gebhart/patrepeval huggingface dataset:
4. Competition Graphs (1999)

This chapter considers intersection graphs of various sorts of neighborhoods in graphs and digraphs, the most studied of which are the “competition graphs” in section 4.2. But, in a generic sense, they all can be thought of in terms of “competition.” The development of these topics differs from that of chordal and interval graphs in that they are intersection graphs of the set of all subgraphs (neighborhoods) of a certain sort, rather than an arbitrary multiset of them. They resemble clique and line graphs in this regard. In particular, each of these topics has an associated graph operator that is discussed more thoroughly in [Prisner, 1995]. 4.1 Neighborhood Graphs Recall that for any graph G and any v ∈ V(G), the open neighborhood of v, denoted , is the subgraph induced by {u : uv ∈ E(G)}. The closed neighborhood of v in G, denoted , is the subgraph induced by . We write N(v) and N[v] when G is clear from the context. 4.1.1 Squared Graphs For any graph G, the square of G, denoted , has the same vertices as G, with two vertices u and v adjacent if and only if in G, where d(u, v) denotes the usual graph distance; this can be thought of as saying that u and v are close enough to “compete” in some sense. A graph G is a squared graph if for some graph H. Example 4.1 The graph G in Figure 4.1 is the square of the graph H.
Gdf-8 Propeptide Binds to GDF-8 and Antagonizes Biological Activity by Inhibiting GDF-8 Receptor Binding (2001)

GDF-8 is a new member of the TGF-beta superfamily which appears to be a negative regulator of skeletal muscle mass. Factors which regulate the biological activity of GDF-8 have not yet been identified. However, the biological activities of TGF-beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from the amino-termini of the TGF-beta precursor proteins. In contrast, the propeptides of other TGF-beta superfamily members do not appear to be inhibitory. In this investigation, we demonstrate that purified recombinant GDF-8 propeptide associates with purified recombinant GDF-8 to form a noncovalent complex, as evidenced by size exclusion chromatography and chemical crosslinking analysis. Furthermore, we show that GDF-8 propeptide inhibits the biological activity of GDF-8 assayed on A204 rhabdomyosarcoma cells transfected with a (CAGA)12 reporter construct. Finally, we demonstrate that GDF-8 propeptide inhibits specific GDF-8 binding to L6 myoblast cells. Collectively, these data identify the GDF-8 propeptide as an inhibitor of GDF-8 biological activity.
Self-Association of Human PCSK9 Correlates with Its LDLR-Degrading Activity (2008)

Genetic studies have demonstrated an important role for proprotein convertase subtilisin/kexin type 9 (PCSK9) as a determinant of plasma cholesterol levels. However, the underlying molecular mechanism is not completely understood. To this end, we have generated a mammalian cell expression system for human PCSK9 and its mutants and produced transgenic mice expressing human PCSK9. HEK293T cells transfected with the human PCSK9 DNA construct expressed and secreted PCSK9 and displayed decreased LDLR levels; functional PCSK9 protein was purified from the conditioned medium. In vitro studies showed that PCSK9 self-associated in a concentration-, temperature-, and pH-dependent manner. A mixture of PCSK9 monomers, dimers, and trimers displayed an enhanced LDLR degrading activity compared to monomeric PCSK9. A gain-of-function mutant, D374Y, displayed greatly increased self-association compared to wild-type PCSK9. Moreover, we demonstrated that the catalytic domain of PCSK9 is responsible for the self-association. Self-association of PCSK9 was enhanced by incubation with mouse apoE-/- VLDL and inhibited by incubation with both human and mouse HDL. When PCSK9 protein was incubated with total serum, it partially associated with LDL and HDL but not with VLDL. In transgenic mice, PCSK9 also associated with LDL and HDL but not with VLDL. We conclude that self-association is an intrinsic property of PCSK9, correlated to its LDLR-degrading activity and affected by plasma lipoproteins. These results provide a basis for developing strategies to manipulate PCSK9 activity in the circulation for the treatment of hypercholesterolemia.
Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers (2007)

This study describes the steady-state pharmacokinetics of LDX, a new pro-drug stimulant. Possible study limitations include an open-label design and a small sample size.
Elevated prothrombin results in clots with an altered fiber structure: a possible mechanism of the increased thrombotic risk (2003)

