gebhart/patrepeval huggingface dataset:
Renal and Vascular Mechanisms of Thiazolidinedione‐Induced Fluid Retention (2008)

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor subtype gamma (PPARgamma) activators that are clinically used as an insulin sensitizer for glycemic control in patients with type 2 diabetes. Additionally, TZDs exhibit novel anti-inflammatory, antioxidant, and antiproliferative properties, indicating therapeutic potential for a wide variety of diseases associated with diabetes and other conditions. The clinical applications of TZDs are limited by the common major side effect of fluid retention. A better understanding of the molecular mechanism of TZD-induced fluid retention is essential for the development of novel therapies with improved safety profiles. An important breakthrough in the field is the finding that the renal collecting duct is a major site for increased fluid reabsorption in response to rosiglitazone or pioglitazone. New evidence also indicates that increased vascular permeability in adipose tissues may contribute to edema formation and body weight gain. Future research should therefore be directed at achieving a better understanding of the detailed mechanisms of TZD-induced increases in renal sodium transport and in vascular permeability.
Biochemical basis of high‐temperature inhibition of ethylene biosynthesis in ripening tomato fruits (1988)

Biggs, M. S., Woodson, W. R. and Handa, A. K. 1988. Biochemical basis of high‐temperature inhibition of ethylene biosynthesis in ripening tomato fruits. Physiol. Plant. 72: 572578 Incubation of fruits of tomato ( Lycopersicon esculentum Mill. cv. Rutgers) at 34°C or above resulted in a marked decrease in ripening‐associated ethylene production. High temperature inhibition of ethylene biosynthesis was not associated with permanent tissue damage, since ethylene production recovered following transfer of fruits to a permissive temperature. Determination of pericarp enzyme activities involved in ethylene biosynthesis following transfer of fruits from 25°C to 35 or 40°C revealed that 1‐aminocyclopropane‐l‐carboxylic acid (ACC) synthase (EC 4.4.1.14) activity declined rapidly while ethylene forming enzyme (EFE) activity declined slowly. Removal of high temperature stress resulted in more rapid recovery of ACC synthase activity relative to EFE activity. Levels of ACC in pericarp tissue reflected the activity of ACC synthase before, during, and after heat stress. Recovery of ethylene production following transfer of pericarp discs from high to permissive temperature was inhibited in the presence of cycloheximide, indicating the necessity for protein synthesis. Ethylene production by wounded tomato pericarp tissue was not as inhibited by high temperature as ripening‐associated ethylene production by whole fruits.
Inhibition of xenogeneic GVHD by PEN110 treatment of donor human PBMNCs (2004)

In these studies PEN110 treatment and gamma irradiation were equally effective at preventing in vivo GVHD responses when the treated cells were injected into SCID recipients. These results are consistent with previous results obtained when these two treatment methods were compared with in vitro studies with PBMNCs and in vivo studies in mouse models.
IrisNet: An architecture for a worldwide sensor web (2003)

We discuss about the IrisNet (Internet-scale resource-intensive sensor network services) project at Intel Research, we design an architecture and build a system that enable easy deployment of such wide-area sensing services. We aim to provide the missing software components for realizing a worldwide sensor Web. Wide-area architectures for pervasive sensing enable a new generation of powerful distributed sensing services. A worldwide sensor Web, in which users can query, as a single unit, vast quantities of data from thousands or even millions of widely distributed, heterogeneous sensors. Internet-connected PCs that source sensor feeds and cooperate to answer users' queries will form the global sensor Web's backbone. Developers of wide-area sensing services (service authors) deploy the services on this distributed infrastructure.
Characterization of Wound Cytokines in the Sponge Matrix Model (1989)

Although different populations of inflammatory cells infiltrate the healing wound, the mechanisms by which they influence the healing process in vivo are poorly defined. In vitro studies suggest that these cells may mediate wound healing by releasing various cytokines within the wound. We measured the levels of interleukin (IL) 1, IL-2, IL-3, IL-4, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor within a subcutaneously implanted polyurethane sponge on various days after injury. Significantly higher levels of IL-1, IL-6, tumor necrosis factor, and macrophage colony-stimulating factor were detected in the wound fluid compared with basal serum levels in nonwounded mice. Tumor necrosis factor, macrophage colony-stimulating factor, and IL-6 peaked earlier than IL-1; however, the levels of these cytokines had fallen by the 13th day after wounding. Interleukin 2, IL-3, and IL-4 could not be detected in the wound fluid, and the wound fluid inhibited the proliferation of the IL-2-dependent cell lines CTLL-2 and HT-2 in response to recombinant IL-2. We hypothesize that tumor necrosis factor, macrophage colony-stimulating factor, IL-1, and IL-6, which are secreted at the site of injury, interact to promote tissue remodeling. The decrease in the levels of these cytokines by the 13th day after wounding may be the result of a regulatory process by the healed wound.
A Survey Method for Characterizing Daily Life Experience: The Day Reconstruction Method (2004)

