gebhart/patrepeval huggingface dataset:
Diminished production of prostaglandin E2 by monocytes of newborns is due to altered fatty acid membrane content and reduced cyclooxygenase activity (1996)

To determine the biochemical basis for reduced PGE2 expression by cord blood monocytes relative to adult peripheral blood monocytes, fatty acid composition of cell membranes together with the amount and activity of enzymes involved in the cyclooxygenase pathway were investigated. Gas chromatographic analysis of mononuclear cell fatty acids showed a significant reduction in long chain fatty acids, including arachidonic acid. Acylase and phospholipase A2 activity, together with lipocortin 1 levels, were similar in cord and adult monocytes. No difference in amounts of the 70-kDa cyclooxygenase type 1 enzyme was observed between the monocyte sources. The 74k-Da cyclooxygenase type 2 enzyme was synthesized de novo upon LPS stimulation in comparable amounts in both cord and adult monocytes, with both monocyte types responding with equal sensitivity to LPS. The ability of microsomes, prepared from cord monocytes, to convert arachidonic acid into eicosanoids of the cyclooxygenase pathway was reduced. In contrast, the ability of acetylated microsomes to convert PGG2 to PGE2 was comparable, suggesting that the deficiency in PGE2 production by cord monocytes is due to reduced activity, specifically at the cyclooxygenase-active site rather than the peroxidase active site. In conclusion, it appears that both reduced fatty acid content and diminished cyclooxygenase activity are responsible for diminished eicosanoid production by cord monocytes.
Novel Nano-Column and Nano-Flower Arrays by Glancing Angle Deposition (2002)

In this letter, we report a method to fabricate nano-column arrays with different shapes and in-plane orientations by glancing angle deposition. By changing the rate of the rotation during each revolution, we can fabricate nano-columns with circular, elliptical, triangle, rectangular, and pentagon shapes. Depending on the nucleation sites, we can even fabricate flowerlike nano-columns. This method has potential application to produce 3-D lattice.
The discovery of potent nonpeptide angiotensin II receptor antagonists: a new class of potent antihypertensives (1990)

A new class of potent antihypertensives has been discovered that exert their effect through blockade of the angiotensin II (AII) receptor. Most AII antagonists reported so far are peptide mimics of the endogenous vasoconstrictor octapeptide angiotensin II. The compounds of this paper are nonpeptides and therefore constitute a new class of potent AII receptor antagonists. Based on the overlap of a conformation of AII with literature lead 3, a hypothesis was developed suggesting the need for an additional acidic functionality to increase the lead's potency. The substitution of an additional carboxylic acid resulted in a 10-fold increase in binding affinity observed for diacid 4. The binding affinities for subsequent compounds were eventually increased 1000-fold over that of the literature leads through a systematic SAR study. Thus the AII receptor binding affinity [IC50 (microM)] of 15 microM for literature lead 1, for example, was increased to 0.018 and 0.012 microM for compounds 33 and 53. A structure-affinity relationship has been found requiring the presence of four key elements for good activity: (1) an additional phenyl ring at the N-benzyl para position of the benzylimidazole nucleus, (2) an acidic functionality at the ortho position of the terminal aromatic ring, (3) a lipophilic side chain at the imidazole 2-position of three to five carbon atoms in length, and (4) a group at the imidazole 5-position capable of hydrogen bonding. The synthesis as well as the pharmacological activity of the compounds in this new series of AII receptor antagonists are presented.
Human Mitochondrial C1-Tetrahydrofolate Synthase (2003)

