimides toward thiol groups suggests the use of maleimido acids and maleoylpeptides for preparing a wide range of conjugates of biochemical interest.
Sustained pharmacological inhibition of δPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats (2007)

Hypertensive encephalopathy is a potentially fatal condition associated with cerebral edema and the breakdown of the blood-brain barrier (BBB). The molecular pathways leading to this condition, however, are unknown. We determined the role of deltaPKC, which is thought to regulate microvascular permeability, in the development of hypertensive encephalopathy using deltaV1-1 - a selective peptide inhibitor of deltaPKC. As a model of hypertensive encephalopathy, Dahl salt-sensitive rats were fed an 8% high-salt diet from 6 weeks of age and then were infused s.c. with saline, control TAT peptide, or deltaV1-1 using osmotic minipumps. The mortality rate and the behavioral symptoms of hypertensive encephalopathy decreased significantly in the deltaV1-1-treated group relative to the control-treated group, and BBB permeability was reduced by more than 60%. Treatment with deltaV1-1 was also associated with decreased deltaPKC accumulation in capillary endothelial cells and in the endfeet of capillary astrocytes, which suggests decreased microvasculature disruption. Treatment with deltaV1-1 prevented hypertension-induced tight junction disruption associated with BBB breakdown, which suggests that deltaPKC may specifically act to dysregulate tight junction components. Together, these results suggest that deltaPKC plays a role in the development of hypertension-induced encephalopathy and may be a therapeutic target for the prevention of BBB disruption.
Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma. (2003)

This is the first demonstration that the expression level of RhoC is correlated to vascular permeation in NSCLC.
Triggering Receptor Expressed on Myeloid Cells-1 in Neutrophil Inflammatory Responses: Differential Regulation of Activation and Survival (2004)

Polymorphonuclear neutrophils (PMN) are crucial in the innate host defense by their ability to rapidly accumulate in inflamed tissues and clear a site of infection from microbial pathogens by their potent effector mechanisms. The triggering receptor expressed on myeloid cells (TREM)-1 is a recently described activating receptor on PMN with an important role in inflammation. However, the effects of TREM-1 stimulation on a cellular level remain to be further defined. To characterize TREM-1-mediated activation of human PMN, we evaluated the effect of receptor ligation on PMN effector functions. Activation via TREM-1 induces immediate degranulation of neutrophilic granules resulting in the release of IL-8, respiratory burst, and phagocytosis. TREM-1 ligation synergizes with the activation by the Toll-like receptors (TLR) ligands LPS, Pam(3)Cys, and R-848. In contrast, no synergy between TREM-1- and TLR-mediated stimulation was observed concerning PMN survival, whereas TLR-mediated stimuli protect PMN from apoptosis, concurrent TREM-1 activation neutralizes these anti-apoptotic effects. These results give a new perspective for the regulation of neutrophil inflammatory responses emphasizing the importance of TREM-1 in innate immunity.
Adoptive Cell Therapy (2010)

Building on the principals that the adoptive transfer of T cells can lead to the regression of established tumors in humans, investigators are now further manipulating these cells using genetic engineering. Two decades of human gene transfer experiments have resulted in the translation of laboratory technology into robust clinical applications. The purpose of this review is to give the reader an introduction to the 2 major approaches being developed to redirect effector T-cell specificity. Primary human T cells can be engineered to express exogenous T-cell receptors or chimeric antigen receptors directed against multiple human tumor antigens. Initial clinical trial results have demonstrated that both T-cell receptor- and chimeric antigen receptor-engineered T cells can be administered to cancer patients and mediate tumor regression.
Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies (2002)

Current techniques for three-dimensional (3D) optical microscopy (deconvolution, confocal microscopy, and optical coherence tomography) generate 3D data by "optically sectioning" the specimen. This places severe constraints on the maximum thickness of a specimen that can be imaged. We have developed a microscopy technique that uses optical projection tomography (OPT) to produce high-resolution 3D images of both fluorescent and nonfluorescent biological specimens with a thickness of up to 15 millimeters. OPT microscopy allows the rapid mapping of the tissue distribution of RNA and protein expression in intact embryos or organ systems and can therefore be instrumental in studies of developmental biology or gene function.
Characterization of the autophosphorylation of Era, an essential Escherichia coli GTPase (1994)

Era is an essential protein in Escherichia coli which binds both GTP and GDP and has an intrinsic GTPase activity. Studies on the role of GTP/GDP binding and GTPase activity in an attempt to understand its function lead to the observation that Era is autophosphorylated. The autophosphorylation reaction is specific for GTP and cannot use ATP as a phosphoryl group donor. The reaction velocity is of first order with respect to protein concentration, suggesting an intramolecular mechanism. Autophosphorylation occurs at serine and threonine residues. The major phosphorylated tryptic peptide isolated after autophosphorylation has been identified as ISITSR, from residue 33 to 38. The peptide contains the site of phosphorylation and two potential sites for serine and threonine phosphorylation. Subsequently, both the threonine residue at position 36 and the serine residue at position 37 were altered to alanine. The double mutant Era, but not individual single mutants, was unable to functionally complement the growth of an E. coli strain which cannot produce wild-type Era protein at high temperature. This suggests that either threonine 36 or serine 37 has to exist for the function of Era in vivo. In vivo phosphorylation of Era was also examined by two-dimensional gel electrophoresis. Era has been previously assigned two distinct positions having two different X-Y co-ordinates: one of the spots (H032.0) was identified as phosphorylated Era, indicating that a substantial portion of Era in the cell is indeed phosphorylated. Therefore, Era autophosphorylation is likely to play an important physiological role in the cell.(ABSTRACT TRUNCATED AT 250 WORDS)