gebhart/patrepeval huggingface dataset:
Preantral Ovarian Follicles in Serum-Free Culture: Suppression of Apoptosis after Activation of the Cyclic Guanosine 3′,5′-Monophosphate Pathway and Stimulation of Growth and Differentiation by Follicle-Stimulating Hormone* (1997)

Progression of preantral follicle development is essential to further follicle maturation and ovulation, but there are few models for studying the regulation of preantral follicle survival and growth. We have evaluated preantral follicle survival in vivo and in vitro, and have developed a serum-free rat follicle culture system that can be used to characterize the regulation of preantral follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation during the first wave of follicle growth in the infantile rat indicated negligible apoptosis up to day 16 of age. However, a major increase in apoptosis was found by day 18, a time point associated with the appearance of large antral follicles. In situ analysis confirmed that apoptotic DNA fragments were limited to antral follicles. Culture of individual preantral follicles mechanically dissected from ovaries of 12- or 14-day-old rats in serum-free conditions led to major increases in follicle cell apoptosis, similar to that seen in cultures of antral and preovulatory follicles. In contrast to antral and preovulatory follicles, treatment of preantral follicles with gonadotropins or cAMP analogs did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum suppressed apoptosis by 75% in cultured preantral follicles. In situ analysis identified granulosa cells as the cell type susceptible to apoptosis regulation. Taking advantage of the ability of the cGMP analog to suppress apoptosis, we evaluated the potential of FSH as a growth factor. In the absence of serum, FSH treatment for 48 h did not affect follicle size compared to controls; however, treatment with the cGMP analog together with FSH increased follicle diameter (13%; P < 0.01) and viable cells (2.4-fold; P < 0.01) compared to control values. Immunoblot analysis further indicated that the inhibin-alpha content of the cultured follicles was increased by treatment with the combination of FSH and 8-bromo-cGMP, demonstrating the induction of follicle cell differentiation during culture. Therefore, we demonstrated that activation of the cGMP pathway promotes the survival of cultured preantral follicles and that in the presence of alpha cGMP analog, FSH is a growth and differentiation factor for preantral follicles. The present serum-free follicle culture model system will be useful in further evaluation of the regulation of growth and differentiation of preantral follicles.
Sequential data assimilation with a nonlinear quasi‐geostrophic model using Monte Carlo methods to forecast error statistics (1994)

A new sequential data assimilation method is discussed. It is based on forecasting the error statistics using Monte Carlo methods, a better alternative than solving the traditional and computationally extremely demanding approximate error covariance equation used in the extended Kalman filter. The unbounded error growth found in the extended Kalman filter, which is caused by an overly simplified closure in the error covariance equation, is completely eliminated. Open boundaries can be handled as long as the ocean model is well posed. Well‐known numerical instabilities associated with the error covariance equation are avoided because storage and evolution of the error covariance matrix itself are not needed. The results are also better than what is provided by the extended Kalman filter since there is no closure problem and the quality of the forecast error statistics therefore improves. The method should be feasible also for more sophisticated primitive equation models. The computational load for reasonable accuracy is only a fraction of what is required for the extended Kalman filter and is given by the storage of, say, 100 model states for an ensemble size of 100 and thus CPU requirements of the order of the cost of 100 model integrations. The proposed method can therefore be used with realistic nonlinear ocean models on large domains on existing computers, and it is also well suited for parallel computers and clusters of workstations where each processor integrates a few members of the ensemble.
ENERGY STORAGE SYSTEMS FOR AUTOMOBILE PROPULSION: 1978 STUDY. 2. DETAILED REPORT (1978)

Volume 2 details the results for FY 1978 of a national, multilaboratory study of energy-storage propulsion systems for automobiles. Presented are the findings and procedures of the five participating panels, including an evaluation of how changing the relationship between specific peak power and specific energy affects electric vehicle performance. Also included are an update of previous results based on new information obtained from ongoing research and development programs, as well as the results of a national energy impact and market penetration analysis of representative future energy storage vehicles. The report contains six sections: (1) Energy Storage Devices; (2) Energy Storage Propulsion; (3) The Evaluation Process; (4) End-Use Analysis Results and Conclusions; (5) National Energy Impact of Energy Storage Automobiles; and (6) Market Demand Forecast for Energy Storage Automobiles.
Cell Cycle Arrest Induced by an Inhibitor of Glucosylceramide Synthase (1995)

