gebhart/patrepeval huggingface dataset:
Abstract 15385: Acute Intravenous Infusion of Bendavia (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular Systolic Function in Dogs with Advanced Heart Failure (2012)

Background: Bendavia (MTP-131) is a novel mitochondria-targeting peptide that improves the efficiency of mitochondria electron transfer chain and improves mitochondria respiration and ATP synthesis. This study examined the acute effects of intravenous Bendavia on left ventricular (LV) systolic function in dogs with advanced heart failure (HF). Methods: Studies were performed in 12 anesthetized dogs with intracoronary microembolization-induced HF. Seven dogs, selected at random, received intravenous Bendavia at a dose of 0.05 mg/kg/hr for 2 hours and 5 dogs received a volume matched placebo control (normal saline) also administered over 2 hours. Hemodynamic and ventriculographic measurements were made at baseline, prior to drug administration, and at the end of 2 hours of drug or placebo infusion. Measurements included heart rate (HR), mean aortic pressure (mAoP), LV ejection fraction (EF), stroke volume (SV), cardiac output (CO), LV peak +dP/dt and systemic vascular resistance (SVR). Results: Data are shown in the table (mean ± SEM). Compared to baseline, saline infusion over 2 hours had no effect on HR, mAoP, EF, ESV, SV, peak +dP/dt and SVR. Infusion of Bendavia also had no effect on HR, mAoP or SVR but significantly increased EF, SV, CO and +dP/dt. Conclusions: In dogs with advanced HF, acute intravenous administration of Bendavia improved LV systolic function without increasing heart rate or decreasing systemic pressure and SVR. The improvement of LV function is likely the result of improved cardiac energetics. The findings support the continued development of Bendavia for the treatment of patients with acute HF syndromes.
"Viable motheaten," a new allele at the motheaten locus. I. Pathology. (1984)

A new spontaneous autosomal recessive mutation has recently occurred at the motheaten (me) locus on Chromosome 6 in strain C57BL/6J mice. Homozygotes for the new allele, designated "viable motheaten" (mev), have a mean life span of 61 +/- 2.4 days, compared with only 22 +/- 1.3 days for C57BL/6J-me/me mice. Like the original motheaten mutation, the immediate cause of death in mev/mev mice appears to be severe pneumonitis associated with accumulations of macrophages, granulocytes, and lymphocytes in the lungs. However, because of its longer life span, progression of the disease in mev/mev mice is more amenable to investigation. Eosinophilic crystalline material in alveolar macrophages from mev/mev mice is associated with extravasation of erythrocytes into alveoli. These crystals are morphologically indistinguishable from hematoidin, which results from hemoglobin breakdown following uptake of erythrocytes by macrophages. Severe macrocytic hypochromic anemia with abnormalities in size and shape of erythrocytes develops by 7 weeks. A two-fold increase in peripheral leukocyte count and a five-fold increase in the percentage of neutrophils is seen by 10 weeks. Viable motheaten mice develop focal granulocytic skin lesions by 4 days of age, show depletion of cells from the thymus cortex by 4 weeks, and lack lymphoid follicles in the lymph nodes, spleen, and Peyer's patches. Excessive erythropoiesis and myelopoiesis in the spleen result in marked splenomegaly. Lymph nodes and spleens from mev/mev mice contain increased numbers of plasma cells by 3 weeks; and by 6 weeks, large numbers of atypical plasma cells with Russell bodies are evident. Development of glomerulonephritis by 10 weeks is characterized by granular depositis of immunoglobulin and complement within glomeruli. A twofold increase of blood urea nitrogen levels is present by 15 weeks. Sterility of male mev/mev mice is associated with Leydig cell depletion in the testes, lowered testosterone levels, and impaired spermatogenesis.
Herpesvirus Transport to the Nervous System and Back Again (2012)

Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities.
Effect of Light Fermions on the Confinement Transition in QCD-Like Theories (2012)

The dependence of the confinement transition parameters on the fermion content provides information on the mechanism of confinement. Recent progress in lattice gauge theories has allowed us to study it for a light flavor number N(f)~O(10) and found this transition to shift toward significantly stronger coupling. We propose an explanation for that: light fermions can occupy the chromomagnetic monopoles, via zero modes, making them "distinguishable" and unsuitable for Bose-Einstein condensation. Such dilution of unoccupied monopoles is compensated by stronger coupling that makes them lighter and more numerous. We also suggest that flavor-carrying quark-monopole objects account for the density beyond the quark Fermi sphere seen in the cold dense phase of N(c)=2 lattice QCD.
Tumor Suppressor p53 as a Component of the Tumor Necrosis Factor-induced, Protein Kinase PKR-mediated Apoptotic Pathway in Human Promonocytic U937 Cells (1998)

