gebhart/patrepeval huggingface dataset:
Turning self-destructing Salmonella into a universal DNA vaccine delivery platform (2012)

We previously developed a biological containment system using recombinant Salmonella Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these S. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases.
Development of a novel ketoprofen transdermal patch: effect of almond oil as penetration enhancers on in-vitro and ex-vivo penetration of ketoprofen through rabbit skin. (2011)

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.
Cell-free coupled transcription-translation system for investigation of linear DNA segments. (1980)

Heretofore the DNA-directed coupled transcription-translation system, most useful in gene expression analysis, has been limited to the use of circular or long linear DNAs. Linear DNAs are degraded in this system by an exonucleolytic activity that can be eliminated by making the synthetic extracts from a suitable recB mutant of Escherichia coli. Using these extracts, we have examined the gene expression of a variety of linear DNAs. In particular, the complex pattern of expression of ribosomal protein genes and RNA polymerase genes in the rpoBC-rplLJ region has been analyzed by comparing the protein products obtained when using lambda rifd18 DNA with the product obtained when using the same DNA segmented with various restriction enzymes. The results obtained confirm the conclusions of others obtained by much more elaborate in vivo techniques. It seems highly likely that this cell-free system will have extensive applications in the area of analysis of gene expression.
Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus (2007)

Nanoparticles larger than the reported mesh-pore size range (10-200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D(eff)) only 4- and 6-fold lower than that for the same particles in water (at time scale tau = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D(eff) was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, D(eff) was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery.
Arterial Blood Pressure Responses to Cell-free Hemoglobin Solutions and the Reaction with Nitric Oxide (1998)

Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM-1 s-1 for both .NO bimolecular association rate constants and the rate constants for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter .NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of .NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.
The PIM-2 Kinase Phosphorylates BAD on Serine 112 and Reverses BAD-induced Cell Death (2003)

Hematopoietic growth factors mediate the survival and proliferation of blood-forming cells, but the mechanisms through which these proteins produce their effects are incompletely known. Recent studies have identified the pim family of kinases as mediators of cytokine-dependent survival signals. Several studies have identified substrates for the pim-1 kinase, but little is known about the other family members, pim-2 and pim-3. We have investigated potential functions for the pim-2 kinase in factor-dependent murine hematopoietic cells. We find that pim-2 mRNA and protein expression are regulated by cytokines similarly to pim-1. Three PIM-2 protein isoforms are produced in cytokine-treated cells. All three forms are active kinases, and the short (PIM-2(34 kDa)) form is the most active at enhancing survival of FDCP1 cells after cytokine withdrawal. This pro-survival function involves inhibition of apoptosis and caspase activation. Enforced expression of PIM-2(34 kDa) kinase does not appear to regulate expression of BCL-2, BCL-xL, BIM, or BAX proteins. However, the kinase can phosphorylate the pro-apoptotic protein BAD on serine 112, which accounts in part for its ability to reverse Bad-induced cell death. Our results indicate that pim-2 functions similarly to pim-1 as a pro-survival kinase and suggest that BAD is a legitimate PIM-2 substrate.
Digestion, absorption, and fermentation of carbohydrates in the newborn. (1996)

In the newborn, sugars present in human milk and formulas are assimilated by both small intestinal digestion and, especially in the case of lactose, colonic bacterial fermentation. Colonic fermentation of carbohydrate serves three major functions: (1) conservation of a fraction of the metabolizable energy of dietary carbohydrate that is not absorbed in the small intestine; (2) prevention of osmotic diarrhea; and (3) production of short-chain fatty acids that stimulate sodium and water absorption, serve as fuel for colonocytes, and stimulate cell replication in colon and small intestine. Diarrhea produced in association with small bowel malabsorption of sugar may be caused by three, potentially overlapping mechanisms: (1) osmotic effects of unfermented sugar, which may cause secondary disruption of fermentation by purging the bacteria or diluting the bacteria mass; (2) damage to the colon mucosa from excessive fermentation leading to SCFA malabsorption and osmotic diarrhea on this basis; and (3) excessive fermentation leading to lowering of luminal pH and inhibition of bacterial enzymes. Therapy aimed at reducing diarrhea associated with sugar malabsorption might involve either slowing of motility to facilitate fermentation or stimulation of fermentative activity, but such interventions would depend on greater understanding of the mechanisms for colonic dysfunction in this condition.
Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1 (2012)

Artemisinin and its main active metabolite dihydroartemisinin, clinically used antimalarial agents with low host toxicity, have recently shown potent anticancer activities in a variety of human cancer models. Although iron mediated oxidative damage is involved, the mechanisms underlying these activities remain unclear. In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners. It decreased iron uptake and disturbed iron homeostasis in cancer cells, which were independent of oxidative damage. Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane. The regulation of dihydroartemisinin to transferrin receptor-1 could be reversed by nystatin, a cholesterol-sequestering agent but not the inhibitor of clathrin-dependent endocytosis. Dihydroartemisinin also induced transferrin receptor-1 palmitoylation and colocalization with caveolin-1, suggesting a lipid rafts mediated internalization pathway was involved in the process. Also, nystatin reversed the influences of dihydroartemisinin on cell cycle and apoptosis related genes and the siRNA induced downregulation of transferrin receptor-1 decreased the sensitivity to dihydroartemisinin efficiently in the cells. These results indicate that dihydroartemisinin can counteract cancer through regulating cell-surface transferrin receptor-1 in a non-classical endocytic pathway, which may be a new action mechanism of DHA independently of oxidative damage.
Increased Collagen Synthesis by Scleroderma Skin Fibroblasts In Vitro A POSSIBLE DEFECT IN THE REGULATION OR ACTIVATION OF THE SCLERODERMA FIBROBLAST (1974)

Cultures of dividing skin fibroblasts from normal and sclerodermatous human skin have permitted estimations of soluble collagen concentration, net collagen accumulation, cell-doubling times, and the comparison of morphologic and ultrastructural characteristics. In vitro, the scleroderma fibroblast produces more soluble collagen, synthesizes collagen more rapidly, and fourfold more of its protein synthetic activity is directed to collagen production than in the normal skin fibroblast. Cell-doubling times and morphologic and ultrastructural observations of cells in culture have not provided clues to the nature of the biologic defect in the regulation or activation of collagen synthesis by the scleroderma fibroblast.
mTOR Inhibition: From Aging to Autism and Beyond (2013)

The mechanistic target of rapamycin (mTOR) is a highly conserved protein that regulates growth and proliferation in response to environmental and hormonal cues. Broadly speaking, organisms are constantly faced with the challenge of interpreting their environment and making a decision between "grow or do not grow." mTOR is a major component of the network that makes this decision at the cellular level and, to some extent, the tissue and organismal level as well. Although overly simplistic, this framework can be useful when considering the myriad functions ascribed to mTOR and the pleiotropic phenotypes associated with genetic or pharmacological modulation of mTOR signaling. In this review, I will consider mTOR function in this context and attempt to summarize and interpret the growing body of literature demonstrating interesting and varied effects of mTOR inhibitors. These include robust effects on a multitude of age-related parameters and pathologies, as well as several other processes not obviously linked to aging or age-related disease.
Some chemical and analytical aspects of polysaccharide modifications. IV. Electron spin resonance studies of nitroxide-labelled chitin and chitosan derivatives (1984)

Nitroxide spin labels have been attached to chitin, chitosan, and their derivatives in order to investigate the solution and gel characteristics of these polymers. Thus, chitin was nonselectively acylated using the chloroacetamide label 3 to afford. the corresponding nitroxide derivative 4. Selective and nonselective labelling of chitosan was accomplished either via reductive alkylation using the keto label 5 and sodium cyanoborohydride or via a chitosan sulfate intermediate using labels 3 or 5. Two branched water soluble chitosan derivatives, carrying C-6 oxidized, terminal galactose side chains were selectively labelled by reductive animation using the amine label 13 to yield derivatives 14 and 15. Motional correlation values of the covalently-linked nitroxide moieties were shown to reflect the nature of the linkage between spin label and polymer, as well as structural differences between the branch residues of derivatives 14 and 15. The spin-probe – spin-label method was employed to demonstrate structural heterogeneities for the chitosan derivatives 7 and 15.
Hereditary obesity and hormone deficiencies in yellow dwarf mice (1965)

Daily injection of 0.05 USPU of ovine growth hormone had no effect on greater fat deposition in yellow dwarf ( A y adwdw) mice of either sex as compared with nonyellow dwarf mice ( aadwdw). No differences between the accelerated growth rates of both genotypes during the injection period were noted nor were there any marked differences in the increase in tail length between the genotypes. Yellow dwarf mice continued gaining weight more rapidly than nonyellow dwarf mice after the end of the injection period. Analysis of the fat and water content of the carcasses indicates that the greater rate of weight gain of yellow dwarf mice is due almost entirely to increased fat deposition. The results of this experiment suggest that the obesity of yellow mice is not due to deficiencies of growth hormone or thyrotrophin.
[Epidemiologic studies on three episodes of acute bacillary dysentery outbreak]. (1995)

Three episodes of illness outbreak, with major symptoms of acute abdominal pain and diarrhea, occurred in 1990 to 1991 in the army forces stationed in Beijing. Bacillary dysentery outbreak caused by Shigella dysentariae were confirmed with epidemiological investigations and pathogen identification. Drug sensitivity tests with Kirby-Bauer method for the strain isolated showed it had obvious resistance to 13 of 14 kinds of antibiotics tested. Detection of plasmid with Birnboim method showed most of the strains had R-plasmid of 120-140 Md and few had small plasmid. It suggested inherent connection between drug-resistance of the strains and plasmid.
Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. (1993)

