gebhart/patrepeval huggingface dataset:
Recent Trends in Targeted Anticancer Prodrug and Conjugate Design (2008)

Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tumors are major therapy limiting factors that result into poor prognosis for patients. Prodrug and conjugate design involves the synthesis of inactive drug derivatives that are converted to an active form inside the body and preferably at the site of action. Classical prodrug and conjugate design have focused on the development of prodrugs that can overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs. The recent targeted prodrug and conjugate design, on the other hand, hinge on the selective delivery of anticancer agents to tumor tissues thereby avoiding their cytotoxic effects on noncancerous cells. Targeting strategies have attempted to take advantage of low extracellular pH, elevated enzymes in tumor tissues, the hypoxic environment inside the tumor core, and tumor-specific antigens expressed on tumor cell surfaces. The present review highlights recent trends in prodrug and conjugate rationale and design for cancer treatment. The various approaches that are currently being explored are critically analyzed and a comparative account of the advantages and disadvantages associated with each approach is presented.
Epidemiology and natural history of HPV. (2006)

Human papillomavirus (HPV) is a highly prevalent, sexually transmitted infection responsible for significant morbidity and mortality. High-risk HPV types are now known to be necessary in the etiology of cervical cancer and to lead to both high-grade and low-grade cervical lesions. They are also implicated in a substantial portion of anal, penile, and head and neck precancers and cancers. HPV 16 and 18 are the most common HPV types found in cervical cancer and are responsible for approximately 70% of these cancers. In contrast, low-risk HPV types, the most common of which are HPV 6 and 11, cause genital warts, low-grade cervical lesions, and recurrent respiratory papillomatosis, but they do not cause cervical or other HPV-related cancers. Infection is most common in young, sexually active populations, and an estimated three fourths of adults will be infected with HPV during their lifetime. Cervical screening programs exist in the United States and other developed countries to identify and treat precancerous cervical lesions, but they do not reach all women and are costly. Until recently, no highly effective primary prevention strategy to reduce the risk of HPV acquisition existed. However, a quadrivalent HPV vaccine, which protects against the most common high-risk and low-risk HPV infections (HPV 16, 18, 6, and 11), is now available. In addition, a bivalent HPV vaccine that protects against high-risk HPV types 16 and 18 is in the late stages of clinical development. If implemented widely, vaccination against HPV promises to dramatically reduce HPV-associated morbidity and mortality.
A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. (1991)

We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for hematopoietic stem and progenitor cells. Sequence analysis of this clone reveals strong homology to the c-Kit subfamily of receptor kinases, and in particular to the Flt gene product. Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked. Flk-1 mRNA is expressed in primitive and more mature hematopoietic cells as well as in a wide variety of nonhematopoietic tissues.
EGFR Antagonists in Cancer Treatment (2008)

Functional activation of growth factors and receptors of the epidermal growth factor receptor (EGFR) family occurs in most epithelial-cell cancers, rendering EGFR a target for cancer treatment. This article discusses the mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer.
Transforming growth factor- -regulated miR-24 promotes skeletal muscle differentiation (2008)

MicroRNAs (miRNAs) have recently been proposed as a versatile class of molecules involved in regulation of a variety of biological processes. However, the role of miRNAs in TGF-beta-regulated biological processes is poorly addressed. In this study, we found that miR-24 was upregulated during myoblast differentiation and could be inhibited by TGF-beta1. Using both a reporter assay and Northern blot analysis, we showed that TGF-beta1 repressed miR-24 transcription which was dependent on the presence of Smad3 and a Smads binding site in the promoter region of miR-24. TGF-beta1 was unable to inhibit miR-24 expression in Smad3-deficient myoblasts, which exhibited accelerated myogenesis. Knockdown of miR-24 led to reduced expression of myogenic differentiation markers in C2C12 cells, while ectopic expression of miR-24 enhanced differentiation, and partially rescued inhibited myogenesis by TGF-beta1. This is the first study demonstrating a critical role for miRNAs in modulating TGF-beta-dependent inhibition of myogenesis, and provides a novel mechanism of the genetic regulation of TGF-beta signaling during skeletal muscle differentiation.
Louis-Georges Tin, L’invention de la culture hétérosexuelle. Paris, Éditions Autrement (Collection Mutations/Sexe en tous genres 249), 2008, 208 pages (2010)

