gebhart/patrepeval huggingface dataset:
Hsp90 Binds and Regulates Gcn2, the Ligand-Inducible Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2 (2000)

The protein kinase Gcn2 stimulates translation of the yeast transcription factor Gcn4 upon amino acid starvation. Using genetic and biochemical approaches, we show that Gcn2 is regulated by the molecular chaperone Hsp90 in budding yeast Saccharomyces cerevisiae. Specifically, we found that (i) several Hsp90 mutant strains exhibit constitutive expression of a GCN4-lacZ reporter plasmid; (ii) Gcn2 and Hsp90 form a complex in vitro as well as in vivo; (iii) the specific inhibitors of Hsp90, geldanamycin and macbecin I, enhance the association of Gcn2 with Hsp90 and inhibit its kinase activity in vitro; (iv) in vivo, macbecin I strongly reduces the levels of Gcn2; (v) in a strain expressing the temperature-sensitive Hsp90 mutant G170D, both the accumulation and activity of Gcn2 are abolished at the restrictive temperature; and (vi) the Hsp90 cochaperones Cdc37, Sti1, and Sba1 are required for the response to amino acid starvation. Taken together, these data identify Gcn2 as a novel target for Hsp90, which plays a crucial role for the maturation and regulation of Gcn2.
Complexation of Retrovirus with Cationic and Anionic Polymers Increases the Efficiency of Gene Transfer (2001)

Previously, we have demonstrated that chondroitin sulfate proteoglycans and glycosaminoglycans inhibit retrovirus transduction. While studying the mechanism of inhibition, we found that the combined addition of equal-weight concentrations (80 microg/ml) of Polybrene and chondroitin sulfate C to retrovirus stocks resulted in the formation of a high-molecular-weight retrovirus-polymer complex that could be pelleted by low-speed centrifugation. The pelleted complex contained more than 80% of the virus particles, but less than 0.3% of the proteins that were originally present in the virus stock. Surprisingly, the virus in the complex remained active and could be used to transduce cells. The titer of the pelleted virus, when resuspended in cell culture medium to the starting volume, was three-fold greater than the original virus stock. The selectivity (CFU/mg protein) of the process with respect to virus activity was more than 1000-fold. When the pelleted virus-polymer complex was resuspended in one-eighth of the original volume and used to transduce NIH 3T3 murine fibroblasts and primary human fibroblasts, gene transfer was increased 10- to 20-fold over the original unconcentrated retrovirus stock. The implications of our findings for the production, processing, and use of retrovirus stocks for human gene therapy protocols are discussed.
Characterization of a murine lymphokine distinct from interleukin 2 and interleukin 3 (IL-3) possessing a T-cell growth factor activity and a mast-cell growth factor activity that synergizes with IL-3. (1986)

Murine mast-cell and T-cell growth factor activities, distinct from interleukins 3 and 2 (IL-3 and IL-2), have been identified and partially purified from the supernatant of the activated helper T-cell line Cl.Ly1+2-/9. This mast-cell growth factor (MCGF) activity supports only low levels of proliferation of several IL-3-dependent mast-cell lines and synergistically enhances the growth of mast cells in the presence of IL-3. The T-cell growth factor (TCGF) stimulates the proliferation of several T-cell lines, but to a lesser extent than recombinant IL-2. The MCGF and TCGF activities were not separable despite multiple biochemical fractionations, suggesting that both activities reside in the same protein. The MCGF/TCGF was separated from endogenous IL-3 by cation-exchange chromatography at neutral pH and could be distinguished from IL-2 by unique elution conditions from reverse-phase columns. Two bands of MCGF/TCGF activity were eluted from gels after sodium dodecyl sulfate/PAGE; under nonreducing conditions, the activities corresponded to molecular masses of 20 and 15 kDa, while after reduction, the molecular masses were 21 and 16 kDa. Thus, both activities may correspond to single polypeptide chains. The majority of the MCGF/TCGF activity appears to reside in the 20-kDa species, which displays a pI of 6.2 on chromatofocusing.
Redox-active alkaline electrolyte for carbon-based supercapacitor with pseudocapacitive performance and excellent cyclability (2012)

