gebhart/patrepeval huggingface dataset:
Myostatin represses physiological hypertrophy of the heart and excitation–contraction coupling (2009)

Although myostatin negatively regulates skeletal muscle growth, its function in heart is virtually unknown. Herein we demonstrate that it inhibits basal and IGF-stimulated proliferation and differentiation and also modulates cardiac excitation-contraction (EC) coupling. Loss of myostatin induced eccentric hypertrophy and enhanced cardiac responsiveness to beta-adrenergic stimulation in vivo. This was due to myostatin null ventricular myocytes having larger [Ca(2+)](i) transients and contractions and responding more strongly to beta-adrenergic stimulation than wild-type cells. Enhanced cardiac output and beta-adrenergic responsiveness of myostatin null mice was therefore due to increased SR Ca(2+) release during EC coupling and to physiological hypertrophy, but not to enhanced myofilament function as determined by simultaneous measurement of force and ATPase activity. Our studies support the novel concept that myostatin is a repressor of physiological cardiac muscle growth and function. Thus, the controlled inhibition of myostatin action could potentially help repair damaged cardiac muscle by inducing physiological hypertrophy.
Ceftazidime versus Aminoglycoside and (Ureido)Penicillin Combination in the Empirical Treatment of Serious Infection (1992)

Urgent treatment of serious infections with broad spectrum antibiotics usually starts before bacteriological evidence of the infective organism(s) becomes available. In this study 471 patients with a clinical diagnosis of sepsis were treated empirically with ceftazidime (CAZ) monotherapy (249 patients), or with an aminoglycoside+(ureido)penicillin combination (AG+PEN) (222 patients) to establish clinical outcome and bacteriological response. Up to 72 h post-treatment 94.5% of patients in the CAZ group and 93.8% in the AG+PEN group were treated successfully (treatment difference 0.7%, P < 0.01, 95% confidence interval -3.8%, 5.2%); 2-4 weeks after treatment neither regimen proved clinically superior. The differences in bacteriological response up to 72 h, and at 2-4 weeks after treatment, were 5.6% and 12.4% in favour of CAZ, however, these were not statistically significant. Overall, 56 patients reported 72 adverse events in the CAZ group, compared with 33 patients reporting 41 adverse events in the AG+PEN group. Deaths, 40 on CAZ and 21 on AG+PEN, were mainly related to their underlying condition. The two regimens were shown to be clinically equivalent in seriously ill patients treated empirically.
Design-Build & Co.: A Brave New World (1997)

There are many inherent risks in overseas work. These are made greater by current project delivery methods, such as design/build operate transfer, and build own operate transfer. The author discusses risks such as cultural differences, schedules, and differing goals for the project. Wage systems, measures of business achievement, competition, employment attitudes and many other matters can differ on overseas projects and all parties need to understand how to deal with them. Access to knowledge, both technical and organizational can differ. Contract documents need to be carefully crafted. The author also points out risks related to the world wide web, suggesting that technology can be misinterpreted and this can result in significant safety risks. He believes that for many projects, standard contract forms are inadequate and that parties need to start legally and contractually from scratch each time.
Use of Oligonucleotide Aptamer Ligands to Modulate the Function of Immune Receptors (2013)

The paucity of costimulation at the tumor site compromises the ability of tumor-specific T cells to eliminate the tumor. The recent U.S. Food and Drug Administration approval of ipilumimab, an antibody that blocks the inhibitory action of CTLA-4, and clinical trials targeting 4-1BB and PD-1 or PD-L1, have underscored the therapeutic potential of using immunomodulatory antibodies to stimulate protective immunity in human patients. Nonetheless, systemic administration of immunomodulatory antibodies has been associated with dose-limiting autoimmune pathologies, conceivably reflecting also the activation of resident autoreactive T cells. Arguably, targeting immunomodulatory ligands to the disseminated tumor lesions of the patient would reduce such drug-associated toxicities. We have recently developed a new class of inhibitory (CTLA-4) and agonistic (4-1BB and OX-40) ligands composed of short oligonucleotide (ODN) aptamers that exhibited bioactivities comparable or superior to that of antibodies. To reduce toxicity, the immunomodulatory aptamers were targeted to the tumor by conjugation to a second aptamer that bound to a product expressed on the surface of the tumor cell, the targeting aptamer, generating a bispecific aptamer conjugate analogous to bispecific antibodies. In a proof-of-concept study in mice, we have shown that an agonistic 4-1BB-binding aptamer conjugated to a prostate-specific membrane antigen (PSMA)-binding aptamer led to the inhibition of PSMA-expressing tumors, was more effective than, and synergized with, vaccination, and exhibited a superior therapeutic index compared with nontargeted costimulation with 4-1BB antibodies or 4-1BB aptamers. The cell-free chemically synthesized ODN aptamers offer significant advantages over antibodies in terms of synthesis, cost, as well as conjugation chemistry needed to generate bispecific ligand fusions.
A Fluorophore‐Doped Polymer Nanomaterial for Referenced Imaging of pH and Temperature with Sub‐Micrometer Resolution (2012)

Abstract A new kind of pH and temperature sensitive material is reported. It is composed of dye‐doped polymer nanoparticles incorporated into a thin film of a polyurethane hydrogel. The new pH/temperature‐sensitive nanoparticles are obtained by post‐staining oxygen‐impermeable amino‐functionalized polyacrylonitrile nanoparticles with a long‐lifetime reference dye. Staining is followed by covalently linking fluorescein isothiocyanate onto the surface of the nanoparticle. The new sensor material has several distinct features: a) it enables imaging of pH via time domain dual‐lifetime referencing; b) effects of temperature on pH sensing may be compensated for; and c) temperature can simultaneously be visualized via rapid lifetime imaging. The new material enables referenced and temperature‐compensated pH imaging with superior spatial resolution due to the use of nanosized sensor nanoparticles.
Interleukin 1 Receptor Dependence of Serum Transferred Arthritis Can be Circumvented by Toll-like Receptor 4 Signaling (2003)

Inflammatory arthritis is associated with the release of a network of key cytokines. In T cell receptor transgenic K/BxN mice interleukin (IL)-1 plays a key role in joint swelling and destruction, as suggested by the ability of anti-IL-1receptor (IL-1R) antibody treatment to delay the onset and slow the progression of this disease. This mechanism is dependent on the signaling pathway intermediary myeloid differentiation factor 88 (MyD88), such that neither IL-1R nor MyD88-deficient mice developed visually detectable synovitis after transfer of arthritogenic sera. The Toll-like receptors (TLRs) share the same signaling pathway through MyD88 as the IL-1R. The administration of a TLR-4 ligand, lipopolysaccharide, concomitant with arthritogenic serum in IL-1 receptor-deficient mice resulted in acute paw swelling, but not in MyD88-deficient mice. Also, serum transferred arthritis was not sustained in TLR-4 mutant mice compared with controls. These results suggest that innate immune functions via TLR-4 might perpetuate inflammatory mechanisms and bypass the need for IL-1 in chronic joint inflammation.
Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats (2013)

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.
4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle (2000)

Maintenance of cellular protein stores in skeletal muscle depends on a tightly regulated synthesis-degradation equilibrium that is conditionally modulated under an extensive range of physiological and pathophysiological circumstances. Recent studies have established the initiation phase of mRNA translation as a pivotal site of regulation for global rates of protein synthesis, as well as a site through which the synthesis of specific proteins is controlled. The protein synthetic pathway is exquisitely sensitive to the availability of hormones and nutrients and employs a comprehensive integrative strategy to interpret the information provided by hormonal and nutritional cues. The translational repressor, eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and the 70-kDa ribosomal protein S6 kinase (S6K1) have emerged as important components of this strategy, and together they coordinate the behavior of both eukaryotic initiation factors and the ribosome. This review discusses the role of 4E-BP1 and S6K1 in translational control and outlines the mechanisms through which hormones and nutrients effect changes in mRNA translation through the influence of these translational effectors.
Fcγ Receptors Inhibit Mouse and Human Basophil Activation (2012)

Besides high-affinity IgE receptors (FcεRI), human basophils express activating (FcγRIIA) and inhibitory (FcγRIIB) low-affinity IgG receptors. IgG receptors (FcγR) were also found on mouse basophils, but not identified. We investigated in this study FcγR and the biological consequences of their engagement in basophils of the two species. We found the following: (1) that mouse basophils also express activating (FcγRIIIA) and inhibitory (FcγRIIB) low-affinity FcγR; (2) that activating FcγR can activate both human and mouse basophils, albeit with different efficacies; (3) that negative signals triggered by inhibitory FcγR are dominant over positive signals triggered by activating FcγR, thus preventing both human and mouse basophils from being activated by IgG immune complexes; (4) that the coengagement of FcεRI with inhibitory and activating FcγR results in a FcγRIIB-dependent inhibition of IgE-induced responses of both human and mouse basophils; (5) that FcγRIIB has a similar dominant inhibitory effect in basophils from virtually all normal donors; and (6) that IL-3 upregulates the expression of both activating and inhibitory FcγR on human basophils from normal donors, but further enhances FcγRIIB-dependent inhibition. FcγR therefore function as a regulatory module, made of two subunits with antagonistic properties, that prevents IgG-induced and controls IgE-induced basophil activation in both mice and humans.
The Influence of Aromatic Substituents on the Polymerization Behavior of Bridged Zirconocene Catalysts (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Influence of Aromatic Substituents on the Polymerization Behavior of Bridged Zirconocene CatalystsWalter Spaleck, Frank Kueber, Andreas Winter, Juergen Rohrmann, Bernd Bachmann, Martin Antberg, Volker Dolle, and Erich F. PaulusCite this: Organometallics 1994, 13, 3, 954–963Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/om00015a032https://doi.org/10.1021/om00015a032research-articleACS PublicationsRequest reuse permissionsArticle Views2098Altmetric-Citations532LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Immunocytochemical staining of ovarian cyst aspirates with monoclonal antibody against inhibin (1998)

Inhibin is a peptide hormone which is produced by ovarian granulosa cells during normal follicular development. It is important that granulosa cells are recognized in fine needle aspirates (FNAs) of ovarian cystic lesions, as this allows definite recognition of a functional cyst and exclusion of a potentially neoplastic epithelial lined cyst. Occasionally the distinction between granulosa and epithelial cells may be difficult, especially when aspirates from functional cysts are unusually cellular. In the present study, FNAs from 33 ovarian cystic lesions were immunostained with a monoclonal antibody against inhibin. Nine cases of peritoneal fluid containing malignant cells in patients subsequently confirmed to have ovarian adenocarcinoma were also stained. Where possible the cytological and immunocytochemical findings were correlated with subsequent biopsy. In most cases in which cytology suggested a functional cyst there was a strong positive staining with anti-inhibin, although occasional cases were negative. One case originally thought to contain epithelial cells stained strongly positive with anti-inhibin and on review was felt to represent a cellular functional cyst. In all other cases where cells were considered to be epithelial there was no staining with anti-inhibin. The study shows that immunocytochemical staining with anti-inhibin may be of value in confirming the presence of granulosa cells, thus establishing a diagnosis of functional cyst. Although negative staining does not exclude a functional cyst, positive staining with anti-inhibin allows exclusion of an epithelial lined cyst and may avoid unnecessary surgical intervention.
Heat Shock Factor 1於口腔鱗狀細胞癌中之表現 (2013)

中文摘要
背景
熱休克蛋白(heat shock proteins, 簡稱HSPs)扮演著伴護蛋白分子(molecular chaperones)的角色，藉由維持細胞內蛋白質的正常摺疊與恆定，這些熱休克蛋白保護細胞免於環境緊迫所造成的蛋白質結構性傷害，並對已受損害的蛋白質進行修復或水解，以恢復蛋白質正常的生理功能，維持蛋白質功能的平衡性。而熱休克轉錄因子1(Heat Shock Factor 1，簡稱HSF1)，是一個82-k Da的轉錄因子，負責調節熱休克蛋白和其他逆境蛋白基因轉錄，引起熱休克反應的中樞。在一些熱休克的反應或是存在外在壓力下的環境，會強烈的活化這個轉錄因子的作用，以產生更多的熱休克蛋白幫助修復在惡劣環境中受到損害的一些蛋白質，好讓細胞得以在惡劣的環境中繼續存活下來。
腫瘤內的細胞，經常暴露在惡劣和變化迅速的微環境中。為了持續生長和發展，癌細胞必須能夠很有效率的適應這樣的微環境，就像前面所提及的生物體應付生存壓力時一樣，癌細胞也會發展出特定的機制來適應環境。許多研究都可以觀察到在不同的人類腫瘤中，如前列腺癌、肺癌、大腸癌、胰臟癌、子宮頸癌、膀胱癌及腦膜瘤等的表現量都有提高的情形。本研究欲探討HSF1於口腔癌病理組織中的表現量及與臨床各參數和存活時間的關係。

材料與方法
本研究利用免疫組織化學染色方法，探討HSF1於92例口腔鱗狀細胞癌(OSCC)、25例口腔上皮變異(OED)及35例正常口腔黏膜(NOM)中的表現，並以陽性染色指標Labeling index記錄其染色程度。利用卡方檢定(Chi-square test)、Kaplan-Meier 存活率方法及Cox proportional hazard regression model來分析HSF1的表現與口腔鱗狀細胞癌患者臨床病理參數及存活率之相關性，並試圖尋找影響存活時間的獨立預後因子。

結果
在正常口腔黏膜HSF1的平均陽性標記指數為12% (最低)，口腔上皮變異組的平均陽性標記指數為34%，口腔癌組的平均陽性標記指數為54% (最高)，從正常口腔黏膜、上皮變異至口腔癌的癌化過程，HSF1表現增加之情形已達統計意義(P < 0.001)。HSF1的表現和患者的腫瘤大小(T status)、淋巴結轉移與否(N status)、癌症臨床分期(Stage)有統計上相關。
各項臨床參數在Cox proportional hazard regression model分析中，單變數分析後發現，腫瘤大小、淋巴結轉移與否、腫瘤臨床分期及HSF1的陽性染色指標(LI)都與存活率有關；多變數分析腫瘤大小、淋巴結轉移與否及HSF1的陽性染色指標(LI)為影響存活時間的獨立因子(independent factor；p 53%，影響病人存活的危險率(hazard ration)高達6.249倍(p=0.043)。
若以Kaplan-Meier plots來觀察臨床病理各項參數、HSF1的陽性染色指標與病人總存活時間(overall survival)，經Log-Rank Test分析後，腫瘤大小、淋巴結轉移與否、腫瘤臨床分期均影響病人的存活時間，且達統計上之意義(p 53%，則明顯降低了口腔癌病人的存活率(p=0.044)。
結論
	在本研究中，HSF1的陽性染色指標在口腔癌病理標本中的表現較高且具統計上意義，且與口腔細胞癌患者在臨床參數及存活時間有關。在口腔癌患者而言，HSF1的表現量較高者其存活時間較短；而HSF1在切片組織中的表現程度，或許可以做為口腔癌的預後指標(prognostic marker)。
The Mortality from Cancer in the Western Hemisphere (1916)

The progress of society is largely measured by the more or less effective prevention of poverty, sickness, and premature death. Within a single generation a veritable revolution has been achieved in the control of many important diseases, and some of the most destructive plagues of mankind have been successfully eliminated, or materially reduced in frequency, in the principal civilized countries of the world. Foremost, in the order of importance, are the diseases attributable to infection or contagion, and in many important countries plague, cholera, yellow fever, leprosy, smallpox, typhoid fever, and tuberculosis, as well as most of the acute infectious diseases of infancy, are now measurably and effectively under sanitary control. By way of illustration, attention may be directed to the balance of mortality for four large American cities for which the data are available in a fairly trustworthy form for the last fifty years. The cities considered are New York, Boston, Philadelphia, and New Orleans, and the data may be relied upon as fairly representative for at least the urban centers of population of the country at large.

DECLINE IN THE DEATH KATE 

In the four cities under consideration Asiatic cholera and yellow fever have been practically eliminated. Smallpox has been reduced from a former rate of 39.5 to a present rate of only 2.4 per 100,000 of population. Scarlet fever, diphtheria and croup, typhoid fever, and pulmonary tuberculosis, as well as the diseases of the stomach and intestines, have materially decreased during the last quarter-century, compared with the twenty-five years preceding the year 1889. The most significant exception to a general decline in the death rate is the increasing mortality from cancer. In the four cities under consideration the cancer death rate has increased from 46.4 to 72.1 per 100,000 of population. In other words, there has been an actual increase in the rate of 25.7 per 100,000 of population, equivalent to a quarter-century increase in the rate of 55.4 per cent.
Fast and reliable collision culling using graphics hardware (2004)

We present a reliable culling algorithm that enables fast and accurate collision detection between triangulated models in a complex environment. Our algorithm performs fast visibility queries on the GPUs for eliminating a subset of primitives that are not in close proximity. To overcome the accuracy problems caused by the limited viewport resolution, we compute the Minkowski sum of each primitive with a sphere and perform reliable 2.5D overlap tests between the primitives. We are able to achieve more effective collision culling as compared to prior object-space culling algorithms. We integrate our culling algorithm with CULLIDE and use it to perform reliable GPU-based collision queries at interactive rates on all types of models, including non-manifold geometry, deformable models, and breaking objects.
100-nm alternating PSM structure discussion for ArF lithography (2001)

Alternating phase-shifting mask (Alt.PSM) technology is the most effective approach to expand resolution limitation and expand the process window of lithography. Currently, etched quartz Alt.PSMs have been introduced not only for device development but also for production use. Adapting the etched quartz structure, we need to consider about transmission difference between etched and un-etched regions. So, side-etching method has been used for structure of Alt.PSMs. We have been supplying Alt.PSMs with side-etching and single trench structures for the mass-production of KrF lithography. As design rule of device pattern have been tightening, in 100nm node and further, narrow chrome width limits the undercut width and which should be optimized for ArF lithography. Moreover, proximity effect has been reported for the shifter edge type Alt.PSMs as pitch dependency of printed line CD. We will report about the side-etching optimization whether limited undercut width can compensate the CD imbalance between etched and un-etched regions. Or, how much bias adding at space width of etched regions can compensate it, or how undercut and space biasing combination affect CD imbalance. We also discuss about whether the line bias can correct to targeted line CD. Finally, we will summarize which structure is recommended for 100nm-node Alt.PSM for ArF lithography. On the other hand, for the case the undercut structure turns out to be difficult in the 100nm-Alt.PSM manufacturing, we will report preliminary manufacturing results of the new structure.
Recursive Directional Ligation by Plasmid Reconstruction Allows Rapid and Seamless Cloning of Oligomeric Genes (2010)

This paper reports a new strategy, recursive directional ligation by plasmid reconstruction (PRe-RDL), to rapidly clone highly repetitive polypeptides of any sequence and specified length over a large range of molecular weights. In a single cycle of PRe-RDL, two halves of a parent plasmid, each containing a copy of an oligomer, are ligated together, thereby dimerizing the oligomer and reconstituting a functional plasmid. This process is carried out recursively to assemble an oligomeric gene with the desired number of repeats. PRe-RDL has several unique features that stem from the use of type IIs restriction endonucleases: first, PRe-RDL is a seamless cloning method that leaves no extraneous nucleotides at the ligation junction. Because it uses type IIs endonucleases to ligate the two halves of the plasmid, PRe-RDL also addresses the major limitation of RDL in that it abolishes any restriction on the gene sequence that can be oligomerized. The reconstitution of a functional plasmid only upon successful ligation in PRe-RDL also addresses two other limitations of RDL: the significant background from self-ligation of the vector observed in RDL, and the decreased efficiency of ligation due to nonproductive circularization of the insert. PRe-RDL can also be used to assemble genes that encode different sequences in a predetermined order to encode block copolymers or append leader and trailer peptide sequences to the oligomerized gene.