gebhart/patrepeval huggingface dataset:
Mesenchymal Stem Cell Therapy for Inflammatory Bowel Disease (2015)

Recent advances in inflammatory bowel disease (IBD) therapeutics include novel medical, surgical, and endoscopic treatments. Among these, stem cell therapy is still in its infancy, although multiple studies suggest that the immunomodulatory effect of stem cell therapy may reduce inflammation and tissue injury in patients with IBD. This review discusses the novel avenue of stem cell therapy and its potential role in the management of ulcerative colitis and Crohn's disease. We conducted a comprehensive literature search to identify studies examining the role of stem cell therapy (without conditioning and immunomodulatory regimens) in IBD. Taken together, these studies suggest a promising role for stem cell therapy in IBD although the substantial challenges, such as cost and inadequate/incomplete characterization of effect, limit their current use in clinical practice.
Direct-write dispenser-printed energy storage devices (2010)

The simultaneous decrease in electronic device form factors yet increase in functionality has motivated a shift in energy storage design and manufacture to accommodate novel and unconventional materials, new device geometries, and nontraditional fabrication methods. We are developing a simple, low-cost, solution-based method for integrating custom energy storage components directly onto a device. A direct write dispenser printing system is used to pattern solutionsbased materials into multilayer devices. Along with this fabrication method, we discuss the materials design and device characterization of two printed energy storage devices: a carbon electrochemical microcapacitor and a zinc-metal oxide microbattery. The two components will be used as a hybrid energy storage system, capable of providing an energy dense storage buffer while also being able to address high power pulse loads, all within a limited footprint area.
The interpretation and application of Rent's rule (2000)

This paper provides a review of both Rent's rule and the placement models derived from it. It is proposed that the power-law form of Rent's rule, which predicts the number of terminals required by a group of gates for communication with the rest of the circuit, is a consequence of a statistically homogeneous circuit topology and gate placement. The term "homogeneous" is used to imply that quantities such as the average wire length per gate and the average number of terminals per gate are independent of the position within the circuit. Rent's rule is used to derive a variety of net length distribution models and the approach adopted in this paper is to factor the distribution function into the product of an occupancy probability distribution and a function which represents the number of valid net placement sites. This approach places diverse placement models under a common framework and allows the errors introduced by the modeling process to be isolated and evaluated. Models for both planar and hierarchical gate placement are presented.
Microwave-Assisted Direct Synthesis of 2-Substituted Benzoxazoles from Carboxylic Acids under Catalyst and Solvent-Free Conditions (2005)

A direct coupling of carboxylic acids with 2-aminophenol under microwave irradiation has been achieved leading to the synthesis of 2-substituted benzoxazoles under metal and solvent-free conditions. Aliphatic, aromatic and heteroaromatic carboxylic acids provide good yields. Benzoxazole formation takes place in the presence of chloro, methoxy, phenoxy, thiophenoxy, and α,β-unsaturated functionalities. In the case of dicarboxylic acids, the reaction proceeds via the formation of the corresponding anhydride with predominant formation of the mono-benzoxazole.
Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models (2010)

Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-drug was synthesized (CP-4126), with an elaidic fatty acid esterified at the 5'position. CP-4126 was tested in cell lines resistant to cytarabine, another dCyd analog or gemcitabine. Activity of gemcitabine and the derivative was comparable in the parent cell lines, while in dCK deficient cells all compounds were inactive. However, inhibition of nucleoside transport increased the IC(50) for gemcitabine up to 200-fold, but not for CP-4126, underlining the independence of a nucleoside transporter. For in vivo evaluation, nude mice bearing a human xenograft were treated intraperitoneally every third day for five doses at the maximal tolerated dose. In melanoma, sarcoma, lung, prostate, pancreatic and breast cancer xenografts, gemcitabine and CP-4126 were equally and highly effective; in four other xenografts moderately but equally active. In contrast to gemcitabine, CP-4126 could be administered orally, with a schedule and dose dependent toxicity and antitumor activity. In a colon cancer xenograft, antitumor activity of orally administered CP-4126 was equal to the intraperitoneally administered drug. In conclusion, CP-4126 is membrane transporter independent. Intraperitoneally administered CP-4126 was as effective as gemcitabine in several xenografts and CP-4126 is tolerated when orally administered. CP-4126 seems to be a promising new anticancer drug.
Probing the Activities and Mechanisms of Leukotriene A4 Hydrolase with Synthetic Inhibitors (1998)

The synthesis of a potent competitive LTA4 hydrolase inhibitor (A, Ki=1.6 nM) prompted an investigation into the biological activity of A against LTB4 biosynthesis, as well as the design, synthesis, and evaluation of a new series of inhibitors B to further probe the active site of LTA4 hydrolase. On the basis of these results, and previously reported site-directed mutagenesis and inhibition studies, the mechanisms of peptide and epoxide hydrolysis catalyzed by LTA4 hydrolase are discussed.
The Role of NHERF and E3KARP in the cAMP-mediated Inhibition of NHE3 (1998)

NHE3 is the apically located Na+/H+ exchanger in the gut and in the renal proximal tubule. Acute inhibition of this transporter by cAMP requires the presence of either of two NHE3-associated proteins, NHERF or E3KARP. It has been suggested that these proteins either directly regulate NHE3 activity after being phosphorylated by protein kinase A (PKA) or that they may serve as adapters that localize PKA near NHE3. We studied the role of NHERF and E3KARP in opossum kidney cells, which endogenously express NHE3, NHERF, and ezrin and display cAMP-dependent inhibition of NHE3. In vivo phosphorylation studies showed that NHERF is a phosphoprotein under basal conditions, but does not change its phosphorylation state after 8-bromo-cAMP treatment, and that E3KARP is not phosphorylated at all. Co-immunoprecipitation showed that NHERF and E3KARP bind both NHE3 and ezrin. Using cAMP analogs it was demonstrated that NHE3 activity, measured as sodium-dependent recovery of the intracellular pH after intracellular acidification, is inhibited by PKA type II. Because others have shown that ezrin binds PKA type II and that NHE3 is phosphorylated by PKA we suggest that NHERF and E3KARP are adapters that link NHE3 to ezrin, thereby localizing PKA near NHE3 to allow NHE3 phosphorylation.
Comparison of the hypotensive and other ocular effects of prostaglandins E2 and F2 alpha on cat and rhesus monkey eyes. (1982)

It is generally accepted that exogenous or endogenous prostaglandins (PGs) can give rise to acute increases in intraocular pressure (IOP) and to the development of flare and other signs of uveitis. It was recently shown, however, that low doses of PGE2 and/or PGF2 alpha topically applied to rabbit or owl monkey eyes significantly reduce IOP. The present experiments show that topical application of 10 to 500 micrograms of PGE2 also causes a highly significant IOP reduction in cat eyes lasting up to 48 hr with little or no development of flare or miosis, whereas similar application of PGF2 alpha causes, in addition to an IOP reduction, the development of profound pupillary constriction. Topical application of either PGF2 alpha or PGE2 to the eyes of rhesus monkeys also causes significant dose-dependent reduction in IOP. The hypotensive response in the rhesus monkey is not associated with detectable flare or consistent pupillary constriction, although at higher PG doses, hypotension tends to be preceded in both species by a brief (15 to 30 min) hypertensive phase. It is concluded that the eyes of different species show different patterns of IOP, miotic, and flare responses to topically applied PGs, the only consistent effect being a reduction in IOP. In some species, most notably in primates, a reduction in IOP is the predominant effect of PGs. Thus, PGs or their analogues may provide a new approach to the clinical control of IOP and the treatment of glaucoma.
Complete Lipopolysaccharide of Plesiomonas shigelloides O74:H5 (Strain CNCTC 144/92). 2. Lipid A, Its Structural Variability, the Linkage to the Core Oligosaccharide, and the Biological Activity of the Lipopolysaccharide, (2006)