C1-tetrahydrofolate (THF) synthase is a trifunctional enzyme found in eukaryotes that contains the activities 10-formyl-THF synthetase, 5,10-methenyl-THF cyclohydrolase, and 5,10-methylene-THF dehydrogenase. The cytoplasmic isozyme of C1-THF synthase is well characterized in a number of mammals, including humans; but a mitochondrial isozyme has been previously identified only in the yeast Saccharomyces. Here, we report the identification and characterization of the human gene encoding a functional mitochondrial C1-THF synthase. The gene spans 236 kilobase pairs on chromosome 6 and consists of 28 exons plus one alternative exon. The gene encodes a protein of 978 amino acids, including an N-terminal mitochondrial targeting sequence. The mitochondrial isozyme is 61% identical to the human cytoplasmic isozyme. Expression of the gene was detected in most human tissues, but transcripts were highest in placenta, thymus, and brain. Two mRNAs were detected, a 3.6-kb transcript and a 1.1-kb transcript, and both transcripts were observed in varying ratios in each tissue. The shorter transcript results from an alternative splicing event, where exon 7 is spliced to exon 8a instead of exon 8. Exon 8a is derived from an exonized Alu sequence, sharing no homology with exon 8 of the long transcript, and encodes just 15 amino acids followed by a stop codon and a polyadenylation signal. This short transcript potentially encodes a bifunctional enzyme lacking 10-formyl-THF synthetase activity. Both transcripts initiate at the same 5'-site, 107 nucleotides up-stream of the ATG start codon. The full-length (2934 bp) cDNA fused to a C-terminal V5 epitope tag was expressed in Chinese hamster ovary cells. Immunoblots of subfractionated cells revealed a 107-kDa protein only in the mitochondrial fractions of these cells, confirming the mitochondrial localization of the protein. Yeast cells expressing the full-length human cDNA exhibited elevated 10-formyl-THF synthetase activity, confirming its identification as the human mitochondrial C1-THF synthase.
Action Spectrum for an Enhancement of Endogenous Respiration by Light in Chlorella (1967)

The oxygen consumption of a starved chlorophyll-free, yellow mutant of Chlorella vulgaris is enhanced by very small amounts of blue light (lambda 450 mmu); a saturation level is reached at about 500 ergs cm(-2) sec(-1). At that intensity the respiration is about 3 times greater than in the dark. An action spectrum for the enhancement of respiration shows 2 peaks around lambda 450 and 375 mmu. Flavins and cis-carotenoids are discussed as the pigments involved.
Current Concepts in Reprogramming Somatic Cells to Pluripotent State (2008)

Recently considerable interests have been roused in nuclear reprogramming by somatic cell nuclear transfer using an egg cytoplasm and/or by other means, such as fusion, cell extracts treatment and genes transfections. However, the very mechanism of reprogramming still remains elusive. Epigenetic modifications, which play a significant role in normal mammalian development in vivo is also involved in the process of reprogramming in vitro. The latter shares some of the other features observed in nuclear reprogramming in vivo. In this review, we discuss the main epigenetic changes involved in nuclear reprogramming and currently available approaches to achieve nuclear reprogramming in vitro and its future prospects.
Rapid/Sustained Anti-anthrax Passive Immunity Mediated by Co-administration of Ad/AAV (2007)

Achieving both immediate and sustained protection against diseases caused by bacterial toxins and extracellular pathogens is a challenge in developing biodefense therapeutics. We hypothesized that a single co-administration of an adenovirus (Ad) vector and an adeno-associated virus (AAV) vector, both expressing a pathogen-specific monoclonal antibody, would provide rapid, persistent passive immunotherapy against the pathogen. In order to test this strategy, we used the lethal toxin of Bacillus anthracis as a target of a monoclonal antibody directed against the protective antigen (PA) component of the toxin, using co-administration of an Ad vector encoding an anti-PA monoclonal antibody (AdalphaPA) and an AAV vector encoding an anti-PA monoclonal antibody (AAVrh.10alphaPA). As early as 1 day after co-administration of AdalphaPA and AAVrh.10alphaPA to mice, serum anti-PA antibody levels were detectable, and were sustained through 6 months. Importantly, animals that received both vectors were protected against toxin challenge as early as 1 day after administration and throughout the 6 month duration of the experiment. These data provide a new paradigm of genetic passive immunotherapy by co-administration of Ad and AAV vectors, each encoding a pathogen-specific monoclonal antibody, as an effective approach for both rapid and sustained protection against a bio-terror attack.
Designing to Facilitate Browsing: A Look Back at the Hyperties Workstation Browser (1991)

