gebhart/patrepeval huggingface dataset:
Granulocyte colony‐stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils (2005)

The granulocyte colony-stimulating factor (G-CSF) promotes angiogenesis. However, the exact mechanism is not known. We demonstrate that vascular endothelial growth factor (VEGF) was released by Gr-1+CD11b- neutrophils but not Gr-1-CD11b+ monocytes prestimulated with G-CSF in vitro and in vivo. Similarly, in vivo, concomitant with an increase in neutrophil numbers in circulation, G-CSF augmented plasma VEGF level in vivo. Local G-CSF administration into ischemic tissue increased capillary density and provided a functional vasculature and contributed to neovascularization of ischemic tissue. Blockade of the VEGF pathway abrogated G-CSF-induced angiogenesis. On the other hand, as we had shown previously, VEGF can induce endothelial progenitor cell (EPC) mobilization. Here, we show that G-CSF also augmented the number of circulating VEGF receptor-2 (VEGFR2) EPCs as compared with untreated controls. Blocking the VEGF/VEGFR1, but to a much lesser extent, the VEGF/VEGFR2 pathway in G-CSF-treated animals delayed tissue revascularization in a hindlimb model. These data clearly show that G-CSF modulates angiogenesis by increasing myelomonocytic cells (VEGFR1+ neutrophils) and their release of VEGF. Our results indicated that administration of G-CSF into ischemic tissue provides a novel and safe therapeutic strategy to improve neovascularization.
UGA Read-Through Artifacts—When Popular Gene Expression Systems Need a pATCH (1998)

pET and similar vectors are widely used for efficient gene expression in Escherichia coli and subsequent protein purification, often by means of a C-terminal histidine (His) tag. We found that the TGA translation termination signal following the His-tag sequence in pET constructs gives rise to a significant fraction of read-through protein extended by 21 amino acids. Mass spectrometry indicated that tryptophan is inserted at the UGA (opal) stop codon in the examined non-opal suppressor strains; no evidence for translational frameshifting was detected. We have shown that the problem of obtaining heterogeneous protein preparations can easily be corrected. Plasmid pATCH1 provides a replacement sequence for the inefficient stop signal and can be used to repair both pET vectors and existing pET-based expression constructs. Our observation illustrates the largely ignored fact that a UGA codon is the worst choice for proper translation termination in efficient overexpression vectors.
A Simple Severity of Disease Index for Systemic Lupus Erythematosus (1993)

Although indices of activity for systemic lupus erythematosus have been developed and validated, a disease staging system requires the measurement of severity as well. We have constructed such a scale, the Lupus Severity of Disease Index (Lupus SDI). Accepted clinical, pathologic and physiologic classification schemes were employed to validate this index at two separate research institutions. The Lupus SDI allows homogenization of patient populations for the purposes of research and, possibly, for case mix adjustment.
Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate (1998)

Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.
Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro (2017)

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. The inhibition of tau aggregation is considered to be one of the important strategies for treating these neurodegenerative diseases. Curcumin, a natural polyphenolic molecule, has been reported to have neuroprotective ability. In this work, curcumin was found to bind to adult tau and fetal tau with a dissociation constant of 3.3±0.4 and 8±1 μM, respectively. Molecular docking studies indicated a putative binding site of curcumin in the microtubule-binding region of tau. Using several complementary techniques, including dynamic light scattering, thioflavin S fluorescence, 90° light scattering, electron microscopy, and atomic force microscopy, curcumin was found to inhibit the aggregation of tau. The dynamic light scattering analysis and atomic force microscopic images revealed that curcumin inhibits the oligomerization of tau. Curcumin also disintegrated preformed tau oligomers. Using Far-UV circular dichroism, curcumin was found to inhibit the β-sheets formation in tau indicating that curcumin inhibits an initial step of tau aggregation. In addition, curcumin inhibited tau fibril formation. Furthermore, the effect of curcumin on the preformed tau filaments was analyzed by atomic force microscopy, transmission electron microscopy, and 90° light scattering. Curcumin treatment disintegrated preformed tau filaments. The results indicated that curcumin inhibited the oligomerization of tau and could disaggregate tau filaments.
Nanostructured Lithium Nickel Manganese Oxides for Lithium-Ion Batteries (2010)

Nanostructured lithium nickel manganese oxides were investigated as advanced positive electrode materials for lithium-ion batteries designated to power plug-in hybrid electric vehicles and all-electric vehicles. The investigation included material characterization and electrochemical testing. In cell tests, the Li(1.375)Ni(0.25)Mn(0.75)O(2.4375) composition achieved high capacity (210 mAh g(-1)) at an elevated rate (230 mA g(-1)), which makes this material a promising candidate for high energy density Li-ion batteries, as does its being cobalt-free and uncoated. The material has spherical morphology with nanoprimary particles embedded in micrometer-sized secondary particles, possesses a multiphase character (spinel and layered), and exhibits a high packing density (over 2 g cm(-3)) that is essential for the design of high energy density positive electrodes. When combined with the Li(4)Ti(5)O(12) stable anode, the cell showed a capacity of 225 mAh g(-1) at the C/3 rate (73 mA g(-1)) with no capacity fading for 200 cycles. Other chemical compositions, Li((1+x))Ni(0.25)Mn(0.75)O((2.25+x/2)) (0.32 &lt; x &lt; 0.65), were also studied, and the relationships among their structural, morphological, and electrochemical properties are reported.
Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study. (1990)

Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection.
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma (2003)

Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.
Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer (2011)

Recently, a subset of IL-17 producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In this study, we investigated the expression level of IL-17 and T helper 17 (Th17)-related cytokines in gastric cancer tissues and assessed the association of their expression with angiogenesis and their clinicopathological parameters. Tumor and adjacent normal tissues were obtained from 82 patients with gastric cancer. IL-17, IL-21 and IL-23 mRNA expression levels were quantified by real-time RT-PCR. Th17 infiltration, microvessel density and neutrophil infiltration in tumor tissues were examined by immunohistochemistry and double immunofluorescence histochemistry. Expression of IL-17, IL-21 and IL-23 mRNA was found to be significantly up-regulated in tumor tissues compared with adjacent normal tissues. The expression level of IL-17 mRNA strongly and positively correlated with that of IL-21 mRNA in tumor tissue. The number of vascular endothelial cells and infiltrating neutrophils was significantly larger in tumors expressing a high level of IL-17 mRNA than in tumors expressing a low level of IL-17 mRNA. In tumor tissues most CD4+ cells were stained with anti-IL-17 antibody. The expression level of IL-17 mRNA in gastric tumors was associated with the depth of the tumors, lymph-vascular invasion and lymph node involvement, suggesting that IL-17 obviously was related to tumor progression. IL-17 and IL-21, which regulates IL-17, would be potential therapeutic targets for the treatment of gastric cancer.
The current status and clinical value of circulating tumor cells and circulating cell-free tumor DNA in bladder cancer (2017)

Urothelial carcinoma of the bladder (UCB) is a complex disease, which is associated with highly aggressive tumor biologic behavior, especially in patients with muscle-invasive and advanced tumors. Despite multimodal therapy options including surgery, radiotherapy and chemotherapy, UCB patients frequently suffer from poor clinical outcome. Indeed, the potential of diverse opportunities for modern targeted therapies is not sufficiently elucidated in UCB yet. To improve the suboptimal treatment situation in UCB, biomarkers are urgently needed that help detecting minimal residual disease (MRD), predicting therapy response and subsequently prognosis as well as enabling patient stratification for further therapies and therapy monitoring, respectively. To date, decision making regarding treatment planning is mainly based on histopathologic evaluation of biopsies predominantly derived from the primary tumors and on clinical staging. However, both methods are imperfect for sufficient outcome prediction. During disease progression, individual disseminated tumor cells and consecutively metastases can acquire characteristics that do not match those of the corresponding primary tumors, and often are only hardly assessable for further evaluation. Therefore, during recent years, strong efforts were directed to establish non-invasive biomarkers from liquid biopsies. Urine cytology and serum tumor markers have been established for diagnostic purposes, but are still insufficient as universal biomarkers for decision-making and treatment of UCB patients. To date, the clinical relevance of various newly established blood-based biomarkers comprising circulating tumor cells (CTCs), circulating cell-free nucleic acids or tumor-educated platelets is being tested in cancer patients. In this review we summarize the current state and clinical application of CTCs and circulating cell-free tumor DNA originating from blood as biomarkers in patients with different UCB stages.
Ultrasensitive proteome analysis using paramagnetic bead technology (2014)

