gebhart/patrepeval huggingface dataset:
Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants (2004)

Cartilage engineering is a strategic experimental goal for the treatment of multiple joint diseases. Based on the process of embryonic chondrogenesis, we hypothesized that cartilage could be engineered by condensing chondrocytes in pellet culture and, in the present study, examined the quality of regenerated cartilage in direct comparison with native cartilage. Chondrocytes isolated from the sterna of chick embryos were cultured in pellets (4 x 10(6) cells per pellet) for 2 weeks. Cartilage explants from the same source were cultured as controls. After 2 weeks, the regenerated cartilage from pellet culture had a disc shape and was on average 9 mm at the longest diameter. The chondrocyte phenotype was stabilized in pellet culture as shown by the synthesis of type II collagen and aggrecan, which was the same intensity as in the explant after 7 days in culture. During culture, chondrocytes also continuously synthesized type IX collagen. Type X collagen was negatively stained in both pellets and explants. Except for fibril orientation, collagen fibril diameter and density in the engineered cartilage were comparable with the native cartilage. In conclusion, hyaline cartilage engineered by chondrocytes in pellet culture, without the transformation of cell phenotypes and scaffold materials, shares similarities with native cartilage in cellular distribution, matrix composition and density, and ultrastructure.
A phase 1a, first-in-human, randomized study of a respiratory syncytial virus F protein vaccine with and without a toll-like receptor-4 agonist and stable emulsion adjuvant (2016)

The safety and immunogenicity results from this study support inclusion of the GLA-SE adjuvant in this RSV vaccine for older adults and also support assessment of the efficacy of the vaccine in a larger clinical trial. Clinicaltrials.gov NCT02115815.
A Decision Theoretic Methodology for Seventy Index Development (1986)

Severity indices are a key element in evaluation of health programs. But the methodologies used in development of such indices are rarely clearly defined. Moreover, there have been no tests of transportability of the index development methodologies that do exist, so there is no guarantee that panels of physicians convened by different facilitators would produce indices with similar performance characteristics. This paper describes a replicable index development strategy, a heart disease severity index developed by using that methodology, and a test of that methodology's transportability.
Temporal whitening: Transient noise perceptually equalizes the 1/f temporal amplitude spectrum (2009)

Naturally occurring luminance distributions are approximately 1/f in their spatial and temporal amplitude spectra. By systematically varying the spatio-temporal profile of broadband noise stimuli, we demonstrate that humans invariably overestimate the proportion of high spatial and temporal frequency energy. Critically, we find that that the strength of this bias is of a magnitude that predicts a perceptually equalized response to the spatio-temporal fall off in the natural amplitude spectrum. This interpretation is supported by our finding that the magnitude of this transient response bias, while evident across a broad range of narrowband spatial frequencies (0.25-8 cycles/deg), decreases above 2 cycles/deg, which itself compensates for the increase in temporal frequency energy previously observed at high spatial frequencies as a consequence of small fixational eye movements (M. Rucci, R. Iovin, M. Poletti, & F. Santini, 2007). Additional temporal masking and adaptation experiments reveal a transiently biased asymmetry. Whereas temporal frequencies >4 Hz mask and adapt 1- and 15-Hz targets, lower masking and adaptation frequencies have much less effect on sensitivity to 15-Hz compared with 1-Hz targets. These results imply that the visual system over-represents its transient input to an extent that predicts an equalized temporal channel response to the low-frequency-biased structure of natural scenes.
Adiponectin Genetic Variability, Plasma Adiponectin, and Cardiovascular Risk in Patients With Type 2 Diabetes (2006)

