gebhart/patrepeval huggingface dataset:
Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance (2009)

PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age-related increases in distribution of oxidative mtDNA damage in sPD but not CTL brains is not clear, tracks with but does not determine the sPD phenotype, and may indicate a unique consequence of aging present in sPD that could contribute to mtDNA deletion generation in addition to mtDNA replication, transcription and sequencing errors. sPD frontal cortex experiences a generalized bioenergetic deficiency above and beyond aging that could contribute to mood disorders and cognitive impairments.
Rituximab as First-Line and Maintenance Therapy for Patients With Indolent Non-Hodgkin’s Lymphoma (2002)

Rituximab is highly active and extremely well tolerated as first-line single-agent therapy for indolent NHL. First-line treatment with scheduled maintenance at 6-month intervals produces high overall and complete response rates and a longer progression-free survival (34 months) than has been reported with a standard 4-week treatment.
Complications and validity of pulmonary angiography in acute pulmonary embolism. (1992)

The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.
Gamma Interferon and Cadmium Treatments Modulate Eukaryotic Initiation Factor 4E-Dependent mRNA Transport of Cyclin D1 in a PML-Dependent Manner (2002)

The eukaryotic initiation factor 4E (eIF4E), when dysregulated, transforms cells. A substantial fraction of eIF4E forms nuclear bodies that colocalize with those associated with the promyelocytic leukemia protein PML. Overexpression studies indicate that nuclear eIF4E promotes the transport of cyclin D1 mRNA from the nucleus to the cytoplasm and that PML is a key negative regulator of this function. Since previous studies used overexpression methods, the physiological relevance of eIF4E mRNA transport function or its interaction with PML remained unknown. Therefore, we monitored whether eIF4E-dependent transport could be modulated in response to environmental conditions. Here we report that cadmium treatment, which disperses PML nuclear bodies, leaves eIF4E bodies intact, leading to increased transport of cyclin D1 mRNA and increased cyclin D1 protein levels. Removal of cadmium allows PML to reassociate with eIF4E nuclear bodies, leading to decreased cyclin D1 transport and reduced cyclin D1 protein levels. In contrast, we show that treating cells with interferon increased the levels of PML protein at the PML-eIF4E nuclear body, leading to nuclear retention of cyclin D1 transcripts and reduced cyclin D1 protein levels. Neither interferon nor cadmium treatment altered cyclin D1 levels in PML(-/-) cells. Consistently, overexpression of a series of PML and eIF4E mutant proteins established that PML eIF4E interaction is required for the observed effects of cadmium and interferon treatment. The present study provides the first evidence that physiological factors modulate the mRNA transport functions of eIF4E and that this regulation is PML dependent.
Integrin α11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells (2007)

Integrin alpha11 (ITGA11/alpha11) is localized to stromal fibroblasts and commonly overexpressed in non-small-cell lung carcinoma (NSCLC). We hypothesized that stromal alpha11 could be important for the tumorigenicity of NSCLC cells. SV40 immortalized mouse embryonic fibroblasts established from wild-type (WT) and Itga11-deficient [knockout (KO)] mice were tested for their tumorigenicity in immune-deficient mice when implanted alone or coimplanted with the A549 human lung adenocarcinoma cells. A549 coimplanted with the fibroblasts showed a markedly enhanced tumor growth rate compared with A549, WT, or KO, which alone formed only small tumors. Importantly, the growth was significantly greater for A549+WT compared with A549+KO tumors. Reexpression of human alpha11 cDNA in KO cells rescued a tumor growth rate to that comparable with the A549+WT tumors. These findings were validated in two other NSCLC cell lines, NCI-H460 and NCI-H520. Gene expression profiling indicated that IGF2 mRNA expression level was >200 times lower in A549+KO compared with A549+WT tumors. Stable short-hairpin RNA (shRNA) down-regulation of IGF2 in WT (WT(shIGF2)) fibroblasts resulted in a decreased growth rate of A549+WT(shIGF2), compared with A549+WT tumors. The results indicate that alpha11 is an important stromal factor in NSCLC and propose a paradigm for carcinoma-stromal interaction indirectly through interaction between the matrix collagen and stromal fibroblasts to stimulate cancer cell growth.
CD200 is induced by ERK and is a potential therapeutic target in melanoma (2007)

Immune-mediated antitumor responses occur in patients with metastatic melanoma (MM), and therapies designed to augment such responses are clinically beneficial. Despite the immunogenicity of melanoma, immunomodulatory therapies fail in the majority of patients with MM. An inability of DCs to sufficiently activate effector cells may, in part, underlie this failure of the antitumor response seen in most patients. In this work, we show that mutation of N-RAS or B-RAF, signature genetic lesions present in most MMs, potently induced the expression of cell-surface CD200, a repressor of DC function. Employing 2 independent, genome-wide microarray analyses, we identified CD200 as a highly dynamic, downstream target of RAS/RAF/MEK/ERK activation in melanoma. CD200 protein was similarly overexpressed in human melanoma cell lines and primary tumors. CD200 mRNA expression correlated with progression and was higher in melanoma than in other solid tumors or acute leukemia. Melanoma cell lines expressing endogenous CD200 repressed primary T cell activation by DCs, while knockdown of CD200 by shRNA abrogated this immunosuppressive effect. These data indicate that in addition to its effects on growth, survival, and motility, ERK activation in MM attenuates a host antitumor immune response, implicating CD200 and its interaction with the CD200 receptor as a potential therapeutic target for MM.
Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”? (2000)

Professional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.
Modulation of 3α-Hydroxysteroid Dehydrogenase Activity by the Redox State of Glutathione (1993)

3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50), purified to homogeneity from rat liver, was strongly inactivated by incubation with a disulfide such as GSSG, L-cystine or L-cystamine, as well as an SH-reagent such as DTNB (5,5'-dithiobis(2-nitrobenzoic acid)), NEM (N-ethylmaleimide) or iodoacetic acid. The inactivation advanced with incubation time. Coenzyme (NADP+) completely protected the enzyme from this inactivation by disulfides, but neither of the substrates (androsterone and benzenedihydrodiol) did. The activity of inactivated enzyme was restored by treatment with thiols such as DTT (dithiothreitol) or GSH. In the GSH/GSSG redox buffer, the enzyme existed in an equilibrium between active (reduced) and inactive (oxidized) forms.
Therapeutic hypothermia with a novel surface cooling device improves neurologic outcome after prolonged cardiac arrest in swine* (2008)

The Life Recovery Systems' ThermoSuit System rapidly and safely induced mild therapeutic hypothermia. Hypothermia improved neurologic outcome in swine after cardiac arrest as compared with normothermia. Further studies are warranted to compare the device with established cooling methods.
Enveloped Virus-Like Particle Expression of Human Cytomegalovirus Glycoprotein B Antigen Induces Antibodies with Potent and Broad Neutralizing Activity (2013)

A prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants is highly desirable. Neutralizing antibodies against HCMV confer significant protection against infection, and glycoprotein B (gB) is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been their failure to induce high-titer persistent neutralizing antibody responses that prevent the infection of epithelial cells. We used enveloped virus-like particles (eVLPs), in which particles were produced in cells after the expression of murine leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing antibodies in mice with a much greater propensity toward epithelial cell-neutralizing activity than that induced with soluble recombinant gB protein. An analysis of gB antibody binding titers and T-helper cell responses demonstrated that high neutralizing antibody titers were not simply due to enhanced immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but not gB plasmid formed syncytia, consistent with a prefusion gB conformation like those of infected cells and viral particles. Two of the five gB-G eVLP-induced monoclonal antibodies we examined in detail had neutralizing activities, one of which possessed particularly potent epithelial cell-neutralizing activity. These data differentiate gB-G eVLPs from gB antigens used in the past and support their use in a CMV vaccine candidate with improved neutralizing activity against epithelial cell infection.
Autoimmunity to Collagen (1981)

Abstract Thirty‐one patients with seronegative psoriatic arthritis, 27 patients with rheumatoid arthritis, 10 with psoriasis alone, and 20 normal volunteers were studied for autoimmunity to human collagens. Cellular and humoral responses were frequently observed in the 2 groups with arthritis, but the subjects without arthritis did not display reactivity to native collagens. These data demonstrate that collagens function as autoantigens in both psoriatic and rheumatoid arthritis.
Proteolytic Cleavage of the p65-RelA Subunit of NF-κB during Poliovirus Infection (2005)

Activation of NF-kappaB during viral infection is one of the critical elements in innate immune response. Several virus-specific factors, such as double-stranded RNA, can trigger host defense mechanisms by inducing NF-kappaB-mediated expression of cytokines and interferons. Early stages of poliovirus infection are also associated with degradation of IkappaB alpha and translocation of NF-kappaB into the nucleus. However, at later stages of poliovirus replication the p65-RelA component of the NF-kappaB complex undergoes a specific cleavage that coincides with the onset of intensive poliovirus protein synthesis and the appearance of the activity of poliovirus protease 3C. Indeed, the p65-RelA amino acid sequence contains the recognition site for 3C, and recombinant protein 3C was shown to be capable of proteolytic cleavage of p65-RelA, generating truncated product similar to that observed during poliovirus infection. Cleavage of p65-RelA occurs during replication of ECHO-1 and rhinovirus 14, suggesting that inactivation of NF-kappaB function by proteolytic cleavage of p65-RelA is the common mechanism by which picornaviruses suppress the innate immune response.
Statistical Modeling of β-galactosidase Inhibition During Lactose Hydrolysis (2006)

A statistical model approach called response surface methodology was used to describe the product and substrate inhibition effect on β-galactosidase enzyme during lactose hydrolysis. The effect of independent variables, namely the initial concentrations of lactose (73 – 146 mM), galactose (44 – 122 mM) and glucose (83 – 167 mM) on the reaction rate of β-galactosidase was evaluated. The enzymatic reaction rate was influenced by both combined and individual effects of all the substrate and products. Although, glucose acted as an activator at low lactose and low galactose concentrations, glucose caused the inhibition of β-galactosidase at higher concentrations of lactose and galactose. The effect of galactose concentration on β-galactosidase enzyme was in the direction of inhibition. At low lactose concentrations and high glucose concentrations, galactose concentration became more effective on the reaction rate.
Chemical synthesis and structure-activity relations for ANF analogues. (1987)

Chemical synthesis of a new peptide hormone allows absolute confirmation of the peptide's structure, allows physiologic and pharmacologic evaluation of the hormone's properties in vivo and in vitro, and permits development of a radioimmunoassay for the hormone. The study of the effects of structure modification on the bioactivity of atrial natriuretic factor (ANF) is at the earliest stages of defining minimum molecular size, aspects of the bioactive conformation, and the contribution of each side chain to receptor binding. A particular problem in the evaluation of structure-function studies with ANF is the diversity of bioassays used by various laboratories.
Vascular Adhesion Molecules in Atherosclerosis (2007)

Numerous reports document the role of vascular adhesion molecules in the development and progression of atherosclerosis. Recent novel findings in the field of adhesion molecules require an updated summary of current research. In this review, we highlight the role of vascular adhesion molecules including selectins, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule1 (ICAM-1), PECAM-1, JAMs, and connexins in atherosclerosis. The immune system is important in atherosclerosis, and significant efforts are under way to understand the vascular adhesion molecule-dependent mechanisms of immune cell trafficking into healthy and atherosclerosis-prone arterial walls. This review focuses on the role of vascular adhesion molecules in the regulation of immune cell homing during atherosclerosis and discusses future directions that will lead to better understanding of this disease.
Atomic Layer Deposition of SiO2 and TiO2 in Alumina Tubular Membranes:  Pore Reduction and Effect of Surface Species on Gas Transport (2000)

The pore diameters in alumina tubular membranes were progressively reduced via SiO2 and TiO2 atomic layer deposition (ALD) using sequential surface reactions. The SiO2 ALD was accomplished using alternating exposures of SiCl4 and H2O. The TiO2 ALD was achieved using alternating exposures of TiCl4 and H2O. The reduction of the pore diameter was observed using in situ N2 conductance measurements. The total conductance, Ct = Q/ΔPt, was measured using a mass flow controller to define a constant gas throughput, Q, and two capacitance manometers to monitor the total pressure drop, ΔPt. These N2 conductance measurements revealed that the SiO2 and TiO2 ALD progressively reduced the pore diameter from an initial diameter of 50 Å to molecular diameters. Using an aperture model for the conductance, the pore diameter was found to decrease at a rate of 1.3 ± 0.1 Å per SiCl4/H2O AB cycle during SiO2 deposition and 3.1 ± 0.9 Å per TiCl4/H2O AB cycle during TiO2 deposition. The N2 conductance measurements were also very sensitive to the functional groups on the surface of the pores. The SiCl4 and TiCl4 exposures leave the pore surface terminated with SiCl* and TiCl* surface species, respectively. Subsequent exposure to H2O converts these surface species to SiOH* or TiOH* species. During SiO2 deposition, the pore diameters are 0.9 ± 0.2 Å larger after the H2O exposure replaces the SiCl* species with the SiOH* species. During TiO2 deposition, the pore diameters are 0.7 ± 0.2 Å larger after the H2O exposure replaces the TiCl* species with the TiOH* species. These pore diameter differences are somewhat smaller than the differences predicted by steric interaction calculations of bond lengths and van der Waals hard sphere radii for these surface functional groups. The N2 conductance measurements illustrate that gas transport through microscopic pores is determined by pore diameters and the effect of the surface species.
Simulation of the transient and steady-state sound propagation in rooms using a new combined ray-tracing/image-source algorithm (1989)