Individuals with elevated prothrombin levels are at increased risk of venous thrombosis. To understand the mechanism behind this observation, we studied the effect of prothrombin concentration on thrombin generation and fibrin clot structure. The pattern of thrombin generation was directly related to the prothrombin level at all concentrations tested. From 0% to 300% of normal plasma levels of prothrombin, increasing the prothrombin concentration increased the initial rate, peak, and total amount of thrombin generated. Importantly, fibrin clot structure was also affected by the prothrombin concentration. Fibrin clots made from prothrombin concentrations less than 10% of plasma levels were weak and poorly formed. Fibrin clots made at 10% to 100% of plasma levels of prothrombin had similar fiber structures (mass-to-length ratio; mu). However, the fiber mass-to-length ratio decreased with increasing prothrombin levels more than 100% of plasma levels, in a dose-dependent manner. These results suggest that increased levels of prothrombin alter thrombin generation and clot structure. Specifically, elevated prothrombin levels produce clots with reduced fibrin mass-to-length ratios compared with normal clots. We hypothesize that this alteration in fibrin clot structure is an important determinant of the risk of thrombosis.
Imaging of human brain creatine kinase activity in vivo (1989)

Creatine kinase activity and high-energy phosphate concentration have been investigated using localized 31P spectroscopy in the human brain in vivo. The phase-modulated rotating frame imaging technique, incorporating magnetization transfer and inversion recovery, has been used to produce a 1-dimensional rate profile map of steady-state enzyme activity. Large differences in the flux from phosphocreatine (PCr) to ATP have been discovered between volumes of human brain consisting of predominantly gray (2.0 cm) and white (4.5 cm) matter. The concentration of PCr changes slightly (2.0 cm = 5.20 +/- 0.45 mmol.l-1, 4.5 cm = 4.63 +/- 0.31 mmol.l-1), while the ATP concentration remains within limits (3.30 +/- 0.4 mmol.l-1). No change in pHi was detected between the two regions in normal volunteers (n = 6). The forward rate constant of the PCr----ATP reaction in regions of predominantly gray matter (0.30 +/- 0.04 s-1) was twice that of white matter (0.16 +/- 0.02 s-1) in vivo.
ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2- and heregulin-deficient mice (1997)

Heregulins bind directly to ErbB3 and ErbB4 receptors, leading to multiple dimerization possibilities including heterodimerization with the ErbB2 receptor. We have generated ErbB3-, ErbB2- and heregulin-deficient mice to assess their roles in development and differentiation. Heregulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a lack of cardiac ventricular myocyte differentiation; ErbB3(-/-) embryos survived until E13.5 exhibiting cardiac cushion abnormalities leading to blood reflux through defective valves. In ErbB3(-/-) embryos, the midbrain/hindbrain region was strikingly affected, with little differentiation of the cerebellar plate. Cranial ganglia defects, while present in all three nulls, were less severe in ErbB3(-/-) embryos. The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ganglia and adrenal chromaffin cells, suggests a generalized effect on the neural crest. Numerous organs, including the stomach and pancreas also exhibited anomalous development.
Stapled α−helical peptide drug development: A potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy (2013)

Stapled α-helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo. Specifically, ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities, shows submicromolar cellular activities in cancer cell lines in the presence of serum, and demonstrates highly specific, on-target mechanism of action. A high resolution (1.7-Å) X-ray crystal structure reveals its molecular interactions with the target protein MDMX, including multiple contacts with key amino acids as well as a role for the hydrocarbon staple itself in target engagement. Most importantly, ATSP-7041 demonstrates robust p53-dependent tumor growth suppression in MDM2/MDMX-overexpressing xenograft cancer models, with a high correlation to on-target pharmacodynamic activity, and possesses favorable pharmacokinetic and tissue distribution properties. Overall, ATSP-7041 demonstrates in vitro and in vivo proof-of-concept that stapled peptides can be developed as therapeutically relevant inhibitors of protein-protein interaction and may offer a viable modality for cancer therapy.
Whirlwind: a new cryptographic hash function (2010)

A new cryptographic hash function Whirlwind is presented. We give the full specification and explain the design rationale. We show how the hash function can be implemented efficiently in software and give first performance numbers. A detailed analysis of the security against state-of-the-art cryptanalysis methods is also provided. In comparison to the algorithms submitted to the SHA-3 competition, Whirlwind takes recent developments in cryptanalysis into account by design. Even though software performance is not outstanding, it compares favourably with the 512-bit versions of SHA-3 candidates such as LANE or the original CubeHash proposal and is about on par with ECHO and MD6.
Pharmacotherapy of eating disorders (2017)

Although pharmacotherapy has established utility in bulimia nervosa and BED, further research on medications for the treatment of eating disorders, particularly anorexia nervosa, is necessary.
Red Mud as an Efficient, Stable and Cost-Free Catalyst for COx-Free Hydrogen Production from Ammonia (2016)

Red mud, one of the mostly produced industrial wastes, was converted into a catalyst with exceptionally high and stable performance for hydrogen production from ammonia. Results showed that iron species produced after reduction of the HCl digested red mud were converted into ε-Fe2N during the induction period of ammonia decomposition reaction at 700 °C. The catalytic performance measurements indicated that the modified red mud catalyst provides a record high hydrogen production rate for a non-noble metal catalyst at this temperature. For instance, stable hydrogen production rates were measured as 72 and 196 mmol H2 min(-1) gcat(-1) for the corresponding space velocities of 72 000 and 240 000 cm(3) NH3 h(-1) gcat(-1), respectively, at 700 °C. These results offer opportunities to utilize one of the key hazardous industrial wastes as an eco-friendly, efficient, stable, and almost cost-free catalyst for COx-free hydrogen production from ammonia decomposition.
The dependence of optimal fractionation schemes on the spatial dose distribution (2012)

We consider the fractionation problem in radiation therapy. Tumor sites in which the dose-limiting organ at risk (OAR) receives a substantially lower dose than the tumor, bear potential for hypofractionation even if the α/β-ratio of the tumor is larger than the α/β-ratio of the OAR. In this work, we analyze the interdependence of the optimal fractionation scheme and the spatial dose distribution in the OAR. In particular, we derive a criterion under which a hypofractionation regimen is indicated for both a parallel and a serial OAR. The approach is based on the concept of the biologically effective dose (BED). For a hypothetical homogeneously irradiated OAR, it has been shown that hypofractionation is suggested by the BED model if the α/β-ratio of the OAR is larger than α/β-ratio of the tumor times the sparing factor, i.e. the ratio of the dose received by the tumor and the OAR. In this work, we generalize this result to inhomogeneous dose distributions in the OAR. For a parallel OAR, we determine the optimal fractionation scheme by minimizing the integral BED in the OAR for a fixed BED in the tumor. For a serial structure, we minimize the maximum BED in the OAR. This leads to analytical expressions for an effective sparing factor for the OAR, which provides a criterion for hypofractionation. The implications of the model are discussed for lung tumor treatments. It is shown that the model supports hypofractionation for small tumors treated with rotation therapy, i.e. highly conformal techniques where a large volume of lung tissue is exposed to low but nonzero dose. For larger tumors, the model suggests hyperfractionation. We further discuss several non-intuitive interdependencies between optimal fractionation and the spatial dose distribution. For instance, lowering the dose in the lung via proton therapy does not necessarily provide a biological rationale for hypofractionation.
Definition of a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27. (1996)

Allelic deletions of chromosome 6q that occur frequently in ovarian cancers imply the presence of a putative tumor suppressor gene in this chromosomal vicinity. We analyzed DNA from 32 patients with ovarian carcinomas for loss of heterozygosity at loci on the distal portion of chromosome 6q and constructed a detailed deletion map. The map indicated a commonly deleted region between loci D6S149 (defined by CI6-24) and A2, which are estimated to be 300 kb apart on the basis of our cosmid contig map. By means of exon trapping, we found that the human AF-6 gene, which is disrupted in acute myeloid leukemia cells that carry a (6;11)(q27;q23) translocation, is located within the commonly deleted region. Subsequent screening of the AF-6 gene in ovarian carcinomas revealed no mutations. However, our mapping results, which narrowed the region containing the putative tumor suppressor gene to a 300-kb segment of 6q27, will facilitate further efforts to identify a gene associated with ovarian cancer.
Cyclin K Functions as a CDK9 Regulatory Subunit and Participates in RNA Polymerase II Transcription (1999)

Important progress in the understanding of elongation control by RNA polymerase II (RNAPII) has come from the recent identification of the positive transcription elongation factor b (P-TEFb) and the demonstration that this factor is a protein kinase that phosphorylates the carboxyl-terminal domain (CTD) of the RNAPII largest subunit. The P-TEFb complex isolated from mammalian cells contains a catalytic subunit (CDK9), a cyclin subunit (cyclin T1 or cyclin T2), and additional, yet unidentified, polypeptides of unknown function. To identify additional factors involved in P-TEFb function we performed a yeast two-hybrid screen using CDK9 as bait and found that cyclin K interacts with CDK9 in vivo. Biochemical analyses indicate that cyclin K functions as a regulatory subunit of CDK9. The CDK9-cyclin K complex phosphorylated the CTD of RNAPII and functionally substituted for P-TEFb comprised of CDK9 and cyclin T in in vitro transcription reactions.
Multiplex Bead Immunoassay Analysis of Aqueous Humor Reveals Distinct Cytokine Profiles In Uveitis (2005)