Adiponectin is an adipocyte-derived hormone that has shown anti-inflammatory and antiatherogenic effects. We assessed the associations of variants in the adiponectin gene (ADIPOQ) with circulating adiponectin levels and cardiovascular risk among women with type 2 diabetes. Of 989 diabetic women from the Nurses' Health Study, 285 developed cardiovascular disease (CVD) during follow-up through 2000. We genotyped five ADIPOQ polymorphisms in the CVD case and control subjects. A promoter polymorphism -11365C-->G was significantly associated with lower plasma adiponectin levels (P = 0.004). The homozygotes of allele -4034C were significantly associated with approximately 60% increased cardiovascular risk (odds ratio 1.62 [95% CI 1.07-2.45]). Adjustment for age, BMI, and other covariates did not appreciably change the associations. In addition, a common haplotype possessing allele +276T (CAATT) was associated with a significantly lower CVD risk than the most common haplotype (CAATG) (0.70 [0.50-0.98]). In our meta-analysis of 827 CVD case and 1,887 CVD-free control subjects, polymorphism +276G-->T was significantly associated with approximately 45% (20-62%) decreased CVD risk under a recessive inheritance mode in diabetic patients. In conclusion, ADIPOQ promoter polymorphism -11365C-->G was associated with plasma adiponectin levels, whereas polymorphisms -4034A-->C and +276G-->T were associated with CVD risk in diabetic patients.
Cellular Reaction in the Footpad and Draining Lymph Nodes of Mice Induced by Mycobacterial Fractions and BCG Bacilli (1971)

Ten micrograms of trehalose-6, 6'-dimycolate (cord factor), injected into the footpad of mice, induced histological changes similar to those following injection of living BCG bacilli. Both materials induced in the draining lymph nodes the formation of granulomas composed of epitheloid cells, macrophages, and small numbers of lymphocytes. Apart from the granulomatous inflammatory process, marked hyperplasia of the lymphoid tissue in the paracortical zone of the nodes and accumulations of macrophages were evident. In some cases, the macrophages were very numerous and replaced part of the lymphoid tissue. Compared to cord factor, wax D showed weak granulomagenic activity. Only slight and transient inflammation was found in the footpads as well as transient slight lymphoid hyperplasia. Wax D also induced small accumulations of macrophages. Complete Freund's adjuvant induced, under the same experimental conditions, large accumulations of macrophages in the draining lymphnode and lymphoid hyperplasia in the paracortical zone. No cellular reaction was seen in the liver, spleen, and lungs after injection of cord factor and BCG into the footpads of the animals. The results and implications are discussed.
Bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cDNAs (1989)

Genetic and biochemical evidence has established that the E2 open reading frame (ORF) of bovine papillomavirus type 1 encodes at least two different site-specific DNA-binding proteins, one which activates and the other which represses expression from a viral promoter (P. F. Lambert, B. A. Spalholz, and P. M. Howley, Cell 50:69-78, 1987). We have obtained data which show that a second form of the repressor gene is expressed in transformed cells harboring stable viral plasmids. The structural details of this gene have been discerned by cDNA cloning, by RNase protection, and by primer extension analysis of in vivo RNA. Moreover, data from in vitro transcription experiments support the notion that this form of the E2 repressor is expressed from a novel viral promoter and that a small exon from another ORF is linked to an active repressor domain in E2. Thus, two different forms of the repressor are expressed from different promoters and might be independently regulated either in the cell cycle or in different tissue types. We show by functional in vivo assays utilizing a cDNA vector encoding this gene that the trans-acting factor has in vivo activities similar to those of the known repressor. Our screen of a cDNA library for cDNA clones representing bovine papillomavirus transcripts has also revealed a number of other novel structures defining new donor and acceptor RNA-processing sites. Notably, clones which conceptually can be translated to yield an E7 protein, the viral M gene, and the entire E2 ORF have been characterized. Finally, truncated versions of putative E8 cDNAs were also obtained.
NITROXYL (HNO): Chemistry, Biochemistry, and Pharmacology (2005)

Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of HNO are not well understood. Moreover, many of the previously accepted chemical properties of HNO have been recently revised, thus requiring reevaluation of possible mechanisms of biological action. Herein, we review these developments in HNO chemistry and biology.
Inhibition of T cell activation by the extracellular matrix protein tenascin. (1994)

Tenascin (TN) is an extracellular matrix protein that is expressed widely in the fetus and sparingly in the adult, but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing. We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co-immobilized with the extracellular matrix protein fibronectin (FN). TN also inhibits proliferation driven by alpha CD3/IL-2 or by phorbol ester/IL-2, and it prevents high level induction of IL-2R. The presence of TN in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with alpha CD3, but at later time points prevents the appearance of functional NF-AT1 transcription factor complexes in T cell nuclear extracts. These findings are consistent with the postulated role for TN as a natural antagonist to FN action, and suggest that T cell responses occurring at tissue sites in which TN is expressed could be influenced by its presence.
Transformation ofMethanococcus maripaludisand identification of aPstI-like restriction system (1994)