The Day Reconstruction Method (DRM) assesses how people spend their time and how they experience the various activities and settings of their lives, combining features of time-budget measurement and experience sampling. Participants systematically reconstruct their activities and experiences of the preceding day with procedures designed to reduce recall biases. The DRM's utility is shown by documenting close correspondences between the DRM reports of 909 employed women and established results from experience sampling. An analysis of the hedonic treadmill shows the DRM's potential for well-being research.
The pluripotent hemopoietic stem cell: its identification and applications. (1990)

The experiments leading to the concept of a pluripotent hemopoietic stem cell (PHSC) are reviewed. The identification and morphological characteristics of the PHSC are presented and a number of current and prospective applications of grafts of PHSC are described.
Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas (2015)

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory.
Jak2 deficiency prevents mice from LPS-induced sepsis by modulating innate immunity without affecting adaptive immunity through STAT5 and STAT6 pathways (91.17) (2009)

Abstract Dendritic cells (DCs) serve as a key component of innate immunity and bridge innate and adaptive immune responses against to bacteria and other pathogens. Many immune disorders are thought to be a consequence of out-of-control of inflammatory response to bacterial toxins, such as sepsis is a result of excessive inflammation with a suppression of adaptive immunity post-sepsis. Therefore, manipulating the function of DC in innate immune response without affecting its capability to initiate adaptive immunity could be a novel therapeutic approach for treatment of sepsis. Using an inducible Jak2 deficiency model, here we have demonstrated that Jak2 could be a perfect target to solely suppress DC's capacity in innate immune response. Other than its functionality in DC development, Jak2 also plays a pivotal role in modulation of innate immune response. DCs deficient for Jak2 display an immature phenotype characterized by low expression of MHC-II and costimulatory molecules and a reduced secretion of pro-inflammatory cytokines upon stimulation. However, their capability to initiate adaptive immune response was not impaired. As a result, mice deficient for Jak2 are resistant to LPS-induced septic shock. Our studies further revealed that Jak2/SATA5 signaling is implicated in DC development, while Jak2/STAT6 signaling is responsible for the regulation of pro-inflammatory cytokine secretion in DCs.
Magnetically Guided Orotracheal Intubation (2001)

A novel method of orotracheal intubation using magnetic guidance is described as achieving a high rate of successful intubations when performed by inexperienced intubators.
Thyroid, renal, and splanchnic circulation in horses at rest and during short-term exercise (1995)

Using radionuclide-labeled 15-microm-diameter microspheres injected into the left ventricle, we examined blood flow to the thyroid gland, adrenal glands, kidneys, and various gastrointestinal tract tissues in 9 healthy horses while they were standing quietly (rest) and during exercise at 2 work intensities (8 and 1 m/s). Hemodynamic measurements were made during steady-state conditions, as judged by the stability of heart rate as well as aortic, pulmonary, and right atrial pressures. The similarity of blood flow values for the left and the right kidneys during each of the 3 conditions indicated adequate mixing of microspheres with blood. In standing horses, of all tissues examined, the thyroid gland had the highest blood flow (1,655.2 +/- 338.5 ml/min/100 g)--being about threefold that in the kidneys. Adrenal blood flow, by contrast, was only 25% of that in the kidneys (589.5 +/- 50.4 ml/min/100 g). Among the gastrointestinal tract tissues, glandular stomach and pancreas had the highest blood flows (214.3 +/- 21.6 and 197.6 +/- 23.4 ml/min/100 g, respectively). Small intestinal perfusion was not different from that in the ventral colon and cecum, but their values exceeded those for the dorsal and small colons. Exercise at 8 and 13 m/s caused significant increase in adrenal blood flow as vascular resistance decreased significantly. In the kidneys, blood flow was only insignificantly affected during exercise at 8 m/s, but at 13 m/s there was a profound reduction in renal blood flow as intense renal vasoconstriction occurred. Vasoconstriction also caused thyroid and pancreatic blood flow to decrease significantly at both levels of exertion. Significant vasoconstriction occurring in all gastrointestinal tract tissues at 8 and 13 m/s caused blood flow to be diverted away from these vascular beds. Thus, our data indicated that renal, adrenal, and splanchnic organ/tissue blood flow responses of strenuously exercising horses closely resemble those described for exercising ponies.
The X Gene of Adeno-Associated Virus 2 (AAV2) Is Involved in Viral DNA Replication (2014)