In order to obtain a systems-level understanding of a complex biological system, detailed proteome information is essential. Despite great progress in proteomics technologies, thorough interrogation of the proteome from quantity-limited biological samples is hampered by inefficiencies during processing. To address these challenges, here we introduce a novel protocol using paramagnetic beads, termed Single-Pot Solid-Phase-enhanced Sample Preparation (SP3). SP3 provides a rapid and unbiased means of proteomic sample preparation in a single tube that facilitates ultrasensitive analysis by outperforming existing protocols in terms of efficiency, scalability, speed, throughput, and flexibility. To illustrate these benefits, characterization of 1,000 HeLa cells and single Drosophila embryos is used to establish that SP3 provides an enhanced platform for profiling proteomes derived from sub-microgram amounts of material. These data present a first view of developmental stage-specific proteome dynamics in Drosophila at a single-embryo resolution, permitting characterization of inter-individual expression variation. Together, the findings of this work position SP3 as a superior protocol that facilitates exciting new directions in multiple areas of proteomics ranging from developmental biology to clinical applications.
Polysaccharide nano crystal reinforced nanocomposites (2008)

There are numerous examples of animals or plants that synthesize extracellular high-performance skeletal biocomposites consisting of a matrix reinforced by nano sized crystalline domains. Cellulose and chitin are classical examples of these reinforcing elements, which occur as whisker-like microfibrils that are biosynthesized and deposited in a continuous fashion. In many cases, this mode of biogenesis leads to crystalline microfibrils that are almost defect-free, and whose axial physical properties therefore approach those of perfect crystals. During the last decade we have attempted to mimic biocomposites by blending cellulose or chitin whiskers from different sources with polymer matrices. Aqueous suspensions of such nano crystals can be prepared by acid hydrolysis of the substrate. The object of this treatment is to dissolve away regions of low lateral order so that the water-insoluble, highly crystalline residue may be converted into a stable suspensoid by subsequent vigorous mechanical shearing action. The resulting nano crystals occur as rod-like particles or whiskers, whose dimensions depend on the nature of the substrate. They are typically a few hundred nm long and between 5 and 20 nm in diameter. Starch can also be used as a source for the production of nano crystals. The constitutive nano crystals appear as platelet-like nano particles with a length ranging between 20 and 40 nm, a width ranging between 15 and 30 nm, and a thickness ranging between 5 and 7 nm. Since the first announcement of using cellulose whiskers as a reinforcing phase, they have been used extensively as model fillers in several kinds of polymeric matrices, including synthetic and natural ones. Casting mixtures of polysaccharide nano crystals and lattices led to the production of nano composite materials with drastically enhanced mechanical properties, especially at T &gt; T g of the matrix, by virtue of the formation of a whiskers network, even when the whisker volume fraction was only a few percent. The formation of this rigid network, resulting from strong interactions between whiskers, was assumed to be governed by a percolation mechanism. This hydrogen-bonded network induced a thermal stabilization of the composite up to 500 K, the temperature at which polysaccharides start to decompose. Any factors that perturb the formation of this percolating network directly affect the reinforcing effect of polysaccharide nano crystals. In addition to some practical applications, the study of these nano composite materials can help researchers understand such physical properties as the geometric and mechanical percolation effect.Key words: nano composites, polysaccharide, polymer, cellulose, nano crystal.
Resilient aggregation in sensor networks (2004)

This paper studies security for data aggregation in sensor networks. Current aggregation schemes were designed without security in mind and there are easy attacks against them. We examine several approaches for making these aggregation schemes more resilient against certain attacks, and we propose a mathematical framework for formally evaluating their security.
Plasma Levels of Nitrite/Nitrate and Platelet cGMP Levels Are Decreased in Patients With Atrial Fibrillation (1997)

Patients with atrial fibrillation have been reported to exhibit abnormal hemostasis. Since nitric oxide (NO) exerts antithrombotic effects and attenuates platelet function, we evaluated two indicators of plasma NO levels, the plasma levels of nitrite and nitrate (NOx), and the levels of cGMP in platelets. We also examined whether indicators of plasma NO levels were associated with abnormalities in parameters related to platelet function, blood coagulation, and fibrinolysis. We evaluated 45 patients with chronic sustained atrial fibrillation (33 men and 12 women, age range 63 +/- 2 years) compared with 45 sex- and age- (+/- 2 years) matched nonhospitalized subjects with sinus rhythm. There were no significant differences between the two groups in the incidence of risk factors for stroke except for ischemic heart disease or in echocardiographic parameters. Plasma levels of NOx measured using the Greiss reagent (mean [interquartile range]: 15.6 [9.5 to 25.7] versus 24.1 [14.2 to 40.8] mumol/L, n = 45) and the platelet cGMP levels (0.33 [0.16 to 0.67] versus 0.63 [0.31 to 1.29] pmol/10(9) platelets, n = 9) were significantly (P < .05) lower in the patients with atrial fibrillation than in the control subjects. Plasma levels of D-dimer, beta-thromboglobulin, and fibrinogen were significantly (P < .05) higher in the patients with atrial fibrillation. The two groups did not differ as to the plasma levels of tissue plasminogen activator or plasminogen activator inhibitor-1. Our findings suggest that a decrease in plasma NO levels may account for the hemostatic abnormalities observed in patients with atrial fibrillation.
3'-end processing and kinetics of 5'-end joining during retroviral integration in vivo (1997)

Retroviral replication depends on integration of viral DNA into a host cell chromosome. Integration proceeds in three steps: 3'-end processing, the endonucleolytic removal of the two terminal nucleotides from each 3' end of the viral DNA; strand transfer, the joining of the 3' ends of viral DNA to host DNA; and 5'-end joining (or gap repair), the joining of the 5' ends of viral DNA to host DNA. The 5'-end joining step has never been investigated, either for retroviral integration or for any other transposition process. We have developed an assay for 5'-end joining in vivo and have examined the kinetics of 5'-end joining for Moloney murine leukemia virus (MLV). The interval between 3'-end and 5'-end joining is estimated to be less than 1 h. This assay will be a useful tool for examining whether viral or host components mediate 5'-end joining. MLV integrates its DNA only after its host cell has completed mitosis. We show that the extent of 3'-end processing is the same in unsynchronized and aphidicolin-arrested cells. 3'-end processing therefore does not depend on mitosis.
Charnley total hip arthroplasty with cement. Fifteen-year results. (1989)

The results of the first 333 Charnley total hip arthroplasties that were performed with cement at the Mayo Clinic were reviewed a minimum of fifteen years postoperatively. Data were available for 166 of 170 hips of patients who were still alive. One hundred and thirty patients died, and thirty-seven hips were revised. At the time of this study, 80 per cent of the living patients had no pain, and 152 of the 160 hips remained much better than before the operation. Kaplan-Meier analysis of probable loosening of one or both components, on the basis of roentgenographic evidence, demonstrated a probability of loosening of 3 per cent incidence at one year after operation, 13 per cent at five years, 19 per cent at ten years, and 32 per cent at fifteen years. The probability of failure (that is, revision or symptomatic loosening) was 0.9 per cent at one year, 4.1 per cent at five years, 8.9 per cent at ten years, and 12.7 per cent at fifteen years. We did not identify a dramatic increase in the incidence of loosening or failure at any of the follow-up periods (one, five, ten, or fifteen years). With the Mayo Clinic clinical and roentgenographic system for scoring the hips, we found that ninety-seven hips had a good or excellent result; fifteen, a fair result; and thirteen, a poor result. (The scoring could not be completed for forty-one hips). The functional results deteriorated slightly over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleosides and nucleotides. Part 25.. Synthesis of a protected 1‐(2′‐deoxy‐β‐D‐ribofuranosyl)‐1 H‐benzimidazole 3′‐phosphate (1987)

Abstract 1‐(2′‐Deoxy‐5′‐ O ‐dimethoxytrityl‐′‐ D ‐ribofuranosyl)‐1 H ‐benzimidazole 3′‐[( p ‐chlorophenyl)(2‐cyanoethyl) phosphate] ( 6 ) has been synthesized from 1‐(β‐ D ‐ribofuranosyl)‐1 H ‐benzimidazole ( 3b ) using regiospecific 2′‐deoxygenation. The latter compound was obtained by glycosylation of benzimidazole with the D ‐ribose derivative 2 leading exclusively of the β‐ D ‐anomer.
Scalability and failure recovery in a linux cluster file system (2000)

In this paper we describe how we implemented journaling and recovery in the Global File System (GFS), a shared-disk, cluster file system for Linux. We also present our latest performance results for a 16-way Linux cluster.
Genetically modified crops: methodology, benefits, regulation and public concerns (2000)

The genetic modification of crop plants from the methodology involved in their production through to the current debate on their use in agriculture are reviewed. Techniques for plant transformation by Agrobacterium tumefaciens and particle bombardment, and for the selection of transgenic plants using marker genes are described. The benefits of currently available genetically modified (GM) crops in reducing waste and agrochemical use in agriculture, and the potential of the technology for further crop improvement in the future are discussed. The legal requirements for containment of novel GM crops and the roles of relevant regulatory bodies in ensuring that GM crops and food are safe are summarized. Some of the major concerns of the general public regarding GM crops and food: segregation of GM and non-GM crops and cross-pollination between GM crops and wild species, the use of antibiotic resistance marker genes, the prevention of new allergens being introduced in to the food chain and the relative safety of GM and non-GM foods are considered. Finally, the current debate on the use of GM crops in agriculture and the need for the government, scientists and industry to persevere with the technology in the face of widespread hostility is studied.