gebhart/patrepeval huggingface dataset:
Recombinant Acyl-CoA:cholesterol Acyltransferase-1 (ACAT-1) Purified to Essential Homogeneity Utilizes Cholesterol in Mixed Micelles or in Vesicles in a Highly Cooperative Manner (1998)

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an integral membrane protein located in the endoplasmic reticulum. It catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acyl coenzyme A. The first gene encoding the enzyme, designated as ACAT-1, was identified in 1993 through an expression cloning approach. We isolated a Chinese hamster ovary cell line that stably expresses the recombinant human ACAT-1 protein bearing an N-terminal hexahistidine tag. We purified this enzyme approximately 7000-fold from crude cell extracts by first solubilizing the cell membranes with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, then proceeding with an ACAT-1 monoclonal antibody affinity column and an immobilized metal affinity column. The final preparation is enzymologically active and migrates as a single band at 54 kDa on SDS-polyacrylamide gel electrophoresis. Pure ACAT-1 dispersed in mixed micelles containing sodium taurocholate, phosphatidylcholine, and cholesterol remains catalytically active. The cholesterol substrate saturation curves of the enzyme assayed either in mixed micelles or in reconstituted vesicles are both highly sigmoidal. The oleoyl-coenzyme A substrate saturation curves of the enzyme assayed under the same conditions are both hyperbolic. These results support the hypothesis that ACAT is an allosteric enzyme regulated by cholesterol.
Focal Adhesions: Transmembrane Junctions Between the Extracellular Matrix and the Cytoskeleton (1988)

Many cells grown in tissue culture adhere tightly to the underlying substrate through discrete regions of the plasma membrane, referred to as adhesion plaques, focal contacts, or focal adhesions. In these regions where the surface of the cell comes closest to the substrate, the plasma membrane is specialized at its cytoplasmic face for anchoring stress fibers, the large bundles of microfilaments that are prominent in many cultured cells. In this review we discuss the composition and organization of focal adhesions. Many of their characteristics indicate that they are structurally and functionally equivalent to the adhesions made by many cells to the extracellular matrix (ECM) in vivo. We also consider the regulatory proteins that have been identified in focal adhesions since these regions are interesting not only as models for studying the links between the extracellular matrix and the cytoskeleton, but also as sites of transmembrane communication between the extracellular environment and the cytoplasm. Many features of focal adhesions, some of which are not considered here, have been reviewed previously (Burridge 1986; Woods and Couchman 1988).
Spin transfer switching current reduction in magnetic tunnel junction based dual spin filter structures (2005)

Spin-transfer-driven magnetization switching was studied in single magnetic tunneling junctions (MTJ: Ta∕PtMn∕CoFe∕Ru∕CoFeB∕Al2O3∕CoFeB∕Ta) and dual spin filters (DSF: Ta∕PtMn∕CoFe∕Ru∕CoFeB∕Al2O3∕CoFeB∕spacer∕CoFe∕PtMn∕Ta) having resistance-area (RA) product in the range of 10–30Ωμm2 and tunnel magnetoresistance (TMR) of 15%–30%. The intrinsic critical current density (Jc0) was estimated by extrapolating experimentally obtained critical current density (Jc) versus pulse width (τ) data to a pulse width of 1ns. Jc, extrapolated to τ of 1ns (∼Jc0), was 7×106 and 2.2×106A∕cm2, respectively, for the MTJ and improved DSF samples having identical free layers. Thus, a significant enhancement of the spin transfer switching efficiency is seen for DSF structures compared to the single MTJ case.
Controlling Elements and the Gene (1956)

In a recent brief review (McClintock, 1956), a description was given of types of elements carried in the maize chromosomes that serve to control gene action and to induce, at the site of the gene, heritable modifications affecting this action. These elements were initially discovered because they do not remain at one position in the chromosome complement. They can appear at new locations and disappear from previously determined locations. The presence of one such element at or near the locus of a known gene may affect the action of this gene. In so doing, it need not alter the action potentials of the genic substances at the locus. Therefore, these elements were called controlling elements. It was also shown that controlling elements fall into groups, the members of each operating as an integrated system in the control of gene action.
A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. (1995)

Construction of a bispecific single-chain antibody derivative is described that consists of two different single-chain Fv fragments joined through a Gly-Ser linker. One specificity of the two Fv fragments is directed against the CD3 antigen of human T cells and the other is directed against the epithelial 17-1A antigen; the latter had been found in a clinical trial to be a suitable target for antibody therapy of minimal residual colorectal cancer. The construct could be expressed in CHO cells as a fully functional protein, while its periplasmic expression in Escherichia coli resulted in a nonfunctional protein only. The antigen-binding properties of the bispecific single-chain antibody are indistinguishable from those of the corresponding univalent single-chain Fv fragments. By redirecting human peripheral T lymphocytes against 17-1A-positive tumor cells, the bispecific antibody proved to be highly cytotoxic at nanomolar concentrations as demonstrated by 51Cr release assay on various cell lines. The described bispecific construct has a molecular mass of 60 kDa and can be easily purified by its C-terminal histidine tail on a Ni-NTA chromatography column. As bispecific antibodies have already been shown to be effective in vivo in experimental tumor systems as well as in phase-one clinical trials, the small CD3/17-1A-bispecific antibody may be more efficacious than intact antibodies against minimal residual cancer cells.
PROGRESS IN SURFACE TREATMENTS OF ULTRAHIGH MOLECULAR WEIGHT POLYETHYLENE FIBER (2002)

In this paper various surface treatments of UHMWPE fibers were introduced in detail, such as plasma, corona charge and chemical reagents oxygenate. The mechanisms of all treatments were discussed separately. After treatment, interfacial bonding strength and mechanical properties of UHMWPE fibers reinforced resin composites were improved obviously. New progress was mentioned especially in the recent years.
Fundamental Bounds and Approaches to Sequence Reconstruction from Nanopore Sequencers (2016)

Nanopore sequencers are emerging as promising new platforms for high-throughput sequencing. As with other technologies, sequencer errors pose a major challenge for their effective use. In this paper, we present a novel information theoretic analysis of the impact of insertion-deletion (indel) errors in nanopore sequencers. In particular, we consider the following problems: (i) for given indel error characteristics and rate, what is the probability of accurate reconstruction as a function of sequence length; (ii) what is the number of `typical' sequences within the distortion bound induced by indel errors; (iii) using replicated extrusion (the process of passing a DNA strand through the nanopore), what is the number of replicas needed to reduce the distortion bound so that only one typical sequence exists within the distortion bound. Our results provide a number of important insights: (i) the maximum length of a sequence that can be accurately reconstructed in the presence of indel and substitution errors is relatively small; (ii) the number of typical sequences within the distortion bound is large; and (iii) replicated extrusion is an effective technique for unique reconstruction. In particular, we show that the number of replicas is a slow function (logarithmic) of sequence length -- implying that through replicated extrusion, we can sequence large reads using nanopore sequencers. Our model considers indel and substitution errors separately. In this sense, it can be viewed as providing (tight) bounds on reconstruction lengths and repetitions for accurate reconstruction when the two error modes are considered in a single model.
MAPKAP kinase 2‐deficiency prevents neurons from cell death by reducing neuroinflammation – relevance in a mouse model of Parkinson’s disease (2008)

The inflammatory response in the brain is closely associated with the pathogenesis of degenerative neurological disorders. A role for the p38 stress-activated protein kinase/MAPK-activated protein kinase 2 (MK2) axis in inflammation and apoptosis is well documented. Here, we provide evidence that neurodegeneration can be prevented by eliminating MK2. In primary mesencephalic neuron-glia co-cultures dopaminergic neurons from MK2-deficient (MK2-/-) mice were significantly more resistant to lipopolysaccharide-induced neurotoxicity compared with cells from wild-type mice. This neuroprotection in MK2-deficient cultures was associated with a reduced inflammatory response, especially with reduced production of the inflammatory mediators tumor necrosis factor alpha, keratinocyte-derived chemokine, interleukin-6, and nitric oxide (NO). Interestingly, in primary neuron-enriched cell cultures p38 MAPK, but not MK2, also participates in NO-mediated neuronal cell death. In the MPTP mouse model for Parkinson's disease, MK2-deficient mice show a reduced neuroinflammation and less degeneration of dopaminergic neurons in the substantia nigra after MPTP lesion compared with wild-type mice. In conclusion, our results reveal that MK2 does not directly participate in neuronal cell death, but indirectly contributes to neurodegeneration by the production of neurotoxic substances, such as NO or tumor necrosis factor alpha, from activated glia cells.
Effect of High‐Dose Acyclovir on Survival in Allogeneic Marrow Transplant Recipients Who Received Ganciclovir at Engraftment or for Cytomegalovirus pp65 Antigenemia (1998)