Application of multiplex bead immunoassays has allowed us to identify distinct patterns of cytokines that relate to both clinical disease and the cellular infiltrates present. Bioinformatics analysis allowed identification of cytokines that differentiate idiopathic uveitis from noninflammatory control AqH and are likely to be important for the pathogenesis of uveitis.
MiRNA expression in urothelial carcinomas: Important roles of miR‐10a, miR‐222, miR‐125b, miR‐7 and miR‐452 for tumor stage and metastasis, and frequent homozygous losses of miR‐31 (2008)

We analyzed 34 cases of urothelial carcinomas by miRNA, mRNA and genomic profiling. Unsupervised hierarchical clustering using expression information for 300 miRNAs produced 3 major clusters of tumors corresponding to Ta, T1 and T2-T3 tumors, respectively. A subsequent SAM analysis identified 51 miRNAs that discriminated the 3 pathological subtypes. A score based on the expression levels of the 51 miRNAs, identified muscle invasive tumors with high precision and sensitivity. MiRNAs showing high expression in muscle invasive tumors included miR-222 and miR-125b and in Ta tumors miR-10a. A miRNA signature for FGFR3 mutated cases was also identified with miR-7 as an important member. MiR-31, located in 9p21, was found to be homozygously deleted in 3 cases and miR-452 and miR-452* were shown to be over expressed in node positive tumors. In addition, these latter miRNAs were shown to be excellent prognostic markers for death by disease as outcome. The presented data shows that pathological subtypes of urothelial carcinoma show distinct miRNA gene expression signatures.
Marrow-Derived Stromal Cells Express Genes Encoding a Broad Spectrum of Arteriogenic Cytokines and Promote In Vitro and In Vivo Arteriogenesis Through Paracrine Mechanisms (2004)

We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.
Vitreous Incarceration in Patients Undergoing Second 20-Gauge Pars Plana Vitrectomy for Recurrent Retinal Detachment (2011)

Purpose. To observe and classify vitreous incarcerations in patients undergoing second 20-gauge pars plana vitrectomy (PPV) for recurrent retinal detachment. Methods. Retrospective noncomparative consecutive case series. Eighty-two consecutive patients with recurrent retinal detachment were included. The previous sclerotomy sites were examined by our sclera depression method and the vitreous incarceration were classified into Grade 0-IV by their severity under surgical microscope before second surgery. The relationship of vitreous incarceration and different ports was statistically investigated in our included patients. Results. Vitreous incarceration in the previous sclerotomy sites were found frequently. Vitreous cutter sites were most involved, but the infusion pipe sites were the least. According to our classification and definition, Grade III and IV of vitreous incarceration in all the three different sclerotomy sites accounted for 32.5%. Grade II of vitreous incarceration consisted of 12.6%. Grade 0 and I in all the three different sclerotomy sites were 54.8%. The frequency of all grades of vitreous incarceration in light port or vitreous cutter port was significant higher than that in infusion port. Conclusions. Vitreous incarceration in light port and vitreous cutter port are found more common than in infusion port for 20-gauge PPV with our new method.
The phylogeny of the genus Yersinia based on 16S rDNA sequences (1993)

The inter- and intrageneric relationships of the genus Yersinia were investigated by sequence analysis of the 16S rRNA gene. A stretch of approximately 1450 nucleotides was sequenced from representatives of ten of the eleven validly described species. Phylogenetic analysis revealed that yersinae form a coherent cluster within the gamma subgroup of Proteobacteria. The intrageneric relationship was characterized by five sublines with Y. enterocolitica, Y. rohdei, and Y. ruckeri forming separates sublines each represented by a single species. A separate subline was formed by Y. pestis, Y. pseudotuberculosis and Y. kristensenii, while Y. molaretii, Y. intermedia, Y. bercovieri, Y. aldovae, and Y. kristensenii formed a fifth subline. The phylogenetic distinctness of the yersiniae sublines is compared to published phenotypic properties and results of DNA-DNA similarity studies.
Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers (2006)

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0.05). During the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05) whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.