gebhart/patrepeval huggingface dataset:
Multiple in vivo effects of interleukin-3 and interleukin-6 on murine megakaryocytopoiesis (1991)

The in vivo effects of interleukin-3 (IL-3), interleukin-6 (IL-6), and a combination of IL-3 plus IL-6 on murine megakaryocytopoiesis and thrombopoiesis were examined. Human recombinant IL-6 was administered subcutaneously as 14 equal injections of 5,000 units each during a 102- hour period. Murine recombinant IL-3 was given as 8 injections of 80,000 units each during the first 54 hours. Megakaryopoiesis and thrombopoiesis were evaluated 120 hours after initial administration of the cytokines. Platelet levels increased by 20% following IL-3 alone, 35% following IL-6 alone and 61% after administration of both IL-3 and IL-6. Platelet production, as measured by 75Se-selenomethionine incorporation, increased by approximately 120% in animals that had received IL-6 or IL-3 plus IL-6. Megakaryocyte ploidy analysis by two- color flow cytometry showed a shift in the modal ploidy class from 16N to 32N and a significant increase in the frequency of 64N cells only in IL-6 treated animals. Both bone marrow and splenic megakaryocyte colony- forming cells were significantly increased following either IL-3 or IL- 6. Bone marrow megakaryocyte size increased 18%, 43%, and 38%, respectively, after administration of IL-3, IL-6, or the combination of IL-3 plus IL-6. Leukocyte counts and hematocrits were unaffected by either cytokine. Additional groups of mice received the same injection schedule as above and the serial effects on peripheral blood cell levels were assessed for 30 days. Platelet levels, which had been elevated by IL-3 or IL-6, fell to control values within 4 days following the last injection. Animals given IL-6 or IL-3 plus IL-6 were subsequently thrombocytopenic relative to controls on days 7 through 9 following cessation of treatment. Temporary ‘cycling’ of platelet levels was observed for 3 weeks following treatment with IL-6 or the combination of IL-3 plus IL-6. We conclude that IL-6 and to a lesser extent IL-3 stimulate platelet production in vivo and that their combined effects on platelet levels are approximately additive. Following discontinuation of IL-3 or IL-6, the effects are rapidly reversed, presumably by negative feedback mechanisms, resulting in a period of ‘rebound thrombocytopenia’ in mice that had received IL-6.
2012(第十二届)北京国际汽车展览会专题 我们需要绿色车 (2012)

近年来,全世界都面临着能源危机和环境恶化的影响,全球变暖、油价不断上涨……日益突出的矛盾,让人们越来越意识到节能环保的重要性。今年两会期间,节能环保毫无意外地再次成为大家强烈关注的话题之一。作为备受社会各界关注的北京车展,是目前全球汽车制造商公认和推崇的具有广泛国际影响力的全球汽车行业盛会,此次北京车展的主题是创新·跨越。这一主题诠释了当今全球汽车工业向创新科技、绿色节能方向发展的趋势以及我国向汽车强国实现跨越式发展的奋斗目标。此次参展的车型,都主打科技、绿色牌,向世人展现了国际汽车工业的创新能力和未来发展前景。
Stimulation by defined parathyroid hormone fragments of cell proliferation in skeletal-derived cell cultures (1990)

We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimulate creatine kinase (CK) activity and [3H]thymidine incorporation into DNA via phosphoinositide turnover, in addition to its other actions via increased cyclic AMP production. We also found that mid-region fragments of PTH stimulate [3H]thymidine incorporation into avian chondrocytes. In the present study of mammalian systems, we demonstrate differential effects of defined synthetic PTH fragments on CK activity and DNA synthesis, as compared with cyclic AMP production, in osteoblast-enriched embryonic rat calvaria cell cultures, in an osteoblast-like clone of rat osteosarcoma cells (ROS 17/2.8) and in chondroblasts from rat epiphysial cartilage cell cultures. Unlike full-length bovine (b)PTH-(1-84) or the fully effective shorter fragment human (h)PTH-(1-34), fragments lacking the N-terminal region of the hormone did not increase cyclic AMP formation, whereas they did stimulate increases in both DNA synthesis and CK activity. Moreover, the PTH fragment hPTH-(28-48) at 10 microM inhibited the increase in cyclic AMP caused by 10 nM-bPTH-(1-84). The increase of CK activity in ROS 17/2.8 cells caused by bPTH-(1-84) or hPTH-(28-48) was completely inhibited by either cycloheximide or actinomycin D, as was shown previously for rat calvaria cell cultures. These results indicated the presence of a functional domain of PTH in the central part of the molecule which exerts its mitogenic-related effects on osteoblast- and chondroblast-like cells in a cyclic AMP-independent manner. Since cyclic AMP formation by PTH leads to bone resorption, specific mid-region fragments of PTH might prove suitable for use in vivo to induce bone formation without concomitant resorption.
Representation of the molecular electrostatic potential by a net atomic charge model (1981)