Plesiomonas shigelloides is a Gram-negative bacterium associated with waterborne infections, which is common in tropical and subtropical habitats. Contrary to the unified antigenic classification of P. shigelloides, data concerning the structure and activity of their lipopolysaccharides (LPS and endotoxin) are limited. This study completes the structural investigation of phenol- and water-soluble fractions of P. shigelloides O74 (strain CNCTC 144/92) LPS with the emphasis on lipid A heterogeneity, describing the entire molecule and some of its biological in vitro activities. Structures of the lipid A and the affinity-purified decasaccharide obtained by de-N,O-acylation of P. shigelloides O74 LPS were elucidated by chemical analysis combined with electrospray ionization multiple-stage mass spectrometry (ESI-MS(n)), MALDI-TOF MS, and NMR spectroscopy. Lipid A of P. shigelloides O74 is heterogeneous, and three major forms have been identified. They all were asymmetric, phosphorylated, and hexaacylated, showing different acylation patterns. The beta-GlcpN4P-(1-->6)-alpha-GlcpN1P disaccharide was substituted with the primary fatty acids: (R)-3-hydroxytetradecanoic acid [14:0(3-OH)] at N-2 and N-2' and (R)-3-hydroxydodecanoic acid [12:0(3-OH)] at O-3 and O-3'. The heterogeneity among the three forms (I-III) of P. shigelloides O74 lipid A was attributed to the substitution of the acyl residues at N-2' and O-3' with the secondary acyls: (I) cis-9-hexadecenoic acid (9c-16:1) at N-2' and 12:0 at O-3', (II) 14:0 at N-2' and 12:0 at O-3', and (III) 12:0 at N-2' and 12:0 at O-3'. The pro-inflammatory cytokine-inducing activities of P. shigelloides O74 LPS were similar to those of Escherichia coli O55 LPS.
Institutional And Non-Institutional Deliveries In Some Slum Areas Of Delhi : Factor Analysis (1999)

Research questions: What are the factors, which determine preference for institutional and non-institutional deliveries in slum area of Delhi? Objective: To study the factors determining preference for institutional or non-institutional deliveries in slum areas of Delhi. Study design: Cross-sectional. Settings: Slum areas of Delhi. Sampling: Ten slum colonies were randomly selected from Delhi by dividing it into five zones and taking two colonies from each zone. Four Hundred households were covered from each colony and information on delivery related aspects were collected from mothers of children up to 2 years of age. Statistical analysis: PC based factor analysis technique was applied to identify factors had also simple tables were generated. Results: Non-institutional deliveries were found to be about 46%. Factor such as â€˜Economic Statusâ€™ was identified as determining one for preference of non-institutional deliveries. Conclusion: Improvement in economic conditions of people may promote institutional deliveries.
CD11c+ Dendritic Cells and B Cells Contribute to the Tumoricidal Activity of Anti-DR5 Antibody Therapy in Established Tumors (2010)

The selective targeting of the tumor-associated death-inducing receptors DR4 and DR5 with agonistic mAbs has demonstrated preclinical and clinical antitumor activity. However, the cellular and molecular mechanisms contributing to this efficacy remain poorly understood. In this study, using the first described C57BL/6 (B6) TRAIL-sensitive experimental tumor models, we have characterized the innate and adaptive immune components involved in the primary rejection phase of an anti-mouse DR5 (mDR5) mAb, MD5-1 in established MC38 colon adenocarcinomas. FcR mediated cross-linking of MD5-1 significantly inhibited the growth of MC38 colon adenocarcinomas through the induction of TRAIL-R-dependent tumor cell apoptosis. The loss of host DR5, TRAIL, perforin, FasL, or TNF did not compromise anti-DR5 therapy in vivo. By contrast, anti-DR5 therapy was completely abrogated in mice deficient of B cells or CD11c(+) dendritic cells (DCs), providing the first direct evidence that these cells play a critical role. Importantly, the requirement for an intact B cell compartment for optimal anti-DR5 antitumor efficacy was also observed in established AT-3 mammary tumors. Interestingly, MD5-1-mediated apoptosis as measured by early TUNEL activity was completely lost in B cell-deficient microMT mice, but intact in mice deficient in CD11c(+) DCs. Overall, these data show that Ab-mediated targeting of DR5 triggers tumor cell apoptosis in established tumors in a B cell-dependent manner and that CD11c(+) DCs make a critical downstream contribution to anti-DR5 antitumor activity.
Preferred end coordinates and somatic variants as signatures of circulating tumor DNA associated with hepatocellular carcinoma (2018)

Circulating tumor-derived cell-free DNA (ctDNA) analysis offers an attractive noninvasive means for detection and monitoring of cancers. Evidence for the presence of cancer is dependent on the ability to detect features in the peripheral circulation that are deemed as cancer-associated. We explored approaches to improve the chance of detecting the presence of cancer based on sequence information present on ctDNA molecules. We developed an approach to detect the total pool of somatic mutations. We then investigated if there existed a class of ctDNA signature in the form of preferred plasma DNA end coordinates. Cell-free DNA fragmentation is a nonrandom process. Using plasma samples obtained from liver transplant recipients, we showed that liver contributed cell-free DNA molecules ended more frequently at certain genomic coordinates than the nonliver-derived molecules. The abundance of plasma DNA molecules with these liver-associated ends correlated with the liver DNA fractions in the plasma samples. Studying the DNA end characteristics in plasma of patients with hepatocellular carcinoma and chronic hepatitis B, we showed that there were millions of tumor-associated plasma DNA end coordinates in the genome. Abundance of plasma DNA molecules with tumor-associated DNA ends correlated with the tumor DNA fractions even in plasma samples of hepatocellular carcinoma patients that were subjected to shallow-depth sequencing analysis. Plasma DNA end coordinates may therefore serve as hallmarks of ctDNA that could be sampled readily and, hence, may improve the cost-effectiveness of liquid biopsy assessment.
Estimation of molar absorptivities and pigment sizes for eumelanin and pheomelanin using femtosecond transient absorption spectroscopy (2009)

Fundamental optical and structural properties of melanins are not well understood due to their poor solubility characteristics and the chemical disorder present during biomolecular synthesis. We apply nonlinear transient absorption spectroscopy to quantify molar absorptivities for eumelanin and pheomelanin and thereby get an estimate for their average pigment sizes. We determine that pheomelanin exhibits a larger molar absorptivity at near IR wavelengths (750 nm), which may be extended to shorter wavelengths. Using the molar absorptivities, we estimate that melanin pigments contain approximately 46 and 28 monomer units for eumelanin and pheomelanin, respectively. This is considerably larger than the oligomeric species that have been recently proposed to account for the absorption spectrum of eumelanin and illustrates that larger pigments comprise a significant fraction of the pigment distribution.
Color filters and processing alternatives for one-chip cameras (1985)

Color images can be obtained from a single solid-state sensor by covering the photosites with a repetitive pattern of color filters. This paper reviews the major issues in selecting appropriate filter patterns and compares different one-chip camera approaches. The processing used to decode the color signals and form acomposite television signal is discussed. The tradeoffs between using primary or complementary filters are considered. Checkerboard geometries are shown to be superior to stripe geometries, and the advantages of horizontally staggered sampling are explained. The constraints imposed by the sensor architecture and by the need for interlaced readout are examined.
An architecture for distributing processing on realtime data streams (1995)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1995.
Treatment and prevention of porcine proliferative enteropathy with oral tiamulin. (1997)

The effect of an oral treatment or prevention programme, incorporating the antibiotic tiamulin, on the development of proliferative enteropathy in experimentally challenged pigs was studied. Twenty weaner pigs were challenged orally with a virulent inoculum of Lawsonia intracellularis strain LR189/5/83, a British isolate of the causative agent of porcine proliferative enteropathy, and seven control pigs were dosed with a buffer solution. Seven of the 20 challenged pigs were left untreated; they gained less weight than the controls and three of them developed mild to moderate diarrhoea two weeks after the challenge. All seven developed lesions, six visible grossly, of proliferative enteropathy, and numerous intracellular L intracellularis were detected in sections of the intestines examined three weeks after the challenge. To test a 'prevention' dosing strategy for tiamulin, six of the challenged pigs were dosed orally with 50 ppm tiamulin, incorporated in a 2 per cent stabilised premix, given from two days before the challenge until they were euthanased. To test a 'treatment' strategy, the remaining group of seven challenged pigs were dosed orally with 150 ppm tiamulin given in the premix from seven days after challenge until they were euthanased. All the control pigs and the 13 pigs treated with tiamulin, either before or after challenge, remained clinically normal and had no specific lesions of proliferative enteropathy in sections of the intestines examined post mortem.
Diagnosis of hypogonadism: clinical assessments and laboratory tests. (2004)

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.
Amplifying Head Movements with Head-Mounted Displays (2003)

The head-mounted display (HMD) is a popular form of virtual display due to its ability to immerse users visually in virtual environments (VEs). Unfortunately, the user's virtual experience is compromised by the narrow field of view (FOV) it affords, which is less than half that of normal human vision. This paper explores a solution to some of the problems caused by the narrow FOV by amplifying the head movement made by the user when wearing an HMD, so that the view direction changes by a greater amount in the virtual world than it does in the real world. Tests conducted on the technique show a significant improvement in performance on a visual search task, and questionnaire data indicate that the altered visual parameters that the user receives may be preferable to those in the baseline condition in which amplification of movement was not implemented. The tests also show that the user cannot interact normally with the VE if corresponding body movements are not amplified to the same degree as head movements, which may limit the implementation's versatility. Although not suitable for every application, the technique shows promise, and alterations to aspects of the implementation could extend its use in the future.
Synthesis and Characterization of a Matrix-Metalloproteinase Responsive Silk–Elastinlike Protein Polymer (2013)

Silk-elastinlike protein polymers (SELPs) are recombinant polymers consisting of tandem repeats of silk (GAGAGS) and elastin (GVGVP) units. By modification of the length and composition of these repeats, the properties of SELP hydrogels can be controlled for specific applications including nucleic acid and virus delivery and tissue engineering. Here, the structure of SELPs is further modified to include a sequence that is sensitive to matrix-metalloproteinases (MMPs). MMPs are a ubiquitous family of extracellular matrix-modifying enzymes that are commonly associated with numerous vital processes. Increased levels of MMPs are found at high levels locally in many types of solid tumors. By modifying the SELP backbone with MMP-sensitive peptide sequences, a hydrogel that is degradable by MMPs was produced. The MMP-sensitivity of the polymer was examined by incubation with MMP-2 and MMP-9, which yielded complete cleavage of all full-length polymers by 36 hours and 48 hours, respectively, with no observable effect on unmodified SELP. Hydrogel sensitivity was tested by exposure to MMP-2 or MMP-9 for 2 weeks, during which samples were taken to analyze protein loss from the hydrogel and release of 100 nm fluorescent beads. Following the incubation period, hydrogels were tested in mechanical compression to examine the loss of hydrogel stiffness due to degradation. It was found that MMP-2 and MMP-9 caused 63% and 44% increased protein loss and 65% and 95% increased release from MMP-sensitive hydrogels, while the compressive modulus decreased by 41% and 29%. These results suggest the potential of MMP-responsive SELPs for localized delivery of bioactive agents where MMPs are overexpressed.