The vitamin D receptor (VDR) binds the vitamin D-responsive element (VDRE) as a heterodimer with an unidentified receptor auxiliary factor (RAF) present in mammalian cell nuclear extracts. VDR also interacts with the retinoid X receptors (RXRs), implying that RAF may be related to the RXRs. Here we demonstrate that highly purified HeLa cell RAF contained RXR beta immunoreactivity and that both activities copurified and precisely coeluted in high-resolution hydroxylapatite chromatography. Furthermore, an RXR beta-specific antibody disrupted VDR-RAF-VDRE complexes in mobility shift assays. These data strongly indicate that HeLa RAF is highly related to or is identical to RXR beta. Consequently, the effect of the 9-cis retinoic acid ligand for RXRs was examined in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-activated gene expression systems. Increasing concentrations of 9-cis retinoic acid (1 nM to 1 microM) markedly reduced 1,25(OH)2D3-dependent accumulation of osteocalcin mRNA in osteoblast-like ROS 17/2.8 cells. All-trans retinoic acid also interfered with vitamin D responsiveness, but it was consistently less potent than the 9-cis isomer. Transient transfection studies revealed that attenuation by 9-cis retinoic acid was at the transcriptional level and was mediated through interactions at the osteocalcin VDRE. Furthermore, overexpression of both RXR beta and RXR alpha augmented 1,25(OH)2D3 responsiveness in transient expression studies. Direct analysis of VDRE binding in mobility shift assays demonstrated that heteromeric interactions between VDR and RXR were enhanced by 1,25(OH)2D3 and were not affected appreciably by 9-cis retinoic acid, except that inhibition was observed at high retinoid concentrations. These data suggest a regulatory mechanism for osteocalcin gene expression that involves 1,25(OH)2D3-induced heterodimerization of VDR and unliganded RXR. 9-cis retinoic acid may attenuate 1,25(OH)2D3 responsiveness by diverting RXRs away from VDR-mediated transcription and towards other RXR-dependent transcriptional pathways.
Induction and Assessment of Immunity at Enteromucosal Surfaces in Humans: Implications for Vaccine Development (1993)

It is now almost axiomatic that vaccines against enteric infections must be able to stimulate the gut lymphoid tissue to be efficacious and that this goal is usually better achieved by administering immunogens orally rather than parenterally. On the basis of the notion of a common mucosal immunologic system that provides immune reactivity not only at the site of antigen deposition but also at remote mucosal sites, there is much interest in developing oral vaccines against infections in the respiratory and urogenital tracts. Recent studies indicate that oral administration of small amounts of protein antigens that are chemically or genetically linked to intestinal binding carrier molecules (such as the B subunit of cholera toxin) can evoke vigorous mucosal and extramucosal immune responses. The apparent compartmentalization of systemic and mucosal immune responses may explain not only why parenteral vaccines are just partly effective in protecting against mucosal pathogens but also why currently employed immunoanalytical methods do not provide accurate information regarding mucosal immune status. Following the developments of oral vaccines against infections due to Vibrio cholerae and enterotoxigenic Escherichia coli, two archetypes of enteropathogens, we have devoted extensive efforts to gaining insight into the humoral and cellular events involved in the development of protective immunity in the human intestinal tract. We have developed preparative and analytical methods for studying vaccine-induced intestinal and extraintestinal immune responses in humans. These include techniques for collecting intestinal fluid and lymphoid cells as well as procedures to quantitate secretory antibodies and lymphokines secreted by activated intestinal immunocytes. These developments should serve the dual purpose of facilitating analyses of human mucosal immune responses in general and assessing the immunogenicity of enteric vaccines in particular.
Therapy for recurrent ovarian cancer. (2003)

Primary treatment of advanced ovarian cancer is well established. The combination of tumor debulking and platinum/taxane polychemotherapy has led to improved treatment results in recent years. However, most patients with ovarian cancer will relapse, rendering treatment of recurrent ovarian cancer of great clinical interest. Relapse therapy should depend on the treatment-free interval. Patients with progressive disease during primary treatment or cancer relapse within 6 months after the completion of primary treatment are platinum refractory, and, therefore, prognostically unfavorable. For these patients with poor outcome, quality of life should be predominantly considered before initiation of treatment. Cancer relapse after an interval of more than 6 months after the completion of primary treatment cannot be cured; however, platinum-based chemotherapy, in individual cases combined with secondary tumor debulking, can lead to persisting remissions.
Efficient Deep Convolutional Neural Networks Accelerator without Multiplication and Retraining (2018)

Recently, low-precision weight method has been considered as a promising scheme to efficiently implement inference of deep convolutional neural networks (DCNN). But it suffers from expensive retraining cost and accuracy degradation. In this paper, a low-bit and retraining-free quantization method, which enables DCNNs to deal inference with only shift and add operations, is proposed. The efficiency is demonstrated in terms of power consumption and chip area. Huffman coding is adopted for further compression. Then by exploring two-level systolic, an efficient hardware accelerator is introduced with respect to the given quantization strategy. Experiment results show that our method achieves higher accuracy than other low-precision networks without retraining process on ImageNet. 5× to 8× compression is obtained on popular models compared to full-precision counterparts. Furthermore, hardware implementation indicates good reduction of slices whereas maintaining throughput.