gebhart/patrepeval huggingface dataset:
Evidence for oxide formation from the single and multiphoton excitation of a porous silicon surface or silicon “nanoparticles” (1998)

Potential oxidation as monitored by single and multiphoton excitation and associated with the laser induced photoluminescence (PL) from silicon nanoparticles and a porous silicon (PS) surface is considered in the light of recent in situ observations of the photoluminescence process coupled with detailed quantum chemical modeling of the silanone based oxyhydrides. The enhanced oxidation of PS surface bound SiHx moieties as they undergo multiphoton excitation through the SiHx stretch vibrational ladder to the quasicontinuum is suggested as a source of the visible PL produced in the 600–800 nm region. Vibrational-to-electronic energy transfer within the SiHx manifold, as previously suggested, is thought to be unlikely. However, the formation of OSiHx constituencies on the PS surface as these are associated with the silanone-based silicon oxyhydrides would appear to be significant. Evidence for these oxyhydrides may also be apparent in the laser induced PL from silicon nanoparticles. All experimental observations are explained without envoking quantum confinement.
Injection of Inactivated Phase I Coxiella burnetii Increases Non‐specific Resistance to Infection and Stimulates Lymphokine Production in Mice (1990)

The encounter of phase I C. burnetii with the host results in seemingly disparate consequences. On the one hand, in vitro lymphocyte responses to mitogens and homologous recall antigen are suppressed. On the other, host resistance to a variety of infectious agents and to a tumor is increased. An explanation for this augmented immune response surely involves the ability of C. burnetii to stimulate cytokines, such as interferon and TNF, which enhance host immune function.
Monodisperse semi-permeable microcapsules for continuous observation of cells (2009)

We present a method for forming monodisperse semi-permeable microcapsules composed of an alginate-poly-L-lysine (PLL) membrane for the observation of encapsulated cells. These microcapsules were prepared with a monolithic three-dimensional microfluidic axisymmetric flow-focusing device by an internal gelation method using glucono-1,5-lactone in order to provide mild conditions for the cells. The microcapsules were sufficiently monodisperse and robust to be trapped in a bead-based microfluidic array system for easy observation. We also confirmed that (i) the alginate-PLL membrane is semi-permeable so that cells and microorganisms cannot pass through it but nutrients and wastes can, (ii) cells are able to move freely inside the semi-permeable microcapsules, and (iii) cells can be successfully proliferated in the microcapsules.
Array CGH as a potential predictor of radiocurability in intermediate risk prostate cancer (2010)

Prostate cancer is the most common male cancer and up to one fi fth of diagnosed patients will die of their disease.Current prognostic variables including T-category (of the TNM staging), the absolute or kinetics of prostatic specifi c antigen (PSA) and the pathologic Gleason score (GS) are utilized to place men in low, intermediate and high-risk prostate cancer risk groupings.There is great heterogeneity within the non-indolent intermediate risk group with respect to clinical response.It is therefore imperative that further genetic and other prognostic factors be identifi ed to better individualize treatment.Somatic alterations in prostate cancer.Herein, we review the potential for somatic alterations in tumor-associated genes (based on comparative genomic hybridization (CGH) in prostate cancers to be novel prognostic, and possibly predictive, factors for prostate cancer radiotherapy response.Intermediate risk prostate cancers show alterations in a number of genes thought to be involved in radiosensitivity, DNA repair, cell death and stem cell renewal.These include deletions at 21q (TMPRSS2: ERG), 13q (RB1), 10q (PTEN), 8p (NKX3.1),additions at 8q21 (containing c-Myc)) and haplo-insuffi ciency for p53, PARP1, ATM and DNA-PKcs.Conclusions.The use of high-resolution CGH for fi ne-mapping of deletions and amplifi cations in pre-radiotherapy prostate cancer biopsies is feasible.Genetic alterations may delineate localized prostate cancer from systemic disease and be used as a predictive factor in that patients would be individually triaged to local (surgery versus radiotherapy) and/or adjuvant (adjuvant androgen ablation or post-operative radiotherapy) therapies in a prospective fashion to improve outcome.The knowledge of abnormal DNA repair pathways within in a given patient could allow for the judicious use of targeted agents (PARP/ATM inhibitors) as personalized medicine.
JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells. (1992)

The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE.
Layer thickness and angular dependence of spin transfer torque in ferromagnetic trilayers (2007)

