gebhart/patrepeval huggingface dataset:
An efficient algorithm for image segmentation, Markov random fields and related problems (2001)

Problems of statistical inference involve the adjustment of sample observations so they fit some a priori rank requirements, or order constraints. In such problems, the objective is to minimize the deviation cost function that depends on the distance between the observed value and the modify value. In Markov random field problems, there is also a pairwise relationship between the objects. The objective in Markov random field problem is to minimize the sum of the deviation cost function and a penalty function that grows with the distance between the values of related pairs--- separation function .We discuss Markov random fields problems in the context of a representative application---the image segmentation problem. In this problem, the goal is to modify color shades assigned to pixels of an image so that the penalty function consisting of one term due to the deviation from the initial color shade and a second term that penalizes differences in assigned values to neighboring pixels is minimized. We present here an algorithm that solves the problem in polynomial time when the deviation function is convex and separation function is linear; and in strongly polynomial time when the deviation cost function is linear, quadratic or piecewise linear convex with few pieces (where “few” means a number exponential in a polynomial function of the number of variables and constraints). The complexity of the algorithm for a problem on n pixels or variables, m adjacency relations or constraints, and range of variable values (colors) U , is O ( T ( n,m ) + n log U ) where T ( n,m ) is the complexity of solving the minimum s, t cut problem on a graph with n nodes and m arcs. Furthermore, other algorithms are shown to solve the problem with convex deviation and convex separation in running time O ( mn log n log nU ) and the problem with nonconvex deviation and convex separation in running time O ( T ( nU, mU ). The nonconvex separation problem is NP-hard even for fixed value of U .For the family of problems with convex deviation functions and linear separation function, the algorithm described here runs in polynomial time which is demonstrated to be fastest possible.
Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV (2005)

Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Vesicular stomatitis virus (VSV) is a nonpathogenic RNA virus with intrinsic oncolytic specificity due to attenuated antiviral responses in many tumors. We report that repeated hepatic arterial infusion of recombinant syncytia-forming VSV vector in advanced multifocal hepatocellular carcinoma (HCC)-bearing rats at a 10-fold reduced vector dose resulted in sustained tumor-selective virus replication until the onset of high-titer neutralizing antibodies in blood. No significant elevations in serum transaminases and liver pathology were noted, indicating a lack of hepatotoxicity. Substantially improved tumor response was achieved with completely necrotic tumor nodules surrounded by mononuclear phagocytic cells, followed by fibrosis and calcification of the lesions, angiogenesis, and regeneration of normal hepatic parenchyma. Survival of tumor-bearing rats treated with repeated vector infusions was not only significantly improved over that of animals after a single injection at 10 times the vector dose (P = .001), but 18% of animals in the former treatment group also achieved long-term and tumor-free survival compared with 0% of animals in the latter treatment group. In conclusion, this treatment regimen will be very useful in the future development of VSV-mediated virotherapy as a novel therapeutic modality for patients with advanced HCC.
Identification of a novel adhesion molecule in human leukocytes by monoclonal antibody LB‐2 (1987)

Monoclonal antibody LB-2 to a surface antigen on human B cells, lymphoblast, monocytes and vascular endothelial cells largely inhibited adhesion among Epstein Barr virus-immortalized normal B cells (EBV-B) and concanavalin A-stimulated blood mononuclear cells (Con A-BMC) before and after phorbol ester treatment. The antibody inhibited to a lesser extent phorbol ester-induced aggregation of monocytes, U937 cells and fresh BMC and had virtually no inhibitory effect on the adhesion among enriched T cells and granulocytes. A surface glycoprotein band of 84 kDa was obtained from EBV-B cells by immunoprecipitation and gel electrophoresis. Immunological and biochemical studies clearly distinguished this molecule from gp90 and associated glycoproteins which also mediate leukocyte adhesion.
Gene Therapy in Peripheral Blood Lymphocytes and Bone Marrow for ADA − Immunodeficient Patients (1995)

Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency, the first genetic disorder treated by gene therapy. Two different retroviral vectors were used to transfer ex vivo the human ADA minigene into bone marrow cells and peripheral blood lymphocytes from two patients undergoing exogenous enzyme replacement therapy. After 2 years of treatment, long-term survival of T and B lymphocytes, marrow cells, and granulocytes expressing the transferred ADA gene was demonstrated and resulted in normalization of the immune repertoire and restoration of cellular and humoral immunity. After discontinuation of treatment, T lymphocytes, derived from transduced peripheral blood lymphocytes, were progressively replaced by marrow-derived T cells in both patients. These results indicate successful gene transfer into long-lasting progenitor cells, producing a functional multilineage progeny.
Hepatitis C virus infection as a major risk factor for hepatocellular carcinoma. (1996)

Evidence of a tumorigenic potential of the hepatitis C virus (HCV) has so far come mainly from epidemiological data. Longitudinal studies have shown that 16 of 62 anti-HCV antibody (ab)-positive Japanese patients developed hepatocellular carcinoma (HCC) within 5 yr. HCC-related deaths were significantly (p = 0.01) higher in Swedish anti-HCV ab-positive patients than in anti-HCV ab-negative controls (18 vs. 4%). The relative frequency of anti-HCV ab in HCC patients has been reported to be as high as 72% in Spain, 49-62% in Italy and 58% in France. It ranges between 9 and 36% in the USA and is about 26% in Germany. In HBV-endemic areas like South East Asia and Equatorial Africa, HCV-related HCCs play a minor role. The relative risk of developing HCC was elevated (up to 69.1-fold) for anti-HCV ab-positive patients as compared to anti-HCV ab-negative controls in almost all geographic areas studied to date. There is some evidence for an increased risk of developing HCC when hepatitis B virus (HBV) coinfection is present. Cirrhosis is likely to represent an additional risk factor for the development of HCC in anti-HCV ab-positive patients. Blood transfusions are the source of infection in barely one third of anti-HCV ab-positive HCC patients. There seems to be no significant difference in age or gender between anti-HCV ab-positive and ab-negative HCC patients. The additional impact of alcohol consumption and of the HCV genotype is presently under investigation. On the molecular level, HCV replication intermediates have been detected in HCC tissue and point mutations within the p53 gene have been demonstrated. However, the pathomechanism leading to HCV-mediated cell transformation remains unsolved.
Identification of the gene (aroK) encoding shikimic acid kinase I of Escherichia coli (1992)

DNA sequence analysis has revealed that an unidentified open reading frame (ufr1) is present immediately preceding the aroB gene of Escherichia coli. The predicted protein product of urf1 contains a consensus ATP-binding-site sequence and shows 34% amino acid homology to shikimate kinase II in a 97-amino-acid region. Inactivation of urf1 by insertion of an antibiotic resistance gene had a polar effect on aroB, indicating that these two genes constitute a transcriptional unit. The auxotrophic requirements of a strain mutant for both urf1 and aroL (encoding shikimate kinase II) are consistent with shikimate kinase deficiency. We propose that urf1 encodes shikimate kinase I and that it be designated aroK.
A new procedure for the isomerisation of substituted and unsubstituted allyl ethers of carbohydrates (1996)

G. Boons, A. Burton and S. Isles, Chem. Commun., 1996, 141 DOI: 10.1039/CC9960000141
Gene-Gun Biolistic Immunization Encoding Glutamic Acid Decarboxylase: A Model for Studying Langerhans Cell Abnormalities and Mimicry in the Nonobese Diabetic Mouse (2005)

Plasmid-DNA gene-gun immunization may be an efficient approach for investigating the role of skin dendritic cells (DCs) in type 1 diabetes (T1D) pathogenesis and the significance of the presentation of peptides that mimic autoantigenic epitopes in aggravating or modulating the autoimmune reaction. Gene-gun immunization has been described as producing long-lasting immune responses elicited by skin DCs, especially Langerhans cells (LCs). Therefore, we tested the immune response and diabetes modulation in nonobese diabetic (NOD) mice and in control BALB/c mice, by gene-gun administration of plasmid-DNA encoding (1) human 65 kDa glutamic acid decarboxylase (hGAD65) mimicking the crucial mouse autoantigen GAD65 (similarity of 95.7%) or (2) beta-galactosidase (betaGAL) as a negative control. Expression of GAD and betaGAL in skin of pc-GAD- and pc-LacZ-injected mice, respectively, was confirmed. It was surprising that both pc-LacZ-injected BALB/c and NOD mice exhibited a betaGAL-specific Th1 immune response: spleen cells of pc-LacZ mice proliferated specifically to betaGAL (P < 10(-4)) and secreted significant amounts of IFNgamma (P < 10(-4)). pc-LacZ mice also developed a betaGAL-specific Th1-related (IgG2a/2c) and Th2-related (IgG1) humoral response. Although pc-GAD BALB/c mice showed Th2-related GAD-specific IgG1 production and a significant secretion of IL4 (P < .03), pc-GAD NOD mice did not generate either an antibody response or a T cell response specific to GAD. Moreover, gene-gun immunization encoding hGAD65 did not clearly modulate diabetes onset in NOD mice. This absence of detectable GAD-specific response may implicate skin DC deficiencies in NOD mice. The gene-gun technique could thus provide an interesting model for studying skin DC abnormalities in NOD mice and their potential implication of presenting mimetic peptides that modulate the autoimmune response in T1D.
Reaction of trimethylsilyldiazomethane with olefins. (1989)

Most of the reactions of trimethylsilyldiazomethane with various olefins in the presence or absence of metal salt catalyses give silylcyclopropanes.
Chemical ecology: a view from the pharmaceutical industry. (1995)

Biological diversity reflects an underlying molecular diversity. The molecules found in nature may be regarded as solutions to challenges that have been confronted and overcome during molecular evolution. As our understanding of these solutions deepens, the efficiency with which we can discover and/or design new treatments for human disease grows. Nature assists our drug discovery efforts in a variety of ways. Some compounds synthesized by microorganisms and plants are used directly as drugs. Human genetic variations that predispose to (or protect against) certain diseases may point to important drug targets. Organisms that manipulate molecules within us to their benefit also may help us to recognize key biochemical control points. Drug design efforts are expedited by knowledge of the biochemistry of a target. To supplement this knowledge, we screen compounds from sources selected to maximize molecular diversity. Organisms known to manipulate biochemical pathways of other organisms can be sources of particular interest. By using high throughput assays, pharmaceutical companies can rapidly scan the contents of tens of thousands of extracts of microorganisms, plants, and insects. A screen may be designed to search for compounds that affect the activity of an individual targeted human receptor, enzyme, or ion channel, or the screen might be designed to capture compounds that affect any step in a targeted metabolic or biochemical signaling pathway. While a natural product discovered by such a screen will itself only rarely become a drug (its potency, selectivity, bioavailability, and/or stability may be inadequate), it may suggest a type of structure that would interact with the target, serving as a point of departure for a medicinal chemistry effort--i.e., it may be a "lead." It is still beyond our capability to design, routinely, such lead structures, based simply upon knowledge of the structure of our target. However, if a drug discovery target contains regions of structure homologous to that in other proteins, structures known to interact with those proteins may prove useful as leads for a medicinal chemistry effort. The specificity of a lead for a target may be optimized by directing structural variation to specificity-determining sites and away from those sites required for interaction with conserved features of the targeted protein structure. Strategies that facilitate recognition and exploration of sites at which variation is most likely to generate a novel function increase the efficiency with which useful molecules can be created.
Tumor Necrosis Factor for the Treatment of Malignancies (1994)