An optimized polyethylene glycol (PEG) method of transformation was developed for Methanococcus maripaludis using the pKAS102 integration vector. The frequency of transformation with 0.8 μg of plasmid and 3×109 cells was 4.8×10−5 transformants cfu−1, or 1.8×105 transformants μg−1, which was four orders of magnitude greater than with the natural transformation method. A PstI restriction activity in M. maripaludis was also identified. Methylation of the plasmid with PstI methylase increased the methanococcal transformation frequency at least four-fold. Also, chromosomal DNA from M. maripaludis was resistant to digestion by the PstI endonuclease.
Activity of ertapenem against Neisseria gonorrhoeae (2004)

1. Normark, B. H. & Normark, S. (2002). Evolution and spread of antibiotic resistance. Journal of Internal Medicine 252, 91–106. 2. Lutkenhaus, J. & Addinall, S. G. (1997). Bacterial cell division and the Z ring. Annual Review of Biochemistry 66, 93–116. 3. Christensen, D. J., Gottlin, E. B., Benson, R. E. et al. (2001). Phage display for target-based antibacterial drug discovery. Drug Discovery Today 6, 721–7. 4. Lowe, J. & Amos, L. A. (1998). Crystal structure of the bacterial cell-division protein FtsZ. Nature 391, 203–6. 5. Wang, J., Galgoci, A., Kodali, S. et al. (2003). Discovery of a small molecule that inhibits cell division by blocking FtsZ, a novel therapeutic target of antibiotics. Journal of Biological Chemistry 278, 44424–8. 6. Nefzi, A., Dooley, C., Ostresh, J. M. et al. (1998). Combinatorial chemistry: from peptides and peptidomimetics to small organic and heterocyclic compounds. Bioorganic and Medicinal Chemistry Letters 8, 2273–8.
Localization of von Willebrand Factor-binding Sites for Platelet Glycoprotein Ib and Botrocetin by Charged-to-Alanine Scanning Mutagenesis (2000)

At sites of vascular injury, von Willebrand factor (VWF) mediates platelet adhesion through binding to platelet glycoprotein Ib (GPIb). Previous studies identified clusters of charged residues within VWF domain A1 that were involved in binding GPIb or botrocetin. The contribution of 28 specific residues within these clusters was analyzed by mutating single amino acids to alanine. Binding to a panel of six conformation-dependent monoclonal antibodies was decreased by mutations at Asp(514), Asp(520), Arg(552), and Arg(611) (numbered from the N-terminal Ser of the mature processed VWF), suggesting that these residues are necessary for domain A1 folding. Binding of (125)I-botrocetin was decreased by mutations at Arg(629), Arg(632), Arg(636), and Lys(667). Ristocetin-induced and botrocetin-induced binding to GPIb both were decreased by mutations at Lys(599), Arg(629), and Arg(632); among this group the K599A mutant was unique because (125)I-botrocetin binding was normal, suggesting that Lys(599) interacts directly with GPIb. Ristocetin and botrocetin actions on VWF were dissociated readily by mutagenesis. Ristocetin-induced binding to GPIb was reduced selectively by substitutions at positions Lys(534), Arg(571), Lys(572), Glu(596), Glu(613), Arg(616), Glu(626), and Lys(642), whereas botrocetin-induced binding to GPIb was decreased selectively by mutations at Arg(636) and Lys(667). The binding of monoclonal antibody B724 involved Lys(660) and Arg(663), and this antibody inhibits (125)I-botrocetin binding to VWF. The crystal structure of the A1 domain suggests that the botrocetin-binding site overlaps the monoclonal antibody B724 epitope on helix 5 and spans helices 4 and 5. The binding of botrocetin also activates the nearby VWF-binding site for GPIb that involves Lys(599) on helix 3.
The Use of Ion‐Exchange Resins as a Blood Preservation System (1979)

A system using ion‐exchange resins for the storage of whole blood was investigated. Blood was collected into CPD, thoroughly mixed and then divided into equal amounts. To one half of the split units, four grams of phosphate charged Amberlite IR‐45 resin were added, while no additions were made to the other split units. Both aliquots were stored at 4 C, adhering to routine blood banking, standards. The blood stored with the resin for up to 28 days maintained high levels of 2,3‐DPG and adequate levels of ATP. This new resin system has several advantages over the present blood preservation technology. There is initial increase in pH that promotes greater glucose utilization. Inorganic phosphate is provided to maintain both ATP and 2,3‐DPG levels. The resin buffers the blood and maintains a narrower pH range for red blood cell enzyme activity. The resin is totally inert, completely filterable and has the ability to adsorb bacteria from the suspending solution.
Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells (2012)

Despite the successes of antiretroviral therapy (ART), HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood-brain barrier (BBB) and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART) (atazanavir, ritonavir, indinavir, and efavirenz). We demonstrate that nanoART transfer from mononuclear phagocytes (MP) to human brain microvascular endothelial cells (HBMEC) can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γ(c)(null) mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three- to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and brain, and diminished brain CD11b-associated glial activation. We postulate that monocyte-macrophage transfer of nanoART to brain endothelial cells could facilitate drug entry into the brain.
Human Cytomegalovirus gH/gL/gO Promotes the Fusion Step of Entry into All Cell Types, whereas gH/gL/UL128-131 Broadens Virus Tropism through a Distinct Mechanism (2015)

The functions of HCMV gH/gL complexes in entry are unclear. Unlike the well-studied Epstein-Barr virus (EBV), where gH/gL and gH/gL/gp42 complexes both seem capable of promoting gB fusion during entry into different cell types, our studies here suggest that for HCMV, gH/gL/gO promotes gB fusion on all cell types, whereas gH/gL/UL128-131 broadens virus tropism through a distinct, as yet unknown mechanism. To our knowledge, this is the first suggestion of a herpesvirus gH/gL that does not act by promoting gB fusion, which might make HCMV a useful model to study the fundamental mechanisms by which herpesvirus gH/gL regulates gB fusion. Moreover, gH/gL/UL128-131 is a candidate vaccine target. Our findings help to explain the cell-type-dependent virus neutralization exhibited by anti-gH/gL/UL128-131 antibodies and underscore the importance of gH/gL/gO as another important part of vaccine or therapeutic strategies.
Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene (2003)

The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8(+)-biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed.
Quantitative Comparison of Anti-Fading Mounting Media for Confocal Laser Scanning Microscopy (2001)

Fading is one of the major obstacles to reliable observation in fluorescence microscopy. Using a confocal laser scanning microscope (CLSM) coupled to a computer, we quantitatively measured fading of fluorescence to formulate an equation, evaluated the anti-fading ability of several anti-fading media, and restored the faded images to the original level according to this equation. NIH 3T3 cells were stained with fluorescein isothiocyanate (FITC)-phalloidin, mounted with several commercial and homemade anti-fade media, and observed with CLSM under repeated illumination. With any mounting medium, attenuation of fluorescence intensity at a certain pixel occurred stepwise and the decrease was proportional to the intensity of the previous scan. From these results, we formulated an equation that has three coefficients: anti-fading factor (A), indicating the ability to retard fading; fluorescent intensity at the first scan (EM(1)); and background fluorescence (B). The fluorescent intensity at a certain point following nth scan is given as EM(n) = EM(1) * A ((n-1)). This equation was available for restoring faded images to their original states, even after the image had faded to only 60% of its original intensity.
On the Oscillations of a Circuit Having a Periodically Varying Capacitance (1934)

A previous theoretical study of a dissipationless oscillatory circuit having a periodically varying capacity predicted the existence of several interesting types of oscillations. An experimental investigation of such a circuit was therefore made. The results of this investigation are presented in this paper. The dissipation was reduced to a minimum by means of an associated vacuum tube in a regenerative connection. An auxiliary condenser and rotating commutator produced the periodic capacity variation. The nature of the oscillations was studied by means of oscillograph and meter measurements of the currents in the several parts of the circuit and by the use of headphones. A quite good agreement with theory was found, consistent with the deviations of the experimental conditions from the theoretically postulated ones. The oscillations were generally of a complicated nonsinusoidal character, but assumed a substantially sinusoidal form for certain adjustments of the circuit. The frequency of these sinusoidal oscillations was twice that of the capacity variation. Periodic oscillations were found to occur when, approximately, α = 2ω <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> /n, n = 1, 2, 3, ..., where ω <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</inf> is the natural angular velocity of the circuit for the mean capacity value and α is the angular velocity of the capacity variation. Failure of all oscillations for certain circuit adjustments was related to the inherent loss of energy in the switching method employed for varying the capacity. The theory had predicted certain unstable conditions for which the amplitude should increase without limit.