A new method for the calculation of room acoustical impulse responses is described, which is based on two well-known computer algorithms, the ray-tracing and the image-source models. With the new method, the procedure of sieving the ‘‘visible’’ image sources out of the enormous quantity of possible sources is carried out by examination of the histories of sound particles. From the obtained list of visible image sources, the impulse response of the enclosure is easily constructed. The new method combines the advantages of the ray-tracing process, namely, the relatively slow increase of computation time with the length of the impulse response, with the accuracy inherent to the image-source model, which is even sufficient to calculate the Fourier transform, i.e., the steady-state transmission function of the room, or to convolve the impulse response with sound signals.
Translational Regulation of Gene Expression by an Anaerobically Induced Small Non-coding RNA in Escherichia coli (2010)

Small non-coding RNAs (sRNA) have emerged as important elements of gene regulatory circuits. In enterobacteria such as Escherichia coli and Salmonella many of these sRNAs interact with the Hfq protein, an RNA chaperone similar to mammalian Sm-like proteins and act in the post-transcriptional regulation of many genes. A number of these highly conserved ribo-regulators are stringently regulated at the level of transcription and are part of major regulons that deal with the immediate response to various stress conditions, indicating that every major transcription factor may control the expression of at least one sRNA regulator. Here, we extend this view by the identification and characterization of a highly conserved, anaerobically induced small sRNA in E. coli, whose expression is strictly dependent on the anaerobic transcriptional fumarate and nitrate reductase regulator (FNR). The sRNA, named FnrS, possesses signatures of base-pairing RNAs, and we show by employing global proteomic and transcriptomic profiling that the expression of multiple genes is negatively regulated by the sRNA. Intriguingly, many of these genes encode enzymes with "aerobic" functions or enzymes linked to oxidative stress. Furthermore, in previous work most of the potential target genes have been shown to be repressed by FNR through an undetermined mechanism. Collectively, our results provide insight into the mechanism by which FNR negatively regulates genes such as sodA, sodB, cydDC, and metE, thereby demonstrating that adaptation to anaerobic growth involves the action of a small regulatory RNA.
An Efficient Synthesis of N-Allylglycosylamides from Unprotected Carbohydrates (1996)

Synthetic, multivalent, carbohydrate assemblies are important tools in studying the avidity of many naturally occuring lectins for their ligands. This report details a simple, high-yielding three-step procedure to convert unprotected carbohydrates into N-allylglycosides. This method compliments the reductive amination procedure but allows the reducing-end pyranose ring to remain intact. No carbohydrate protecting groups are needed, and the resulting N-allylglycosylamide can be easily linked to other molecules. Two examples of analogs of silyl Lewisx and sulfo Lewisx have been derivatized by this process.
Design of a pilot-activated recovery system using genetic search methods (1999)

Abstract : Control design tasks often require the use of trial and error search methods to obtain a satisfactory solution. Depending upon the nature and the number of tuning parameters or functions, the search process can be very discontinuous and nonconvex. The genetic search methods are a recently developed family of techniques for optimization which offer certain advantages over other techniques. These include greater freedom in defining cost functions and constraints, and the ability to automate the design process. Most notably, though, is the ability to construct new control laws and the potential to generate non-intuitive solutions as well. This paper demonstrates the application of genetic search methods to design a Pilot-Activated Recovery System (PARS) for a modern fighter aircraft. The PARS is a guidance law that transfers the aircraft from any initial attitude to a wings level, nose-up, recovered flight condition. This system is useful in cases of pilot disorientation. A 6 degree-of freedom nonlinear model of a modern, high performance aircraft is used for design. The genetic search seeks to produce nonlinear feedback functions to meet the specified goals and constraints. This intricate problem highlights some of the advantages of this emerging search technique.