A simple method has been implemented to prepare a stable and effective redox-active alkaline electrolyte by doping m-phenylenediamine into a conventional KOH electrolyte for a carbon-based supercapacitor. The quick electron transfer and reversible Faradic process in the new electrolyte system results in additional pseudocapacitive contribution for a carbon-based supercapacitor. The specific capacitance of the supercapacitor based on the new electrolyte is 78.01 F g−1, which is an increase of 114.16% over that of a supercapacitor based on a conventional KOH electrolyte (36.43 F g−1). Additionally, the supercapacitor exhibits an excellent cyclical stability.
Novel Insights on Human NK Cells’ Immunological Modalities Revealed by Gene Expression Profiling (2004)

As part of the innate immune system, human NK cells play a critical role early in the systemic host defense against pathogens and tumor cells. Recent studies suggest a more complex view of NK cell behavior, as different functions and tissue localizing capabilities seem to be preferentially assigned to distinct subpopulations of NK cells, CD56(dim)CD16(+) or CD56(bright)CD16(-). In this study, we used oligonucleotide microarrays to compare the expression profile of approximately 20,000 genes in three NK cell subpopulations: peripheral blood-derived CD56(dim)CD16(+), CD56(bright)CD16(-), and in vitro-activated CD16(+) NK cells. The differential expression of selected genes was verified by flow cytometry and functional assays. When comparing CD56(dim)CD16(+) and CD56(bright)CD16(-) subsets, a new heterogeneous molecular basis for the functional and developmental differences between these two subsets was revealed. Furthermore, systematic analysis of transcriptional changes in activated CD16(+) NK cells provided us with a better understanding of NK function in inflamed tissues. We highlight a number of genes that were overexpressed upon activation (e.g., OX40 ligand, CD86, Tim3, galectins, etc.), that enable these cells to directly cross-talk with other innate and adaptive immune effectors. The overexpressed genes assign novel intriguing immunomodulatory functions to activated NK cells, in addition to their potent cytotoxic abilities.
Thymocytopoiesis is maintained by blood-borne precursors throughout postnatal life. A study in parabiotic mice (1992)

This study was designed to resolve the long standing controversy as to whether hematogenous precursors or resident intrathymic precursors maintain thymocytopoiesis in postnatal life. The kinetics of thymic chimerism was examined over a 21-wk period in 105 pairs of nonirradiated, Thy-1-alloantigen-disparate, parabiotic B10.S mice. Thymic chimerism reached reached maximum levels of 25% in the Thy-1b and 16% in the Thy-1a partners (mean 20.5% and 9.8%, respectively) 6 to 7 wk after parabiotic union. Most of the donor-origin thymocytes were located in the thymus cortex and expressed high levels of Thy-1 Ag and terminal deoxynucleotidyl transferase. Thymic chimerism did not reach 50% because circulating prothymocytes, unlike peripheral T cells, do not distribute randomly in the blood of parabiotic partners. This was shown in irradiated pairs of Thy-1-alloantigen-identical parabiotic mice, one member of which was injected i.v. with Thy-1-alloantigen-disparate bone marrow cells. Only 10% of the total donor-origin prothymocyte activity was detected in the opposite parabiont 72 h later. Similarly, the level of thymic chimerism in nonirradiated, Thy-1-alloantigen-disparate parabionts closely corresponded to the donor: host ratio of prothymocytes in the blood (i.e., between 10 and 20%), as determined directly by an intrathymic adoptive transfer assay. The continued dependence of thymic chimerism on blood-borne precursors was formally demonstrated by surgically separating mice 9 wk after parabiosis. Twelve weeks later, thymic chimerism was 50 to 80% lower in the separated parabionts than in sham-operated controls. The possible role of "stress" in initiating or maintaining thymic chimerism during parabiosis appeared to be excluded by the existence of similar kinetics of thymocytopoiesis (including the onset of thymic involution) in parabiotic and nonparabiotic mice; and by the occurrence of similar levels of thymic chimerism in adrenalectomized and nonadrenalectomized parabiotic mice. Thus these experiments demonstrate that the maintenance of thymocytopoiesis in postnatal life, as in prenatal life, is primarily dependent upon blood-borne prothymocytes, and that intrathymic precursors are replaced at an average rate of 2 to 3%/day.
Analysis of Exchange-Coupled Magnetic Thin Films (1970)