In an attempt to define the basis for sphingolipid regulation of cell proliferation, we studied the effects of glucosylceramide (GlcCer) synthase inhibition by threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on NIH 3T3 cells overexpressing insulin-like growth factor-1 (IGF-1) receptor. PDMP treatment resulted in a time-dependent decrease in GlcCer levels and an increase in cellular ceramide levels. PDMP abolished serum and IGF-1-stimulated cell proliferation, as measured by a reduction in [3H]thymidine incorporation, protein, and DNA levels. However it did not affect IGF-1-mediated early signaling events, including receptor tyrosine kinase, MAP kinase, and phosphatidylinositol 3-kinase activities. Two-color flow cytometry with propidium iodide and 5-bromo-2'-deoxyuridine monophosphate labeling revealed an arrest of the cell cycle at G1/S and G2/M transitions in an asynchronous population of cells. These changes were time dependent, with maximal effects seen by 12-24 h. Removal of PDMP from the cell medium resulted in reversal of the cell cycle changes, with cells re-entering the S phase. The cell cycle arrest at the G1/S and G2/M transitions was confirmed in cells synchronized by pretreatment with nocodazole, aphidicolin, or hydroxyurea, and released from blockade in the presence of PDMP. A decrease in the activities of two cyclin-dependent kinases, p34cdc2 kinase and cdk2 kinase, was observed with PDMP treatment. When cell ceramide levels were increased by N-acetylsphingosine, comparable changes in the cell cycle distribution were seen. However, sphingomyelinase treatment was without effect. Therefore, it appears that ceramide mediates in part the inhibitory effect of GlcCer synthase inhibition on IGF-1-induced cell proliferation in 3T3 cells. The rapid production of decreased cyclin-dependent kinase activities by PDMP suggests that one of the crucial sites of action of the inhibitor lies in this area.
Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 41) : Variation of the Basic Structure (2000)

A range of 11 derivatives of flavone-8-acetic acid (FAA) in which the structure has been substantially altered in different ways have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. The generally poor activity observed shows that the basic structure cannot be altered much without destroying the activity.
Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates (2009)

Point-of-care diagnostics will strongly benefit from miniaturization based on microfluidics because microfluidics integrate functions that can together preserve valuable samples and reagents, increase sensitivity of a test, and accelerate mass transport limited reactions. But a main challenge is to incorporate reagents into microfluidics and to make microfluidics simple to use. Here, we integrate microfluidic functional elements, some of which were developed earlier, and reagents such as detection antibodies (dAbs), capture antibodies (cAbs) and analyte molecules for making one-step immunoassays: the integrated device only requires the addition of sample to trigger a cascade of events powered by capillary forces for effecting a sandwich immunoassay that is read using a fluorescence microscope. The microfluidic elements comprise a sample collector, delay valves, flow resistors, a deposition zone for dAbs, a reaction chamber sealed with a polydimethylsiloxane (PDMS) substrate, and a capillary pump and vents. Parameters for depositing 3.6 nL of a solution of dAb on the chip using an inkjet are optimized and the PDMS substrate is patterned with analytes, which provide a positive control, and cAbs. Various storage conditions of the patterned PDMS are investigated for up to 6 months revealing that storage with a desiccant preserved at least 51% of the activity of the cAbs. C-reactive protein (CRP), a general inflammation and cardiac marker, is detected using this one-step chip using only 5 microL of human serum by measuring fluorescent signals from 30 x 100 microm(2) areas of the PDMS substrate in the wet reaction chamber. The one-step chip can detect CRP at a concentration of 10 ng mL(-1) in less than 3 min and below 1 ng mL(-1) within 14 min. The work presented here may spur the adoption of fluorescence immunoassays using capillary driven microfluidics and PDMS substrates for point-of-care diagnostics.
从比较和历史发展的角度考察专门知识与国家政策的关系:英德、美三国的律师与医师职业 (1990)

各国内部的专门职业:它们的地位,赋予的权力和政策方向在英语中,专门职业和政策这两个术语已获得的外延虽不够明确、但它的含义毕竟是清楚的,而其他语言中却缺乏与它们完全对应的词。但另一方面,在西方各国,像律师与医师这样的特定专门职业,却在不同情况下保持了颇为相似的意义和特性。然而在各国内部,法律和医疗专门职业的各个组成部分,在历史发展过程中彼此之间的关系发生了变化,它们与国家和委托人(顾客)之间的关系也发生了变化。所以,对它们的
Molecular cloning and expression of gene fragments from corynebacteriophage beta encoding enzymatically active peptides of diphtheria toxin (1983)

Two restriction fragments from corynebacteriophage beta vir tox+ that encode peptides similar to diphtheria toxin fragment A and the chain termination fragment, CRM45, have been cloned into Escherichia coli in plasmid pBR322. Clones containing the recombinant plasmids produced gene products that were active in catalyzing the ADP ribosylation of elongation factor 2 and were reactive with diphtheria toxin antiserum. Toxin-related peptides were found primarily in the periplasmic compartment and were degraded to nonimmunoreactive forms within 1 to 2 h of synthesis. The expression of both gene fragments appears to have originated from the diphtheria toxin promoter.
Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides (2013)

The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3'5'-3'5' cyclic GMP-AMP (3'3' cGAMP) produced by Vibrio cholerae and metazoan second messenger 2'5'-3'5' Cyclic GMP-AMP (2'3' cGAMP). Analysis of single nucleotide polymorphism (SNP) data from the 1000 Genome Project revealed that R71H-G230A-R293Q (HAQ) occurs in 20.4%, R232H in 13.7%, G230A-R293Q (AQ) in 5.2%, and R293Q in 1.5% of human population. In the absence of exogenous ligands, the R232H, R293Q and AQ SNPs had only modest effect on the stimulation of IFN-β and NF-κB promoter activities in HEK293T cells, while HAQ had significantly lower intrinsic activity. The decrease was primarily due to the R71H substitution. The SNPs also affected the response to the cyclic dinucleotides. In the presence of c-di-GMP, the R232H variant partially decreased the ability to activate IFN-βsignaling, while it was defective for the response to c-di-AMP and 3'3' cGAMP. The R293Q dramatically decreased the stimulatory response to all bacterial ligands. Surprisingly, the AQ and HAQ variants maintained partial abilities to activate the IFN-β signaling in the presence of ligands due primarily to the G230A substitution. Biochemical analysis revealed that the recombinant G230A protein could affect the conformation of the C-terminal domain of STING and the binding to c-di-GMP. Comparison of G230A structure with that of WT revealed that the conformation of the lid region that clamps onto the c-di-GMP was significantly altered. These results suggest that hSTING variation can affect innate immune signaling and that the common HAQ haplotype expresses a STING protein with reduced intrinsic signaling activity but retained the ability to response to bacterial cyclic dinucleotides.
Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator. (1984)

Thrombospondin (TSP), a multifunctional alpha-granule glycoprotein of platelets, binds fibrinogen, fibronectin, heparin, and histidine-rich glycoprotein and thus may play an important role in regulating thrombotic influences at vessel surfaces. In this study we have demonstrated that purified human platelet TSP formed a complex with purified human plasminogen (Plg). Complex formation was detected by rocket immunoelectrophoresis of mixtures of the purified radiolabeled proteins. Significant complex formation of fluid-phase Plg with adsorbed TSP was also demonstrated by enzyme-linked immunosorbent assay (ELISA). The complex formation was specific, saturable, and inhibited by excess fluid-phase TSP, with an apparent KD of approximately 35 nM. In both ELISA and rocket immunoelectrophoresis systems, complex formation was inhibited by 10 mM epsilon-amino-n-caproic acid, implying that there is a role for the lysine binding sites of Plg in mediating the interaction. TSP also formed a complex with plasmin as detected by ELISA but did not directly inhibit plasmin activity measured with a synthetic fluorometric substrate or with a 125I-fibrin plate assay. TSP, when incubated with Plg before addition to 125I-fibrin plates significantly inhibited the generation of plasmin activity by tissue plasminogen activator (TPA) in a manner that was calcium dependent. A kinetic study of Plg activation by TPA in the presence of TSP demonstrated that Michaelis-Menten kinetics were followed and that TSP acted as a noncompetitive inhibitor. These studies support the hypothesis that TSP, acting as a multifunctional regulator in focal areas of active hemostasis, could serve as a prothrombotic influence, leading to increased deposition of fibrin.
Preventing Internet denial-of-service with capabilities (2004)

In this paper, we propose a new approach to preventing and constraining denial-of-service (DoS) attacks. Instead of being able to send anything to anyone at any time, in our architecture, nodes must first obtain "permission to send" from the destination; a receiver provides tokens, or capabilities, to those senders whose traffic it agrees to accept. The senders then include these tokens in packets. This enables verification points distributed around the network to check that traffic has been certified as legitimate by both endpoints and the path in between, and to cleanly discard unauthorized traffic. We show that our approach addresses many of the limitations of the currently popular approaches to DoS based on anomaly detection, traceback, and pushback. Further, we argue that our approach can be readily implemented in today's technology, is suitable for incremental deployment, and requires no more of a security infrastructure than that already needed to fix BGP's security weaknesses. Finally, our proposal facilitates innovation in application and networking protocols, something increasingly curtailed by existing DoS measures.
Chemoselective Asymmetric N‐Allylic Alkylation of Indoles with Morita–Baylis–Hillman Carbonates (2009)

Give me convenience: The title transformation has been developed by employing metal-free catalysis of modified cinchona alkaloids. Moderate to excellent enantioselectivities have been achieved for a broad array of substrates (see scheme). This reaction also provides a convenient method to prepare multiply functionalized pyrrolo[1,2-a]indole and pyrrolo[3,2,1-ij]quinoline derivatives. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant. (1997)

Hydroxyapatite bioceramic was used for the manufacture of an orbital floor prosthesis from spiral CT data acquired transaxially at 1-mm beam collimation, pitch of 1, and 0.2-mm reconstruction intervals. CT data were converted to vector file format for subsequent prosthesis manufacture on a stereo-lithography machine. The orbital floor prosthesis was engrafted onto an acrylic model of the orbit as a qualitative indication of its overall accuracy. High anatomic accuracy was achieved, as determined by visual inspection. Cross-hatching of the vector file data allowed a porous internal architecture of the prosthesis. Refinements in chemical structure of the hydroxyapatite bioceramic are expected to enhance mechanical properties.
Parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acids are widely distributed in rat tissues. (1993)

PTH/PTH-related peptide (PTHrP) receptor mRNAs are widely distributed in rat tissues. PTH and PTHrP, a peptide responsible for hypercalcemia associated with cancers, bind equivalently to common receptors that initially were cloned from rat bone and opossum renal cell cDNA libraries. In this study we used rat PTH/PTHrP receptor cDNA to probe for receptor expression in different rat tissues by Northern blot analysis. PTH/PTHrP receptor transcripts are highly expressed in PTH target tissues, kidney and bone. Receptor transcripts, however, also are expressed in many other tissues, including aorta, adrenal gland, bladder, brain, cerebellum, breast, heart, ileum, liver, lung, skeletal muscle, ovary, placenta, skin, spleen, stomach, uterus, and testes. The major transcript in most tissues is 2.3-2.5 kilobases in size. At least two larger mRNAs are observed in kidney and liver, and smaller transcripts are found in kidney, skin, and testes. The most abundant testicular transcript is 1.4-1.5 kilobases in size, and it hybridizes with two different cDNA probes that encode portions of the receptor sequence from the putative fourth transmembrane domain to its C-terminal end. It does not hybridize, however, with a probe encoding the first 107 residues of the receptor sequence. Although, PTH/PTHrP receptor mRNAs are highly expressed in kidney and bone, classic PTH targets that are associated with calcium homeostasis, their wide tissue distribution suggests that PTH and/or PTHrP have other physiological roles, particularly in these other tissues. The mechanisms leading to tissue-specific expression of PTH/PTHrP receptor transcripts of different sizes and the functions of these mRNAs remain to be determined.
Effect of Electrolyzed Water on Wound Healing (2000)

Electrolyzed water accelerated the healing of full-thickness cutaneous wounds in rats, but only anode chamber water (acid pH or neutralized) was effective. Hypochlorous acid (HOCl), also produced by electrolysis, was ineffective, suggesting that these types of electrolyzed water enhance wound healing by a mechanism unrelated to the well-known antibacterial action of HOCl. One possibility is that reactive oxygen species, shown to be electron spin resonance spectra present in anode chamber water, might trigger early wound healing through fibroblast migration and proliferation.
A 2,3-cis-selective synthesis of aziridines bearing a vinyl group from allyl methyl carbonates and allyl mesylates (1998)

A convenient method for the synthesis of synthetically useful chiral 2-vinylaziridines from natural α-amino acids is described. Satisfactory 2,3-cis-selectivities are obtained by exposure of methyl carbonates of various allylic alcohols bearing an N-protected amino group to a catalytic amount of tetrakis(triphenylphosphine)palladium(>0>), Pd(PPh3)4, in aprotic solvents such as THF. Base-promoted aziridination of mesylates of various N-protected amino allylic alcohols followed by Pd(PPh3)4 catalyzed isomerization for the 2,3-cis-selective synthesis of vinylaziridines is also presented.
Sentient Data Access via a Diverse Society of Devices (2003)

It has been more than ten years since such "information appliances" as ATMs and grocery store UPC checkout counters were introduced. For the office environment, Mark Weiser began to articulate the notion of UbiComp and identified some of the salient features of the trends in 1991. Embedded computation is also becoming widespread. Microprocessors, for example, are finding themselves embedded into seemingly conventional pens that remember what they have written. Anti-lock brake systems in cars are controlled by fuzzy logic. And as a result of wireless computing, miniaturization, and new economies of scale, such technologies as PDAs, IM, and mobile access to the Internet are almost taken for granted.
Resistance of Fc receptor- deficient mice to fatal glomerulonephritis. (1998)

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.
6-Mercaptopurine Is Effective in Crohn’s Disease Without Concomitant Steroids (2004)

6-MP is an effective medication for use in steroid-naive patients and is likely to be effective in patients who have received steroids in the past but are not currently receiving them. Relapses occur despite continued therapy, but are often easily treated, and do not require initiating steroids.