gebhart/patrepeval huggingface dataset:
Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia (2009)

Oxidative damage in the brain may contribute in part to the pathological process in BD and schizophrenia. This finding also suggests antioxidative stress as a probable alternative approach to the pharmacological treatment of these psychiatric disorders.
Contribution of Gene Loss to the Pathogenic Evolution of Burkholderia pseudomallei and Burkholderia mallei (2004)

Burkholderia pseudomallei is the causative agent of melioidosis. Burkholderia thailandensis is a closely related species that can readily utilize l-arabinose as a sole carbon source, whereas B. pseudomallei cannot. We used Tn5-OT182 mutagenesis to isolate an arabinose-negative mutant of B. thailandensis. Sequence analysis of regions flanking the transposon insertion revealed the presence of an arabinose assimilation operon consisting of nine genes. Analysis of the B. pseudomallei chromosome showed a deletion of the operon from this organism. This deletion was detected in all B. pseudomallei and Burkholderia mallei strains investigated. We cloned the B. thailandensis E264 arabinose assimilation operon and introduced the entire operon into the chromosome of B. pseudomallei 406e via homologous recombination. The resultant strain, B. pseudomallei SZ5028, was able to utilize l-arabinose as a sole carbon source. Strain SZ5028 had a significantly higher 50% lethal dose for Syrian hamsters compared to the parent strain 406e. Microarray analysis revealed that a number of genes in a type III secretion system were down-regulated in strain SZ5028 when cells were grown in l-arabinose, suggesting a regulatory role for l-arabinose or a metabolite of l-arabinose. These results suggest that the ability to metabolize l-arabinose reduces the virulence of B. pseudomallei and that the genes encoding arabinose assimilation may be considered antivirulence genes. The increase in virulence associated with the loss of these genes may have provided a selective advantage for B. pseudomallei as these organisms adapted to survival in animal hosts.
Role of the Background Gas in the Morphology and Optical Properties of Laser-Microstructured Silicon (2005)

We irradiated silicon with a train of femtosecond pulses in the presence of SF6, H2S, H2, SiH4, and a mixture of Ar and SF6 in order to analyze the role of the background gas in determining the morphology and the optical properties of the resultant surfaces. We discuss factors that affect the surface morphology created during irradiation and show that the presence of sulfur in these gases is important in creating sharp microstructures. We also show that the presence of sulfur is necessary to create the near-unity absorptance for both above-band and below-band gap radiation (0.25−2.5 μm) by silicon; only samples with sulfur concentrations higher than 0.6% absorb 95% for above-band gap radiation and have a flat, featureless absorptance of 90% for below-band gap radiation.
Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors (2002)

Genomic DNA copy number alterations are key genetic events in the development and progression of human cancers. Here we report a genome-wide microarray comparative genomic hybridization (array CGH) analysis of DNA copy number variation in a series of primary human breast tumors. We have profiled DNA copy number alteration across 6,691 mapped human genes, in 44 predominantly advanced, primary breast tumors and 10 breast cancer cell lines. While the overall patterns of DNA amplification and deletion corroborate previous cytogenetic studies, the high-resolution (gene-by-gene) mapping of amplicon boundaries and the quantitative analysis of amplicon shape provide significant improvement in the localization of candidate oncogenes. Parallel microarray measurements of mRNA levels reveal the remarkable degree to which variation in gene copy number contributes to variation in gene expression in tumor cells. Specifically, we find that 62% of highly amplified genes show moderately or highly elevated expression, that DNA copy number influences gene expression across a wide range of DNA copy number alterations (deletion, low-, mid- and high-level amplification), that on average, a 2-fold change in DNA copy number is associated with a corresponding 1.5-fold change in mRNA levels, and that overall, at least 12% of all the variation in gene expression among the breast tumors is directly attributable to underlying variation in gene copy number. These findings provide evidence that widespread DNA copy number alteration can lead directly to global deregulation of gene expression, which may contribute to the development or progression of cancer.
Protective Effect of WC3 Vaccine Against Rotavirus Diarrhea in Infants During a Predominantly Serotype 1 Rotavirus Season (1988)

We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.
CXCR2 Is Required for Neutrophil Recruitment to the Lung during Influenza Virus Infection, But Is Not Essential for Viral Clearance (2007)

Neutrophils traffic to the lungs in large numbers during influenza virus infection. Although the ability of these cells to respond to numerous chemotactic stimuli has been described in other systems, the chemokine receptors mediating recruitment of neutrophils to the lungs during influenza virus infection and the role of this cell type in viral clearance are currently undefined. In the present study, we used CXCR2(/) mice to investigate the role of the chemokine receptor CXCR2 in neutrophil recruitment to the lungs during influenza virus infection and to determine the role of neutrophils in viral clearance. We infected CXCR2(/) or wild-type mice with influenza and assessed the level of inflammation, the cellular composition of the inflammatory infiltrate, and viral titers in the lungs. Absence of CXCR2 ablated neutrophil recruitment to the lungs, but had no effect on peak viral titers or on the kinetics of viral clearance. Thus, it appears that CXCR2 is the major receptor mediating neutrophil trafficking to the lung during influenza virus infection, but that neutrophils do not play an essential role in viral clearance.
CEACAM engagement by human pathogens enhances cell adhesion and counteracts bacteria-induced detachment of epithelial cells (2005)

Exfoliation, which is the detachment of infected epithelial cells, is an innate defense mechanism to prevent bacterial colonization. Indeed, infection with Neisseria gonorrhoeae induced epithelial detachment from an extracellular matrix (ECM) substrate in vitro. Surprisingly, variants of N. gonorrhoeae that bind to human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) failed to induce detachment and, instead, promoted enhanced host cell adhesion to the ECM. Microarray analysis revealed that CEACAM engagement by several human pathogens triggers expression of CD105. Blockage of CD105 expression by antisense oligonucleotides abolished infection-induced cell adhesion. The expression of full-length CD105 promoted cell adhesion to the ECM and was sufficient to prevent infection-induced detachment. The CD105-mediated increase in cell adhesion was dependent on the presence and function of integrin beta1. CD105 expression did not elevate cellular integrin levels but caused a dramatic increase in the ECM-binding capacity of the cells, suggesting that CD105 affects integrin activity. The exploitation of CEACAMs to trigger CD105 expression and to counteract infection-induced cell detachment represents an intriguing adaptation of pathogens that are specialized to colonize the human mucosa.
Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: Implications for the design of antifungal agents (1996)

The three-dimensional structure of a secreted aspartic protease from Candida albicans complexed with a potent inhibitor reveals variations on the classical aspartic protease theme that dramatically alter the specificity of this class of enzymes. The structure presents: (1) an 8-residue insertion near the first disulfide (Cys 45-Cys 50, pepsin numbering) that results in a broad flap extending toward the active site; (2) a 7-residue deletion replacing helix hN2 (Ser 110-Tyr 114), which enlarges the S3 pocket; (3) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and (4) an ordered 11-residue addition at the carboxy terminus. The inhibitor binds in an extended conformation and presents a branched structure at the P3 position. The implications of these findings for the design of potent antifungal agents are discussed.
Editor's Introduction (1989)

The fifty-five ethnic minorities in China constitute about 6.7 percent of the population. The majority are located along the border areas, with some of their members living in neighboring countries. Because of their strategic geographical positions, the minorities' political importance outweighs their absolute numbers. This issue of Chinese Education examines the educational condition of this important segment of China's population. Section I reviews the official Chinese policies toward minority education since 1949; section II consists of selected research reports on the education of minorities living in both rural and urban areas; and section III provides statistics on the educational attainment of these groups.
Preliminary clinical results from an electroenzymatic glucose sensor implanted in subcutaneous tissue (1992)

A glucose-oxidase based electroenzymatic glucose sensor has been developed using thin/thick film processing techniques. This processing scheme has provided the ability to mass-produce the sensors in a cost effective and reproducible manner. The small, flexible sensors are designed for implantation in the subcutaneous tissue. Previous in vitro characterization studies and in vivo rabbit studies have shown the sensor's performance to be acceptable. Glucose measurements obtained with sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation with glucose measurements obtained from capillary, finger-stick blood and intravenous blood.
Lipid vesicles as carriers for introducing materials into cultured cells: influence of vesicle lipid composition on mechanism(s) of vesicle incorporation into cells. (1976)

The mechanisms involved in the uptake of uni- and multi-lamellar lipid vesicles by BALB/c mouse 3T3 cells have been investigated. Vesicles are incorporated into cells both by endocytosis and by a nonendocytotic mechanism which we propose involves fusion of vesicles with the plasma membrane. The nonendocytotic pathway predominates in the uptake of negatively charged vesicles composed of phospholipids that are "fluid" (phosphatidylserine/phosphatidylcholine) at 37 degrees. Neutral fluid vesicles (phosphatidylcholine) and negatively charged vesicles prepared from "solid" phospholipids (phosphatidylserine/distearylphosphatidylcholine/dipalmitoylphosphatidylcholine) are instead incorporated largely by endocytosis. Uptake of the latter classes of vesicle is reduced (80-90% inhibition) by inhibitors of cellular energy metabolism and by cytochalasin B.
CapProbe (2004)

We present a new capacity estimation technique, called CapProbe. CapProbe combines delay as well as dispersion measurements of packet pairs to filter out samples distorted by cross-traffic. CapProbe algorithms include convergence tests and convergence speed-up techniques by varying probing parameters. Our study of CapProbe includes a probability analysis to determine the time it takes CapProbe to converge on the average. Through simulations and measurements, we found CapProbe to be quick and accurate across a wide range of traffic scenarios. We also compared CapProbe with two previous well-known techniques, pathchar and pathrate. We found CapProbe to be much more accurate than pathchar and similar in accuracy to pathrate, while providing faster estimation than both. Another advantage of CapProbe is its lower computation cost, since no statistical post processing of probing data is required.
Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters (2020)

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death<sup>1-4</sup>. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters<sup>5-7</sup> and nonhuman primates<sup>8-10</sup> have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates<sup>11-13</sup>. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.
Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers (2012)

One of the advantages of nanotechnology is the feasibility to construct therapeutic particles carrying multiple therapeutics with defined structure and stoichiometry. The field of RNA nanotechnology is emerging. However, controlled assembly of stable RNA nanoparticles with multiple functionalities which retain their original role is challenging due to refolding after fusion. Herein, we report the construction of thermodynamically stable X-shaped RNA nanoparticles to carry four therapeutic RNA motifs by self-assembly of reengineered small RNA fragments. We proved that each arm of the four helices in the X-motif can harbor one siRNA, ribozyme, or aptamer without affecting the folding of the central pRNA-X core, and each daughter RNA molecule within the nanoparticle folds into their respective authentic structures and retains their biological and structural function independently. Gene silencing effects were progressively enhanced as the number of the siRNA in each pRNA-X nanoparticles gradually increased from one to two, three, and four. More importantly, systemic injection of ligand-containing nanoparticles into the tail-vein of mice revealed that the RNA nanoparticles remained intact and strongly bound to cancers without entering the liver, lung or any other organs or tissues, while remaining in cancer tissue for more than 8 h.
A Novel Interaction between Perlecan Protein Core and Progranulin (2003)

In an in vivo search of novel partners for perlecan, a major heparan sulfate proteoglycan of basement membranes and cell surfaces, we identified progranulin, a secreted growth factor, as a strong interacting protein. Unambiguous interaction, first observed with the yeast two-hybrid system, was corroborated by co-immunoprecipitation studies using cell-free transcription/translation and transient cell transfection assays. The interaction of progranulin with perlecan domain V involved the first two laminin- and epidermal growth factor-like repeats. Within progranulin, the subdomains interacting most with perlecan harbored granulins F and B. Kinetics analysis of the interaction using surface plasmon resonance showed a saturable binding of relative low affinity (KD approximately 1 microM). These results were supported by significant expression overlap of these two proteins in a series of ovarian tumor tissue microarrays. Progranulin was present within proliferating blood vessels of ovarian carcinomas and perivascular matrices, with a distribution similar to perlecan. Notably, both progranulin and domain V stimulated the growth of adrenal carcinoma cells. However, when used together in equimolar amounts, the two proteins counteracted each other's activity. Thus, progranulin/perlecan interaction could contribute to a fine regulation of tumor angiogenesis and could ultimately affect cancer growth.
Characterization of the Five Replication Factor C Genes of Saccharomyces cerevisiae (1995)

Replication factor C (RFC) is a five-subunit DNA polymerase accessory protein that functions as a structure-specific, DNA-dependent ATPase. The ATPase function of RFC is activated by proliferating cell nuclear antigen. RFC was originally purified from human cells on the basis of its requirement for simian virus 40 DNA replication in vitro. A functionally homologous protein complex from Saccharomyces cerevisiae, called ScRFC, has been identified. Here we report the cloning, by either peptide sequencing or by sequence similarity to the human cDNAs, of the S. cerevisiae genes RFC1, RFC2, RFC3, RFC4, and RFC5. The amino acid sequences are highly similar to the sequences of the homologous human RFC 140-, 37-, 36-, 40-, and 38-kDa subunits, respectively, and also show amino acid sequence similarity to functionally homologous proteins from Escherichia coli and the phage T4 replication apparatus. All five subunits show conserved regions characteristic of ATP/GTP-binding proteins and also have a significant degree of similarity among each other. We have identified eight segments of conserved amino acid sequences that define a family of related proteins. Despite their high degree of sequence similarity, all five RFC genes are essential for cell proliferation in S. cerevisiae. RFC1 is identical to CDC44, a gene identified as a cell division cycle gene encoding a protein involved in DNA metabolism. CDC44/RFC1 is known to interact genetically with the gene encoding proliferating cell nuclear antigen, confirming previous biochemical evidence of their functional interaction in DNA replication.
Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells (2004)

Cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) exerts antineoplastic effects on various types of human cancer. We recently showed that treatment with 15d-PGJ(2) induces apoptosis accompanied by downregulation of the oncogenic signal transducer and activator of transcription 3 (Stat3) signalling in human oral squamous cell carcinoma (SCC) cells. The current study examines the effects of 15d-PGJ(2) on the epidermal growth factor receptor (EGFR) and Janus Kinase (JAK)-mediated signalling pathways. Inhibition of Stat3 by 15d-PGJ(2) was abolished by exogenous stimulation with transforming growth factor alpha (TGF-alpha), but not interleukin 6 (IL-6), supporting a selective effect of 15d-PGJ(2) on IL-6-mediated signalling. Importantly, 15d-PGJ(2) selectively abrogated constitutive and IL-6-mediated JAK phosphorylation without affecting EGFR-activated levels. Moreover, the inhibitory effect of 15d-PGJ(2) on JAK signalling required the reactive alpha,beta-unsaturated carbon within the cyclopentenone ring. Targeting of JAK signalling using a specific JAK inhibitor also abolished Stat3 phosphorylation and resulted in apoptosis in oral SCC cells. Our findings provide the first evidence for 15d-PGJ(2)-mediated downregulation of constitutive and IL-6-induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR-independent Stat3 activation by 15d-PGJ(2) represent a promising approach for induction of apoptosis in oral SCC cells.
Extraction of compositional information for trafficability mapping from hyperspectral data (2000)

Trafficability refers to the extent to which the terrain will permit continued movement of any and/or all types of traffic, an issue that ground forces must address in advance of military operations to ensure their success. Multispectral remote sensing technology is currently used by terrain analysts to help assess trafficability, but its utility in producing classical measures of trafficabilty has been limited. This paper describes a hyperspectral trafficability mapping methodology supported by a case history using Airborne Visible/Inffared Imaging Spectrometer (AVIRIS) data. The strong points of the hyperspectral data for trafficability mapping are detection, identification, and mapping of surface composition. Selected spectral libraries were reviewed in the context of trafficability to generate classes of materials with specific trafficability characteristics. These were used in conjunction with scene-based hyperspectral analysis methodologies to produce prototype trafficability products from AVIRIS data. The AVIRIS analysis illustrates that while considerable important information regarding trafficability can be extracted from hyperspectral data, analysis of these data alone can not produce the desired “classical” trafficability products and that data fusion is required to enhance information extracted from hyperspectral data. The principal limitations of hyperspectral data, are 1. That only certain materials have unique spectral features or character that can be detected, 2. that it measures only the very surface and may not be indicative of bulk materials, and 3. That it doesn’t provide any textural information, critical for determining classical trafficability measures. Specific additional required information includes terrain information related to topography, and surface texture. This information can be obtained from supporting datasets such as high resolution digital elevation models (DEM), and Synthetic Aperture Radar (SAR).