Presented in this paper are some new analytical results for two exchange-coupled magnetic thin films. The formulation of the problem which is used is similar to that of Goto et al., who reduced the determination of the magnetic configuration of the films in the presence of an external magnetic field to the evaluation of elliptic integrals. Derived herein is an expression for the second variation of the magnetic energy, thereby allowing an investigation of the stability of previously determined magnetic configurations. Evaluation of this expression, as well as determination of the magnetic configuration, must be done numerically, and tables giving magnetic configurations and critical fields are included for a variety of thickness combinations and magnetic parameters. In addition, new analytical results are presented for several limiting cases. Transcendental equations have been derived which give the threshold fields for arbitrary film parameters when the easy axes are mutually parallel in the two films and when the external field is either parallel or perpendicular to the common easy axis. Expressions are also developed for the critical fields in composites involving both very thin and very thick films, and the magnetic properties of a pair of very thin films are shown to be simple combinations of the constituents' magnetic properties. Finally, several discrepancies are discussed between the approximate results of Goto et al. and the exact results obtained herein.
Diabetic foot: evaluation and management. (2002)

Diabetic foot disease in the form of ulceration, charcot joint fracture, and amputation affects 20% of patients with diabetes. This results in tremendous morbidity, mortality, and health care cost. The magnitude of this problem has been underrecognized by health care professionals. Impaired glucose control over a period of years affects peripheral nerve function by loss of protective sensation, muscle atrophy, foot deformity, and neuropathic fractures. Yearly foot examinations can identify risk factors. Regular nail care, callus removal, and education can prevent plantar ulceration. Protective footwear and custom orthotics improve function by reducing force and shear impact on the fragile foot and accommodate the patient's deformities. A cost-effective strategy of yearly comprehensive foot examinations, education, and appropriate interventions can improve both the quality and duration of life for those with diabetes mellitus.
Ectopic atrial tachycardias with early activation at His site: radiofrequency ablation through a retrograde approach (2008)

In patients with EATs and early atrial activation at the His site, tachycardia may arise in the non-coronary aortic sinus or from the mitral annulus. Radiofrequency energy ablation can be performed through a retrograde approach in the majority of these patients and is safe and effective in eliminating this type of tachycardia.
The Factor IX γ-Carboxyglutamic Acid (Gla) Domain Is Involved in Interactions between Factor IX and Factor XIa (2003)

During hemostasis, factor IX is activated to factor IXabeta by factor VIIa and factor XIa. The glutamic acid-rich gamma-carboxyglutamic acid (Gla) domain of factor IX is involved in phospholipid binding and is required for activation by factor VIIa. In contrast, activation by factor XIa is not phospholipid-dependent, raising questions about the importance of the Gla for this reaction. We examined binding of factors IX and IXabeta to factor XIa by surface plasmon resonance. Plasma factors IX and IXabeta bind to factor XIa with K(d) values of 120 +/- 11 nm and 110 +/- 8 nm, respectively. Recombinant factor IX bound to factor XIa with a K(d) of 107 nm, whereas factor IX with a factor VII Gla domain (rFIX/VII-Gla) and factor IX expressed in the presence of warfarin (rFIX-desgamma) did not bind. An anti-factor IX Gla monoclonal antibody was a potent inhibitor of factor IX binding to factor XIa (K(i) 34 nm) and activation by factor XIa (K(i) 33 nm). In activated partial thromboplastin time clotting assays, the specific activities of plasma and recombinant factor IX were comparable (200 and 150 units/mg), whereas rFIX/VII-Gla activity was low (<2 units/mg). In contrast, recombinant factor IXabeta and activated rFIX/VIIa-Gla had similar activities (80 and 60% of plasma factor IXabeta), indicating that both proteases activate factor X and that the poor activity of zymogen rFIX/VII-Gla was caused by a specific defect in activation by factor XIa. The data demonstrate that factor XIa binds with comparable affinity to factors IX and IXabeta and that the interactions are dependent on the factor IX Gla domain.
Cotransplantation of HLA-Identical Sibling Culture-Expanded Mesenchymal Stem Cells and Hematopoietic Stem Cells in Hematologic Malignancy Patients (2005)

