gebhart/patrepeval huggingface dataset:
In Vitro Evidence That Metabolic Cooperation Is Responsible for the Bystander Effect Observed with HSV tk Retroviral Gene Therapy (1993)

Tumor cells transduced with a retroviral vector expressing a herpes virus thymidine kinase (HSV tk) gene are rendered sensitive to the antiherpetic drug, ganciclovir. The bystander effect refers to the observation that not all cells need be transduced to eradicate the cell population by treatment with ganciclovir. We demonstrate that metabolic cooperation can account for this bystander effect. When HT1080 human fibrosarcoma cells marked with a lacZ gene (LZ+5) were cocultured with HT1080 cells transduced with a retrovirus expressing HSVtk (HT1080tk11), at a density at which the majority of cells were in contact, both HT1080tk11 and LZ+5 cells were killed by ganciclovir. When cells were cocultured at a low density where the majority of cells are not in contact with one another, however, only the HT1080tk11 cells were killed. This result suggests that cell contact with HT1080tk11 cells is necessary to render the HSVtk– LZ+5 cells sensitive to ganciclovir. Because involvement of metabolic cooperation in the killing of the LZ+5 cells would require not only contact between HT1080tk11 and LZ+5 cells but also the capacity to transfer small cytotoxic molecules from the former cell to the latter, transfer of radioactive molecules between the two cell lines was assessed by autoradiography after treatment of a coculture with [3H]ganciclovir. Isolated HT1080tk11 cells incorporated the labeled ganciclovir into their nuclei, whereas isolated LZ+5 cells did not. LZ+5 cells incorporated [3H]ganciclovir, only when in contact with HT1080tk11 cells. These findings indicate that a ganciclovir metabolic product, presumably a phosphorylated form, can pass from HSV tk+ to HSV tk– cells and mediate cytotoxicity as a consequence of direct contact. The use of retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV tk) gene has an intrinsic significant advantage as a strategy for gene therapy of tumours. Not all cells of a tumor need to be infected to render the tumor sensitive of the antiherpetic drug, ganciclovir. The conferral of ganciclovir sensitivity to uninfected cells has been designated as the "bystander effect." This paper explores the possibility that metabolic cooperation plays a major role in the manifestation of this phenomenon. Metabolic cooperation involves the transfer of low-molecular-weight molecules (< 1,000) between adjacent cells via gap junctions. During ganciclovir treatment, phosphorylated ganciclovir derived from HSV tk+ cells can be transferred to adjacent HSV tk– cells and cause the death of these uninfected cells.
FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0 (2009)

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.
Risk indicators in childhood malignancies (1975)

A series of 972 childhood malignancies was compared with a control series of healthy children matched for date and place of birth. Several variables were tested for possible aetiological significance. The information was obtained from the Finnish Cancer Registry and from the antenatal records of the mothers. No significant associations were found between the various types of malignancies and the variables studied. In the group consisting of all malignancies, a risk ratio of 2.0 could be significantly excluded for most variables. In the leukaemia group, both pelvic X-ray and polio vaccination were associated with slightly elevated risk ratios, but the differences between this group and the match controls were not statistically significant. BCG vaccination was performed during the perinatal period in 90% of the children, but the proportion was the same in the study and control groups, and hence the hypothesis that this vaccination confers protection was not supported. The information is considered prospective and relatively reliable, and the authors suggest that these data may be useful when more extensive series are compiled from various sources.
Exploiting inter-file access patterns using multi-collective I/O (2002)

I/O (MCIO) that extends conventional collective I/O to optimize I/O accesses to multiple arrays simultaneously. In this approach, as in collective I/O, multiple processors co-ordinate to perform I/O on behalf of each other if doing so improves overall I/O time. However, unlike collective I/O, MCIO considers multiple arrays simultaneously; that is, it has a more global view of the overall I/O behavior exhibited by application. This paper shows that determining optimal MCIO access pattern is an NPcomplete problem, and proposes two different heuristics for the access pattern detection problem (also called the assignment problem).
Functional assembly of a randomly cleaved protein. (1992)

The sequence of a 939-amino acid polypeptide that is a member of the aminoacyl-tRNA synthetase class of enzymes has been aligned with sequences of 15 related proteins. This alignment guided the design of 18 fragment pairs that were tested for internal sequence complementarity by reconstitution of enzyme activity. Reconstitution was achieved with fragments that divide the protein at both nonconserved and conserved sequences, including locations proximal to or within elements believed to form critical elements of secondary structure. Structure assembly is sufficiently flexible to accommodate fusion of short segments of unrelated sequences at fragment junctions. Complementary chain packing interactions and chain flexibility appear to be widely distributed throughout the sequence and are sufficient to reconstruct large three-dimensional structures from an array of disconnected pieces. The results may have implications for the evolution and assembly of large proteins.
Central Role of Glycogen Synthase Kinase-3β in Endoplasmic Reticulum Stress-induced Caspase-3 Activation (2002)

Stress of the endoplasmic reticulum (ER), which is associated with many neurodegenerative conditions, can lead to the elimination of affected cells by apoptosis through only partially understood mechanisms. Thapsigargin, which causes ER stress by inhibiting the ER Ca(2+)-ATPase, was found to not only activate the apoptosis effector caspase-3 but also to cause a large and prolonged increase in the activity of glycogen synthase kinase-3beta (GSK3beta). Activation of GSK3beta was obligatory for thapsigargin-induced activation of caspase-3, because inhibition of GSK3beta by expression of dominant-negative GSK3beta or by the GSK3beta inhibitor lithium blocked caspase-3 activation. Thapsigargin treatment activated GSK3beta by inducing dephosphorylation of phospho-Ser-9 of GSK3beta, a phosphorylation that normally maintains GSK3beta inactivated. Caspase-3 activation induced by thapsigargin was blocked by increasing the phosphorylation of Ser-9-GSK3beta with insulin-like growth factor-1 or with the phosphatase inhibitors okadaic acid and calyculin A, but the calcineurin inhibitors FK506 and cyclosporin A were ineffective. Insulin-like growth factor-1, okadaic acid, calyculin A, and lithium also protected cells from two other inducers of ER stress, tunicamycin and brefeldin A. Thus, ER stress activates GSK3beta through dephosphorylation of phospho-Ser-9, a prerequisite for caspase-3 activation, and this process is amenable to pharmacological intervention.
Adaptation of a Luciferase Gene Reporter and lac Expression System to Borrelia burgdorferi (2007)

The development of new genetic systems for studying the complex regulatory events that occur within Borrelia burgdorferi is an important goal of contemporary Lyme disease research. Although recent advancements have been made in the genetic manipulation of B. burgdorferi, there still remains a paucity of basic molecular systems for assessing differential gene expression in this pathogen. Herein, we describe the adaptation of two powerful genetic tools for use in B. burgdorferi. The first is a Photinus pyralis firefly luciferase gene reporter that was codon optimized to enhance translation in B. burgdorferi. Using this modified reporter, we demonstrated an increase in luciferase expression when B. burgdorferi transformed with a shuttle vector encoding the outer surface protein C (OspC) promoter fused to the luciferase reporter was cultivated in the presence of fresh rabbit blood. The second is a lac operator/repressor system that was optimized to achieve the tightest degree of regulation. Using the aforementioned luciferase reporter, we assessed the kinetics and maximal level of isopropyl-beta-D-thiogalactopyranoside (IPTG)-dependent gene expression. This lac-inducible expression system also was used to express the gene carried on lp25 required for borrelial persistence in ticks (bptA). These advancements should be generally applicable for assessing further the regulation of other genes potentially involved in virulence expression by B. burgdorferi.
Rho Kinase Inhibitor Fasudil Protects againstβ-Amyloid-Induced Hippocampal Neurodegeneration in Rats (2013)

Fasudil can protect against Aβ-induced hippocampal neurodegeneration by suppressing inflammatory response, suggesting that fasudil might be a promising agent for the prevention and treatment of inflammation-related diseases, such as AD.
DNA and RNA Quadruplex-Binding Proteins (2014)

Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.
A Cysteine-Rich Serine Protease Inhibitor (Guamerin II) from the Non-Blood Sucking Leech Whitmania Edentula: Biochemical Characterization and Amino Acid Sequence Analysis (1996)

A cysteine-rich serine protease inhibitor (Guamerin II) was isolated from the non-blood sucking leech Whitmania edentula. The new inhibitor was identified as a low molecular weight (6,012 Da) polypeptide with some sequence similarities to antistasin, hirustasin and guamerin. The inhibitor contained 56 amino acid residues with 76.8% sequence similarity to guamerin, 48.2% to hirustasin and 28.6% to the first domain of antistasin. This new inhibitor was the first completely sequenced serine protease inhibitor from a non-blood sucking leech. Analysis of the inhibitor revealed that it was active against neutrophil elastase and chymotrypsin, but had no activity against a variety of other proteases. The PI reactive site residue was identified as methionine and the residues surrounding the PI site were hydrophobic amino acids. The primary structure of the inhibitor showed no similarity to well-known elastase inhibitors from leeches such as eglin.
Sustained Release of BMP-2 in Bioprinted Alginate for Osteogenicity in Mice and Rats (2013)

The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs) was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.
Treatment of viral warts with cimetidine: an open-label study (2000)

The immunomodulatory actions of cimetidine, an H2-receptor antagonist, and its use in the treatment of viral warts has been described previously but its effectiveness is still debated. We report the results in 47 patients with multiple, nongenital viral warts who were treated with oral cimetidine in a 3-month open-label study. The drug was generally well tolerated and 87% of children and 68% of adults improved with treatment. Follow-up data in 65% of the patients showed that there had been no recurrence in the majority of those whose warts had cleared completely during treatment, whereas warts tended to persist or recur in those who had stopped treatment before all the warts had resolved. Our data suggests that cimetidine may be helpful in the treatment of viral warts in both adults and children and supports the need for a randomized controlled trial.
Determination of gene products and coding regions from the murE-murF region of Escherichia coli (1988)

We report the cloning of murE and murF genes and the identification of their gene products. The murE and murF genes encode diaminopimelic acid- and D-alanyl-D-alanine-adding enzymes, respectively, and both genes are involved in cell wall peptidoglycan biosynthesis in Escherichia coli.
A yeast protein phosphatase related to the vaccinia virus VH1 phosphatase is induced by nitrogen starvation. (1992)

A phosphatase related to the vaccinia virus VH1 phosphatase has been cloned from Saccharomyces cerevisiae. The yeast phosphatase is related to the Schizosaccharomyces pombe cdc25 gene product and to a protein encoded by a mammalian open reading frame known as 3CH134, which is an immediate early gene responding to serum stimulation. The phosphatase activity of the yeast gene product appears to be restricted to the hydrolysis of phosphotyrosine-containing substrates, whereas the vaccinia phosphatase hydrolyzes both phosphoserine- and phosphotyrosine-containing substrates. The mRNA encoding the yeast phosphatase is dramatically induced by nitrogen starvation. Inactivation of the yeast phosphatase gene results in a decrease in growth rate.
The release of N-acetyl- and N-glycolloyl-neuraminic acid from soluble complex carbohydrates and erythrocytes by bacterial, viral and mammalian sialidases (1981)

A series of substrates, sialyl(2 leads to 6)GalNAc and ganglioside GM3, containing either N-acetylneuraminic acid (AcNeu) or N-glycolloylneuraminic acid (GcNeu), has been prepared. The trisaccharide GcNeu(2 leads to 3)lactose was preapred by ozonolysis of GcNeu-GM3, and the disaccharides AcNeu(2 leads to 6)GalNAc and GcNeu(2 leads to 6)GalNAc were isolated from bovine submandibular-gland mucin by alkali elimination. Sialidases from Newcastle-disease virus, fowl-plague virus, influenza virus A2, Clostridium perfringens, Vibrio cholerae, Arthrobacter ureafaciens and human liver lysosomes were studied with the above substrates and all showed poorer cleavage of GcNeu-containing substrates when compared with the corresponding AcNeu-containing compounds. This was reflected in the Km and Vmax. values of these sialidases. Differences between viral and bacterial sialidases could be detected on the basis of their kinetic constants and time curves of sialic acid release. Preferred release of AcNeu relative to GcNeu was also observed with bovine submandibular gland mucin and a mixture of human and porcine erythrocytes, macromolecular substrates containing both AcNeu and GcNeu. The significance of differential cleavage of AcNeu and GcNeu by sialidases is considered together with examples of the role of GcNeu in physiologicaL systems.
Viral infection and Toll‐like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte‐derived dendritic cells (2004)

In humans, the type I interferon (IFN) family consists of 13 IFN-alpha subtypes, IFN-beta and IFN-omicron the newly discovered IFN-like family consists of IFN-lambda1, -lambda2 and -lambda3. We have investigated the expression of type I and lambda IFN genes following virus infections or Toll-like receptor (TLR) triggering in monocyte-derived DC (MDDC) and plasmacytoid DC (pDC). We found that all IFN-alpha, -beta, -omicron and -lambda subtypes are expressed in influenza-virus-infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR-9 stimulation by CpG DNA induced the expression of all IFN-alpha, -beta, -omicron and -lambda subtypes in pDC, whereas TLR-4 stimulation by LPS, or TLR-3 stimulation by poly I:C, induced only IFN-beta and IFN-lambda gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)-5 and IRF-7 in MDDC and pDC was also determined. IRF-5 was constitutively expressed in the two DC subsets whereas IRF-7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN-lambda with IFN-beta would be of crucial importance for the maturation of DC.
Atomic solvation parameters applied to molecular dynamics of proteins in solution (1992)

A solvation energy function for use in the molecular simulation of proteins is proposed. It is based on the accessible surface areas of atoms in the protein and on atomic solvation parameters derived from empirical vapor-to-water free energies of transfer of amino acid side-chain analogs. The energy function and its derivatives were added to the CHARMM molecular simulation program (Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., & Karplus, M., 1983, J. Comput. Chem. 4(2), 187-217). The effect of the added energy term was evaluated by 110 ps of molecular dynamics on the 26-residue protein melittin. The melittin monomer and tetramer were studied both with and without the added term. With the added energy term the monomer partially unfolded, while the secondary structure of the tetramer was preserved, in agreement with reported experiments (Brown, L.R., Lauterwein, J., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 231-244; Lauterwein, J., Brown, L.R., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 219-230).
Preclinical assessment of curcumin as a potential therapy for B‐CLL (2006)

Curcumin, the principle component of the spice turmeric, has been used as an anti-inflammatory medication in India and China for centuries. Recent studies, predominantly using actively dividing cell lines, have suggested that this compound could be used as a chemopreventative or therapeutic agent for epithelial tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity that would be expected to induce apoptosis in B cell malignancies, we sought to determine whether curcumin induces apoptosis in vitro in primary chronic lymphocytic leukemia (B-CLL) cells. Primary leukemic cells were incubated with varying dosages of curcumin, followed by assessment for apoptosis. The role of PPARgamma or NF-kappaB signaling in curcumin-induced apoptosis was examined by cotreatment with a PPARgamma antagonist or EMSA of nuclear NFkappaB complexes. We also examined whether a clinically achievable concentration of curcumin (1 microM) would augment the apoptotic effects of fludarabine, dexamethasone, vincristine or the PDE4 inhibitor rolipram. In B-CLL cells from 14 patients, curcumin-induced apoptosis with a mean EC(50) of 5.5 microM. In contrast, the EC(50) for whole mononuclear cells from a healthy donor was 21.8 microM. In a 48 hr wash-out time course, curcumin-induced apoptosis was time-dependent, with a substantial reduction in apoptosis observed when curcumin was removed after 5 hr. Curcumin treatment reduced basal nuclear NF-kappaB levels and 1 microM curcumin augmented both vinca alkaloid and PDE4 inhibitor-induced apoptosis in B-CLL cells. Our studies suggest that curcumin may augment the efficacy of established or experimental therapies for B-CLL.
Serotonin Modulates Behavioral Reactions to Unfairness (2008)

Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.
Recombination patterns in maize reveal limits to crossover homeostasis (2015)

Significance During meiosis, chromosomes exchange segments in a process of crossing-over. The crossover number is tightly regulated so that at least one crossover (but not many more) is formed per chromosome. The process of crossover homeostasis is thought to play a major role in this regulation by ensuring a stable crossover number even if the number of DNA breaks that initiate crossover formation varies. However, we found that, in maize, the crossover number changes with the number of DNA breaks, suggesting that different species exhibit different crossover control mechanisms. Plant breeders rely on recombination to create new combinations of alleles. Our data suggest that increasing recombination rates in plants may be accomplished by increasing the number of DNA breaks.