Tumor necrosis factor (TNF) is a cytokine produced in vivo by activated macrophages and monocytes with pleiotropic effects on normal and malignant cells. TNF is cytotoxic to several tumor cell lines in vitro and in vivo. Phase I and phase II trials have been conducted to determine toxicity to humans and to evaluate responses. Recent investigations will be reviewed. Despite promising results in vitro and in vivo, data from systemic administration in the treatment of malignancies have been disappointing. Local administration has been successful. Therefore, we suggest that future efforts concerning TNF administration in the treatment of malignancies should aim at local treatment.
Ovalbumin(323−339) Peptide Binds to the Major Histocompatibility Complex Class II I-AdProtein Using Two Functionally Distinct Registers (1999)

Proteins of the class II major histocompatibility complex (MHC) bind antigenic peptides that are subsequently presented to T cells. Previous studies have shown that most of the residues required for binding of the chicken ovalbumin (Ova) 323-339 peptide to the I-A(d) MHC class II protein are contained within the shorter 325-336 peptide. This observation is somewhat inconsistent with the X-ray structure of the Ova peptide covalently attached to I-A(d) ( structure) in which residues 323 and 324 form binding interactions with the protein. A second register for the Ova(325-336) peptide is proposed where residues 326 and 327 occupy positions similar to residues 323 and 324 in the structure. Two Ova peptides that minimally encompass the and alternate registers, Ova(323-335) and Ova(325-336), respectively, were found to dissociate from I-A(d) with distinct kinetics. The dissociation rates for both peptides were enhanced when the His81 residue of the MHC beta-chain was replaced with an asparagine. In the structure the betaH81 residue forms a hydrogen bond to the backbone carbonyl of I323. If the Ova(325-336) peptide were also bound in the register, there would be no comparable hydrogen-bond acceptor for the betaH81 side chain that could explain this peptide's sensitivity to the betaH81 replacement. The Ova(323-335) peptide that binds in the register does not stimulate a T-cell hybridoma that is stimulated by Ova(325-336) bound in the alternate register. These results demonstrate that a single peptide can bind to an MHC peptide in alternate registers producing distinct T-cell responses.
Domain Name System (DNS) IANA Considerations (2000)

Internet Assigned Number Authority (IANA) parameter assignment considerations are given for the allocation of Domain Name System (DNS) classes, Resource Record (RR) types, operation codes, error codes, etc.
Dependence of T c on hole concentration in the superconductors Bi4Sr3Ca3−xYxCu4O16+δ (1988)

Substitution of Y for Ca in the high Tc superconductor system Bi4Sr3Ca3−xYxCu4O16+δ (0≤x≤1.5) is accompanied by an increase in oxygen concentration δ≊0.34+0.3x that is insufficient to compensate for the increase in counter-cation valence. Nevertheless, Tc≊86 K remains nearly constant in the interval 0≤x≤0.5; it drops smoothly to zero in the interval 0.5&amp;lt;x≤1.15. Correlation of the compositional limit x=0.5 of the Tc plateau with the onset of trapping of holes could indicate that any oxygen atom in excess of O16.5 occupies a different crystallographic position where it traps two holes either as Bi5+ or as (O2)2−.
Hybrid Liveness-Enforcing Policy for Generalized Petri Net Models of Flexible Manufacturing Systems (2012)

This paper proposes a hybrid liveness-enforcing method for a class of Petri nets, which can well model many flexible manufacturing systems. The proposed method combines elementary siphons with a characteristic structure-based method to prevent deadlocks and enforce liveness to the net class under consideration. The characteristic structure-based method is further advanced in this work. It unveils and takes a full advantage of an intrinsically live structure of generalized Petri nets, which hides behind the arc weights, to achieve the liveness enforcement without any external control agent such as monitors. This hybrid method can identify and remove redundant monitors from a liveness-enforcing supervisor designed according to existing policies, improve the permissiveness, reduce the structural complexity of a controlled system, and consequently save the control implementation cost. Several examples are used to illustrate this method.
Attenuation of Vascular Permeability by Methylnaltrexone (2007)

Endothelial cell (EC) barrier dysfunction (i.e., increased vascular permeability) is observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that preserve vascular integrity have important clinical therapeutic implications. We examined the effects of methylnaltrexone (MNTX), a mu opioid receptor (mOP-R) antagonist, on human pulmonary EC barrier disruption produced by edemagenic agents including morphine, the endogenous mOP-R agonist DAMGO, thrombin, and LPS. Pretreatment of EC with MNTX (0.1 muM, 1 h) or the uncharged mOP-R antagonist naloxone attenuated morphine- and DAMGO-induced barrier disruption in vitro. However, MNTX, but not naloxone, pretreatment of EC inhibited thrombin- and LPS-induced barrier disruption, indicating potential mOP-R-independent effects of MNTX. In addition, intravenously delivered MNTX attenuated LPS-induced vascular hyperpermeability in the murine lung. We next examined the mechanistic basis for this MNTX barrier protection and observed that silencing of mOP-R attenuated the morphine- and DAMGO-induced EC barrier disruption, but not the permeability response to either thrombin or LPS. Because activation of the sphingosine 1-phosphate receptor, S1P(3), is key to a number of barrier-disruptive responses, we examined the role of this receptor in the permeability response to mOP-R ligation. Morphine, DAMGO, thrombin, and LPS induced RhoA/ROCK-mediated threonine phosphorylation of S1P(3), which was blocked by MNTX, suggesting S1P(3) transactivation. In addition, silencing of S1P(3) receptor expression (siRNA) abolished the permeability response to each edemagenic agonist. These results indicate that MNTX provides barrier protection against edemagenic agonists via inhibition of S1P(3) receptor activation and represents a potentially useful therapeutic agent for syndromes of increased vascular permeability.
Pixel masks for screen-door transparency (1998)

Rendering objects transparently gives additional insight in complex and overlapping structures. However, traditional techniques for the rendering of transparent objects such as alpha blending are not very well suited for the rendering of multiple transparent objects in dynamic scenes. Screen door transparency is a technique to render transparent objects in a simple and efficient way: no sorting is required and intersecting polygons can be handled without further preprocessing. With this technique, polygons are rendered through a mask: only where the mask is present, pixels are set. However, artifacts such as incorrect opacities and distracting patterns can easily occur if the masks are not carefully designed. The requirements on the masks are considered. Next, three algorithms are presented for the generation of pixel masks. One algorithm is designed for the creation of small (e.g. 4/spl times/4) masks. The other two algorithms can be used for the creation of larger masks (e.g. 32/spl times/32). For each of these algorithms, results are presented and discussed.
Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation (2008)

Previously, we reported a transgenic mouse line, TG-3, that develops spontaneous melanoma with 100% penetrance. We demonstrated that ectopic expression of Grm1 in melanocytes was sufficient to induce melanoma in vivo. In this present study, the transforming properties of Grm1 in two cultured immortalized melanocytes were investigated. We showed that, in contrast to parental melanocytes, these Grm1-clones have lost their requirement of TPA supplement for proliferation and have acquired the ability to form colonies in semi-solid medium. Xenografts of these cells formed robust tumors in both immunodeficient nude and syngeneic mice with a short latency (3-5 days). The malignancy of these cells was demonstrated by angiogenesis and invasion to the muscle and the intestine. The requirement of Grm1 expression for the maintenance of transformation was demonstrated by an inducible siRNA system. Induction of expression of siRNA for Grm1 reduced the number of proliferating/viable cells in vitro and suppressed in vivo xenografted tumor growth in comparison with control. Taken together, these results showed that expression of exogeneously introduced Grm1 is sufficient to induce full transformation of immortalized melanocytes.
The Synthesis of Oxalacetic Acid-1-C14 and Orotic Acid-6-C14 1 (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of Oxalacetic Acid-1-C14 and Orotic Acid-6-C14 1Charles Heidelberger and Robert B. HurlbertCite this: J. Am. Chem. Soc. 1950, 72, 10, 4704–4706Publication Date (Print):October 1, 1950Publication History Published online1 May 2002Published inissue 1 October 1950https://pubs.acs.org/doi/10.1021/ja01166a099https://doi.org/10.1021/ja01166a099research-articleACS PublicationsRequest reuse permissionsArticle Views384Altmetric-Citations39LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts