gebhart/patrepeval huggingface dataset:
Anti-Glycan Antibodies as Biomarkers for Diagnosis and Prognosis (2006)

Glycans (sugars or carbohydrates) are predominant surface components of cells such as erythrocytes, immune cells and microorganisms. As such, they give rise to high levels of anti-glycan antibodies of all classes. Antibodies to certain defined mono, di and oligosaccharides that are common in bacterial, fungal and parasite cells exist in human sera and can be profiled using glycan arrays. The use of glycan arrays for systematic screening of blood samples from multiple sclerosis (MS) and Crohn's disease (CD) patients in versus to blood samples from control groups, have lead to the discovery of a few anti glycan antibodies biomarkers enabling diagnosis and prognosis in MS and CD patients. Anti-Glc(alpha1,4)Glc(alpha) IgM antibodies were found to be specific for MS patients, enabling differentiation between MS patients and patients with other neurological diseases, with 54% sensitivity and 85% specificity. Anti-Glc(alpha1,4)Glc(alpha) IgM were found to be predictive for the conversion of patients in first acute neurological event to clinically defined MS. Anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-chitobioside (ACCA) antibodies were found to be specific for CD. The combined use of these antibodies enables improved diagnosis of CD versus ulcerative colitis and other gastrointestinal diseases, as well as stratification of CD patients with a more complicated disease and high risk for surgery. Anti-glycan antibodies profiling (AGAP) is a new and promising approach for development of biomarkers for diagnosis and prognosis.
Diet-Induced Obesity Dramatically Reduces the Efficacy of a 2009 Pandemic H1N1 Vaccine in a Mouse Model (2011)

Our results show that prophylactic immune responses and protectiveness induced by 2009 H1N1 vaccine could be extremely compromised in diet-induced obesity. These results suggest that novel vaccination strategies for high-risk groups, including the obese population, are required.
A synthetic early promoter from a baculovirus: Roles of the TATA box and conserved start site CAGT sequence in basal levels of transcription (1992)

Many baculovirus early genes and insect genes transcribed by RNA polymerase II have a conserved transcription start site sequence (CAGT) located downstream of a consensus TATA box. To examine the functions and interactions of these two motifs in initiating accurately positioned basal transcription, a 43-nt synthetic promoter was synthesized from the TATA box and start site sequences of the gp64 early promoter from the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV). The synthetic promoter initiated accurately and was also transactivated by the baculovirus transcriptional activator, IE1. To determine the roles of sequences within the 43-nt synthetic promoter, a series of linker-scanning and spacing mutations were analyzed for transcriptional activity, start site selection, and transactivation. Linker-scanning mutations were examined in vivo by transient expression and reporter gene assays. To examine transcription start site selection, promoter constructs were used for in vitro transcription in nuclear extracts from uninfected Spodoptera frugiperda (Sf9) cells. In vivo and in vitro analyses show that the TATA box, and not the start site CAGT, is the primary element controlling start site selection. Substitution of the conserved start site CAGT sequence resulted in a reduction of both reporter gene activity and in vitro transcripts, although transcripts initiated accurately. Data from linker-scanning and spacing mutations indicate that the conserved start site CAGT sequences are not required for accurate initiation but sequences at the start site play an important role in initiation efficiency.
Identification of the vibriobactin receptor of Vibrio cholerae (1992)

Vibrio cholerae produces the novel phenolate siderophore vibriobactin and several outer membrane proteins in response to iron starvation. To determine whether any of these iron-regulated outer membrane proteins serves as the receptor for vibriobactin, the classical V. cholerae strain 0395 was mutagenized by using TnphoA, and iron-regulated fusions were analyzed for vibriobactin transport. One mutant, MBG14, was unable to bind or utilize exogenous vibriobactin and did not grow in low-iron medium. However, synthesis of the siderophore and transport of other iron complexes, including ferrichrome, hemin, and ferric citrate, were unaffected in MBG14. Analysis of membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated the loss from the mutant of a 74-kDa iron-regulated outer membrane protein present in the parental strain when grown in iron-limiting conditions. This protein partitioned into the detergent phase during Triton X-114 extraction, suggesting that it is a hydrophobic membrane protein. DNA sequences encoding the gene into which TnphoA had inserted, designated viuA (vibriobactin uptake), restored the wild-type phenotype to the mutant; the complemented mutant expressed the 74-kDa outer membrane protein under iron-limiting conditions and possessed normal vibriobactin binding and uptake. These data indicate that the 74-kDa outer membrane protein of V. cholerae serves as the vibriobactin receptor.
Chimeric mice derived from human—mouse hybrid cells (1978)

Mouse teratocarcinoma cells from the OTT6050 ascites tumor were established in tissue culture and selected for 5-bromodeoxyuridine (BrdUrd) resistance. The embryonal carcinoma cells grew without a feeder layer, remained deficient for thymidine kinase (EC 2.7.1.75), and differentiated like the original tumor into various tissues after subcutaneous injection into 129 mice. We fused the BrdUrd-resistant mouse teratocarcinoma cells with HT1080-6TG human diploid fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and selected for hybrid cells in hypoxanthine/aminopterin/thymidine medium. The resulting hybrid cells segregated human chromosomes quickly and retained one to three human chromosomes including chromosome 17 that carries the human genes for thymidine kinase and galactokinase (EC 2.7.1.6). Single hybrid cells from five independent clones containing human chromosome 17 were injected into mouse blastocysts bearing several genetic markers that affect the coat color phenotype and strain-specific enzyme variants in order to detect tissue differentiation derived from the injected cells. After the injection of single hybrid cells into a total of 103 experimental blastocysts that had been surgically transferred to pseudopregnant foster mothers, 49 mice were born and 2 of them clearly revealed coat mosaicism. In 2 of 17 mice thus far analyzed, the injected hybrid cells proved to be capable of participating substantially in development of seven different organs. However, human gene products have not yet been detected unequivocally in those tissues and weak human-specific galactokinase activity could be recovered only from two mosaic tissues. Our results demonstrate that, after in vitro culture and selection, at least some of the human-mouse hybrid cells still retain their in vivo potential to differentiate and become functionally integrated in the living organism. It now seems feasible to cycle mouse teratocarcinoma cells carrying human genetic material through mice via blastocyst injection to study human gene expression during differentiation.
Speaker diarization based on locally linear embedding (2016)

Speaker diarization is a significant part of many applications in today's fast growing user-end software and technologies. In the last decade, speaker diarization has attracted significant research effort, however most of the speaker diarization methods deeply rely on statistical models which become unreliable in case of short utterances diarization and in noisy conditions. In this paper, we introduce a speaker diarization system which is based on the Locally Linear Embedding (LLE). The LLE enables to extract the inherent structure of the data and thus provide better clustering. Experimental results show error rates lower than 10% and improved stability in comparison with a conventional speaker diarization method.
Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation (2012)

Nicotine is an important chemical compound in nature that has been regarded as an environmental toxicant causing various preventable diseases. Several bacterial species are adapted to decompose this heterocyclic compound, including Pseudomonas and Arthrobacter. Pseudomonas putida S16 is a bacterium that degrades nicotine through the pyrrolidine pathway, similar to that present in animals. The corresponding late steps of the nicotine degradation pathway in P. putida S16 was first proposed and demonstrated to be from 2,5-dihydroxy-pyridine through the intermediates N-formylmaleamic acid, maleamic acid, maleic acid, and fumaric acid. Genomics of strain S16 revealed that genes located in the largest genome island play a major role in nicotine degradation and may originate from other strains, as suggested by the constructed phylogenetic tree and the results of comparative genomic analysis. The deletion of gene hpo showed that this gene is essential for nicotine degradation. This study defines the mechanism of nicotine degradation.
Crystal structures of the Teonanácatl hallucinogens. Part I. Psilocybin C12H17N2O4P (1974)

The crystal structure of psilocybin, the major hallucinogenic component of Teonanácatl, the sacred mushroom of Mexico, has been determined in crystals of the monomethanolate. Crystals are monoclinic, space group P21/c, a= 1264(1), b= 2911(2), c= 884·7(6) pm, β= 107·37(2)°, and contain two molecules of psilocybin and two molecules of methanol of solvation per asymmetric unit. Data were collected on a four-circle diffractometer; the structure was solved by direct methods and refined by block-diagonal least squares to R 0·049 over 4217 significant reflections. The two independent molecules are both zwitterions, have different conformations, and are involved in a complex hydrogen-bonding scheme in which there are very short phosphate–phosphate hydrogen bonds, and in which the methanol of solution also takes part. Significant deviations of the substituents from the indole plane are apparent. Bond lengths have been determined to a precision of 0·5 pm.
Accessory proteins bind a primed template and mediate rapid cycling of DNA polymerase III holoenzyme from Escherichia coli. (1987)

DNA polymerase III holoenzyme was assembled from pure proteins onto a primer template scaffold. The assembly process could be divided into two stages. In the time-consuming first stage, beta subunit and gamma.delta subunit complex were required in forming a tightly bound ATP-activated "preinitiation complex" with a single-stranded DNA bacteriophage circle uniquely primed with a synthetic pentadecadeoxyribonucleotide. This finding substantiates an earlier study using crude protein preparations in a homopolymer system lacking Escherichia coli single-stranded DNA binding protein (Wickner, S. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 3511-3515). In the second stage, the polymerase III core and the tau subunit rapidly seek out and bind the preinitiation complex to form DNA polymerase III holoenzyme capable of rapid and entirely processive replication of the circular DNA. ATP is not required beyond formation of the preinitiation complex. It is remarkable that the fully assembled DNA polymerase III holoenzyme is so stably bound to the primed DNA circle (4-min half-time of dissociation), yet upon completing a round of synthesis the polymerase cycles within 10 s to a new preinitiation complex on a challenge primed DNA circle. Efficient polymerase cycling only occurred when challenge primed DNA was endowed with a preinitiation complex implying that cycling is mediated by a polymerase subassembly which dissociates from its accessory proteins and associates with a new preinitiation complex. These subunit dynamics suggest mechanisms for polymerase cycling on the lagging strand of replication forks in a growing chromosome.
BiP binds type I procollagen pro alpha chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta. (1993)

Of 20 fibroblast cell strains from patients with osteogenesis imperfecta (OI), a disease caused by mutations in the genes encoding type I procollagen, three had increased synthesis of BiP (GRP78), an hsp70-related, endoplasmic reticulum-resident protein. All three strains carry unique mutations in pro alpha 1(I) chains which impair type I procollagen chain association. Immunoprecipitation and pulse-chase experiments show that BiP (immunoglobulin heavy chain-binding protein) stably binds pro alpha 1(I) chains in these three cell strains after a brief lag. Ascorbate, which increases procollagen synthesis, increases BiP synthesis and content in these three strains and not in the others. In one of these three strains, BiP content is constitutively elevated prior to ascorbate treatment, and BiP is less inducible. This strain also has relatively high levels of synthesis and content of GRP94, another endoplasmic reticulum-resident stress protein. Pretreating each of the three cell strains to increase their BiP content reduces subsequent ascorbate-mediated BiP induction. BiP synthesis in the 17 other OI strains examined, which had a variety of type I procollagen mutations, was normal. These results suggest that BiP is induced by and binds procollagen with specific types of mutations: ones in the carboxyl-terminal propeptide that interfere with chain association. The recognition by BiP of such procollagen in OI cell strains shows that BiP plays a role in the physiological response to the production of some disease-producing abnormal proteins.
Silicon-on-sapphire MOSFET transmit / receiveswitch for L and S band transceiver applications (1997)

A single-pole double-throw transmit/receive switch has been fabricated with MOSFETs in silicon-on-sapphire technology. The switch has an insertion loss of 1.7 dB and an isolation of &gt; 30 dB at 2.4 GHz. The switch was targeted for 2.4 GHz operation, but is broadband with only a 2.0 dB insertion loss at 5 GHz. The same switch was also fabricated on SIMOX as a comparison. Owing to capacitive losses to the substrate, the SIMOX switch had a much higher insertion loss: 4.9 dB at 2.4 GHz and 6.2 dB at 5 GHz.
Organization and expression of the immediate early genes of human cytomegalovirus (1983)

The immediate early genes of human cytomegalovirus were characterized according to map location, RNA transcripts, and translation products. Three regions in the large unique component (0.709 to 0.751 map units) were transcribed in the presence of an inhibitor of protein synthesis (anisomycin). A single size class of polyadenylated mRNA, 1.95 kilobases (kb), was transcribed abundantly relative to the other size classes. The predominant 1.95-kb viral RNA was transcribed from right to left on the prototype arrangement of the viral genome and spanned a region of approximately 2.8 kb (0.739 to 0.751 map units). This mRNA codes for a 75,000-dalton protein that represents the predominant immediate early protein detected in infected cells. Immunoprecipitation of viral proteins synthesized in vitro as well as in vivo demonstrated that the predominant immediate early protein is synthesized as a protein of 75,000 daltons, but is presumably modified in vivo, resulting in a broad banding pattern ranging from 75,000 to 68,000 daltons. A different immediate early viral gene (0.732 to 0.739 map units) is transcribed from left to right at relatively low levels. The 3' ends of the above viral RNAs terminate at approximately 230 base pairs apart in the region of approximately 0.739 map units. Five RNA size classes ranging from 2.25 to 1.10 kb were detected, but the 1.75-kb and 1.40-kb RNA size classes were more abundant from this region. At least four minor proteins are coded by these mRNAs, with apparent molecular weights ranging from 56,000 to 16,500. Last, a 1.95-kb mRNA was transcribed from a third region (0.709 to 0.728 map units). This viral mRNA was present at relatively low concentration and coded for a minor protein of 68,000 daltons. Since immediate early gene expression of human cytomegalovirus is dominated by the synthesis of an mRNA from the region of 0.739 to 0.751 map units that codes for the predominant immediate early protein found in the infected cell, we hypothesize that this protein is the major regulatory protein influencing the switch from restricted to extensive transcription.
Designing drugs that combat kidney damage (2015)

Inflammation, cell death and fibrosis are key therapeutic targets to combat kidney damage. While the specific targeting of drugs to kidney cells would be desirable, the technology is only working at the preclinical stage and with mixed success. Nanomedicines hold promise in this respect. Most drugs undergoing clinical trials for kidney disease have been repurposed from other indications. Currently, the chemokine receptor inhibitor CCX140 holds promise for CKD and the p53 inhibitor QPI-1002 for AKI.
Revisiting epithelial-to-mesenchymal transition through adenoid cystic carcinoma. (2012)

Adenoid cystic carcinoma (ACC) has a 5-year survival rate of 90%. The 15-year survival rate drops to 10% due to recurrence and invasion. ACC has three subtypes: cribriform, tubular, and solid. The cribriform subtype has the best prognosis and the solid subtype has the worst prognosis. By immunohistochemistry of tissue sections, we showed that the solid form expresses αvβ6 integrin and tenascin-C, which are known promoters of epithelial-to-mesenchymal transition (EMT). We also defined two ACC cell lines with the characteristics of the cribriform and solid subtype. The SACC83 cells grow in basaloid-like clusters and express high levels of E-cadherin. In contrast, the ACCh cells are more myoepithelial-like and express high levels of vimentin and of αvβ6 integrin. The ACCh cells are highly invasive and this behavior is dependent upon the αvβ6 integrin function. Our results suggest that the transition from the cribriform to solid form may occur through EMT.
Clinical Resistance to Enfuvirtide Does Not Affect Susceptibility ofHuman Immunodeficiency Virus Type 1 to Other Classes of Entry Inhibitors (2007)

The clinical use of the human immunodeficiency virus (HIV) fusion inhibitor enfuvirtide (ENF) can select for drug-resistant HIV-1 strains bearing mutations in the HR1 region of the viral envelope (Env) protein. We analyzed the properties of multiple Env proteins isolated from five patients who experienced an initial decline in viral load after ENF therapy followed by subsequent rebound due to emergence of ENF-resistant HIV-1. Prior to ENF therapy, each patient harbored genetically and phenotypically diverse Env proteins that used CCR5 and/or CXCR4 to elicit membrane fusion. Coreceptor usage patterns of the Envs isolated from two patients underwent homogenization following ENF therapy, whereas in the other three patients, recombination appeared to allow the introduction of a single HR1 sequence with ENF resistance mutations into phenotypically distinct Env proteins. Analysis of individual Env clones also revealed that prior to ENF therapy, there was sometimes marked heterogeneity in the susceptibility of individual Env proteins to coreceptor inhibitors. After virologic failure, all Envs acquired resistance to ENF but exhibited no consistent change in their sensitivity to the fusion inhibitor T-1249 or to coreceptor inhibitors. In summary, using patient-derived Env proteins, we found that ENF failure was associated with emergence of high-level resistance to ENF due largely to mutations in HR1 but that susceptibility to other entry inhibitors was unaffected, that in these late-stage patients there was greater clonal variability to coreceptor than to fusion inhibitors, and that recombination events in vivo could sometimes restore Env genotypic and phenotypic heterogeneity by introducing drug-resistant gp41 sequences into heterologous gp120 backgrounds.
Single-walled carbon nanotubes as specific targeting and Raman spectroscopic agents for detection and discrimination of single human breast cancer cells (2013)

Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) are prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized to bond covalently with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, which is specific to the highly expressed EpCAM antigen on the surface of breast cancer cells (MCF-7), but not on normal cells. The Raman nano-complexes demonstrate excellent ability to detect in vitro single breast cancer cells (MCF-7) and discriminate between them and normal fibroblast cells during the first 30 min of the targeting process. Raman linearity scanning is collected from a monolayer cell mixture, including both cancer cells and normal cells incubated with anti-EpCAM-SWCNTs, using a 633-nm laser excitation. The results shows that the Raman signal collected from targeted MCF-7 cells is extremely high, whereas there is little signal from the normal cells.
A real-time, flat-panel, amorphous silicon, digital x-ray imager. (1995)

As part of the development necessary for implementing a fully digital radiology department, the authors have investigated thin-film photodiodes and transistors for use in new photoelectronic imaging devices. One such device, a large-area, flat-panel, amorphous silicon imaging array, has been developed and is currently being tested. The array has a format of 512 x 560 pixels, a pixel-to-pixel pitch of 450 microns, and an area of 230 x 252 mm2, making it the largest self-scanning, solid-state imaging array developed to date. The array is used in conjunction with an overlying x-ray converter. Although specifically designed for megavoltage imaging, the device can produce high-quality, low spatial resolution, diagnostic x-ray images. Qualitative comparisons of array images of anthropomorphic head, chest, and pelvic phantoms and a spatial resolution pattern suggest that much of the information content of the film images at low spatial resolution is present in the corresponding array images. Current trends in the development of large-area, flat-panel imaging technology hold the promise of higher resolution arrays in the near future.
Single-Bead Immunoassays Using Magnetic Microparticles and Spectral-Shifting Quantum Dots (2007)

This paper reports a single-bead immunoassay method based on the combined use of magnetic microparticles (MMPs) for target capturing/enrichment and antibody-conjugated semiconductor quantum dots (QDs) for fluorescence detection. In comparison with organic dyes and fluorescent proteins, QDs exhibit unique optical properties such as size-tunable fluorescence emission (spectral shifting), large absorption coefficients, improved brightness, and superior photostability. Magnetic beads, composed of iron oxide nanoparticles embedded in polymeric matrices, provide a platform for rapid capturing and enrichment of biomolecules and pathogens in dilute biological and environmental samples. However, a major problem in using magnetic beads for fluorescence immunoassays is that the bead's autofluorescence strongly interferes with the target detection signal. This spectral overlapping problem can be overcome by using semiconductor QDs as a new class of spectral-shifting labels. By shifting the QD emission signals away from the bead autofluorescence, it is possible to detect biomolecular antigens such as tumor necrosis factor (TNF-alpha) at femtomolar (10-15 M) concentrations when the target molecules are captured and enriched on the magnetic bead surface. This sensitivity is almost 1000 times higher that that of traditional immunoabsorbent assays and more than 100 times higher than immunofluorescent assays using organic dyes.