gebhart/patrepeval huggingface dataset:
Measurement and Interpretation of Electrokinetic Phenomena (IUPAC Technical Report) (2005)

Abstract In this report, the status quo and recent progress in electrokinetics are reviewed. Practical rules are recommended for performing electrokinetic measurements and interpreting their results in terms of well-defined quantities, the most familiar being the z-potential or electrokinetic potential. This potential is a property of charged interfaces, and it should be independent of the technique used for its determination. However, often the z-potential is not the only property electrokinetically characterizing the electrical state of the interfacial region; the excess conductivity of the stagnant layer is an additional parameter. The requirement to obtain the z-potential is that electrokinetic theories be correctly used and applied within their range of validity. Basic theories and their application ranges are discussed. A thorough description of the main electrokinetic methods is given; special attention is paid to their ranges of applicability as well as to the validity of the underlying theoretical models. Electrokinetic consistency tests are proposed in order to assess the validity of the z-potentials obtained. The recommendations given in the report apply mainly to smooth and homogeneous solid particles and plugs in aqueous systems; some attention is paid to nonaqueous media and less ideal surfaces.
Monitoring of crystallisation phenomena by ultrasound (1999)

Nucleation and crystal growth from solution have been monitored in real time using ultrasound. A stainless steel test cell was designed in which a small volume of hot saturated copper (II) sulphate solution cools and crystallises. The hardware and software developed could be modified for in-line crystallisation monitoring.
Robust schedules and disruption management for job shops (2013)

This dissertation documents the results of research evaluating policies to schedule for unanticipated disruptions in job shops. The disruptions studied in this research are of two types - machine failure and job release-time. The study was conducted using modified classical job shop problems with the minimize maximum completion time (Cmax) objective. Best random non-delay schedules (BRS) provided job sequences for each machine. Different slack policies based on frequency, duration and location of slacks in the schedule were used to strategically insert slack in the BRS schedule. The resulting robust schedules proactively managed machine or job releasetime disruptions. The change in Cmax quantified schedule robustness. Simulation was used to generate and modify the BRS schedules with and without slacks and disruptions, simulate disruption events and evaluate schedule performance. It was observed that policies that equally distribute slack to all tasks on heavily utilized machines and those that equally distribute slack to all tasks on all machines performed best. When the number of jobs to process was more than the number of machines and "big jobs" with long processing times on heavily utilized machines were present, the policy distributing slack tasks equally on heavily utilized machines exhibited superior performance. For systems with less variability both policies performed equally well. By comparing the average, minimum and maximum schedule deviations across all policies, the study concluded that strategically distributing slack to tasks on heavily utilized machines results in good robust schedules that can absorb the effects of disruptions.
Home cleaning-disinfection procedure for tracheal suction catheters (1986)

The cost effectiveness of home care for pediatric tracheostomy patients has become a concern. One major cost component of this care is the tracheal suction catheter. This study was designed to assess the microbiologic effectiveness of a practical cleaning-disinfection procedure, consisting of hydrogen peroxide, 100 degrees C soapy water and 100 degrees C rinse water, which might permit reuse of tracheal suction catheters in the home setting. The procedure was found to be highly effective, completely eliminating bacterial growth from more than 90% of catheters seeded with Staphylococcus aureus or Pseudomonas aeruginosa in the laboratory. Further, studies with catheters used for suctioning patients in the Pediatric Intensive Care Unit confirmed the eradication of all bacterial organisms.
Integration of heterogeneous databases without common domains using queries based on textual similarity (1998)

Most databases contain “name constants” like course numbers, personal names, and place names that correspond to entities in the real world. Previous work in integration of heterogeneous databases has assumed that local name constants can be mapped into an appropriate global domain by normalization. However, in many cases, this assumption does not hold; determining if two name constants should be considered identical can require detailed knowledge of the world, the purpose of the user's query, or both. In this paper, we reject the assumption that global domains can be easily constructed, and assume instead that the names are given in natural language text. We then propose a logic called WHIRL which reasons explicitly about the similarity of local names, as measured using the vector-space model commonly adopted in statistical information retrieval. We describe an efficient implementation of WHIRL and evaluate it experimentally on data extracted from the World Wide Web. We show that WHIRL is much faster than naive inference methods, even for short queries. We also show that inferences made by WHIRL are surprisingly accurate, equaling the accuracy of hand-coded normalization routines on one benchmark problem, and outperforming exact matching with a plausible global domain on a second.
Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons. (1998)

IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-alpha2a and IFN-alpha2b were approved for the treatment of hairy cell leukemia just 11 years ago. Today, alpha-IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases. Although the exact mechanism of action of IFN-alpha in the treatment of such diseases is not fully understood, many advances have been made in the characterization of the physicochemical and diverse biological properties of this highly pleiotropic cytokine. Here we review recent developments in our understanding of the antiviral and immunoregulatory properties of IFN-alpha, the nature of the multisubunit IFN-alpha receptor, and the molecular mechanisms of signal transduction. Where available, we have included comparative data on recombinant alpha-IFNs derived from both naturally occurring and nonnaturally occurring synthetic genes. We also review clinical data and data on the side effects and antigenicity of different sources of recombinant alpha-IFNs in humans. These latter topics are of clinical interest, because they may potentially affect the efficacy of these various products. Hopefully, what is already known about IFN will prompt further exploration into the mechanism(s) of action of IFN-alpha and thus deliver new applications for this prototypic cytokine, whose full therapeutic potential is yet to be realized.
Isosterism and bioisosterism in drug design (1991)

In every scientific undertaking that is to break new ground, one has to have a goal, a working hypothesis, or a leading idea or fact. This will encourage research and help in the pursuit of a worth-while objective, be it the enrichment of knowledge or the elaboration of a practical purpose. A medicinal scientist who hopes to find a new biologically active drug will have to be guided by such considerations.
Stanniocalcin 1 Alters Muscle and Bone Structure and Function in Transgenic Mice (2002)

Fish stanniocalcin (STC) inhibits uptake of calcium and stimulates phosphate reabsorption. To determine the role of the highly homologous mammalian protein, STC-1, we created and characterized transgenic mice that express STC-1 under control of a muscle-specific promoter. STC-1 transgenic mice were smaller than wild-type littermates and had normal growth plate cartilage morphology but increased cartilage matrix synthesis. In STC-1 mice, the rate of bone formation, but not bone mineralization, was decreased. Increased cortical bone thickness and changes in trabeculae number, density, and thickness in STC-1 mice indicated a concomitant suppression of osteoclast activity, which was supported by microcomputed tomography analyses and histochemistry. Skeletal muscles were disproportionately small and showed altered function and response to injury in STC-1 mice. Electron microscopy indicated that muscle mitochondria were dramatically enlarged in STC-1 mice. These changes in STC-1 mice could not be explained by deficits in blood vessel formation, as vascularity in organs and skeletal tissues was increased as was induction of vascularity in response to femoral artery ligation. Our results indicate that STC-1 can affect calcium homeostasis, bone and muscle mass and structure, and angiogenesis through effects on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells.
Arrest of Motor Neuron Disease in wobbler Mice Cotreated with CNTF and BDNF (1994)

Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) each promote the survival and differentiation of developing motor neurons, but do so through distinct cellular signaling pathways. Administration of either factor alone has been shown to slow, but not to arrest, progression of motor neuron dysfunction in wobbler mice, an animal model of motor neuron disease. Because CNTF and BDNF are known to synergize in vitro and in ovo, the efficacy of CNTF and BDNF cotreatment was tested in the same animal mode. Subcutaneous injection of the two factors on alternate days was found to arrest disease progression in wobbler mice for 1 month, as measured by several behavioral, physiological, and histological criteria.
Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. (1983)

We wished to construct cell lines that supply the gene products of gag, pol, and env for the growth of replication-defective reticuloendotheliosis retrovirus vectors without production of the helper virus. To do this, first we located by S1 mapping the donor and acceptor splice sites of reticuloendotheliosis virus strain A. The donor splice site is ca. 850 base pairs from the 5' end of proviral DNA. It is close to or overlaps the encapsidation sequences for viral RNA. The splice acceptor site is ca. 5.6 kilobase pairs from the 5' end of proviral DNA. Therefore, the encapsidation sequences and the donor splice site were removed from viral DNA to give expression of the gag and pol genes without virus production. The promoter in the long terminal repeat was fused to a site near the first ATG codon of the env gene, thereby deleting the encapsidation sequences and the gag and pol genes to give expression of the env gene without virus production. The permissive canine cell line D17 was transfected with the two modified viral DNAs. Two cell clones that contain both modified viral DNAs support the production of replication-defective spleen necrosis virus-thymidine kinase recombinant retrovirus vectors without the production of helper virus. To prevent recombination, the vector contains deletions that overlap with deletions in the integrated helper virus DNAs. This helper cell-vector system will be useful to derive infectious recombinant virus stocks of high titer (over 10(5) thymidine kinase transforming units per ml) which are able to infect avian, rat, and dog cells without the aid of helper virus.
Prospects for gene therapy of familial hypercholesterolemia. (1990)

Familial hypercholesterolemia is an inherited disease in humans that is caused by a deficiency in the receptor that mediates the internalization and degradation of low density lipoprotein. Patients that inherit two abnormal low density lipoprotein receptor alleles have severe hypercholesterolemia, advanced atherosclerosis, and life-threatening coronary artery disease that is refractory to conventional therapies. In this review, we discuss the prospects for gene therapy in the treatment of familial hypercholesterolemia.
Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma (2012)

We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.
Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein transferases. (1991)

Farnesyl-protein transferase (FTase) purified from rat or bovine brain is an alpha/beta heterodimer, comprised of subunits having relative molecular masses of approximately 47 (alpha) and 45 kDa (beta). In the yeast Saccharomyces cerevisiae, two unlinked genes, RAM1/DPR1 (RAM1) and RAM2, are required for FTase activity. To explore the relationship between the mammalian and yeast enzymes, we initiated cloning and immunological analyses. cDNA clones encoding the 329-amino acid COOH-terminal domain of bovine FTase alpha-subunit were isolated. Comparison of the amino acid sequences deduced from the alpha-subunit cDNA and the RAM2 gene revealed 30% identity and 58% similarity, suggesting that the RAM2 gene product encodes a subunit for the yeast FTase analogous to the bovine FTase alpha-subunit. Antisera raised against the RAM1 gene product reacted specifically with the beta-subunit of bovine FTase, suggesting that the RAM1 gene product is analogous to the bovine FTase beta-subunit. Whereas a ram1 mutation specifically inhibits FTase, mutations in the CDC43 and BET2 genes, both of which are homologous to RAM1, specifically inhibit geranylgeranyl-protein transferase (GGTase) type I and GGTase-II, respectively. In contrast, a ram2 mutation impairs both FTase and GGTase-I, but has little effect on GGTase-II. Antisera that specifically recognized the bovine FTase alpha-subunit precipitated both bovine FTase and GGTase-I activity, but not GGTase-II activity. Together, these results indicate that for both yeast and mammalian cells, FTase, GGTase-I, and GGTase-II are comprised of different but homologous beta-subunits and that the alpha-subunits of FTase and GGTase-I share common features not shared by GGTase-II.
Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation (2015)

Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-β and -α4. The TRIF signaling pathway, downstream of both of these TLRs, also leads to DC maturation, and it has been proposed that the type I IFNs act in cis to induce DC maturation and subsequent effects on adaptive immunity. The present study was designed to understand the molecular mechanisms of TRIF-mediated DC maturation. We have discovered that TLR4-TRIF-induced DC maturation was independent of both IRF3 and type I IFNs. In contrast, TLR3-mediated DC maturation was completely dependent on type I IFN feedback. We found that differential activation of mitogen-activated protein kinases by the TLR4- and TLR3-TRIF axes determined the type I IFN dependency for DC maturation. In addition, we found that the adjuvanticity of LPS to induce T-cell activation is completely independent of type I IFNs. The important distinction between the TRIF-mediated signaling pathways of TLR4 and TLR3 discovered here could have a major impact in the design of future adjuvants that target this pathway.
Mouse hematopoietic stem cell identification and analysis (2008)

Hematopoietic stem cells (HSCs) remain by far the most well-characterized adult stem cell population both in terms of markers for purification and assays to assess functional potential. However, despite over 40 years of research, working with HSCs in the mouse remains difficult because of the relative abundance (or lack thereof) of these cells in the bone marrow. The frequency of HSCs in bone marrow is about 0.01% of total nucleated cells and approximately 5,000 can be isolated from an individual mouse depending on the age, sex, and strain of mice as well as purification scheme utilized. This prohibits the study of processes in HSCs, which require large amounts of starting material. Adding to the challenge is the continual reporting of new markers for HSC purification, which makes it difficult for the uninitiated in the field to know which purification strategies yield the highest proportion of long-term, multilineage HSCs. This report will review different hematopoietic stem and progenitor purification strategies and compare flow cytometry profiles for HSC sorting and analysis on different instruments. We will also discuss methods for rapid flow cytometric analysis of peripheral blood cell types, and novel strategies for working with rare cell populations such as HSCs in the analysis of cell cycle status by BrdU, Ki-67, and Pyronin Y staining. The purpose of this review is to provide insight into some of the recent experimental and technical advances in mouse hematopoietic stem cell biology.
Bile acids: regulation of synthesis (2009)

Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and energy metabolism. The enterohepatic circulation of bile acids exerts important physiological functions not only in feedback inhibition of bile acid synthesis but also in control of whole-body lipid homeostasis. In the liver, bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces an atypical nuclear receptor small heterodimer partner, which subsequently inhibits nuclear receptors, liver-related homolog-1, and hepatocyte nuclear factor 4alpha and results in inhibiting transcription of the critical regulatory gene in bile acid synthesis, cholesterol 7alpha-hydroxylase (CYP7A1). In the intestine, FXR induces an intestinal hormone, fibroblast growth factor 15 (FGF15; or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signaling to inhibit bile acid synthesis. However, the mechanism by which FXR/FGF19/FGFR4 signaling inhibits CYP7A1 remains unknown. Bile acids are able to induce FGF19 in human hepatocytes, and the FGF19 autocrine pathway may exist in the human livers. Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome.
Reactions of Mental Health Social Workers following a Client Suicide Completion: A Qualitative Investigation (2005)

The impact of client suicidal behavior on mental health social workers is slowly receiving increased empirical attention. This qualitative study examined the impact of client suicide on social workers. Results indicate that social workers experience multiple personal and professional reactions immediately following a client suicide completion. Long-term effects, such as the continual experience of emotional reactions and permanent behavior changes, including changing practice strategies, are also reported. The results of this study have significant implications for the preparation of social workers and other mental health therapists for practice with suicidal clients.
Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety (2018)

Bispecific molecules redirecting the cytotoxicity of T-cells are a growing class of therapeutics with numerous molecules being tested in clinical trials. However, it has been a long way since the proof of concept studies in the mid 1980's. In the process we have learnt about the impact of different variables related to the bispecific molecule and the target antigen on the potency of this type of drugs. This work reviews the insights gained and how that knowledge has been used to design more potent bispecific T-cell engagers. The more recent advancement of antibodies with this modality into safety studies in non-human primates and as well as in clinical studies has revealed potential toxicity liabilities for the mode of action. Modifications in existing antibody formats and new experimental molecules designed to mitigate these problems are discussed.
Confidence Intervals for Microbial Density Using Serial Dilutions with MPN Estimates (1996)

Abstract An alteration to Woodward's methods is recommended for deriving a 1 — α confidence interval for microbial density using serial dilutions with most‐probable‐number (MPN) estimates. Outcomes of the serial dilution test are ordered by their MPNs. A lower limit for the confidence interval corresponding to an outcome y is the density for which y and all higher ordered outcomes have total probability α/2. An upper limit is derived in the analogous way. An alteration increases the lowest lower limits and decreases the highest upper limits. For comparison, a method that is optimal in the sense of null hypothesis rejection is described. This method ranks outcomes dependent upon the microbial density in question, using proportional first derivatives of the probabilities. These and currently used methods are compared. The recommended method is shown to be more desirable in certain respects, although resulting in slightly wider confidence intervals than De Man's (1983) method.
Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors (1995)

The mechanism of inhibition of HIV-1 reverse transcriptase by three nonnucleoside inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the nucleotide-induced conformational change. Rather, in the presence of saturating concentrations of the inhibitors, the nucleoside triphosphate bound tightly (Kd, 100 nM), but nonproductively. The data suggest that an inhibitor combining the functionalities of a nonnucleoside inhibitor and a nucleotide analog could bind very tightly and specifically to reverse transcriptase and could be effective in the treatment of AIDS.