Abstract Electrostatic potentials and Mulliken net atomic charges were calculated from STO ‐3G, 6‐31G, and 6‐31G** SCF ‐ MO wavefunctions for hydrogen fluoride, water, ammonia, methane, acetylene, ethylene, carbon dioxide, formaldehyde, methanol, formamide, formic acid, acetonitrile, diborane, and carbonate ion. In each case optimized net atomic charges (potential‐derived charges) were also obtained by fitting the electrostatic potentials calculated directly from the wavefunctions in a shell enveloping the molecules outside of their van der Waals surfaces. The electrostatic potentials calculated from the potential‐derived charge distributions were then compared with the defined quantum mechanical electrostatic potentials and with the electrostatic potentials of the Mulliken charge distributions.
Towards the identification of the common features of bacterial biofilm development. (2006)

Microorganisms can live and proliferate as individual cells swimming freely in the environment, or they can grow as highly organized, multicellular communities encased in a self-produced polymeric matrix in close association with surfaces and interfaces. This microbial lifestyle is referred to as biofilms. The intense search over the last few years for factors involved in biofilm development has revealed that distantly related bacterial species recurrently make use of the same elements to produce biofilms. These common elements include a group of proteins containing GGDEF/EAL domains, surface proteins homologous to Bap of Staphylococcus aureus, and some types of exopolysaccharides, such as cellulose and the poly-beta-1,6-N-acetylglucosamine. This review summarizes current knowledge about these three common elements and their role in biofilm development.
RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection (2014)

AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations. We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5' to 3' LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS.
Toll–Like Receptor 4 Mediates Inflammatory Signaling by Bacterial Lipopolysaccharide in Human Hepatic Stellate Cells (2003)

Bacterial lipopolysaccharide (LPS) stimulates Kupffer cells and participates in the pathogenesis of alcohol-induced liver injury. However, it is unknown whether LPS directly affects hepatic stellate cells (HSCs), the main fibrogenic cell type in the injured liver. This study characterizes LPS-induced signal transduction and proinflammatory gene expression in activated human HSCs. Culture-activated HSCs and HSCs isolated from patients with hepatitis C virus-induced cirrhosis express LPS-associated signaling molecules, including CD14, toll-like receptor (TLR) 4, and MD2. Stimulation of culture-activated HSCs with LPS results in a rapid and marked activation of NF-kappaB, as assessed by in vitro kinase assays for IkappaB kinase (IKK), IkappaBalpha steady-state levels, p65 nuclear translocation, NF-kappaB-dependent luciferase reporter gene assays, and electrophoretic mobility shift assays. Lipid A induces NF-kappaB activation in a similar manner. Both LPS- and lipid A-induced NF-kappaB activation is blocked by preincubation with either anti-TLR4 blocking antibody (HTA125) or Polymyxin B. Lipid A induces NF-kappaB activation in HSCs from TLR4-sufficient (C3H/OuJ) mice but not from TLR4-deficient (C3H/HeJ) mice. LPS also activates c-Jun N-terminal kinase (JNK), as assessed by in vitro kinase assays. LPS up-regulates IL-8 and MCP-1 gene expression and secretion. LPS-induced IL-8 secretion is completely inhibited by the IkappaB super repressor (Ad5IkappaB) and partially inhibited by a specific JNK inhibitor, SP600125. LPS also up-regulates cell surface expression of ICAM-1 and VCAM-1. In conclusion, human activated HSCs utilize components of TLR4 signal transduction cascade to stimulate NF-kappaB and JNK and up-regulate chemokines and adhesion molecules. Thus, HSCs are a potential mediator of LPS-induced liver injury.
Development of New Vaccines and Drugs For TB: Limitations and Potential Strategic Errors (2011)

The concomitant HIV and TB epidemics pose an enormous threat to humanity. After invading the host Mycobacterium tuberculosis initially behaves as an intracellular pathogen, which elicits the emergence of acquired specific resistance in the form of a T-helper-1 T-cell response, and involves the secretion of a myriad of cytokines and chemokines to drive protective immunity and granuloma formation. However, after that, a second phase of the disease process involves survival of bacilli in an extracellular state that is still poorly understood. This article briefly reviews the various strategies currently being used to improve both vaccination and drug therapy of TB, and attempts to make the argument that current viewpoints that dominate [both the field and the current literature] may be seriously flawed. This includes both the choice of new vaccine and drug candidates, and also the ways these are being tested in animal models, which in the opinion of the author run the risk of driving the field backwards rather than forward.
Ubiquitous House and Unconstrained Monitoring Devices for Home Healthcare System (2007)