Consequence a la fois du mouvement de l’histoire des femmes et du genre et de l’histoire des sexualites, un nouveau champ d’etude tres prometteur s’ouvre aux historien-ne-s, celui de l’heterosexualite. Les etudes sur cette autre « omnipresence invisible » (pour plagier l’expression utilisee par John Tosch a propos des hommes en tant qu’etres sexues) n’en sont qu’a leurs balbutiements en Europe (il s’est tenu a Louvain, en octobre 2007, un colloque intitule « L’histoire contemporaine des heter...
Suppression of insulin-like growth factor type I receptor by a triple-helix strategy inhibits IGF-I transcription and tumorigenic potential of rat C6 glioblastoma cells (1997)

Homopurine (AG) and homopyrimidine (CT) oligodeoxyribonucleotides predicted to form triple-helical (triplex) structures have been shown to specifically suppress gene expression when supplied to cultured cells. Here we present evidence that homopurine RNA (effector) sequences designed to form a triplex with a homopurine. homopyrimidine sequence 3' to the termination codon of the insulin-like growth factor type I receptor (IGF-IR) structural gene can efficiently suppress IGF-IR gene transcription. Transfection vectors were constructed to drive transcription of either AG or CT variant triplex-forming strands. To increase the probability of obtaining stable transfectants with adequate expression of effector sequences, these were designed to be transcribed together with cDNA sequences conferring neomycin resistance as a fusion transcript. Rat C6 glioblastoma cells transfected with the AG variant showed dramatic reduction of IGF-IR transcripts compared with untransfected cells. The AG transfectants also exhibited marked down-regulation of the IGF-I, and an enhanced accumulation of serine protease inhibitor nexin-I mRNA. Similar changes in gene expression were observed following transfection of C6 cells with constructs transcribing antisense RNA to IGF-IR transcripts, but were not observed in C6 cells transfected with either the CT triplex variant or with vector lacking triplex-forming sequences. Moreover, C6 cells transfected with AG triplex variant displayed a dramatic inhibition of tumor growth when injected into nude mice. The results suggest that a triple-helix strategy can be used to inhibit transcription elongation of the IGF-IR gene, and emphasize the efficacy of triplex-mediated gene inhibition in an animal model.
Effects of prebiotic oligosaccharides and trehalose on growth and production of bacteriocins by lactic acid bacteria (2007)

This study offers useful information for not only a new application of FOS and trehalose, but also the potential improvement of food preservation.
Knockout mutagenesis of thekpsEgene ofCampylobacter jejuni81116 and its involvement in bacterium–host interactions (2007)

Campylobacter jejuni is a common cause of bacterial enteritis. The surface capsular polysaccharides are important for this bacterium to survive in the environment, but little is known about their involvement in bacterium-host interactions. This study showed that the C. jejuni capsular polysaccharides play an important role in adherence to and invasion of human embryonic epithelial cells. However, no significant role of capsular polysaccharides was shown in colonization of the chicken gut.
Neutrophil Elastase as a Target in Lung Cancer (2012)

Human neutrophil elastase (HNE), a main actor in the development of chronic obstructive pulmonary diseases, has been recently involved in non-small cell lung cancer progression. It can act at several levels (i) intracellularly, cleaving for instance the adaptor molecule insulin receptor substrate-1 (IRS-1) (ii) at the cell surface, hydrolyzing receptors as CD40 (iii) in the extracellular space, generating elastin fragments i.e. morphoelastokines which potently stimulate cancer cell invasiveness and angiogenesis. Since decades, researchers identified natural compounds and/or synthesized agents which antagonize HNE activity that will be described in this review article. Some of these compounds might be of value as therapeutic agents in lung cancer. However, it is now widely accepted that lung tumor invasion and metastasis involve proteolytic cascades. Accordingly, we will here mainly focus our attention to natural substances able to display a dual inhibitory capacity (i.e. lipids and derivatives, phenolics) towards HNE and matrix metalloproteinases (MMPs), particularly MMP-2. To that purpose, we recently synthesize substances named "LipoGalardin" (Moroy G. et al., Biochem. Pharmacol., 2011, 81(5), 626-635) exhibiting such inhibitory bifunctionality. At last, we will propose an original synthetic scheme for designing a potent biheaded HNE/MMP-2 inhibitor.
Mining recent temporal patterns for event detection in multivariate time series data (2012)

Improving the performance of classifiers using pattern mining techniques has been an active topic of data mining research. In this work we introduce the recent temporal pattern mining framework for finding predictive patterns for monitoring and event detection problems in complex multivariate time series data. This framework first converts time series into time-interval sequences of temporal abstractions. It then constructs more complex temporal patterns backwards in time using temporal operators. We apply our framework to health care data of 13,558 diabetic patients and show its benefits by efficiently finding useful patterns for detecting and diagnosing adverse medical conditions that are associated with diabetes.
Zonulin, regulation of tight junctions, and autoimmune diseases (2012)

Recent studies indicate that besides digestion and absorption of nutrients and water and electrolytes homeostasis, another key function of the intestine is to regulate the trafficking of environmental antigens across the host mucosal barrier. Intestinal tight junctions (TJs) create gradients for the optimal absorption and transport of nutrients and control the balance between tolerance and immunity to nonself antigens. To meet diverse physiological challenges, intestinal epithelial TJs must be modified rapidly and in a coordinated fashion by regulatory systems that orchestrate the state of assembly of the TJ multiprotein network. While considerable knowledge exists about TJ ultrastructure, relatively little is known about their physiological and pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led us to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases.
Crystal Structure of Polygalacturonase from Erwinia carotovora ssp. carotovora (1998)

The crystal structure of the 40-kDa endo-polygalacturonase from Erwinia carotovora ssp. carotovora was solved by multiple isomorphous replacement and refined at 1.9 A to a conventional crystallographic R-factor of 0.198 and Rfree of 0.239. This is the first structure of a polygalacturonase and comprises a 10 turn right-handed parallel beta-helix domain with two loop regions forming a "tunnel like" substrate-binding cleft. Sequence conservation indicates that the active site of polygalacturonase is between these two loop regions, and comparison of the structure of polygalacturonase with that of rhamnogalacturonase A from Aspergillus aculeatus enables two conserved aspartates, presumed to be catalytic residues, to be identified. An adjacent histidine, in accord with biochemical results, is also seen. A similarity in overall electrostatic properties of the substrate-binding clefts of polygalacturonase and pectate lyase, which bind and cleave the same substrate, polygalacturonic acid, is also revealed.
Novel view synthesis with residual error feedback for FTV (2010)

The availability of multi-view images of a scene makes possible new and exciting applications, including Free-viewpoint TV (FTV). FTV allows us to change viewpoint freely in a 3D world, where the virtual viewpoint images are synthesized by Depth-Image-Based Rendering (DIBR). In this paper, we propose a new method of DIBR using multi-view images acquired in a linear camera arrangement. The proposed method improves virtual viewpoint images by predicting the residual errors. For virtual viewpoint image synthesis, it is necessary to estimate the depth maps with multi-view images. Some algorithms to estimate depth map were proposed, but it is difficult to estimate accurate depth map. As a result, rendered virtual viewpoint images have some errors due to the depth errors. Therefore, our proposed method takes into account those depth errors and improves the quality of the rendered virtual viewpoint images. In the proposed method, the virtual images of each camera position are generated using the real images from each other camera. Then, the residual errors can be calculated between the generated images and the real images acquired by the actual cameras. The residual errors are processed and fed back to predict the residual errors that can be happened to virtual viewpoint images generated by conventional method. In the experiments, PSNR could be improved for few decibels compared with the conventional method.
433. Some heterocyclic analogues of stilbenes (1948)

D. M. Brown and G. A. R. Kon, J. Chem. Soc., 1948, 2147 DOI: 10.1039/JR9480002147
Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes (1997)

Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the β and γ components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15–contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-γ (IFN-γ) and IL-4. IFN-γ inhibited IL-15–induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.
Deoxyhypusine Synthase Activity Is Essential for Cell Viability in the Yeast Saccharomyces cerevisiae (1998)

Deoxyhypusine synthase catalyzes the first step in the posttranslational synthesis of an unusual amino acid, hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. The null mutation in the single copy gene, yDHS, encoding deoxyhypusine synthase results in the loss of viability in the yeast Saccharomyces cerevisiae. Upon depletion of deoxyhypusine synthase, and consequently of eIF-5A, cessation of growth was accompanied by a marked enlargement of cells, suggesting a defect in cell cycle progression or in cell division. Two residues of the yeast enzyme, Lys308 and Lys350, corresponding to Lys287 and Lys329, respectively, known to be critical for the activity of the human enzyme, were targeted for site-directed mutagenesis. The chromosomal ydhs null mutation was complemented by the plasmid-borne yDHS wild-type gene, but not by mutated genes encoding inactive proteins, including that with Lys350-->Arg substitution or with substitutions at both Lys308 and Lys350. The mutated gene ydhs (K308R) encoding a protein with diminished activities (< 1% of wild type) could support growth but only to a very limited extent. These findings provide strong evidence that the hypusine modification is indeed essential for the survival of S. cerevisiae and imply a vital function for eIF-5A in all eukaryotes.
A reliable wide-area WDM-PON using wavelength-shifted protection scheme (2005)