Adeno-associated virus (AAV) (type 2) is a popular human gene therapy vector with a long active transgene expression period and no reported vector-induced adverse reactions. Yet the basic molecular biology of this virus has not been fully addressed. One potential gene at the far 3' end of the AAV2 genome, previously referred to as X (nt 3929 to 4393), overlapping the 3' end of the cap gene, has never been characterized, although we did previously identify a promoter just up-stream (p81). Computer analysis suggested that X was involved in replication and transcription. The X protein was identified during active AAV2 replication using a polyclonal antibody against a peptide starting at amino acid 98. Reagents for the study of X included an AAV2 deletion mutant (dl78-91), a triple nucleotide substitution mutant that destroys all three 5' AUG-initiation products of X, with no effect on the cap coding sequence, and X-positive-293 cell lines. Here, we found that X up-regulated AAV2 DNA replication in differentiating keratinocytes (without helper virus, autonomous replication) and in various forms of 293 cell-based assays with help from wild type adenovirus type 5 (wt Ad5) or Ad5 helper plasmid (pHelper). The strongest contribution by X was seen in increasing wt AAV2 DNA replication in keratinocytes and dl78-91 in Ad5-infected X-positive-293 cell lines (both having multi-fold effects). Mutating the X gene in pAAV-RC (pAAV-RC-3Xneg) yielded approximately a ∼33% reduction in recombinant AAV vector DNA replication and virion production, but a larger effect was seen when using this same X-knockout AAV helper plasmid in X-positive-293 cell lines versus normal 293 cells (again, multi-fold). Taken together these data strongly suggest that AAV2 X encodes a protein involved in the AAV life cycle, particularly in increasing AAV2 DNA replication, and suggests that further studies are warranted.
Genetic diagnosis of Mendelian disorders via RNA sequencing (2017)

Across a variety of Mendelian disorders, ∼50-75% of patients do not receive a genetic diagnosis by exome sequencing indicating disease-causing variants in non-coding regions. Although genome sequencing in principle reveals all genetic variants, their sizeable number and poorer annotation make prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to molecularly diagnose 10% (5 of 48) of mitochondriopathy patients and identify candidate genes for the remainder. We find a median of one aberrantly expressed gene, five aberrant splicing events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establish disease-causing roles for each kind. Private exons often arise from cryptic splice sites providing an important clue for variant prioritization. One such event is found in the complex I assembly factor TIMMDC1 establishing a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants and provides examples of intronic loss-of-function variants with pathological relevance.
1,2,4‐Triazines. Synthesis of selected members of the s‐triazolo[3,4‐f]‐ [1,2,4] triazine and tetrazolo[1,5‐f] [1,2,4] triazine ring systems (1979)

Abstract A convenient synthesis of 3‐amino‐6‐hydrazino‐5(2 H )[1,2,4]triazinone 4 has been developed and a study of the reactions of 4 with aliphatic acids, orthoesters and miscellaneous active carbonyl reagents has been undertaken. When 4 was refluxed in either neat acid or orthoester in dimethylformamide, a facile ring closure reaction with the N‐1 nitrogen of the 1,2,4‐triazine ring occurs affording a novel series of 3‐aIkyl(aryl)‐8(5 H )‐ s ‐triazolo[3,4‐ f ] [1,2,4]triazinones ( 6–11 ). Ring closure with carbon disulfide and cyanogen bromide is also reported affording 6‐amino‐3(2 H )thio‐8(5 H )‐ s ‐triazolo[3,4‐ f ] [1,2,4]triazinone 12 and 3,6‐diamino‐8(5 H )‐ s ‐triazolo‐[3,4‐ f ] [1,2,4]triazinone 14 , respectively. In addition 4 has been converted into 3‐amino‐6‐azido‐5(2 H )‐1,2,4‐triazinone 15 which was employed in a study of azide‐tetrazole equilibrium affording 6‐amino‐8(5 H )tetrazolo[1,5‐ f ][1,2,4]triazinone 16 . Rates for interconversion at various temperatures were measured and an activation energy for the process determined.
Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology (2005)

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn's disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.
Human 5-HT1A receptor expressed in insect cells activates endogenous G(o)-like G protein(s). (1994)

Insect cell expression systems are used to characterize signaling components such as G protein-coupled receptors. As such, one must know whether endogenous G proteins couple to non-native receptors. We examined G protein linkages after infection of Sporodoptera frugiperda (Sf9) cells with a baculovirus encoding the 5-HT1A receptor. Receptor expression was confirmed by immunoblot. Some of the receptors were functional, showing guanine nucleotide-sensitive binding to the specific agonist ligand [3H]8-hydroxy-2-(di-n-propylamino)-1,2,3,4-tetranaphthalene). Peak expression (approximately 150 fmol/mg of membrane protein) was attained approximately 72-96 h post-infection. 5-HT-increased covalent binding of [32P]GTP-azidoanilide to a 40 kDa band, which was identified as a G protein by nucleotide blocking, Mg2+ dependence, and immunoblot and immunoprecipitation studies. The band comigrated with 1) pertussis toxin substrate(s), and 2) a band recognized by two G(o) alpha antisera and one common to heterotrimeric G protein alpha-subunits, but not by sera specific for Gs alpha or G(i) alpha. Labeled species could be precipitated with a G(o) alpha antiserum. 5-HT-increased labeling of the band was prevented by preincubation with pertussis toxin. These studies suggest that the 5-HT1A receptor couples effectively to native insect cell G(o)-like proteins.
Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer (1986)

The 7,909-nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer, has been determined and used to deduce the corresponding genome arrangement. Extensive sequence homologies and other genetic features are shared with the related oncogenic virus, human papillomavirus type 16, especially in the major reading frames. A surprising difference was found in the noncoding region of human papillomavirus type 33 as, unlike all other sequenced papillomaviruses, it contains a perfect 78-base pair tandem repeat.
Biocompatible or biodegradable hyperbranched polymers: from self-assembly to cytomimetic applications (2012)

Self-assembly of amphiphilic hyperbranched polymers (HBPs) is a newly emerging research area and has attracted increasing attention due to the great advantages in biomedical applications. This tutorial review focuses on the self-assembly of biocompatible or biodegradable amphiphilic HBPs and their cytomimetic applications, and specialities or advantages therein owing to the hyperbranched structure have also been summarized. As shown here, various supramolecular structures including micelles, vesicles, tubes, fibers and films have been prepared through the primary self-assembly processes. The primary self-assemblies can be further assembled into more complex structures through hierachical self-assembly processes. Besides, the hyperbranched polymer vesicles have demonstrated great potential to be used as model membranes to mimic cellular behaviors, such as fusion, fission and cell aggregation. Other biomedical applications of HBPs as well as their self-assemblies are also briefly summarized.
Complexity Classification of Local Hamiltonian Problems (2014)

The calculation of ground-state energies of physical systems can be formalised as the k-local Hamiltonian problem, which is the natural quantum analogue of classical constraint satisfaction problems. One way of making the problem more physically meaningful is to restrict the Hamiltonian in question by picking its terms from a fixed set S. Examples of such special cases are the Heisenberg and Ising models from condensed-matter physics. In this work we characterise the complexity of this problem for all 2-local qubit Hamiltonians. Depending on the subset S, the problem falls into one of the following categories: in P, NP-complete, polynomial-time equivalent to the Ising model with transverse magnetic fields, or QMA-complete. The third of these classes contains NP and is contained within StoqMA. The characterisation holds even if S does not contain any 1-local terms, for example, we prove for the first time QMA-completeness of the Heisenberg and XY interactions in this setting. If S is assumed to contain all 1-local terms, which is the setting considered by previous work, we have a characterisation that goes beyond 2-local interactions: for any constant k, all k-local qubit Hamiltonians whose terms are picked from a fixed set S correspond to problems either in P, polynomial-time equivalent to the Ising model with transverse magnetic fields, or QMA-complete. These results are a quantum analogue of Schaefer's dichotomy theorem for boolean constraint satisfaction problems.
The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems (2012)

An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.