gebhart/patrepeval huggingface dataset:
Depsipeptide (FR901228): A Novel Therapeutic Agent With Selective, In Vitro Activity Against Human B-Cell Chronic Lymphocytic Leukemia Cells (1999)

Therapy of B-cell chronic lymphocytic leukemia (CLL) has been limited by both the nonselectivity of therapeutic agents toward normal residual immune cells and inherent drug resistance. Identification of agents that spare normal immune effector cells, thus facilitating addition of immune-based therapies, and that modulate factors associated with drug resistance in CLL might represent a major therapeutic advance. Depsipeptide (FR901228) is a novel agent entering clinical trials that has selective in vitro activity against resistant leukemia cell lines. To assess its in vitro activity in CLL, we exposed peripheral mononuclear cells from CLL patients (n = 10) to varying concentrations of this agent. Viability of the CLL cells was reduced by 50% (LC50) at 4 hours, 24 hours, and 4 days at depsipeptide concentrations of 0.038, 0.024, and 0.015 μmol/L, respectively. Depsipeptide had marked selective cytotoxicity when compared with normal blood mononuclear cells, in which the LC50 was 3.44 μmol/L at 4 hours (P = .03), 0.965 μmol/L at 24 hours (P = .01), and 0.0318 μmol/L at 96 hours (P = .04). Inhibition of bone marrow progenitor cell growth was also minimal after incubation with 0.015 μmol/L (19% inhibition of colony forming unit-granulocyte-macrophage [CFU-GM]; 17% inhibition burst forming unit-erythroid [BFU-E]) and 3.44 μmol/L (24% inhibition of CFU-GM; 57% inhibition BFU-E) of depsipeptide for 4 hours, followed by a 14-day incubation period. Expression of apoptotic proteins after depsipeptide exposure (0.015 μmol/L) included no change in bcl-2, elevation of bax, and decreased expression of p27. These data demonstrate that depsipeptide has significant selective in vitro activity against human CLL cells concurrent with favorable alterations of the bcl-2:bax protein ratio and decrease in p27 expression. Such findings strongly support the early introduction of depsipeptide into clinical trials for patients with CLL.
Effect of Mineral Content of Orchardgrass (Dactylis glomerata L.) on Mineral Balance of Goats (1993)

Orchardgrass(Dactylis glomerata L.) hays, which had been harvested in different seasons and grown with different levels of potassium (K)fertilizer, were fed to foats in metabolic cages in order to know the effect forage mineral content on mineral balance of goats. The K contents of the feed were 3.4, 4.9 and 5.8% and magnesium (Mg) contents were 0.26, 0.21 and 0.21% on a det matter(DM) basis in K-low, K0medium and K-high treatments, respectively. Urinary K excretion was significantly more on K-high than on K-low treatment. Faecal and urinary Mg excrerions on K-low were higher than those on K-medium and K-high feeds. And there was a tendency of positive relation between urinary Mg excretion and serum Mg concentrarion. Goats on K-high treatment seemed to drink more water and excrete more urine than those on the other feeds.
Activation of Signaling Lymphocytic Activation Molecule Triggers a Signaling Cascade That Enhances Th1 Responses in Human Intracellular Infection (2004)

T cell production of IFN-gamma contributes to host defense against infection by intracellular pathogens, including mycobacteria. Lepromatous leprosy, the disseminated form of infection caused by Mycobacterium leprae, is characterized by loss of cellular response against the pathogen and diminished Th1 cytokine production. Relieving bacterial burden in Ag-unresponsive patients might be achieved through alternative receptors that stimulate IFN-gamma production. We have previously shown that ligation of signaling lymphocytic activation molecule (SLAM) enhances IFN-gamma in mycobacterial infection; therefore, we investigated molecular pathways leading from SLAM activation to IFN-gamma production in human leprosy. The expression of the SLAM-associated protein (an inhibitory factor for IFN-gamma induction) on M. leprae-stimulated cells from leprosy patients was inversely correlated to IFN-gamma production. However, SLAM ligation or exposure of cells from lepromatous patients to a proinflammatory microenvironment down-regulated SLAM-associated protein expression. Moreover, SLAM activation induced a sequence of signaling proteins, including activation of the NF-kappaB complex, phosphorylation of Stat1, and induction of T-bet expression, resulting in the promotion of IFN-gamma production, a pathway that remains quiescent in response to Ag in lepromatous patients. Therefore, our findings reveal a cascade of molecular events during signaling through SLAM in leprosy that cooperate to induce IFN-gamma production and strongly suggest that SLAM might be a focal point for therapeutic modulation of T cell cytokine responses in diseases characterized by dysfunctional Th2 responses.
Impairment of the ubiquitin?proteasome system by truncated cardiac myosin binding protein C mutants (2005)

Truncated cMyBP-Cs are preferentially degraded by the UPS, which, in turn, may competitively inhibit breakdown of other UPS substrates. Since the UPS plays an important role in a variety of fundamental cellular processes, we propose impairment of this system by mutant cMyBP-Cs as a contributing factor to the pathogenesis of FHC.
Heat-Assisted Magnetic Recording (2006)

Due to the limits of conventional perpendicular magnetic recording, it appears that alternative technologies are needed at areal densities >500 Gb/in <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Heat-assisted magnetic recording (HAMR) is a promising approach to extend areal densities to 1 Tb/in <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and beyond. All of the unique components necessary for a working HAMR system have been demonstrated. Although HAMR permits writing on high Hc media with lower magnetic fields and can produce higher write gradients than conventional magnetic recording, head/media spacing and the development of high Hc media with small grains remains challenging
Endometriosis and Infertility (2002)

A bstract : Two major methodological problems that impact clinical research in endometriosis are the absence of a low‐cost, highly reliable method for diagnosing endometriosis and the possibility that endometriosis is actually multiple different diseases that we have not yet been able to differentiate. Animal models of endometriosis clearly demonstrate that advanced endometriosis causes reduced fertility. In humans, endometriosis and infertility are commonly associated. However, few data from high‐quality clinical trials demonstrate that endometriosis causes infertility in humans. Future research should focus on the implications of the observation that, in ovarian endometriosis cysts, the epithelium is monoclonal. This observation suggests that nonrandom somatic mutations cause ovarian endometriosis cysts. If somatic mutations cause ovarian endometriosis cysts, it is likely that a small number of genes can be identified that play a central role in pathogenesis of this disease.
Triple Stimulus-Responsive Polypeptide Nanoparticles That Enhance Intratumoral Spatial Distribution (2012)

To address the limited tumor penetration of nanoparticle drug delivery vehicles, we report the first pH-responsive polypeptide micelle that dissociates at the low extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide block copolymer self-assembles at 37 °C into spherical micelles that are stabilized by Zn(2+) and are disrupted as the pH drops from 7.4 to 6.4. These pH-sensitive micelles demonstrate better in vivo penetration and distribution in tumors than a pH-insensitive control.
Cycloaddition Chemistry of 1,3-Dienes on the Silicon(001) Surface:  Competition between [4 + 2] and [2 + 2] Reactions (1998)

The reactions of 1,3-dienes with the Si(001) surface have been investigated using scanning tunneling microscopy (STM) and Fourier transform infrared spectroscopy (FTIR), and the relative efficiencies of [2 + 2] and [4 + 2] reactions have been determined. STM and FTIR studies show that the 2,3-dimethyl-1,3-butadiene molecule has two bonding configurations; 80% of the molecules bond via a [4 + 2] reaction involving both alkene groups with the remaining 20% bonding via a [2 + 2] reaction involving only one alkene group. The molecule 1,3-cyclohaxadiene shows three separate bonding configurations in the STM, and the FTIR shows at least four separate peaks in the alkene stretching region. The [4 + 2] product is found to comprise 55% of the surface species, the [2 + 2] product 35%, and an unknown product 10%. The surface temperature is found to have little affect on the product distribution. The formation of multiple products and the lack of temperature effects indicate that the product distribution is controlled primarily by the kinetics of the adsorption process, not by the thermodynamics. Thus, although [4 + 2] reactions are predicted to be more stable, [2 + 2] reactions occur nearly as frequently.
NEUTROPHIL INFILTRATION AS AN IMPORTANT FACTOR IN LIVER ISCHEMIA AND REPERFUSION INJURY (1993)

To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.
Cytomimetic Biomaterials. 4. In-Situ Photopolymerization of Phospholipids on an Alkylated Surface (2000)

A stable, substrate-supported phospholipid film was created by in-situ photopolymerization of an acrylate functionalized lipid assembly. The lipid film was generated on alkylated substrates by vesicle fusion and polymerized by irradiation with visible light, using eosin Y/triethanolamine as the photoinitiating species. Optimal experimental conditions were determined with respect to vesicle fusion time and duration of irradiation. The resulting polymeric lipid film was characterized by contact angle measurements, angle-resolved ESCA, and polarized external reflectance infrared spectroscopy. Static stability and desorption studies indicate enhanced stability of the photopolymerized system when compared with a heat-initiated analogue prepared by classical free-radical techniques.
REVIEW ARTICLE: The Unique Properties of Uterine NK Cells (2010)

Natural killer (NK) cells are lymphocytes of the innate immunity system that are able to kill various hazardous pathogens and tumors. However, it is now widely accepted that NK cells also possess non-destructive functions, as has been demonstrated for uterine NK cells. Here, we review the unique properties of the NK cells in the uterine mucosa, prior to and during pregnancy. We discuss the phenotype and function of mouse and human endometrial and decidual NK cells and suggest that the major function of decidual NK cells is to assist in fetal development. We further discuss the origin of decidual NK cells and suggest several possibilities that might explain their accumulation in the decidua during pregnancy.
Self-complementary adeno-associated viral vectors for gene therapy of hemophilia B: progress and challenges (2011)

Therapies currently used for hemophilia involve injection of protein concentrates that are expensive, invasive and associated with side effects such as development of neutralizing antibodies (inhibitors) that diminish therapeutic efficacy. Gene transfer is an attractive alternative to circumvent these issues. However, until now, clinical trials using gene therapy to treat hemophilia have failed to demonstrate sustained efficacy, although a vector based on a self-complementary adeno-associated virus has recently shown promise. This article will briefly outline a novel gene-transfer approach using self-complementary adeno-associated viral vectors using hemophilia B as a target disorder. This approach is currently being evaluated in the clinic. We will provide an overview of the development of self-complementary adeno-associated virus vectors as well as preclinical and clinical data with this vector system.
Access audit trails: en route to security. (2000)

An electronic access audit trail can be an effective security tool if the right conditions are in place. In this article, learn how to ensure that your organization has the right technology, procedures, mechanisms, and plans to implement an audit trial.
Nuclease-resistant ribozymes decrease stromelysin mRNA levels in rabbit synovium following exogenous delivery to the knee joint. (1996)

Catalytic RNA molecules, or ribozymes, have generated significant interest as potential therapeutic agents for controlling gene expression. Although ribozymes have been shown to work in vitro and in cellular assays, there are no reports that demonstrate the efficacy of synthetic, stabilized ribozymes delivered in vivo. We are currently utilizing the rabbit model of interleukin 1-induced arthritis to assess the localization, stability, and efficacy of exogenous antistromelysin hammerhead ribozymes. The matrix metalloproteinase stromelysin is believed to be a key mediator in arthritic diseases. It seems likely therefore that inhibiting stromelysin would be a valid therapeutic approach for arthritis. We found that following intraarticular administration ribozymes were taken up by cells in the synovial lining, were stable in the synovium, and reduced synovial interleukin 1 alpha-induced stromelysin mRNA. This effect was demonstrated with ribozymes containing various chemical modifications that impart nuclease resistance and that recognize several distinct sites on the message. Catalytically inactive ribozymes were ineffective, thus suggesting a cleavage-mediated mechanism of action. These results suggest that ribozymes may be useful in the treatment of arthritic diseases characterized by dysregulation of metalloproteinase expression.
Detection of eukaryotic translation initiation factor 4E and its clinical significance in hepatocellular carcinoma (2012)

In summary, eIF4E expression is associated with liver cancer, and patients with high eIF4E expression levels have a higher risk of recurrence.
Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China (2011)

A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Allogeneic Bone Marrow Transplantation from Unrelated Human T-Cell Leukemia Virus-I–negative Donors for Adult T-Cell Leukemia/Lymphoma: Retrospective Analysis of Data from the Japan Marrow Donor Program (2007)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-matched related donor has been suggested to improve the poor prognosis of adult T-cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I-infected cells from HTLV-I-positive related donors could lead to the development of donor-derived ATLL under immunosuppressive conditions. Although most ATLL patients lack a suitable HLA-matched related donor and require an HTLV-I-negative unrelated donor, little information is currently available regarding the outcome of unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall survival (OS), progression-free survival, and cumulative incidence of disease progression and progression-free mortality at 1 year after UBMT were 49.5%, 49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient age as an independent prognostic factor for OS (P = .044). Patients age >or=50 years who showed nonremission at transplantation tended to have higher rates of treatment-related mortality. Our observations suggest that UBMT could represent a feasible treatment option for ATLL patients and warrant further investigation based on these risk factors.
FIBRONECTIN AND ITS RECEPTORS (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. (1998)

The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling assay and nuclear staining, respectively (P < 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5% ethanol (P < 0.001). HuH-7 cells exhibited increased apoptosis with 1 nM TGF-beta1 (P < 0. 001) or DCA at >/= 100 microM (P < 0.001), as did Hep G2 cells after incubation with anti-Fas antibody (P < 0.001). Finally, incubation with okadaic acid induced significant apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with each of the apoptosis-inducing agents was associated with a 50-100% inhibition of apoptotic changes (P < 0.001) in all the cell types. Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P < 0.001). FACS(R) analysis revealed that the apoptosis-inducing agents decreased the mitochondrial transmembrane potential and increased reactive oxygen species production (P < 0.05). Coadministration of UDCA was associated with significant prevention of mitochondrial membrane alterations in all cell types. The results suggest that UDCA plays a central role in modulating the apoptotic threshold in both hepatocytes and nonliver cells, and inhibition of MPT is at least one pathway by which UDCA protects against apoptosis.
Electrochemically Mediated Atom Transfer Radical Polymerization (2011)

Atom transfer radical polymerization is a versatile technique for exerting precise control over polymer molecular weights, molecular weight distributions, and complex architectures. Here, we show that an externally applied electrochemical potential can reversibly activate the copper catalyst for this process by a one-electron reduction of an initially added air-stable cupric species (Cu(II)/Ligand). Modulation of polymerization kinetics is thereby tunable in real time by varying the magnitude of applied potential. Application of multistep intermittent potentials successfully triggers initiation of polymerization and subsequently toggles the polymerization between dormant and active states in a living manner. Catalyst concentrations down to 50 parts per million are demonstrated to maintain polymerization control manifested in linear first-order kinetics, a linear increase in polymer molecular weight with monomer conversion, and narrow polymer molecular weight distributions over a range of applied potentials.
Cells within the bulge region of mouse hair follicle transiently proliferate during early anagen: heterogeneity and functional differences of various hair cycles (1994)

Based on cell kinetic, morphological and several biological considerations, we have recently proposed that hair follicle stem cells reside in the bulge area of the upper follicle. We predicted that during early anagen the normally slow-cycling bulge stem cells may be activated by the abutting dermal papilla cells to undergo transient proliferation giving rise to keratinocytes of the lower follicle. In the present work, we performed tritiated thymidine-labeling of DNA-synthesizing cells and colcemid-arrest of mitotic figures on the skins of 20-23 and 75-80 day old SENCAR mice, when the follicles entered the anagen phase of the 2nd and 3rd hair cycles. The results clearly indicate that the normally slow-cycling bulge cells indeed undergo transient proliferation during early anagen. Similar results were obtained when the telogen follicles are experimentally induced to enter the 3rd hair cycle by plucking and by topical applications of phorbol ester or tretinoin. These results support the notion that bulge cells are follicular stem cells, and that transient proliferation of these cells is a critical feature of early anagen. However, the long duration of the 2nd telogen (> 30 days in mouse) suggests that a new anagen phase does not automatically result from the physical proximity of dermal papilla to the bulge cells, and that another 'factor' is required for the initiation of the 3rd anagen. The tremendous difference in the durations of the first and second telogen (lasting for 2-3 days and > 50 days, respectively) suggests that follicles can exist in a non-cycling state that may be conceptually equivalent to the G0 state of the cell cycle. Our results also underscore the fact that the first hair cycle is distinct from all the subsequent hair cycles in their cellular origin and morphological sequence, and thus should be regarded as a neogenic event.
Correlation of the rates of solvolysis of allyl and benzyl arenesulphonates (1984)

Analysis of the specific rates of solvolysis of allyl arenesulphonates in terms of the extended Grunwald–Winstein equation indicates a marked dependence on both the solvent nucleophilicity (high l value) and the solvent ionizing power (highm value). As the charge delocalization in the leaving group increases, both l and m values fall. For allyl toluene-p-sulphonate solvolysis in 28 solvents at 50.0 °C, values for l(0.83) and for m(0.63), based on the use of NKL and Y values, are very similar to the equivalent values of 0.90 and 0.67 previously reported for benzyl toluene-p-sulphonate solvolysis. Related extended Grunwald–Winstein analyses are considered and the need for variety in the choice of solvents is emphasized.
OUTROS CORPOS ESTÃO EM MOVIMENTO, OUTROS CAMPOS AMPLIAM AS DISPUTAS (2011)

O texto aborda os chamados novos movimentos sociais e tenta levantar algumas questoes que ainda nao podem ser completamente compreendidas. Dos movimentos sociais parte para os movimentos culturais, fundamentalmente aqueles que sao produzidos pelos jovens das periferias urbanas. Levanta alguns aspectos dessa producao e da complexa relacao destes jovens com a politica e com os sentidos mais tradicionais de “movimento social” e as suas cumplicidades com as tecnologias da informacao e da comunicacao (tics) Apresenta, como materializacao destas iniciativas, o Movimento Enraizados, de Morro Agudo, Nova Iguacu. Finaliza tentando levantar - e nao responder - algumas outras questoes para a educacao, para as praticas pedagogicas, para a escola.