We propose and demonstrate a wavelength-shifted protection scheme suitable for wide-area, carrier-distributed WDM-PONs. An experiment simulating the failure of a 40-km WDM transmission line is conducted and the protection performance is evaluated. (2 pages)
Long-Term Effectiveness and Safety of Lisdexamfetamine Dimesylate in School-Aged Children with Attention-Deficit/Hyperactivity Disorder (2008)

Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.
De novo design of biomimetic antimicrobial polymers (2002)

The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor with both fundamental and practical implications. Recently, a number of nonnatural peptides with designed sequences have been elaborated to provide biologically active structures; in particular, facially amphiphilic peptides built from beta-amino acids have been shown to mimic both the structures as well as the biological function of natural antimicrobial peptides such as magainins and cecropins. However, these natural peptides as well as their beta-peptide analogues are expensive to prepare and difficult to produce on a large scale, limiting their potential use to certain pharmaceutical applications. We therefore have designed a series of facially amphiphilic arylamide polymers that capture the physical and biological properties of this class of antimicrobial peptides, but are easy to prepare from inexpensive monomers. The design process was aided by molecular calculations with density functional theory-computed torsional potentials. This new class of amphiphilic polymers may be applied in situations where inexpensive antimicrobial agents are required.
Potent inhibition of tumoral hypoxia-inducible factor 1α by albendazole (2010)

These results demonstrate for the first time the effects of an acute dose of ABZ in profoundly suppressing both HIF-1alpha and VEGF within the tumor. This dual inhibition may provide additional value in inhibiting angiogenesis and be at least partially effective in inhibiting tumoral HIF-1alpha surge, tumor invasiveness and metastasis.
Performance model of the Argonne Voyager multimedia server (2002)

The Argonne Voyager Multimedia Server is being developed in the Futures Lab of the Mathematics and Computer Science Division at Argonne National Laboratory. As a network based service for recording and playing multimedia streams, it is important that the Voyager system be capable of sustaining certain minimal levels of performance in order for it to be a viable system. In this article, we examine the performance characteristics of the server. As we examine the architecture of the system, we try to determine where bottlenecks lie, show actual vs potential performance, and recommend areas for improvement through custom architectures and system tuning.
Reduction of Photoautotrophic Productivity in the Cyanobacterium Synechocystis sp. Strain PCC 6803 by Phycobilisome Antenna Truncation (2012)

Truncation of the algal light-harvesting antenna is expected to enhance photosynthetic productivity. The wild type and three mutant strains of Synechocystis sp. strain 6803 with a progressively smaller phycobilisome antenna were examined under different light and CO(2) conditions. Surprisingly, such antenna truncation resulted in decreased whole-culture productivity for this cyanobacterium.
Expression of NLRP7 (PYPAF3, NALP7) protein in endometrial cancer tissues. (2008)

Tumor-produced NLRP7, associated with myometrial invasion, might provide additional prognostic information in endometrial cancer patients.
Both Duration and Timing of Sleep are Important to Memory Consolidation (2010)

THE STUDY IN THIS ISSUE BY HAGEWOUD AND COLLEAGUES1 CONTRIBUTES AN IMPORTANT NOVEL PIECE OF EVIDENCE TO THE LITERATURE ON SLEEP and memory. Using a rodent model, they found that it is not only the timing of sleep relative to learning that was important to memory consolidation, but also the total amount of sleep obtained. Hagewoud et al.1 observed that 6 h sleep deprivation immediately after training in the light (sleep) period impaired contextual fear conditioning whereas 6 h immediate or delayed sleep deprivation in the dark (waking) phase after training had no effect on learning. They also found that when training occurred near the onset of the dark (waking) period, a full 12 h of sleep deprivation was needed to achieve a deficit in learning. As they point out, 12 h sleep deprivation in the dark period may have deprived the animals of an equivalent amount of sleep as 6 h of deprivation in the light period, since these animals sleep about 30% to 60% less in the dark phase than the light phase. This study is novel in that, while many have described a critical sleep window, none have yet quantified the length of sleep needed to effectively consolidate memories. The study raises some interesting questions for the field.
Discussion (2007)

Pittsburgh, Pa. Received for publication March 12, 2006. J. Peter Rubin, M.D., University of Pittsburgh, 3380 Boulevard of the Allies, Suite 180, Pittsburgh, Pa. 15213, [email protected]