Despite what is known about the early signaling events in tumor necrosis factor (TNF) alpha-induced apoptosis, characterization of the downstream events remains largely undefined. It is now known that a cross-talk exists between the interferon and TNF-alpha pathways. This linkage allows recruitment of the cell proliferation suppressor PKR (dsRNA-dependent protein kinase) from the interferon pathway to play a pivotal role in TNF-alpha-induced apoptosis. In this study, we took advantage of the differential TNF-alpha susceptibilities of human promonocytic U937 subclones, deficient in or overexpressing PKR, to further characterize the role of PKR in apoptosis. By reverse transcription-polymerase chain reaction, we demonstrated that TNF-alpha transiently induces the tumor suppressor p53 in U937 cells. This p53 induction lags behind the TNF-alpha induction of PKR by 1 h. By cell viability determination, ultrastructural studies, apoptotic DNA laddering, and antisense techniques, it was shown that inhibition of p53 expression in PKR-overexpressing U937 cells abrogates the TNF-alpha-induced apoptosis in these cells. Conversely, overexpressing wild type p53 in PKR-deficient U937 cells confers the susceptibility of these cells to TNF-alpha-induced apoptosis. This latter result indicates that p53 induction is an event downstream of TNF-alpha-induced up-regulation of PKR, thereby further establishing the critical role of p53 in TNF-alpha-induced apoptosis in U937 cells. PKR-overexpressing U937 cells were found to possess a constitutively higher level of p53, which partly explains why these cells spontaneously undergo apoptosis even without TNF-alpha treatment. Finally, a model is presented on the interplay between PKR and p53 in effecting TNF-alpha-induced apoptosis in U937 cells.
A multicenter, randomized, double‐blind, placebo‐controlled trial of adjuvant methotrexate treatment for giant cell arteritis (2002)

The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.
A New Triglycyl Peptide Linker for Antibody–Drug Conjugates (ADCs) with Improved Targeted Killing of Cancer Cells (2016)

A triglycyl peptide linker (CX) was designed for use in antibody -: drug conjugates (ADC), aiming to provide efficient release and lysosomal efflux of cytotoxic catabolites within targeted cancer cells. ADCs comprising anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-EGFR antibodies with maytansinoid payloads were prepared using CX or a noncleavable SMCC linker (CX and SMCC ADCs). The in vitro cytotoxic activities of CX and SMCC ADCs were similar for several cancer cell lines; however, the CX ADC was more active (5-100-fold lower IC50) than the SMCC ADC in other cell lines, including a multidrug-resistant line. Both CX and SMCC ADCs showed comparable MTDs and pharmacokinetics in CD-1 mice. In Calu-3 tumor xenografts, antitumor efficacy was observed with the anti-EpCAM CX ADC at a 5-fold lower dose than the corresponding SMCC ADC in vivo Similarly, the anti-EGFR CX ADC showed improved antitumor activity over the respective SMCC conjugate in HSC-2 and H1975 tumor models; however, both exhibited similar activity against FaDu xenografts. Mechanistically, in contrast with the charged lysine-linked catabolite of SMCC ADC, a significant fraction of the carboxylic acid catabolite of CX ADC could be uncharged in the acidic lysosomes, and thus diffuse out readily into the cytosol. Upon release from tumor cells, CX catabolites are charged at extracellular pH and do not penetrate and kill neighboring cells, similar to the SMCC catabolite. Overall, these data suggest that CX represents a promising linker option for the development of ADCs with improved therapeutic properties. Mol Cancer Ther; 15(6); 1311-20. ©2016 AACR.
Theory of quantum error-correcting codes (1997)

Quantum error correction will be necessary for preserving coherent states against noise and other unwanted interactions in quantum computation and communication. We develop a general theory of quantum error correction based on encoding states into larger Hilbert spaces subject to known interactions. We obtain necessary and sufficient conditions for the perfect recovery of an encoded state after its degradation by an interaction. The conditions depend only on the behavior of the logical states. We use them to give a recovery-operator-independent definition of error-correcting codes. We relate this definition to four others: the existence of a left inverse of the interaction, an explicit representation of the error syndrome using tensor products, perfect recovery of the completely entangled state, and an information theoretic identity. Two notions of fidelity and error for imperfect recovery are introduced, one for pure and the other for entangled states. The latter is more appropriate when using codes in a quantum memory or in applications of quantum teleportation to communication. We show that the error for entangled states is bounded linearly by the error for pure states. A formal definition of independent interactions for qubits is given. This leads to lower bounds on the number of qubits required to correct e errors and a formal proof that the classical bounds on the probability of error of e-error-correcting codes applies to e-error-correcting quantum codes, provided that the interaction is dominated by an identity component.
Status of research with transgenic farm animals (1993)

Microinjection is the predominant method used to transfer genes into farm animals. Current research is devoted to improvement of productivity traits, enhancement of animal health, and production of biomedically useful human health products. Initial transgenic research primarily involved genes coding for growth hormone (GH), growth hormone-releasing factor (GRF), and insulin-like growth factor I (IGF-I). More recent investigations have attempted to stimulate muscle development, to use bacterial enzymes so animals can synthesize certain essential amino acids, to induce expression of specific immunoglobulin or disease-resistance genes, and to direct expression of human proteins to the mammary gland, specific organs, or specific cells for production of useful human health products. The main limitations to progress are the lack of useful cloned genes for productivity traits and disease resistance and the insufficient knowledge of mechanisms involved in regulation of transgenes.
Decrease in cellularity and expression of adhesion molecules by anti–tumor necrosis factor α monoclonal antibody treatment in patients with rheumatoid arthritis (1996)

The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.
Recognition of Fungal Protease Activities Induces Cellular Activation and Eosinophil-Derived Neurotoxin Release in Human Eosinophils (2009)

Eosinophils are multifunctional leukocytes implicated in the pathogenesis of asthma and in immunity to certain organisms. Associations between exposure to an environmental fungus, such as Alternaria, and asthma have been recognized clinically. Protease-activated receptors (PARs) are G protein-coupled receptors that are cleaved and activated by serine proteases, but their roles in innate immunity remain unknown. We previously found that human eosinophils respond vigorously to Alternaria organisms and to the secretory product(s) of Alternaria with eosinophils releasing their proinflammatory mediators. In this study, we investigated the roles of protease(s) produced by Alternaria and of PARs expressed on eosinophils in their immune responses against fungal organisms. We found that Alternaria alternata produces aspartate protease(s) and that human peripheral blood eosinophils degranulate in response to the cell-free extract of A. alternata. Eosinophils showed an increased intracellular calcium concentration in response to Alternaria that was desensitized by peptide and protease ligands for PAR-2 and inhibited by a PAR-2 antagonistic peptide. Alternaria-derived aspartate protease(s) cleaved PAR-2 to expose neo-ligands; these neo-ligands activated eosinophil degranulation in the absence of proteases. Finally, treatment of Alternaria extract with aspartate protease inhibitors, which are conventionally used for HIV-1 and other microbes, attenuated the eosinophils' responses to Alternaria. Thus, fungal aspartate protease and eosinophil PAR-2 appear critical for the eosinophils' innate immune response to certain fungi, suggesting a novel mechanism for pathologic inflammation in asthma and for host-pathogen interaction.
Cloning, sequence determination, and expression of a 32-kilodalton-protein gene of Mycobacterium tuberculosis (1989)

We describe the identification of the gene encoding an immunodominant 32-kilodalton (kDa) protein of Mycobacterium tuberculosis. The 32-kDa antigen is abundantly secreted into the culture supernatant of a variety of mycobacteria and appears to be a major stimulant of cellular and humoral immunity against mycobacteria. Recombinant clones expressing a 140- or 125-kDa beta-galactosidase fusion protein reactive with rabbit polyclonal anti-32 kDa protein serum were detected. The corresponding DNA sequence contains a 1,008-base-pair coding region. The deduced amino acid sequence corresponds to a 336-residue protein including the previously determined NH2-terminal sequence of the 32-kDa protein (J. De Bruyn, K. Huygen, R. Bosmans, M. Fauville, R. Lippens, J. P. Van Vooren, P. Falmagne, M. Weckx, H. G. Wiker, M. Harboe, and M. Turneer, Microb. Pathog. 2:351-366, 1987). Upstream of this NH2-terminal region, the gene codes for a signal peptide required for the secretion of a 294-amino-acid-long mature protein. A putative promoter sequence could be located upstream of the open reading frame. Comparison of the M. tuberculosis 32-kDa antigen with the Mycobacterium bovis BCG alpha-antigen (K. Matsuo, R. Yamaguchi, A. Yamazaki, H. Tasaka, and T. Yamada, J. Bacteriol. 170:3847-3854, 1988) revealed 73.8% homology between DNA sequences and 72.8% homology between amino acid sequences (signal and mature protein). Finally, the 140-kDa fusion protein could selectively be recognized by human tuberculous sera. This result confirms our previous finding that the 32-kDa antigen could be a valuable tool for the serological diagnosis of tuberculosis. Moreover, the availability of recombinant proteins opens perspectives for the localization of relevant B- and T-cell epitope regions on the 32-kDa antigen.
Salmonella typhimurium delta aroA delta aroD mutants expressing a foreign recombinant protein induce specific major histocompatibility complex class I-restricted cytotoxic T lymphocytes in mice (1993)

Recombinant Salmonella typhimurium aroA aroD mutants which expressed ovalbumin were constructed. The two expression constructs used were based on either pUC18 or pBR322. The pBR322-based construct was more stable in vitro and in vivo than the pUC-based construct. Salmonellae containing the stable pBR322-based plasmid induced major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL), in contrast to salmonellae containing the pUC18-based expression construct. The priming of MHC class I-restricted CTL was increased by multiple immunizations. The study described in this report suggest that S. typhimurium delta aro mutants have the capacity to induce MHC class I-restricted CTL against carried antigens and that MHC class I-restricted CTL responses require stable in vivo expression of the target antigen. Further, the results indicate that the Salmonella typhi delta aro mutants currently undergoing evaluation in studies with humans may be good carriers of viral antigens with CTL determinants.
A zirconium methacrylate oxocluster as precursor for the low-temperature synthesis of porous zirconium(iv) dicarboxylates (2009)

The exchange of the monocarboxylate ligand of the zirconium methacrylate oxocluster Zr(6)O(4)(OH)(4)(OMc)(12) (OMc = CH(2)=CH(CH(3))COO) with dicarboxylic acids (trans,trans muconic acid and terephthalic acid) leads to porous zirconium dicarboxylates exhibiting the UiO-66 architecture; the mild reaction conditions allow the control of their particle size.
Nitrite‐derived nitric oxide: a possible mediator of ‘acidic–metabolic’ vasodilation (2001)

The fundamental, yet poorly understood, physiological mechanism known as 'acidic-metabolic' vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non-enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 microM. Nitrite-evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non-enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto-regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.
Therapeutic Effects and Adverse Reactions to Oral Hypoglycemic Agents (1976)

The purpose of this study is to investigate the controlled blood sugar level and incidence of adverse reactions in the controlled diabetic out-patients who had been treated with oral hypoglycemic agents. Change in blood sugar level and body weight of each of the 427 patients were recorded before and after the start of the therapy, and the variety and incidence of adverse reactions were analyzed. Of the 427 cases, 90% showed good or fair control indicating satisfactory blood sugar level. Weight reduction appeared to be mild in the group of patients receiving sulfonylurea, as compared with the group on biguanide. It was felt that more effective dietary care should be taken for this group. Low blood sugar level was noted in 10.4% of the sulfonylurea group. The results of this study indicate that in order to maintain an appropriate blood sugar control by sulfonylurea, occurrence of some mild cases of low blood sugar level are unavoidable.
Autophagy and Human Disease (2007)

As a conserved cellular degradative pathway in eukaryotes, autophagy relieves cells from various types of stress. There are different forms of autophagy, and the ongoing studies of the molecular mechanisms and cellular functions of these processes are unraveling their significant roles in human health. Currently, the best-studied of these pathways is macroautophagy, which is linked to a range of human disease. For example, as part of the host immune defense mechanism, macroautophagy is activated to eliminate invasive pathogenic bacteria; however, in some cases bacteria subvert this process for their own replication. Autophagy also contributes to endogenous major histocompatibility complex class II antigen presentation, reflecting its role in adaptive immunity. In certain neurodegenerative diseases, which are associated with aggregation-prone proteins, macroautophagy plays a protective role in preventing or reducing cytotoxicity by clearance of the toxic proteins; however, the autophagy-dependent processing of some components correlates with the pathogenesis of certain myopathies. Finally, autophagy acts as a mechanism for tumor suppression, although some cancer cells use it as a cytoprotective mechanism. Thus, a fundamental paradox of autophagy is that it can act to promote both cell survival and cell death, depending on the specific conditions.
A Physical model for shear-wave velocity prediction (1994)

A velocity model for clay-sand mixtures has been developed by Xu and White (1993). In this model, the total pore space is assumed to consist of two parts: (1) pores associated with sand grains and (2) pores associated with clays. It is further assumed that the geometry of sand-related pores is significantly different from that of clay-related pores. This hypothesis has been used to predict published laboratory measurements and recorded sonic logs with better accuracy than standard velocity-porosity models.