Mesenchymal stem cells (MSCs) are found in a variety of tissues, including human bone marrow; secrete hematopoietic cytokines; support hematopoietic progenitors in vitro; and possess potent immunosuppressive properties. We hypothesized that cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs) from HLA-identical sibling donors after myeloablative therapy could facilitate engraftment and lessen graft-versus-host disease (GVHD); however, the safety and feasibility of this approach needed to be established. In an open-label, multicenter trial, we coadministered culture-expanded MSCs with HLA-identical sibling-matched HSCs in hematologic malignancy patients. Patients received either bone marrow or peripheral blood stem cells as the HSC source. Patients received 1 of 4 study-specified transplant conditioning regimens and methotrexate (days 1, 3, and 6) and cyclosporine as GVHD prophylaxis. On day 0, patients were given culture-expanded MSCs intravenously (1.0-5.0 x 10(6)/kg) 4 hours before infusion of either bone marrow or peripheral blood stem cells. Forty-six patients (median age, 44.5 years; range, 19-61 years) received MSCs and HLA-matched sibling allografts. MSC infusions were well tolerated, without any infusion-related adverse events. The median times to neutrophil (absolute neutrophil count > or = 0.500 x 10(9)/L) and platelet (platelet count > or = 20 x 10(9)/L) engraftment were 14.0 days (range, 11.0-26.0 days) and 20 days (range, 15.0-36.0 days), respectively. Grade II to IV acute GVHD was observed in 13 (28%) of 46 patients. Chronic GVHD was observed in 22 (61%) of 36 patients who survived at least 90 days; it was extensive in 8 patients. Eleven patients (24%) experienced relapse at a median time to progression of 213.5 days (range, 14-688 days). The probability of patients attaining disease- or progression-free survival at 2 years after MSC infusion was 53%. Cotransplantation of HLA-identical sibling culture-expanded MSCs with an HLA-identical sibling HSC transplant is feasible and seems to be safe, without immediate infusional or late MSC-associated toxicities. The optimal MSC dose and frequency of administration to prevent or treat GVHD during allogeneic HSC transplantation should be evaluated further in phase II clinical trials.
Nitric oxide inhalation therapy in very low‐birthweight infants with hypoplastic lung due to oligohydramnios (2004)

The majority of the infants with pulmonary hypoplasia due to oligohydramnios had persistent pulmonary hypertension. iNO improved the arterial oxygenation and significantly improved the survival rate. A controlled study to determine whether iNO therapy improves the survival rate of preterm infants with pulmonary hypoplasia due to oligohydramnios is necessary.
Sequential Monte Carlo without likelihoods (2007)

Recent new methods in Bayesian simulation have provided ways of evaluating posterior distributions in the presence of analytically or computationally intractable likelihood functions. Despite representing a substantial methodological advance, existing methods based on rejection sampling or Markov chain Monte Carlo can be highly inefficient and accordingly require far more iterations than may be practical to implement. Here we propose a sequential Monte Carlo sampler that convincingly overcomes these inefficiencies. We demonstrate its implementation through an epidemiological study of the transmission rate of tuberculosis.
Identification and Cloning of the Fowlpox Virus Thymidine Kinase Gene Using Vaccinia Virus (1986)

Using vaccinia virus as a selection and cloning vehicle, a thymidine kinase (TK) gene of fowlpox virus (FPV) has been identified. A plasmid, pF130, containing part of the HindIII-F region of vaccinia virus was used to shotgun clone EcoRI fragments of FPV DNA into TK- vaccinia virus and select for TK+ recombinants. The TK+ recombinant vaccinia virus contained a 5.5 kb EcoRI fragment of FPV. This FPV fragment was cloned into pUC9 and the presence of the TK gene in this fragment was confirmed by its ability to rescue TK+ vaccinia virus from TK- virus, when inserted into pF130. A recombinant vaccinia virus containing this FPV fragment induced TK enzyme activity in the cytoplasm of infected cells. The vaccinia virus RNA polymerase appeared able to recognize the FPV promoter sequences of the FPV TK gene since the fragment operated in the marker rescue, irrespective of its orientation to the vaccinia virus promoter in pF130. Using restriction enzyme analysis, insertion of subfragments of the 5.5 kb FPV fragment into pF130 and marker rescue, we were able to map the position of the TK gene in the 5.5 kb EcoRI fragment. This approach may facilitate identification and cloning of TK genes from other poxviruses.
Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. (1990)