Since browsing hypertext can present a formidable cognitive challenge, user interface design plays a major role in determining acceptability. In the Unix workstation version of Hyperties, a research-oriented prototype, we focussed on design features that facilitate browsing. We first give a general overview of Hyperties and its markup language. Customizable documents can be generated by the conditional text feature that enables dynamic and selective display of text and graphics. In addition we present: — an innovative solution to link identification: pop-out graphical buttons of arbitrary shape.— application of pie menus to permit low cognitive load actions that reduce the distraction of common actions, such as page turning or window selection.— multiple window selection strategies that reduce clutter and housekeeping effort. We preferred piles-of-tiles, in which standard-sized windows were arranged in a consistent pattern on the display and actions could be done rapidly, allowing users to concentrate on the contents.
Quality Assessment in Magnetic Resonance Images (2010)

Assessing quality of medical images is critical because the subsequent course of actions depend on it. Extensive use of clinical magnetic resonance (MR) imaging warrants a study in image indices used for MR images. The quality of MR images assumes particular significance in the determination of their reliability for diagnostics, response to therapies, synchronization across different imaging cycles, optimization of interventional imaging, and image restoration. In this paper, we review various techniques developed for the assessment of MR image quality. The reported quality indices can be broadly classified as subjective/objective, automatic/semi-automatic, region-of-interest/non-region-of-interest-based, full-reference/no-reference and HVS incorporated/non-HVS incorporated. The trade-of across the various indices lies in the computational complexity, assumptions, repeatability, and resemblance to human perception. Because images are eventually viewed by the human eye, it is found that it is important to incorporate aspects of human visual response, sensitivity, and characteristics in computing quality indices. Additionally, no-reference metrics are the most relevant due to the lack of availability of a golden standard against which images could be compared. Techniques that are objective and automatic are preferred for their repeatability and to eliminate avoidable errors due to factors like stress, which arise in human intervention.
A parallel packet screen for high speed networks (2003)

The paper demonstrates why security issues related to the continually increasing bandwidth of high speed networks (HSN) cannot be addressed with conventional firewall mechanisms. A single packet screen running on a fast computer is not capable of filtering all packets traversing a Fast/Gigabit Ethernet. This problem can be addressed by using parallel processing methods to implement a fast, scalable packet screen for Ethernets. The paper shows how hardware may be utilized to distribute the network load among such parallel packet screens. Empirical results using 'off-the-shelf' equipment indicate that this approach is usable.
Changes in in vitro susceptibility of influenza A H3N2 viruses to a neuraminidase inhibitor drug during evolution in the human host (2004)

This study demonstrates that recent clinical isolates of influenza A H3N2 virus no longer agglutinate chicken RBCs, but despite significant receptor binding changes as a result of changes in HA, there was little variation in sensitivity of the NA to zanamivir.
Ethnic-affiliation estimation by use of population-specific DNA markers. (1997)

During the past 10 years, DNA analysis has revolutionized the determination of identity in a forensic context. Statements about the biological identity of two human DNA samples now can be made with complete confidence. Although DNA markers are very powerful for distinguishing among individuals, most offer little power to distinguish ethnicity or to support any statement about the physical characteristics of an individual. Through a search of the literature and of unpublished data on allele frequencies we have identified a panel of population-specific genetic markers that enable robust ethnic-affiliation estimation for major U.S. resident populations. In this report, we identify these loci and present their levels of allele-frequency differential between ethnically defined samples, and we demonstrate, using log-likelihood analysis, that this panel of markers provides significant statistical power for ethnic-affiliation estimation. In addition to their use in forensic ethnic-affiliation estimation, population-specific genetic markers are very useful in both population- and individual-level admixture estimation and in mapping genes by use of the linkage disequilibrium created when populations hybridize.
A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation (2017)

Proteolysis targeting chimeras (PROTACs) are bispecific molecules containing a target protein binder and an ubiquitin ligase binder connected by a linker. By recruiting an ubiquitin ligase to a target protein, PROTACs promote ubiquitination and proteasomal degradation of the target protein. The generation of effective PROTACs depends on the nature of the protein/ligase ligand pair, linkage site, linker length, and linker composition, all of which have been difficult to address in a systematic way. Herein, we describe a "click chemistry" approach for the synthesis of PROTACs. We demonstrate the utility of this approach with the bromodomain and extraterminal domain-4 (BRD4) ligand JQ-1 (3) and ligase binders targeting cereblon (CRBN) and Von Hippel-Lindau (VHL) proteins. An AlphaScreen proximity assay was used to determine the ability of PROTACs to form the ternary ligase-PROTAC-target protein complex and a MSD assay to measure cellular degradation of the target protein promoted by PROTACs.
Herpesvirus-specific RNA and protein in carcinoma of the uterine cervix. (1982)

Cloned probes of herpes simplex virus type 2 DNA were used in cytological hybridization experiments to detect herpesvirus RNA transcripts in the neoplastic cells of tumors of the uterine cervix. Virus-specific RNA was shown to represent transcription of limited regions of the genome, of which one is known to code for a DNA-binding protein that can be found by immunoperoxidase staining in the neoplastic cells of these tumors and has also been detected in cells transformed in vitro by this virus.
Antigen specificity can be irrelevant to immunocytokine efficacy and biodistribution (2015)

Cytokine therapy can activate potent, sustained antitumor responses, but collateral toxicity often limits dosages. Although antibody-cytokine fusions (immunocytokines) have been designed with the intent to localize cytokine activity, systemic dose-limiting side effects are not fully ameliorated by attempted tumor targeting. Using the s.c. B16F10 melanoma model, we found that a nontoxic dose of IL-2 immunocytokine synergized with tumor-specific antibody to significantly enhance therapeutic outcomes compared with immunocytokine monotherapy, concomitant with increased tumor saturation and intratumoral cytokine responses. Examination of cell subset biodistribution showed that the immunocytokine associated mainly with IL-2R-expressing innate immune cells, with more bound immunocytokine present in systemic organs than the tumor microenvironment. More surprisingly, immunocytokine antigen specificity and Fcγ receptor interactions did not seem necessary for therapeutic efficacy or biodistribution patterns because immunocytokines with irrelevant specificity and/or inactive mutant Fc domains behaved similarly to tumor-specific immunocytokine. IL-2-IL-2R interactions, rather than antibody-antigen targeting, dictated immunocytokine localization; however, the lack of tumor targeting did not preclude successful antibody combination therapy. Mathematical modeling revealed immunocytokine size as another driver of antigen targeting efficiency. This work presents a safe, straightforward strategy for augmenting immunocytokine efficacy by supplementary antibody dosing and explores underappreciated factors that can subvert efforts to purposefully alter cytokine biodistribution.
Role of the casein kinase I isoform, Hrr25, and the cell cycle-regulatory transcription factor, SBF, in the transcriptional response to DNA damage in Saccharomyces cerevisiae (1997)

In the budding yeast, Saccharomyces cerevisiae, DNA damage or ribonucleotide depletion causes the transcriptional induction of an array of genes with known or putative roles in DNA repair. The ATM-like kinase, Mec1, and the serine/threonine protein kinases, Rad53 and Dun1, are required for this transcriptional response. In this paper, we provide evidence suggesting that another kinase, Hrr25, is also involved in the transcriptional response to DNA damage through its interaction with the transcription factor, Swi6. The Swi6 protein interacts with Swi4 to form the SBF complex and with Mbp1 to form the MBF complex. SBF and MBF are required for the G1-specific expression of G1 cyclins and genes required for S-phase. We show that Swi6 associates with and is phosphorylated by Hrr25 in vitro. We find that swi4, swi6, and hrr25 mutants, but not mbp1 mutants, are sensitive to hydroxyurea and the DNA-damaging agent methyl methane-sulfonate and are defective in the transcriptional induction of a subset of DNA damage-inducible genes. Both the sensitivity of swi6 mutants to methyl methanesulfonate and hydroxyurea and the transcriptional defect of hrr25 mutants are rescued by overexpression of SWI4, implicating the SBF complex in the Hrr25/Swi6-dependent response to DNA damage.
Molecular biology and pathogenesis of the human T‐cell leukaemia/lymphotropic virus Type‐1 (HTLV‐1) (2001)

Retroviruses are associated with a variety of diseases, including immunological and neurological disorders, and various forms of cancer. In humans, the Human T-cell Leukaemia/Lymphotropic virus type 1 (HTLV-1), which belongs to the Oncovirus family, is the aetiological agent of two diverse diseases: Adult T-cell leukaemia/lymphoma (ATLL) (Poiesz et al. 1980; Hinuma et al. 1981; Yoshida et al. 1982), as well as the neurological disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (Gessain et al. 1985; Rodgers-Johnson et al. 1985; Osame et al. 1986). HTLV-1 is the only human retrovirus known to be the aetiological agent of cancer. A genetically related virus, HTLV-2, has been identified and isolated (Kalyanaraman et al. 1982). However, there has been no demonstration of a definitive aetiological role for HTLV-2 in human disease to date. Simian T-cell lymphotropic viruses types 1 and 2 (STLV-1 and -2) and bovine leukaemia virus (BLV) have also been classified in same group, Oncoviridae, based upon their similarities in genetic sequence and structure to HTLV-1 and -2 (Burny et al. 1988; Dekaban et al. 1995; Slattery et al. 1999). This article will focus on HTLV-1, reviewing its discovery, molecular biology, and its role in disease pathogenesis.
Bidirectional isotachophoresis on a planar chip with integrated conductivity detection (2002)

The use of a miniaturised planar separation device with integrated conductivity detection for performing bidirectional isotachophoresis (ITP) is described. The chips were produced in poly(methyl methacrylate) (PMMA) using a milling procedure. To enable bidirectional ITP the devices were designed to inject samples into the centre of the section channel and incorporated two integrated on-column conductivity detectors, positioned at opposite ends of this channel. When used with a hydrodynamic sample transport system the devices were used for the analysis of a range of small ions: NH4+; Na+; Mg2+; Ca2+; Li+; NO3-; ClO4-; SO4(2-); F-. Results sucessfully achieved included the simultaneous separation of three anions and three cations.
Multicomponent Quantitative Analysis (1984)

Abstract Reduction in the time required for performing chemical analyses is all-important a s long a s it is not attained by sacrificing required accuracy o r precision. The time for an analysis can be translated into productivity which, in the long run, means money. In analytical laboratories which perform hundreds or even thousands of analyses daily, a time savings of minutes per analysis can be financially rewarding.
Hardwood log bucking and loading efficiency in West Virginia (2007)

The efficiency of bucking and loading central Appalachian hardwood logs was investigated by using a knuckleboom loader together with a sawbuck. Bucked tree stems averaged 15.32 inches in butt diameter with lengths ranging from 19.50 to 106.00 feet. The average number of logs bucked per stem was 3.4 with an average volume of 47.29 board feet (BF) Doyle scale per log. The majority of logs bucked were saw and peeler logs (68%), followed by pulpwood and scragg logs (31%). Hourly bucking production was 4.56 thousand BF per productive machine hour (MBF/PMH) with a unit cost of $14.65/MBF. The loader grappled an average of two logs per turn with an average small-end diameter of 10.50 inches and average length of 9.61 feet. The loading productivity was 7.19 MBF/PMH with a unit cost of $9.29/MBF. Results indicated a typical knuckleboom loader with a sawbuck can be employed efficiently in the region with a typical balanced manual harvesting system or a mechanized harvesting system.
Blockchain based trust & authentication for decentralized sensor networks (2017)

Sensor networks and Wireless Sensor Networks (WSN) are key components for the development of the Internet of Things. These networks are subject of two kinds of constraints. Adaptability by the mean of mutability and evolutivity, and constrained node resources such as energy consumption, computational complexity or memory usage. In this context, none of the existing protocols and models allows reliable peer authentication and trust level management. In the field of virtual economic transactions, Bitcoin has proposed a new decentralized and evolutive way to model and acknowledge trust and data validity in a peer network by the mean of the blockchain. We propose a new security model and its protocol based on the blockchain technology to ensure validity and integrity of cryptographic authentication data and associate peer trust level, from the beginning to the end of the sensor network lifetime.
Attacks on Steganographic Systems (2000)

The majority of steganographic utilities for the camouflage of confidential communication suffers from fundamental weaknesses. On the way to more secure steganographic algorithms, the development of attacks is essential to assess security. We present both visual attacks, making use of the ability of humans to clearly discern between noise and visual patterns, and statistical attacks which are much easier to automate.