This study sought to determine whether high-dose acyclovir improves posttransplant survival in cytomegalovirus (CMV)-seropositive patients when ganciclovir is given for prophylaxis or as early therapy. Three groups were studied: Group 1 (n = 112) received ganciclovir from engraftment without prior acyclovir treatment, group 2 (n = 114) was given ganciclovir for CMV pp65 antigenemia without prior acyclovir, and group 3 (n = 133) received ganciclovir at engraftment with prior intravenous acyclovir (500 mg/m2 every 8 h) from day 5 before transplant until engraftment. In a multivariable Cox model, there was no significant difference in the adjusted risk of transplant survival between the groups during the first 2 years after transplant (relative risk for mortality: group 1, 1.0; group 2, 0.75 (95% confidence interval [CI], 0.52-1.1); group 3, 1.04 (95% CI, 0.74-1.47). The incidence of CMV disease and CMV-related mortality was not significantly different between the groups. Thus, high-dose acyclovir does not appear to improve survival when ganciclovir is given either at engraftment or for CMV pp65 antigenemia.
Embryonic Lethality and Tumorigenesis Caused by Segmental Aneuploidy on Mouse Chromosome 11 (1998)

Chromosome engineering in mice enables the construction of models of human chromosomal diseases and provides key reagents for genetic studies. To begin to define functional information for a small portion of chromosome 11, deficiencies, duplications, and inversions were constructed in embryonic stem cells with sizes ranging from 1 Mb to 22 cM. Two deficiencies and three duplications were established in the mouse germline. Mice with a 1-Mb duplication developed corneal hyperplasia and thymic tumors, while two different 3- to 4-cM deficiencies were embryonically lethal in heterozygous mice. A duplication corresponding to one of these two deficiencies was able to rescue its haplolethality.
Gemcitabine Selectively Eliminates Splenic Gr-1+/CD11b+ Myeloid Suppressor Cells in Tumor-Bearing Animals and Enhances Antitumor Immune Activity (2005)

These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.
C1-Tetrahydrofolate synthase from rabbit liver. Structural and kinetic properties of the enzyme and its two domains. (1985)

C1-Tetrahydrofolate synthase is a multifunctional enzyme which catalyzes three reactions in 1-carbon metabolism: 10-formyltetrahydrofolate synthetase; 5,10-methenyltetrahydrofolate cyclohydrolase; 5,10-methylenetetrahydrofolate dehydrogenase. A rapid 1-day purification procedure has been developed which gives 40 mg of pure enzyme from 10 rabbit livers. The 10-formyltetrahydrofolate synthetase activity of this trifunctional enzyme has a specific activity that is 4-fold higher than the enzyme previously purified from rabbit liver. Conditions have been developed for the rapid isolation of a tryptic fragment of the enzyme which contains the methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. This fragment is a monomer exhibiting a subunit and native molecular weight of 36,000 in most buffers. However, in phosphate buffers the native molecular weight suggests that the fragment is a dimer. Conditions are also given whereby chymotryptic digestion allows the simultaneous isolation from the native enzyme of a large fragment containing the 10-formyltetrahydrofolate synthetase activity and a smaller fragment containing the dehydrogenase and cyclohydrolase activities. The large fragment is a dimer with a subunit molecular weight of 66,000. The small fragment retains all of the dehydrogenase and cyclohydrolase activities of the native enzyme. The large fragment is unstable but retains most of the 10-formyltetrahydrofolate synthetase activity. Km values of substrates for the two fragments are the same as the values for the native enzyme. The 10-formyltetrahydrofolate synthetase activity of the native enzyme requires ammonium or potassium ions for expression of full catalytic activity. The effect of these two ions on the catalytic activity of the large chymotryptic fragment is the same as with the native enzyme. We have shown by differential scanning calorimetry that the native enzyme contains two protein domains which show thermal transitions at 47 and 60 degrees C. Evidence is presented that the two domains are related to the two protein fragments generated by proteolysis of the native enzyme. The larger of the two domains contains the active site for the 10-formyltetrahydrofolate synthetase activity while the smaller domain contains the active site which catalyzes the dehydrogenase and cyclohydrolase reactions. Replacement of sodium ion buffers with either ammonium or potassium ions results in an increase in stability of the large domain of the native enzyme. This change in stability is not accompanied by a change in the quaternary structure of the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)
Oxidative stress‐induced cataract: mechanism of action (1995)

This review examines the hypothesis that oxidative stress is an initiating factor for the development of maturity onset cataract and describes the events leading to lens opacification. Data are reviewed that indicate that extensive oxidation of lens protein and lipid is associated with human cataract found in older individuals whereas little oxidation (and only in membrane components) is found in control subjects of similar age. A significant proportion of lenses and aqueous humor taken from cataract patients have elevated H2O2 levels. Because H2O2, at concentrations found in cataract, can cause lens opacification and produces a pattern of oxidation similar to that found in cataract, it is concluded that H2O2 is the major oxidant involved in cataract formation. This viewpoint is further supported by experiments showing that cataract formation in organ culture caused by photochemically generated superoxide radical, H2O2, and hydroxyl radical is completely prevented by the addition of a GSH peroxidase mimic. The damage caused by oxidative stress does not appear to be reversible and there is an inverse relationship between the stress period and the time required for loss of transparency and degeneration of biochemical parameters such as ATP, GPD, nonprotein thiol, and hydration. After exposure to oxidative stress, the redox set point of the single layer of the lens epithelial cells (but not the remainder of the lens) quickly changes, going from a strongly reducing to an oxidizing environment. Almost concurrent with this change is extensive damage to DNA and membrane pump systems, followed by loss of epithelial cell viability and death by necrotic and apoptotic mechanisms. The data suggest that the epithelial cell layer is the initial site of attack by oxidative stress and that involvement of the lens fibers follows, leading to cortical cataract.
Telomere length and body temperature—independent determinants of mammalian longevity? (2013)

OPINION article Front. Genet., 13 June 2013Sec. Genetics of Aging https://doi.org/10.3389/fgene.2013.00111
Troubleshooting multihop wireless networks (2005)

Effective network troubleshooting is critical for maintaining efficient and reliable network operation. Troubleshooting is especially challenging in multihop wireless networks because the behavior of such networks depends on complicated interactions between many unpredictable factors such as RF noise, signal propagation, node interference, and traffic flows. In this paper we propose a new direction for research on fault diagnosis in wireless networks. Specifically, we present a diagnostic system that employs trace-driven simulations to detect faults and perform root cause analysis. We apply this approach to diagnose performance problems caused by packet dropping, link congestion, external noise, and MAC misbehavior. In a 25 node multihop wireless network, we are able to diagnose over 10 simultaneous faults of multiple types with more than 80% coverage. Our framework is general enough for a wide variety of wireless and wired networks.
Adipose Tissue‐Derived Plasminogen Activator Inhibitor‐1 Function and Regulation (2016)

Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner. Adipocyte-derived PAI-1, predominantly expressed in visceral fat, is released into the circulation in parallel with increased fat mass, and it functions as a crucial adipokine that negatively affects physiological metabolism and vascular biology. Elevated PAI-1 levels induce insulin resistance and metabolic abnormalities during proinflammatory processes involving several cytokines and chemokines in diabetes. Several studies have indicated that PAI-1 plays crucial roles in insulin actions on liver, muscle, and fat. Accumulated fat and enhanced adipose tissue-derived PAI-1 influence metabolism and vessels in relation to macrophage infiltration, chronic inflammation, and free fatty acid release in obese states. PAI-1-induced fibrinolysis abnormalities are associated with metabolic syndrome, leading to cardiovascular disease through dysregulated vascular coagulation, endothelial dysfunction, and metabolic abnormalities. Adipose tissue-derived PAI-1 is involved in insulin resistance, osteoporosis, and sarcopenia induced by glucocorticoid excess in mice. Moreover, PAI-1 is involved in the other pathological states, such as nonalcoholic fatty liver disease, and cancer. As such, PAI-1 may be exploited as a marker of disease activity as well being a target for clinical drug development. © 2016 American Physiological Society. Compr Physiol 6:1873-1896, 2016.
Application of Poly(oxyethylene) Homopolymers in Sustained Release Solid Formulations (1995)

Water soluble poly(oxyethylene) homopolymers, with molecular mass ranging from four hundred thousand to four million, were used as carriers to generate, by direct compression techniques, sustained release matrix tablets of both water-soluble and insoluble bioactive agents. Dissolution studies showed that the release kinetics of the tablets depends upon the solubility and molecular mass of polymer, solubility of drug, and the ratio of the drug to polymer in the tablets. Following drug release, the tablet components dissolved leaving behind no residue, or “ghost”, as is commonly observed with wax-based systems.
Clonal characterization of bone marrow derived stem cells and their application for bone regeneration (2010)

Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate single- cell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homo- geneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo
Comparative assessment of CDS, CLSI disc diffusion and Etest techniques for antimicrobial susceptibility testing ofNeisseria gonorrhoeae: a 6-year study (2012)

The CDS technique is an attractive alternative for N. gonorrhoeae susceptibility testing and is recommended for monitoring the antimicrobial susceptibility in less developed and resource-poor settings to facilitate enhanced antimicrobial resistance surveillance when the WHO Gonococcal Antimicrobial Surveillance Programme is undergoing expansion to meet the ongoing challenges of surveillance and control of gonococcal antimicrobial resistance.