P-glycoprotein is a highly conserved membrane protein shown to be overexpressed in many multidrug-resistant tumor cell lines. P-glycoprotein is encoded by a small gene family in mammalian cells. Class I and II isoforms cause multidrug resistance, whereas class III does not. In this report, we have characterized three P-glycoprotein-specific monoclonal antibodies (mAbs) by high-resolution epitope mapping with a series of hexapeptides. mAb C494 is gene specific, binding to a sequence present only in the class I isoform of hamster and human. The mAb C32 recognizes a sequence conserved in hamster class I and II isoforms but not in class III isoforms. In contrast, the mAb C219 recognizes a highly conserved amino acid sequence found in all P-glycoprotein isoforms characterized to date. These mAbs were used to reveal differential expression and specific localization of the three P-glycoprotein isoforms in hamster tissues by immunohistochemical staining and competition with epitope-specific peptides. Colonic epithelial cells expressed predominantly the class I isoform in a polarized manner, adrenal cortical cells expressed predominantly the class II isoform, whereas a small percentage of skeletal muscle fibers expressed the class III isoform of P-glycoprotein. These findings suggest that the P-glycoprotein isoforms have distinct physiological roles associated with specialized cell functions.
Viability of fibroblast‐seeded ligament analogs after autogenous implantation (1998)

Fibroblast-seeded collagen scaffolds or ligament analogs are potentially useful for reconstruction of the anterior cruciate ligament of the knee. To provide lasting benefits, the seeded cells must survive implantation within the harsh synovial environment of the knee joint. Our objective was to determine the in vivo fate of autogenous fibroblast-seeded ligament analogs as a function of fibroblast source (anterior cruciate ligament or skin), implantation site (knee joint or subcutaneous space), and time after implantation (1, 2, 4, 6, or 8 weeks). Before implantation, fibroblasts were labeled with PKH26-GL, a fluorescent membrane dye. Immediately after retrieval of the implant, the viability of the labeled seeded cells was assessed under a fluorescent microscope. Viable seeded fibroblasts remained attached to the collagen fibers within the ligament analogs for at least 4 weeks (skin fibroblasts) or 6 weeks (anterior cruciate ligament fibroblasts) after implantation. A larger number of viable seeded cells were consistently observed in the subcutaneous space than in the knee joint. Scaffold resorption prevented observation at the 8-week time period. Fibroblast-seeded ligament analogs remained viable for prolonged periods in the knee joint and therefore have the potential to influence the formation and remodeling of neoligament tissue after reconstruction of the anterior cruciate ligament.
Characterization of deoxyribonucleic acid synthesis in reconstituted nuclear systems (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of deoxyribonucleic acid synthesis in reconstituted nuclear systemsTakemi Enomoto, Seiichi Tanuma, and Masaatsu YamadaCite this: Biochemistry 1983, 22, 5, 1128–1133Publication Date (Print):March 1, 1983Publication History Published online1 May 2002Published inissue 1 March 1983https://pubs.acs.org/doi/10.1021/bi00274a021https://doi.org/10.1021/bi00274a021research-articleACS PublicationsRequest reuse permissionsArticle Views15Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Histopathologic analysis of intraarterial polyvinyl alcohol microemboli in rat cerebral cortex. (1984)

Polyvinyl alcohol (PVA) foam particles have been used with success in both experimental and clinical embolization of vascular lesions. Cellular response to PVA has been well documented outside, but not within, the central nervous system. This study was directed specifically at the cellular response to PVA in rat brain vasculature. By using small numbers of microparticles, an effort was made to define the response to PVA alone, rather than associated occlusions or infarctions. It was determined that PVA elicited no significant inflammatory response in the embolized vessels nor in the surrounding tissue. The isolated fragments did not appear to alter the blood-brain barrier. The PVA microemboli were extremely adherent to vascular endothelium, lodging in vessels of larger diameter and in relatively high-flow locations without actually wedging within the vessel lumen. On the basis of this analysis, it was determined that PVA foam has properties suitable for an intracerebral vascular embolic agent.