This paper suggests a healthcare monitoring system using unconstrained measurement devices with ubiquitous techniques. These measurement devices are developed into built-in type and sensor type. The first devices are built-in the households (bed, sofa and toilet seat) and measure the patient's heart and respiration activity and estimate a blood pressure. The second devices are placed in a kitchen, front door and every room and detect the patient's movements and activities. All digitized raw signals are transmitted to a main PC using Bluetooth wireless network from all ubiquitous devices and sent to hospital laboratory after an analyzing process. This paper suggest ubiquitous healthcare house (u-House) for a practical models of home healthcare system. And it can monitor the patient's daily health condition and activity in an unconstrained manner.
Serological methods for detection and identification of viral and bacterial plant pathogens: a laboratory manual (1990)

Serological methods for detection and identification of viral and bacterial plant pathogens: a laboratory manual , Serological methods for detection and identification of viral and bacterial plant pathogens: a labor... , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016)

Recombinant adeno-associated virus vectors (rAAV) are being explored as gene delivery vehicles for the treatment of various inherited and acquired disorders. rAAVs are attractive vectors for several reasons: wild-type AAVs are nonpathogenic, and rAAVs can trigger long-term transgene expression even in the absence of genome integration-at least in postmitotic tissues. Moreover, rAAVs have a low immunogenic profile, and the various AAV serotypes and variants display broad but distinct tropisms. One limitation of rAAVs is that their genome-packaging capacity is only ∼5 kb. For most applications this is not of major concern because the median human protein size is 375 amino acids. Excluding the ITRs, for a protein of typical length, this allows the incorporation of ∼3.5 kb of DNA for the promoter, polyadenylation sequence, and other regulatory elements into a single AAV vector. Nonetheless, for certain diseases the packaging limit of AAV does not allow the delivery of a full-length therapeutic protein by a single AAV vector. Hence, approaches to overcome this limitation have become an important area of research for AAV gene therapy. Among the most promising approaches to overcome the limitation imposed by the packaging capacity of AAV is the use of dual-vector approaches, whereby a transgene is split across two separate AAV vectors. Coinfection of a cell with these two rAAVs will then-through a variety of mechanisms-result in the transcription of an assembled mRNA that could not be encoded by a single AAV vector because of the DNA packaging limits of AAV. The main purpose of this review is to assess the current literature with respect to dual-AAV-vector design, to highlight the effectiveness of the different methodologies and to briefly discuss future areas of research to improve the efficiency of dual-AAV-vector transduction.
Detection of Bladder Cancer in Urine by a Tumor Suppressor Gene Hypermethylation Panel (2004)

Promoter hypermethylation of tumor suppressor genes is common in bladder cancer and was found in all grades and stages of tumors examined. Hypermethylation was detected in the urine DNA from 39 of 45 (87%) patients, including cases of early-stage disease amenable to cure. MSP may enhance early detection of bladder cancer using a noninvasive urine test.
Statins and Cardiovascular Diseases: From Cholesterol Lowering to Pleiotropy (2009)

Statins are 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are prescribed extensively for cholesterol lowering in the primary and secondary prevention of cardiovascular disease. Recent compelling evidence suggests that the beneficial effects of statins may not only be due to their cholesterol lowering effects, but also, to their cholesterol-independent or pleiotropic effects. Through these so-called pleiotropic effects, statins are directly involved in restoring or improving endothelial function, attenuating vascular remodeling, inhibiting vascular inflammatory response, and perhaps, stabilizing atherosclerotic plaques. These cholesterol-independent effects of statins are predominantly due to their ability to inhibit isoprenoid synthesis, the products of which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil containing protein kinase (ROCK), has emerged as the principle mechanisms underlying the pleiotropic effects of statins. This review provides an update of statin-mediated vascular effects beyond cholesterol lowering and highlights recent findings from bench to bedside to support the concept of statin pleiotropy.
Treatment of Cervical Intraepithelial Neoplasia Levels 2 and 3 with Adapalene, a Retinoid-Related Molecule (2001)

The lack of side effects and practicality of home use make adapalene a nontoxic and safe alternative to surgical therapy in patients with CIN2 and CIN3.
Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans (2010)

African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
Glycosylation requirements for intracellular transport and function of the hemagglutinin of influenza virus (1992)

The contribution of each of the seven asparagine-linked oligosaccharide side chains on the hemagglutinin of the A/Aichi/68 (X31) strain of influenza virus was assessed with respect to its effect on the folding, intracellular transport, and biological activities of the molecule. Twenty mutant influenza virus hemagglutinins were constructed and expressed, each of which had one or more of the seven glycosylation sites removed. Investigations of these mutant hemagglutinins indicated that (i) no individual oligosaccharide side chain is necessary or sufficient for the folding, intracellular transport, or function of the molecule, (ii) at least five oligosaccharide side chains are required for the X31 hemagglutinin molecule to move along the exocytic pathway to the plasma membrane, and (iii) mutant hemagglutinins having less than five oligosaccharide side chains form intracellular aggregates and are retained in the endoplasmic reticulum.
Physiological Mechanisms of Tumor-Cell Invasion and Migration (2005)

Recent advances in understanding the complex biology of the microenvironment that underlies tumor invasion and migration have revealed novel and promising therapeutic targets. Pharmacological blockade of intra- and extracellular signaling events that regulate migration and survival of multiple cell types may disrupt the host-tumor conspiracy that allows escape from normal developmental regulation.
Strategy for the synthesis of large peptides: An application to the total synthesis of human parathyroid hormone [hPTH(1–84)] (1981)

Abstract A strategy suitable for the synthesis of larger peptides is proposed. It involves the following four considerations: (1) all of the side‐chain functional groups are protected by benzyl‐type protective groups; (2) a water‐soluble carbodiimide, 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide, is used for the fragment‐condensation reactions together with 1‐hydroxybenzotriazole as the additive; (3) all the protective groups are cleaved simultaneously by the HF method in the final stage of the synthesis; and (4) side products formed are detected and removed by an efficient high‐performance liquid chromatography procedure. The usefulness of these procedures is demonstrated taking the synthesis of human parathyroid hormone [hPTH(1–84)] as an example.
Catalytic Mechanism of Sep-tRNA:Cys-tRNA Synthase (2011)

Sep-tRNA:Cys-tRNA synthase (SepCysS) catalyzes the sulfhydrylation of tRNA-bound O-phosphoserine (Sep) to form cysteinyl-tRNA(Cys) (Cys-tRNA(Cys)) in methanogens that lack the canonical cysteinyl-tRNA synthetase (CysRS). A crystal structure of the Archaeoglobus fulgidus SepCysS apoenzyme provides information on the binding of the pyridoxal phosphate cofactor as well as on amino acid residues that may be involved in substrate binding. However, the mechanism of sulfur transfer to form cysteine was not known. Using an in vivo Escherichia coli complementation assay, we showed that all three highly conserved Cys residues in SepCysS (Cys(64), Cys(67), and Cys(272) in the Methanocaldococcus jannaschii enzyme) are essential for the sulfhydrylation reaction in vivo. Biochemical and mass spectrometric analysis demonstrated that Cys(64) and Cys(67) form a disulfide linkage and carry a sulfane sulfur in a portion of the enzyme. These results suggest that a persulfide group (containing a sulfane sulfur) is the proximal sulfur donor for cysteine biosynthesis. The presence of Cys(272) increased the amount of sulfane sulfur in SepCysS by 3-fold, suggesting that this Cys residue facilitates the generation of the persulfide group. Based upon these findings, we propose for SepCysS a sulfur relay mechanism that recruits both disulfide and persulfide intermediates.
300mm Heterogeneous 3D Integration of Record Performance Layer Transfer Germanium PMOS with Silicon NMOS for Low Power High Performance Logic Applications (2019)

We report a short channel high performance Ge PMOS integrated with Si NMOS in sequential monolithic 3D stacking. A layer transfer Ge PMOS with record I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ON</sub> = 497 μA/μm at I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> = 8nA/μm and I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ON</sub> = 630 μA/μm at I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> = 100nA/μm and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DS</sub> = -0.5V is achieved for the first time. Optimized design of metal gate and contact on bottom Si NMOS device layer, along with a low process thermal budget developed for Ge layer transfer and top Ge PMOS device fabrication, allow for sequential stacking with no degradation on each MOS device characteristics. Heterogeneous 3D stacked Ge-Si CMOS inverter is also successfully demonstrated with drive performance maintained on Ge PMOS and Si NMOS.
SU‐E‐T‐202: Comprehensive Quality Assurance Procedures for Uniform Scanning Proton Therapy Machines (2012)

QA standards are desired in Radiation Oncology, but not many standards are developed and available for proton therapy. In the mean time, facility-specific QA procedures should be developed based on the equipment failure modes and available resources.
Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis (2004)

Previous reports have identified a circulating pool of CD45(+) collagen I(+) CXCR4(+) (CD45(+)Col I(+)CXCR4(+)) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45(+)Col I(+)CXCR4(+) circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45(+)Col I(+)CXCR4(+) fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab's inhibited intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis.