gebhart/patrepeval huggingface dataset:
Ligation-anchored PCR: a simple amplification technique with single-sided specificity. (1992)

A simple, efficient, and sensitive technique has been developed for amplification of cDNAs encoding molecules with 5' regions of unknown sequence. In this ligation-anchored PCR, T4 RNA ligase is used to covalently link an "anchor" oligonucleotide to first-strand cDNAs. These anchored cDNAs are then amplified by using one PCR primer specific for the anchor and another specific for a sequence within the molecule of interest. The anchor oligonucleotide has been especially designed to facilitate subsequent analysis and cloning of the resultant PCR products. This three-stage procedure does not require purification of product between steps and avoids many of the technical difficulties associated with established anchored PCR protocols. The efficacy of ligation-anchored PCR was demonstrated by amplification of a specific IgG1 cDNA; total RNA equivalent to as few as 100 cells yielded the expected PCR product.
Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro. (1993)

Transforming growth factor-beta (TGF-beta) has been shown to be produced in the central nervous system (CNS). The functions of TGF-beta, however, remain to be elucidated. We investigated the effects of TGF-beta on the proliferation, activation, and cytokine production of isolated microglia in vitro. TGF-beta dose-dependently suppressed the acid phosphatase activity of and formation of superoxide anion by LPS activated microglia. It also suppressed the IFN-gamma-induced expression of class II MHC Ag- and the production of cytokines, IL-1, IL-6, and TNF-alpha, by these cells. TGF-beta also inhibited the proliferation of microglia that was induced by either GM-CSF or M-CSF. Because various immunoregulatory cytokines are produced in the CNS that serve as autocrine or paracrine mediators it is suggested that TGF-beta could be a negative regulator in the CNS cytokine network. It may play a role in the development of various disease processes in the CNS by inhibiting the function of microglia in inflammation or in immunoregulation.
Signed networks in social media (2010)

Relations between users on social media sites often reflect a mixture of positive (friendly) and negative (antagonistic) interactions. In contrast to the bulk of research on social networks that has focused almost exclusively on positive interpretations of links between people, we study how the interplay between positive and negative relationships affects the structure of on-line social networks. We connect our analyses to theories of signed networks from social psychology. We find that the classical theory of structural balance tends to capture certain common patterns of interaction, but that it is also at odds with some of the fundamental phenomena we observe --- particularly related to the evolving, directed nature of these on-line networks. We then develop an alternate theory of status that better explains the observed edge signs and provides insights into the underlying social mechanisms. Our work provides one of the first large-scale evaluations of theories of signed networks using on-line datasets, as well as providing a perspective for reasoning about social media sites.
Concise, Stereoselective Route to the Four Diastereoisomers of 4-Methylproline (2008)

The full stereochemical characterization of 4-methylproline, a rare amino acid found in a number of peptidic secondary metabolites, has often been hindered by long reaction sequences or low stereoselectivity in the synthesis leading to reference samples. The preparation of the four diastereoisomers of 4-methylproline by a concise and stereoselective route is presented and features a six-step route with late-stage stereodivergence, good stereoselectivity for both cis- and trans-series (75% and 88% de, respectively), and good overall yields (cumulative yields of 30–40%). Additional data on the Marfey’s derivatives of the stereoisomers are also presented.
Temperature dependence of DNA translocations through solid-state nanopores (2015)

In order to gain a better physical understanding of DNA translocations through solid-state nanopores, we study the temperature dependence of λ-DNA translocations through 10 nm diameter silicon nitride nanopores, both experimentally and theoretically. The measured ionic conductance G, the DNA-induced ionic-conductance blockades [Formula: see text] and the event frequency Γ all increase with increasing temperature while the DNA translocation time τ decreases. G and [Formula: see text] are accurately described when bulk and surface conductances of the nanopore are considered and access resistance is incorporated appropriately. Viscous drag on the untranslocated part of the DNA coil is found to dominate the temperature dependence of the translocation times and the event rate is well described by a balance between diffusion and electrophoretic motion. The good fit between modeled and measured properties of DNA translocations through solid-state nanopores in this first comprehensive temperature study, suggest that our model captures the relevant physics of the process.
From system F to typed assembly language (1998)

We motivate the design of a statically typed assembly language (TAL) and present a type-preserving translation from System F to TAL. The TAL we present is based on a conventional RISC assembly language, but its static type system provides support for enforcing high-level language abstractions, such as closures, tuples, and objects, as well as user-defined abstract data types. The type system ensures that well-typed programs cannot violate these abstractions. In addition, the typing constructs place almost no restrictions on low-level optimizations such as register allocation, instruction selection, or instruction scheduling.Our translation to TAL is specified as a sequence of type-preserving transformations, including CPS and closure conversion phases; type-correct source programs are mapped to type-correct assembly language. A key contribution is an approach to polymorphic closure conversion that is considerably simpler than previous work. The compiler and typed assembly language provide a fully automatic way to produce proof carrying code, suitable for use in systems where untrusted and potentially malicious code must be checked for safety before execution.
Differential cardioprotective properties of the l- and d- enantiomers of bucindolol in a canine model of heart failure. (1985)

In previous studies racemic bucindolol was found to reverse the effects of pentobarbital-induced heart failure in anesthetized dogs. Reductions of right ventricular contractile force (RVCF), left ventricular (LV) dp/dt, and aortic blood flow (ABF) serve as indicators of depressed cardiac function in this model. In this study, racemic bucindolol (0.25 mumol/kg +0.25 mumol/kg/hr) again evoked pronounced and sustained stimulant effects on these depressed parameters. l-Bucindolol (0.125 mumol/kg +0.125 mumol/kg/hr) was a more effective stimulator of cardiac function than d-bucindolol in this model. l-Bucindolol elicited maximal increases in RVCF, ABF, LV dp/dt and heart rate of 66, 19, 30 and 11%, respectively. In comparison, d-bucindolol maximally increased these parameters only 20, 14, 12 and 4%, respectively. Total peripheral resistance was reduced 29% by l-bucindolol and 19% by d-bucindolol. The responses to l-bucindolol and racemic bucindolol were essentially the same. The myocardial stimulation and vasodilation profile derived from l-bucindolol (at one-half the molar dose of bucindolol) suggests the possible preference for its use in clinical management of congestive heart failure over bucindolol, the racemic compound. The results further suggest that l-bucindolol could also be used to treat hypertensive patients with depressed cardiac function.
New Antimalarial Drugs (2003)

Approximately 40% of the world population live in areas with the risk of malaria. Each year, 300-500 million people suffer from acute malaria, and 0.5-2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used. The development of new antimalarial drugs has been neglected since the 1970s owing to the end colonialism, changes in the areas of military engagement, and the restricted market potential. Only in recent years, in part supported by public funding programs, has interest in the development of antimalarial drugs been renewed. New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease.
Novel "p-encapsulated" InP JFETs with very low leakage for optoelectronic integration with infrared focal plane arrays (2002)

Recently, we have demonstrated a monolithic near-infrared FPA in which InGaAs photodiodes, sensitive in the 1.3-1.5 /spl mu/m wavelength spectral region, are integrated with InP junction field-effect transistor (JFET) switches at each pixel. In this array, sources of all the JFETs in each column are connected in parallel and tied to the drain of a column-addressing JFET, while sources of all column-addressing JFETs are connected in parallel at the output. To ensure high sensitivity of such arrays, it is necessary that switching JFETs have very small gate and channel leakage, since leakage currents of an entire column of pixels add up at the output, thereby limiting the maximum array dimensions and sensitivity. To minimize channel leakage, a novel JFET design was employed which is described in this paper.
Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1receptors on peripheral sympathetic nerves (1996)

1. Activation of CB1 receptors by plant cannabinoids or the endogenous ligand, anandamide, causes hypotension via a sympathoinhibitory action in anaesthetized rats. In mouse isolated vas deferens, activation of CB1 receptors inhibits the electrically evoked twitch response. To determine if these effects are related to presynaptic inhibition of noradrenaline (NA) release, we examined the effects of delta 9-tetrahydrocannabinol (delta 9-THC), anandamide and the CB1 antagonist, SR141716A, on exocytotic NA release in rat isolated atria and vasa deferentia. 2. In isolated atria and vasa deferentia preloaded with [3H]-NA, electrical field stimulation caused [3H]-NA release, which was abolished by tetrodotoxin 0.5 microM and concentration-dependently inhibited by delta 9-THC or anandamide, 0.3-10 microM. The inhibitory effect of delta 9-THC and anandamide was competitively antagonized by SR 141716A, 1-10 microM. 3. Tyramine, 1 microM, also induced [3H]-NA release, which was unaffected by tetrodotoxin, delta 9-THC or anandamide in either atria or vasa deferentia. 4. CB1 receptor mRNA is present in the superior cervical ganglion, as well as in whole brain, cerebellum, hypothalamus, spleen, and vas deferens and absent in medulla oblongata and atria, as demonstrated by reverse transcription-polymerase chain reaction. There was no evidence of the presence of CB1A receptor mRNA in ganglia, brain, or cerebellum. These results suggest that activation of presynaptic CB1 receptors located on peripheral sympathetic nerve terminals mediate sympathoinhibitory effects in vitro and in vivo.
Clinical Significance of Programmed Death-1 Ligand-1 and Programmed Death-1 Ligand-2 Expression in Human Esophageal Cancer (2005)

These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.
Label‐Free Biosensing with Hydrogel Microlenses (2006)

Soft lenses: Reversible antibody–antigen cross-links at the surface of a hydrogel microlens allow focal tuning of the microlens in response to soluble antigens (see picture; PBS=phosphate-buffered saline) to form the basis of a label-free biosensor/bioassay technique, whose sensitivity can be tuned by controlling the number of cross-links required to effect a specific swelling response.
Identification of candidate substrates for ectodomain shedding by the metalloprotease-disintegrin ADAM8 (2006)

ADAM proteases are type I transmembrane proteins with extracellular metalloprotease domains. As for most ADAM family members, ADAM8 (CD156a, MS2) is involved in ectodomain shedding of membrane proteins and is linked to inflammation and neurodegeneration. To identify potential substrates released under these pathologic conditions, we screened 10-mer peptides representing amino acid sequences from extracellular domains of various membrane proteins using the ProteaseSpot system. A soluble ADAM8 protease containing a pro- and metalloprotease domain was expressed in E. coli and purified as active protease owing to autocatalytic prodomain removal. From 34 peptides tested in the peptide cleavage assay, significant cleavage by soluble ADAM8 was observed for 14 peptides representing membrane proteins with functions in inflammation and neurodegeneration, among them the beta-amyloid precursor protein (APP). The in vivo relevance of the ProteaseSpot method was confirmed by cleavage of full-length APP with ADAM8 in human embryonic kidney 293 cells expressing tagged APP. ADAM8 cleaved APP with similar efficiency as ADAM10, whereas the inactive ADAM8 mutant did not. Exchanging amino acids at defined positions in the cleavage sequence of myelin basic protein (MBP) revealed sequence criteria for ADAM8 cleavage. Taken together, the results allowed us to identify novel candidate substrates that could be cleaved by ADAM8 in vivo under pathologic conditions.
Successful prediction of prostate cancer recurrence by gene profiling in combination with clinical data: a 5-year follow-up study. (2003)

We show here that gene expression profiling, performed with conventional techniques and focused on a selected group of genes, when used in combination with standard clinical information, provides reliable prognostic prediction of prostate cancer (CaP). We showed previously that changes in the expression of metabolically related genes are involved in CaP progression. We then proceeded to search further for correlations between patients' gene profiling and recurrence with a 5-year follow-up study conducted on the same cohort of patients in which the molecular data were obtained. CaP prognosis was first assessed on the basis of gene expression profiling alone; then the result was compared with the prediction obtained using clinical and pathological information (Gleason score, Tumor-Node-Metastasis staging, prostate volume, or prostate-specific antigen levels at the time of diagnosis). The best result was obtained with a selected combination of gene profiling and clinical/pathological parameters, which resulted in prediction of recurrence in 95.7% of patients.
A novel experimental design for comparative two‐dimensional gel analysis: Two‐dimensional difference gel electrophoresis incorporating a pooled internal standard (2003)

The comparison of two-dimensional (2-D) gel images from different samples is an established method used to study differences in protein expression. Conventional methods rely on comparing images from at least 2 different gels. Due to the high variation between gels, detection and quantification of protein differences can be problematic. Two-dimensional difference gel electrophoresis (Ettan trade mark DIGE) is an emerging technique for comparative proteomics, which improves the reproducibility and reliability of differential protein expression analysis between samples. In the application of DIGE different samples are labelled with mass and charge matched spectrally resolvable fluorescent dyes and are then separated on the same 2-D gel. Using an Escherichia coli lysate "spiked" with varying amounts of four different known proteins, we have tested a novel experimental design that exploits the sample multiplexing capabilities of DIGE, by including a standard sample in each gel. The standard sample comprises equal amounts of each sample to be compared and was found to improve the accuracy of protein quantification between samples from different gels allowing accurate detection of small differences in protein levels between samples.
Let's feed the preterm lung (2006)

he lung is generally viewed as a static structureonce growth has occurred. Its size or ability to regeneratebecomes interesting with disease or physiologic stresses.The general teaching is that the adult human lungseptates beginning at about 32-36 weeks of gestation toform alveoli, and this process continues until the child isseveral years of age. Subsequent growth is in lung size,with a constant number of about500 million alveoli until about 20years of age. Alveolar number andlung elasticity then decreaseprogressively with age. Alveolar lossby destruction in emphysemaappears to be an irreversible process.Yet, lung growth and alveolarizationcan occur even in the mature lung.Lung resection in young animals results in promptgrowth and expansion of the gas surface area in theremaining lung. More directly relevant to the article onnutritional effects on the developing lung published byMataloun et al.
Efficiently scaling out-of-order cores for simultaneous multithreading (2016)

Simultaneous multithreading (SMT) out-of-order cores waste a significant portion of structural out-of-order core resources on instructions that do not need them. These resources eliminate false ordering dependences. However, because thread interleaving spreads dependent instructions, nearly half of instructions dynamically issue in program order after all false dependences have resolved. These in-sequence instructions interleave with other reordered instructions at a fine granularity within the instruction window. We develop a technique to efficiently scale in-flight instructions through a hybrid out-of-order/in-order microarchitecture, which can dispatch instructions to efficient in-order scheduling mechanisms---using a FIFO issue queue called the shelf ---on an instruction-by-instruction basis. Instructions dispatched to the shelf do not allocate out-of-order core resources in the reorder buffer, issue queue, physical registers, or load-store queues. We measure opportunity for such hybrid microarchitectures and design and evaluate a practical dispatch mechanism targeted at 4-threaded cores. Adding a shelf to a baseline 4-thread system with 64-entry ROB improves normalized system throughput by 11.5% (up to 19.2% at best) and energy-delay product by 10.9% (up to 17.5% at best).
Efficacy of Salmeterol Xinafoate in the Treatment of COPD (1999)

These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.
Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy (2013)

X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.
Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4 (2006)

Pathological cardiac hypertrophy is considered a precursor to clinical heart failure. Understanding the transcriptional regulators that suppress the hypertrophic response may have profound implications for the treatment of heart disease. We report the generation of transgenic mice that overexpress the transcription factor CHF1/Hey2 in the myocardium. In response to the alpha-adrenergic agonist phenylephrine, they show marked attenuation in the hypertrophic response compared with wild-type controls, even though blood pressure is similar in both groups. Isolated myocytes from transgenic mice demonstrate a similar resistance to phenylephrine-induced hypertrophy in vitro, providing further evidence that the protective effect of CHF1/Hey2 is mediated at the myocyte level. Induction of the hypertrophy marker genes ANF, BNP, and beta-MHC in the transgenic cells is concurrently suppressed in vivo and in vitro, demonstrating that the induction of hypertrophy-associated genes is repressed by CHF1/Hey2. Transfection of CHF1/Hey2 into neonatal cardiomyocytes suppresses activation of an ANF reporter plasmid by the transcription factor GATA4, which has previously been shown to activate a hypertrophic transcriptional program. Furthermore, CHF1/Hey2 binds GATA4 directly in coimmunoprecipitation assays and inhibits the binding of GATA4 to its recognition sequence within the ANF promoter. Our findings demonstrate that CHF1/Hey2 functions as an antihypertrophic gene, possibly through inhibition of a GATA4-dependent hypertrophic program.
Long-term cognitive deficits in patients with good outcomes after aneurysmal subarachnoid hemorrhage from anterior communicating artery. (2006)

Despite good outcome after subarachnoid hemorrhage, persistent cognitive consequences were still manifest, limiting the patients' psychosocial functioning. The correlation between neuropsychological and neurophysiological measures indicated frontal lobe damage, which in some patients persisted for years after the hemorrhage.