We investigate the spin transfer torque arising from a perpendicular-to-plane current in a ferromagnetic (FM)-nonmagnetic-FM trilayer. Our analysis is based on the spin drift-diffusion model, modified for the case of noncollinear magnetization, i.e., with arbitrary angle θ between the magnetization orientation of the two FM layers. By solving the electrochemical potential and spin accumulation across the trilayer, we obtain the θ dependence of the magnetoresistance and spin transfer torque in the free FM layer. The optimal magnetization orientation θmax and the corresponding maximum torque τmax are investigated as a function of the FM layer thicknesses. Based on the analysis, we propose that (i) the free (fixed) FM layer thickness be set at approximately the transverse (longitudinal) spin relaxation lengths, and (ii) the relative FM orientation be biased at some intermediate angles instead of the conventional collinear configuration, in order to maximize the current-induced magnetization switching effect.
Habitat and Weather Effects on Northern Bobwhite Brood Movements (2017)

We observed radio-marked northern bobwhite (Colinus virginianus) broods (adults with chicks :S21 days old; n = 12) in Kansas during 1991-94 to test effects of weather (temperature and precipitation) and macrohabitat (composition, relative diversity, and mean distance to grassland) variables on brood home range size and daily movements at large (28.5 km2), intermediate (3.14 km2), and small (about 0.14 km2) spatial scales surrounding habitats available for broods. Principal component analyses followed by stepwise multiple linear regression indicated neither weather nor habitat influenced (P 2: 0.1) home range size at the large and intermediate scales. However, the principal component representing mean distance to grassland and percent cropland within the home range (i.e., at a small scale) was positively related to home range size. Neither temperature nor habitat influenced daily distance of movements. We concluded that brood mobility was independent of landscape-scale features, but that habitat management at smaller spatial scales could influence movements. To create optimal habitat for bobwhite, managers should consider relationships among habitat attributes and the movement of individuals, including the spatial scales at which these relationships are most important.
Genetic and Molecular Basis of Epithelial Cell Invasion by Shigella Species (1991)

Bacteria that belong to the four species of the genus Shigella cause a dysenteric syndrome by means of their unique capacity to invade the human colonic mucosa. The various steps of invasion of epithelial cells are controlled by a 220-kilobase plasmid. Plasmid genes that encode for entry into cells through bacterium-directed phagocytosis have been identified. Among these, ipa genes encode four highly immunogenic polypeptides. The ability of intracellular bacteria to multiply subsequently in an efficient manner is attributable to their capacity to lyse phagocytic membrane with a plasmid-encoded contact hemolysin that also determines bacterial entry capacity. In a further step, bacteria that lie free within the cytosol spread intracellularly and infect adjacent cells by inducing rapid polymerization of actin or accumulation of actin. Another plasmid gene, icsA (virG), that encodes a 120-kDa outer-membrane protein accounts for this phenotype. Finally, intracellular shigellae kill host cells rapidly by means of an unknown mechanism that does not seem to involve production of Shiga toxin or Shiga-like toxin. The invasion genes are controlled by both positive and negative regulatory systems.
Tumour therapy using Salmonella (2000)

The development of novel therapies that are selective for cancer cells, with limited toxicity to normal tissues, has been a challenge for oncology researchers. Genetically modified Salmonella typhimurium, which is capable of multiplying selectively in tumours and inhibiting their growth, represents a new approach for cancer treatment. Because of its selectivity for tumour tissues, S. typhimurium would also be an ideal vector for delivering therapeutic proteins to tumours. VNP20009, an attenuated strain of S. typhimurium with deletions in msbB and purI genes, possesses desirable attributes, such as low toxicity, tumour-selective multiplication and an intrinsic tumouricidal activity, making it particularly promising. VNP20009 accumulates preferentially in tumours of mice bearing B16F10 melanoma and M019 lung carcinoma. This preferential accumulation also occurs in animals implanted sc. with human tumour xenografts Lox, C8186, DLD1, SW620, HCT116, HTB177, DU145, MDA-MB-231 and Caki. VNP20009 proliferates and accumulates to levels between 1 x 108 and 2 x 109 colony-forming units (cfu)/g tumour after 4 - 5 days, following a single iv. injection of VNP20009 at 1 x 106 cfu/mouse. The amount of VNP20009 accumulating in liver is between 3 x 104 and 2 x 106 cfu/g. VNP20009 also inhibits the growth of a wide spectrum of murine transplantable tumours and human tumour xenografts and is currently undergoing Phase I clinical trials in cancer patients.
[Expression of fatty acid binding protein in human breast cancer tissues]. (2007)

E-, L-, and H-FABP may play a key role in the progress of invasiveness and metastasis in human breast cancer. Furthermore, the secretion of these FABPs has the potential to serve as a diagnostic marker for breast cancer.
MDR1 Gene Expression in Brain of Patients with Medically Intractable Epilepsy (1995)

Why some patients with seizures are successfully treated with antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration is a possible mechanism of resistance to AEDs. The multiple drug resistance gene (MDR1) encodes P-glycoprotein, an energy-dependent efflux pump that exports planar hydrophobic molecules from the cell. If P-glycoprotein is expressed in brain of some patients with intractable epilepsy and AEDs are exported by P-glycoprotein, lower intraparenchymal drug concentrations could contribute to lack of drug response in such patients. Eleven of 19 brain specimens removed from patients during operation for intractable epilepsy had MDR1 mRNA levels > 10 times greater than those in normal brain, as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Immunohistochemistry for P-glycoprotein from 14 of the patients showed increased staining in capillary endothelium in samples from epileptic patients as compared with staining in normal brain samples. In epileptic brain specimens with high MDR1 mRNA levels, expression of P-glycoprotein in astrocytes also was identified. Last, steady-state intracellular phenytoin (PHT) concentrations in MDR1 expressing neuroectodermal cells was one fourth that in MDR1-negative cells. MDR1 expression is increased in brain of some patients with medically intractable epilepsy, suggesting that the patients' lack of response to medication may be caused by inadequate accumulation of AED in brain.
Spatially Resolved Electrochemiluminescence on an Array of Electrode Tips (2003)

An array of electrode tips with 6-microm center-to-center spacing, fabricated through chemical etching of an optical fiber bundle, and coated with gold, was used for initiating electrochemiluminescence (ECL) in an aqueous solution of Ru(bpy)3(2+) and tri-n-propylamine (TPrA). ECL generated at the tips of the electrodes in the array was detected with a CCD camera and exhibited both high sensitivity and high resolution. In the case in which the ECL signal could not be distinguished from the background, ECL signals could be obtained by pulsing the array and summing multiple CCD images. The behavior of this array was compared to a second array that consisted of individual electrodes insulated with an electrophoretic paint.
Novel insights into class switch recombination (2002)

The discovery of activation-induced cytidine deaminase, a putative RNA editing enzyme essential for both class switch recombination and somatic hypermutation, marked the field of isotype switching studies in the year 2000. More recent work from the same group now highlights some essential mechanistic aspects of the switch recombination process. In particular, much has been learnt about the relationship between transcription and recombination and the transcriptional competence of intronic promoters on looped-out circular DNA uncoupled from the proximal and distal enhancers. These findings have far-reaching implications, particularly for studies of class switch recombination in tissues. Although these important advances do not directly relate to interleukin-4-dependent immunoglobulin E switching, the conceptual and experimental tools developed through these studies are certain to foster progress in the immunoglobulin E field.
Pathophysiologic and Prognostic Role of Cytokines in Dengue Hemorrhagic Fever (1998)

Dengue shock syndrome is a severe complication of dengue hemorrhagic fever (DHF), characterized by a massive increase in vascular permeability. Plasma cytokine concentrations were prospectively studied in 443 Vietnamese children with DHF, of whom 6 died. Shock was present in 188 children on admission to hospital, and in 71 children it developed later. Contrary to expectations, certain inflammatory markers (interleukin-6 and soluble intercellular adhesion molecule-1) were lower in the group with shock, and this may reflect the general loss of protein from the circulation due to capillary leakage. Only soluble tumor necrosis factor receptor (TNFR) levels showed a consistent positive relationship with disease severity. In patients with suspected DHF without shock, admission levels of sTNFR-75 in excess of 55 pg/mL predicted the subsequent development of shock, with a relative risk of 5.5 (95% confidence interval, 2.3 -13.2). Large-scale release of soluble TNFR may be an early and specific marker of the endothelial changes that cause dengue shock syndrome.
Defocus-based image segmentation (2002)

Foreground and background features are focused (or defocused) differently in an image because corresponding objects are at different depths in the scene. This paper presents a novel approach for segmenting foreground and background in video images based on feature defocus. A modified defocus measurement that distinguishes between high-contrast defocused edges and low-contrast focused edges is presented. Defocus-based segmentation is desirable because defocus techniques are computationally simple. Results indicate that the foreground is easily segmented from moving background. This approach, coupled with motion detection, can segment complex scenes containing both moving background and stationary foreground.
Toxins A and B from Clostridium difficile differ with respect to enzymatic potencies, cellular substrate specificities, and surface binding to cultured cells. (1997)

Clostridium difficile toxins A and B together are responsible for the symptoms of pseudomembranous colitis. Both toxins intoxicate cultured cells by the same mechanism but they differ in cytotoxic potency, toxin B being generally 1,000 times more potent than toxin A. Don and T84 cells were used to determine differences in the intoxication process exerted by both toxins. Three main differences were identified: (a) the specific binding of radiolabeled toxins to the cell surfaces correlated with the cytotoxic potency, (b) toxin B was found to have a 100-fold higher enzymatic activity than toxin A, and (c) toxin A was found to modify an additional substrate, Rap. The relative contribution of (a) and (b) to the difference in cytotoxic potency was determined by microinjection of the toxins. The differing enzymatic activities turned out to be the main determinant of the difference in cytotoxic potency, whereas the difference in binding contributes to a lesser degree. These findings are discussed in the context of the pathophysiological role of the toxins.
Impaired Synaptic Vesicle Release and Immaturity of Neuromuscular Junctions in Spinal Muscular Atrophy Mice (2009)

The motor neuron disease spinal muscular atrophy (SMA) causes profound muscle weakness that most often leads to early death. At autopsy, SMA is characterized by loss of motor neurons and muscle atrophy, but the initial cellular events that precipitate motor unit dysfunction and loss remain poorly characterized. Here, we examined the function and corresponding structure of neuromuscular junction (NMJ) synapses in a mouse model of severe SMA (hSMN2/delta7SMN/mSmn-/-). Surprisingly, most SMA NMJs remained innervated even late in the disease course; however they showed abnormal synaptic transmission. There was a two-fold reduction in the amplitudes of the evoked endplate currents (EPCs), but normal spontaneous miniature EPC (MEPC) amplitudes. These features in combination indicate reduced quantal content. SMA NMJs also demonstrated increased facilitation suggesting a reduced probability of vesicle release. By electron microscopy, we found a decreased density of synaptic vesicles that is likely to contribute to the reduced release probability. In addition to presynaptic defects, there were postsynaptic abnormalities. EPC and MEPC decay time constants were prolonged because of a slowed switch from the fetal acetylcholine receptor (AChR) gamma-subunit to the adult epsilon-subunit. There was also reduced size of AChR clusters and small myofibers, which expressed an immature pattern of myosin heavy chains. Together these results indicate that impaired synaptic vesicle release at NMJs in severe SMA is likely to contribute to failed postnatal maturation of motor units and muscle weakness.
Bezlotoxumab (Zinplava) for Clostridium Difficile Infection: The First Monoclonal Antibody Approved to Prevent the Recurrence of a Bacterial Infection. (2017)

Bezlotoxumab (Zinplava) to prevent the recurrence of <i>Clostridium difficile</i> infection.
Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial. (2006)

clinicaltrials.gov Identifier: NCT00288574.
Domain−Domain Interactions in the Aminoglycoside Antibiotic Resistance Enzyme AAC(6‘)-APH(2‘ ‘) (2004)

The most common determinant of aminoglycoside antibiotic resistance in Gram positive bacterial pathogens, such as Staphylococcus aureus, is a modifying enzyme, AAC(6')-APH(2' '), capable of acetylating and phosphorylating a wide range of antibiotics. This enzyme is unique in that it is composed of two separable modification domains, and although a number of studies have been conducted on the acetyltransferase and phosphotransferase activities in isolation, little is known about the role and impact of domain interactions on antibiotic resistance. Kinetic analysis and in vivo assessment of a number of N- and C-terminal truncated proteins have demonstrated that the two domains operate independently and do not accentuate one another's resistance activity. However, the two domains are structurally integrated, and mutational analysis has demonstrated that a predicted connecting alpha-helix is especially critical for maintaining proper structure and function of both activities. AAC(6')-APH(2' ') detoxifies a staggering array of aminoglycosides, where one or both activities make important contributions depending on the antibiotic. Thus, to overcome antibiotic resistance associated with AAC(6')-APH(2' '), aminoglycosides resistant to modification and/or inhibitors against both activities must be employed. Domain-domain interactions in AAC(6')-APH(2' ') offer a unique target for inhibitor strategies, as we show that their disruption simultaneously inhibits both activities >90%.
Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor (2008)

ST-246 is a novel, potent orthopoxvirus egress inhibitor that is being developed to treat pathogenic orthopoxvirus infections of humans. This phase I, double-blind, randomized, placebo-controlled single ascending dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 in healthy human volunteers. ST-246 was administered in single oral doses of 500, 1,000, and 2,000 mg to fasting healthy volunteers and 1,000 mg to nonfasting healthy volunteers. ST-246 was generally well tolerated with no serious adverse events, and no subject was withdrawn from the study due to ST-246. The most commonly reported drug-related adverse event was neutropenia, which was found, upon further analysis, not to be treatment related. ST-246 was readily absorbed following oral administration with mean times to maximum concentration from 2 h to 3 h. Absorption was greater in nonfasting volunteers than in fasting volunteers. Administration of ST-246 resulted in exposure levels predicted to be sufficient for inhibiting orthopoxvirus replication compared to exposure levels in nonhuman primates in which ST-246 protected animals from lethal orthopoxvirus infection.
PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma (2019)

The current study unveils the unique features of PD1<sup>Hi</sup> CD8<sup>+</sup> exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies.