gebhart/patrepeval huggingface dataset:
A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo. (1998)

Evidence of apoptosis was detected for the United States porcine reproductive and respiratory syndrome virus (PRRSV) in ATCC CRL11171 cells inoculated with strain ATCC VR2385 and in the tissues of pigs infected with the same strain. Apoptosis was detected by agarose gel electrophoresis, transmission electron microscopy and terminal deoxytransferase dUTP nick end labelling (TUNEL) techniques. By electron microscopy and double-labelling techniques, apoptosis was detected primarily in uninfected bystander cells in the continuous cell line rather than the PRRSV-infected cells. In the lungs, the apoptotic cells were predominantly alveolar and pulmonary intravascular macrophages, and mononuclear cells in the alveolar septa. In the lymph nodes, the apoptotic cells were predominantly tingible body macrophages and mononuclear cells. The induction of apoptosis in a large number of mononuclear cells in the lungs and lymph nodes appears to be a mechanism of PRRSV pathogenesis and might be an explanation for a dramatic reduction in the number of alveolar macrophages and circulating lymphocytes and monocytes in PRRSV-infected pigs.
Structure–activity relationships of aminoglycoside‐arginine conjugates that bind HIV‐1 RNAs as determined by fluorescence and NMR spectroscopy (2004)

We present here a new set of aminoglycoside-arginine conjugates (AACs) that are either site-specific or per-arginine conjugates of paromomycin, neamine, and neomycin B as well as their structure-activity relationships. Their binding constants (KD) for TAR and RRE RNAs, measured by fluorescence anisotropy, revealed dependence on the number and location of arginines in the different aminoglycoside conjugates. The binding affinity of the per-arginine aminoglycosides to TAR is higher than to RRE, and hexa-arginine neomycin B is the most potent binder (KD=5 and 23 nM, respectively). The 2D TOCSY NMR spectrum of the TAR monoarginine-neomycin complex reveals binding at the bulge region of TAR.
The rapid rejection of allogeneic lymphocytes by a non-adaptive, cell-mediated mechanism (NK activity). (1985)

The fate of allogeneic lymphocytes (AO or DA) transferred to non-immune PVG recipients was studied in the light of previous evidence (Heslop & McNeilage, 1983; Rolstad & Ford, 1983) that allogeneic lymphocytes can be rapidly destroyed in certain strain combinations of rats and mice by a mechanism that is distinct from either T-cell mediated immunity or an alloantibody response. AO lymphocytes injected into PVG recipients were discriminated from syngeneic lymphocytes within 15-30 min of i.v. injection, as testified by the excess release of 51Cr into the lymph plasma of the recipient. The following experiments were intended to distinguish between natural antibody and natural killer (NK) cells as the mechanism responsible for the allogeneic lymphocyte cytotoxicity (ALC) displayed by PVG rats. Nude rats treated from birth with anti-mu chain serum and shown to be lacking B and T lymphocytes, as well as being profoundly deficient in immunoglobulin, displayed more aggressive ALC than did control nude rats which, in turn, showed stronger ALC than did euthymic rats. Serum from PVG nude rats exerted no inhibitory or destructive effect on allogeneic lymphocytes in an antibody-dependent cellular cytotoxicity system, an assay of graft-versus-host activity, or when injected into 3-4-week-old PVG rats which had not yet developed ALC. Treatment of nude rats with anti-asialo GM 1 antiserum depressed ALC and NK activity in parallel, thus adding to a wide range of circumstances in which ALC and NK activity are closely correlated. In conclusion, ALC is implemented by a non-adaptive, cell-mediated mechanism independent of immunoglobulin, but the precise identity of the effector cell in the recipients' lymphatic tissues remains to be settled.
Identification of novel species-specific antigens of Mycoplasma hyopneumoniae by preparative SDS-PAGE ELISA profiling (1997)

Mycoplasma hyopneumoniae, M. hyorhinis and M. flocculare are commonly isolated from the respiratory tract of pigs and are phylogenetically related. The identification and characterization of antigens specific for M. hyopneumoniae is crucial for the development of serological reagents and for understanding the mechanisms of pathogenicity of this pathogen. Protein and antigen profiles of six strains of M. hyopneumoniae, four strains of M. hyorhinis and a type strain of M. flocculare were compared using SDS-PAGE and immunoblotting. Five strains of M. hyopneumoniae originally isolated from diverse geographical regions produced similar protein and antigen profiles. One strain, C1735/2, produced a unique protein profile and was poorly immunoreactive, suggesting that some strains of M. hyopneumoniae may possess a structurally modified repertoire of antigens. Major M. hyopneumoniae antigens with molecular masses of approximately 36, 43, 48, 52, 76, 78, 80, 82, 94, 106, 114 and 200 kDa were identified by immunoblotting using hyperimmune pig sera raised against both high and low passage strains of M. hyopneumoniae. Porcine hyperimmune sera raised against the GDL type strain of M. hyorhinis reacted strongly with all M. hyorhinis strains although the profiles displayed considerable variation. Major antigens of molecular mass 42, 49, 52, 78, 80 and 82 kDa were identified in type strains GDL and BTS-7 and field strain 2; however, field strain 1 produced a unique profile. A preparative SDS-PAGE profiling (PPP) technique was developed which enabled quantification of the immunoreactivity of denatured antigens with porcine serum by ELISA. PPP facilitated the rapid identification of species-specific and cross-reactive antigens among the three mycoplasma species. PPP studies revealed several strongly immunoreactive M. hyopneumoniae-specific antigens of 43, 76, 94, 114 and 200 kDa as well as antigens of molecular mass between 52 and 62 kDa which were not apparent in immunoblotting studies. Rabbit monospecific anti-42 kDa serum reacted specifically with a 43 kDa antigen in whole cell lysates of geographically diverse strains of M. hyopneumoniae and failed to cross-react with M. flocculare or M. hyorhinis whole cell lysates. This study has identified a number of M. hyopneumoniae-specific antigens which warrant further investigation to determine their potential as diagnostic reagents and the role they play, if any, in pathogenicity.
Binding to the Extracellular Matrix and Proteolytic Processing: Two Key Mechanisms Regulating Vascular Endothelial Growth Factor Action (2010)

Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. One feature of VEGF is the existence of multiple isoforms arising from alternative exon splicing. Our initial biochemical and biological studies indicated that such isoforms are uniquely suited to generate angiogenic gradients by virtue of their differential ability to interact with the extracellular matrix (ECM). Although ECM-bound VEGF was bioactive, processing by physiologically relevant proteases such as plasmin was identified as a key mechanism to convert ECM-bound VEGF into freely diffusible forms. This retrospective article examines the early studies and also emphasizes the subsequent progress in our understanding of these processes in health and disease.
Characterization of Aloeride, a New High-Molecular-Weight Polysaccharide from Aloe vera with Potent Immunostimulatory Activity (2000)

We have characterized a new immunostimulatory polysaccharide called Aloeride from commercial aloe vera (Aloe barbadensis) juice. Aloeride is between 4 and 7 million Da, and its glycosyl components include glucose (37.2%), galactose (23.9%), mannose (19.5%), and arabinose (10.3%). At 0.5 microg/mL Aloeride increased NF-kappa B directed luciferase expression in THP-1 human monocytic cells to levels 50% of those achieved by maximal concentrations (10 microg/mL) of LPS. Aloeride induced the expression of the mRNAs encoding IL-1beta and TNF-alpha to levels equal to those observed in cells maximally activated by LPS. Acemannan, the major carbohydrate component from aloe, used at 200 microg/mL in the macrophage assay resulted in negligible NF-kappa B activation. Analysis of acemannan and Aloeride using size-exclusion chromatography suggests that the low activity of acemannan is due to trace amounts of Aloeride. Although Aloeride comprises only 0.015% of the aloe juice dry weight, its potency for macrophage activation accounts fully for the activity of the crude juice.
Injectable and redox-responsive hydrogel with adaptive degradation rate for bone regeneration (2013)

Hydrogel systems with adaptive degradation behavior are of interest for application in tissue regeneration. In the present study, an in situ crosslinkable poly(ethylene glycol) (PEG) hydrogel was developed as an injectable scaffold. The hydrogel formed rapidly via oxidation of thiolated PEG precursors. The phase transition was further proved by injecting in vivo under physiological conditions. The gelation time could be controlled expediently, as well as the storage modulus ranging from 351 Pa to 10.6 kPa. Inversely, disentanglement of the disulfide-bridged network occurred at low concentration of reduced glutathione (GSH) which served as scissors to cleave the disulfide moieties. Degradation time can be modulated from 2 days to 32 days, resulting in corresponding protein release kinetics from 5 days to 32 days. In addition, obvious cell spreading and migration were observed within the gel. Moreover, the osteoinductive growth factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), was loaded into the hydrogel and ectopic bone formation was induced along with gel degradation and release of rhBMP-2. Overall, the obtained results clearly demonstrate a disulfide crosslinked hydrogel with inherent advantages including redox-responsive gelation and degradation, cell ingrowth and tunable release profile, thus it may provide a promising injectable carrier for tissue regeneration in terms of non-invasive and cytokine delivery strategies.
Insights into the Formation Mechanisms of Si−OR Monolayers from the Thermal Reactions of Alcohols and Aldehydes with Si(111)−H1 (2000)

Hydrogen-terminated Si(111) reacts thermally at moderate temperatures with alcohols (RCH₂OH) and aldehydes (RCHO) to form the corresponding Si-OCH₂R films. The films are characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). While FTIR and XP spectroscopies suggest that films of similar composition are formed, AFM and the relative chemical stabilities of the organic films show that the two reactions do not result in structurally identical films. A mechanism for the reaction of the aldehyde with Si(111)-H is proposed which is analogous to the well-known hydrosilylation of aldehydes. The reaction proceeds either by nucleophilic addition/hydride transfer or by a radical chain mechanism via adventitious radical initiation. The alcohol reaction is similar to the chemical etching of Si(111)-H by water and short-chain alcohols. This reaction proceeds by nucleophilic attack followed by loss of dihydrogen. Traces of ammonium fluoride or water on the surface result in etching of the terraces on a time scale which is much faster than the reaction of the alcohol but not of the aldehyde. This etching can be completely suppressed by the addition of chlorotrimethylsilane to the reaction mixture. This reagent quickly scavenges both water and fluoride from the surface and reaction mixture. It is suggested that this may be a useful reagent to scavenge undesirable nucleophiles during wet chemical modification of Si(111)-H.
Isolation of cholesterol oxidases from Rhodococcus equi ATCC 33706 (1991)

Rhodococcus equi ATCC 33706 was shown to possess a membrane-bound and a secreted form of cholesterol oxidase. Several detergents (n-octyl glucoside, Tween-20, Tween-60, Tween-80, and Brij-35) were tested for efficacy to release protein from membrane fragments and prevent aggregation of the secreted enzyme. Polyoxyethylene-23-lauryl ether (Brij-35) was most efficient at 0.5%, releasing 35% of membrane-bound protein. Under experimental conditions, 50% of the total cholesterol oxidase activity detected in pelleted fragments was solubilized
High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry (2008)

A newly developed high-throughput desorption electrospray ionization (DESI) source was characterized in terms of its performance in quantitative analysis. A 96-sample array, containing pharmaceuticals in various matrices, was analyzed in a single run with a total analysis time of 3 min. These solution-phase samples were examined from a hydrophobic PTFE ink printed on glass. The quantitative accuracy, precision, and limit of detection (LOD) were characterized. Chemical background-free samples of propranolol (PRN) with PRN-d(7) as internal standard (IS) and carbamazepine (CBZ) with CBZ-d(10) as IS were examined. So were two other sample sets consisting of PRN/PRN-d(7) at varying concentration in a biological milieu of 10% urine or porcine brain total lipid extract, total lipid concentration 250 ng/microL. The background-free samples, examined in a total analysis time of 1.5 s/sample, showed good quantitative accuracy and precision, with a relative error (RE) and relative standard deviation (RSD) generally less than 3% and 5%, respectively. The samples in urine and the lipid extract required a longer analysis time (2.5 s/sample) and showed RSD values of around 10% for the samples in urine and 4% for the lipid extract samples and RE values of less than 3% for both sets. The LOD for PRN and CBZ when analyzed without chemical background was 10 and 30 fmol, respectively. The LOD of PRN increased to 400 fmol analyzed in 10% urine, and 200 fmol when analyzed in the brain lipid extract.
Osteochondral Differentiation of Fluorescent Multireporter Cells on Zonally-Organized Biomaterials (2018)

This study represents significant advancement in the use of biomimetic scaffolds to direct zonal osteochondral tissue formation. We describe the use of a novel fluorescent reporter system that enables the real-time evaluation of cellular differentiation in a nondestructive manner. In this study, we use this tool to confirm the osteogenic and chondrogenic capabilities of our scaffold alongside control scaffolds, and use cryohistological methods to probe zone-specific differences in cell and tissue quality. We believe this approach can be widely adopted by others for a variety of biomaterial and cell systems in the development of tissue engineered therapeutics.
Data Cache Prefetching Using a Global History Buffer (2005)

Over the past couple of decades, trends in both microarchitecture and underlying semiconductor technology have significantly reduced microprocessor clock periods. These trends have significantly increased relative main-memory latencies as measured in processor clock cycles. To avoid large performance losses caused by long memory access delays, microprocessors rely heavily on a hierarchy of cache memories. But cache memories are not always effective, either because they are not large enough to hold a program's working set, or because memory access patterns don't exhibit behavior that matches a cache memory's demand-driven, line-structured organization. To partially overcome cache memories' limitations, we organize data cache prefetch information in a new way, a GHB (global history buffer) supports existing prefetch algorithms more effectively than conventional prefetch tables. It reduces stale table data, improving accuracy and reducing memory traffic. It contains a more complete picture of cache miss history and is smaller than conventional tables.
Uptake of 85Sr, 134Cs and 57Co by antimony silicates doped with Ti4+, Nb5+, Mo6+ and W6+ (2001)

Antimony silicate ion exchangers were prepared by precipitation using two different procedures. A crystalline product with a pyrochlore structure (SbSi) was obtained by mixing SbCl5 in HCl with sodium silicate solution (pHfinal < 1) and heating it at 60 °C overnight. An amorphous material (KSbSi) formed when KSb(OH)6 was mixed with tetraethylorthosilicate (TEOS) in acidic conditions and heated overnight at 77 °C. In both cases the Sb∶Si molar ratio was 1∶1 in the starting mixture. The products showed high 85Sr selectivity in acidic conditions, distribution coefficients (KD) being 35 500 mL g−1 for SbSi and 19 700 mL g−1 for amorphous KSbSi in 0.1 M HNO3. They are very selective for 85Sr over a wide pH range, making them superior to other strontium selective ion exchangers such as zeolites, sodium titanates and silicotitanates, which function effectively only in neutral or alkaline conditions. The antimony silicate products had also a high or reasonable selectivity for 57Co, 59Fe and 63Ni, but the selectivity for 134Cs was low. An attempt was made to increase the selectivity for 134Cs by doping the antimony silicates with Ti4+, Nb5+, Mo6+ or W6+. The best results were obtained by doping SbSi with W, which resulted in a 10-fold increase in caesium selectivity. The original pyrochlore structure was retained in the W-doped SbSi.
Device-Independent Color via Spectral Sharpening (1994)

Color sensors in scanners and color copiers are not colorimetric&#x2014;RGB values are not a linear transformation away from device-independent XYZ tristimulus values. For a given set of targets or dyes one can readily find a best linear transform or use interpolation. However, when the possible targets are unknown, a data-independent transform is needed.Here, we set out a very simple linear transform for forming XYZ from RGB, developed in analogy with a well-known solution for the color constancy problem in computer vision, based on using narrow-band sensors. In a scanner, we know the illuminant. Therefore the color constancy paradigm&#x2014;illumination-independent colors&#x2014;is not applicable. Instead, we change filters&#x2014;from RGB to XYZ. The von Kries adaptation form of the color constancy solution can then apply if we can &#x201C;sharpen&#x201D; both the RGB sensors and the XYZ color-matching functions. Recently, we developed just such a &#x201C;sharpening&#x201D; basis transform: most of the sensitivity of the new possibly partly negative sensors is isolated in a particular wavelength interval. Here we &#x201C;sharpen&#x201D; both sensor sets; after dividing by sharpened white-spot values an inverse transform results in recovered XYZ values. Applying the method to 462 Munsell chips yields a median CIELAB error of only 3 units for two different systems.
Efficacy of Multiple- or Single-Dose Cidofovir against Vaccinia and Cowpox Virus Infections in Mice (2003)

Orthopoxviruses, including variola and monkeypox, pose risks to human health through natural transmission or potential bioterrorist activities. Since vaccination has not recently been utilized for control of these infections, there is renewed effort in the development of antiviral agents not only for postexposure smallpox therapy but also for treatment of adverse reactions following vaccination. The objectives of this study were to expand on the results of others that cidofovir (CDV) is effective in mice inoculated with cowpox virus (CV) or vaccinia virus (VV) and to document the efficacy of single and interval dosing beginning prior to or after infection, particularly including evaluations using suboptimal doses of CDV. We utilized BALB/c or SCID mice inoculated with CV or VV as models for systemic poxvirus infections. BALB/c mice were inoculated intranasally with CV or VV and treated with CDV prior to or after virus inoculation. CDV, at concentrations as low as 0.7 to 6.7 mg/kg of body weight/day for 5 days, conferred significant protection when treatment was initiated as late as 72 to 96 h postinfection. A single-dose pretreatment or posttreatment with CDV at 3 to 100 mg/kg was effective when given as early as 5 days prior to infection or as late as 3 days after infection with either VV or CV. Interval treatments given every third day beginning 72 h postinfection using 6.7 or 2 mg of CDV/kg also proved effective against CV infections. When SCID mice were inoculated intraperitoneally with CV or VV and treated for 7 to 30 days with CDV, all the mice eventually died during or after cessation of treatment; however, significant delays in time to death and reduction of virus replication in organs occurred in most treated groups, and no resistance to CDV was detected.
Therapeutic Levels of Factor IX Expression Using a Muscle-Specific Promoter and Adeno-Associated Virus Serotype 1 Vector (2004)

Extensive studies in animal models of the X-linked bleeding disorder hemophilia B (deficiency in functional coagulation factor IX, F.IX) have shown that muscle-directed adeno-associated (AAV)-mediated F.IX gene transfer can be used to treat this disease. However, large vector doses of AAV-2 vector are required for therapeutic levels of expression, and the number of vector doses that can be injected per intramuscular site is limited. Several studies have shown that some of these limitations can be overcome by use of AAV serotype 1 vector. Here, we demonstrate levels of F.IX transgene expression from a synthetic muscle-specific promoter (C5-12) that were higher than from the cytomegalovirus (CMV) immediate-early enhancer-promoter in cultured muscle cells in vitro and approximately 50% of CMV-driven expression in vivo in murine skeletal muscle after AAV-1 gene transfer. These data show for the first time that a tissue-specific promoter can be used to achieve therapeutic levels of muscle-derived F.IX expression in the context of viral gene transfer. However, use of a muscle-specific promoter did not prevent antibody formation in response to a murine F.IX transgene product in mice with F.IX gene deletion, indicating that the risk of humoral immune responses remains in the context of an immunologically unfavorable mutation.
Proteomic Analysis of Ubiquitinated Proteins from Human MCF-7 Breast Cancer Cells by Immunoaffinity Purification and Mass Spectrometry (2005)

Post-translational modification of proteins via the covalent attachment of Ubiquitin (Ub) plays an important role in the regulation of protein stability and function in eukaryotic cells. In the present study, we describe a novel method for identifying ubiquitinated proteins from a complex biological sample, such as a whole cell lysate, using a combination of immunoaffinity purification and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. We have demonstrated the applicability of this approach by identifying 70 ubiquitinated proteins from the human MCF-7 breast cancer cell line after treatment with the proteasome inhibitor MG132. This method will aid the study of protein ubiquitination and may be used as a tool for the discovery of novel biomarkers that are associated with disease progression.
CRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes (2017)

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing. Efficacy and versatility of this pipeline was exemplified by producing different CRISPR/Cas9-HCAdV targeting the human papillomavirus (HPV) 18 oncogene E6, the dystrophin gene causing Duchenne muscular dystrophy (DMD) and the HIV co-receptor C-C chemokine receptor type 5 (CCR5). All CRISPR/Cas9-HCAdV proved to be efficient to deliver the respective CRISPR/Cas9 expression units and to introduce the desired DNA double strand breaks at their intended target sites in immortalized and primary cells.