gebhart/patrepeval huggingface dataset:
Synthesis and hybridization analysis of a small library of peptide- oligonucleotide conjugates (1998)

A small library of 49 peptide-oligonucleotide conjugates were synthesized to explore the influence of various peptide side chains on the hybridization properties of the DNA. An invariant 8mer oligonucleotide was coupled to a peptide portion that contained a five residue variable region composed of the cationic amino acids lysine, ornithine, histidine and arginine, the hydrophobic amino acid tryptophan, and alanine as a spacer. Melting temperature analysis indicated that T m depended principally on the number of cationic residues. The free energies of binding for polycationic peptide-oligonucleotides were enhanced compared with the unmodified 8mer. The origin of this stabilizing effect was found to be derived from a more exothermic enthalpic term. Improvement in Delta G vH was found to depend on the presence of positive charge and also the exact identity of the cationic amino acid, with the polyarginine peptide giving the most favourable Delta G vH value and the most exothermic Delta H vH. Further exploration suggested that the cationic peptide fragments interacted mainly with single-stranded rather than duplex DNA. A study of pH dependence showed that the polyhistidine conjugate was particularly sensitive to pH changes near neutrality, as indicated by a significant rise in T m from 19.5 degrees C at pH 8.0 to 28.5 degrees C at pH 6.0.
Quantum ghost imaging experiments (2006)

Quantum ghost imaging was explored by use of a chaotic laser light source, a photon effcient charged coupled device (CCD) camera, a stencil mask, a photon bucket detector, and computer processing. We investigated and successfully achieved quantum ghost imaging of the stencil letters ARL from macroscopic time integration scales of 1ms to 10ms. Importantly, quantum ghost images were obtained from photons which did not interact with the letter object. In addition to the timescale effect on ghost imaging we investigated the role of speckle spatial size in resolving images. Results are presented from our investigations of these components of the time and space correlations of photons emanating from chaotic laser light and ending in both the photon bucket detector arm and the CCD arm. Important applications for quantum imaging and quantum ghost imaging are also discussed.
Quinoline derivatives as antiallergy agents (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuinoline derivatives as antiallergy agentsCharles M. Hall, Herbert G. Johnson, and John B. WrightCite this: J. Med. Chem. 1974, 17, 7, 685–690Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://pubs.acs.org/doi/10.1021/jm00253a006https://doi.org/10.1021/jm00253a006research-articleACS PublicationsRequest reuse permissionsArticle Views299Altmetric-Citations29LEARN 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-Alertsclose Get e-Alerts
Two-dimensional electron gas charge-coupled devices (2DEG-CCDs) (1991)

The two-dimensional electron gas charge-coupled device (2DEG-CCD) structure is an outgrowth of recent advances in 2DEG-FET structures for digital logic circuitry and microwave devices. The 2DEG-FET structures, which are known by severalacronyms such as HEMT, SDHT, TEGFET, HIGFET, and MODFET, utilize the abrupt heterointerface between two semiconductor materials and consequent conduction band discontinuity to confine electrons [1]. Due to confinement in the direction perpendicular to the interface, the resultant electron distribution is known as a two-dimensional electron gas. Because of the confinement dimensions and the low electron effective mass usually associated with group 111-V materials, quantum mechanics plays an important role in broadening the spatial electron distribution and defining allowed energy states. However, quantum effects typically play a minor role in understanding device behavior at temperatures above 77 K. 2DEG-FET devices have several attributes which include very high mobility of the channel charge (typically in excess of 5,000 cm2/V-sec at room temperature), high transconductance, and low voltage swing requirements.
Evidence for an Erythropoietin-Stimulating Factor in Patients with Renal and Hepatic Disease (1983)

Recently, a factor was discovered in the serum of hepatectomized animals which was capable of augmenting the hepatic erythropoietin response to hypoxia when injected into normal rats. This substance was localized in the liver via an in situ perfusion technique and was termed the hepatic erythropoietic factor (HEF). Patients with kidney disease, liver disease, and combined renal and hepatic disease were studied in this report. Detectable HEF levels were found in the plasma of patients with both liver and kidney disease and were highest in anephric patients with various liver diseases. However, HEF levels were negligible in normal humans or in patients manifesting renal disease with no hepatic involvement. The data suggest that HEF-induced hepatic erythropoietin synthesis may occur in humans as well as in animals.
Identification and characterization of cells infiltrating the graft and aqueous humour in rat corneal allograft rejection (1997)

In a rat model of corneal transplantation, Fischer 344 (RT1(lv1)) rats received orthotopic corneal isografts or Wistar-Furth (RT1(u)) donor allografts. Rejection was observed in 25 of 26 allograft recipients, at a median time of 18 days, with all isografts surviving > 100 days. Flow cytometric analysis of aqueous humour identified cellular infiltration of the aqueous at the time of allograft rejection, in contrast to the acellular aqueous found in isografts at corresponding times following transplantation. A higher proportion of CD8+ than CD4+ cells was found at days 1-3 following rejection, whereas there was a higher proportion of CD4+ cells at days 5-8. No changes in peripheral blood T cell subsets were found at the time of rejection. Immunohistochemical analysis of cells infiltrating recipient iris and grafted cornea undertaken at days 1-2, 4 and 7-10 following onset of rejection, demonstrated inflammatory cells in the graft epithelium, stroma and aggregated on the endothelium. Large numbers of macrophages, T cells (CD4+ > CD8+ at all time points), natural killer (NK) cells and neutrophils were detected in graft tissue at days 1-2 and 4, diminishing after that time. Most infiltrating cells expressed MHC class II antigen, and a smaller number expressed IL-2R. Expression of the co-stimulatory marker B7 was identified in a few cells at day 4 in the region of the graft-host wound. The immune response in graft rejection was characterized at day 4 also by expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells of iris and corneal vessels, demonstration of interferon-gamma on mononuclear cells in the peripheral (recipient) cornea, and tumour necrosis factor-alpha on aggregated mononuclear cells on the graft, but not recipient, endothelium. Only sparse cellular infiltrates were found in isograft controls, with inflammation located at the graft-host wound. These findings suggest that inflammatory cells reach a corneal allograft by two routes--from vessels in the peripheral recipient cornea, and from vessels in the recipient iris via the aqueous humour. Different aqueous and intragraft T cell subset proportions were seen early in rejection, although a preponderance of CD4+ cells was found in both aqueous and graft at later times.
False sharing and spatial locality in multiprocessor caches (1994)

The performance of the data cache in shared-memory multiprocessors has been shown to be different from that in uniprocessors. In particular, cache miss rates in multiprocessors do not show the sharp drop typical of uniprocessors when the size of the cache block increases. The resulting high cache miss rate is a cause of concern, since it can significantly limit the performance of multiprocessors. Some researchers have speculated that this effect is due to false sharing, the coherence transactions that result when different processors update different words of the same cache block in an interleaved fashion. While the analysis of six applications in the paper confirms that false sharing has a significant impact on the miss rate, the measurements also show that poor spatial locality among accesses to shared data has an even larger impact. To mitigate false sharing and to enhance spatial locality, we optimize the layout of shared data in cache blocks in a programmer-transparent manner. We show that this approach can reduce the number of misses on shared data by about 10% on average.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DNA polymerase III accessory proteins. IV. Characterization of chi and psi (1993)

The gamma complex (gamma delta delta' chi psi) subassembly of the Escherichia coli replicase initiates processive replication upon assembling the ring-shaped beta subunit around DNA. The beta ring acts as a clamp to hold the replicase down to DNA for highly processive synthesis. In this report we characterize the chi and psi subunits of the gamma complex. Both chi and psi are monomeric, and they associate to form a 1:1 complex. The chi subunit does not form a complex with gamma, but psi binds gamma tightly thereby acting as a bridge to assimilate chi into the gamma complex structure. The psi subunit stimulated the ATPase and replication activities of gamma. The chi subunit only stimulated the activities of gamma when the psi subunit was also present thus reflecting the structure where psi bridges the interaction of chi with gamma.
Artificial intelligence in clinical and genomic diagnostics (2019)

Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algorithms and the graphics processing units (GPUs) that power their training, have led to a recent and rapidly increasing interest in medical AI applications. In clinical diagnostics, AI-based computer vision approaches are poised to revolutionize image-based diagnostics, while other AI subtypes have begun to show similar promise in various diagnostic modalities. In some areas, such as clinical genomics, a specific type of AI algorithm known as deep learning is used to process large and complex genomic datasets. In this review, we first summarize the main classes of problems that AI systems are well suited to solve and describe the clinical diagnostic tasks that benefit from these solutions. Next, we focus on emerging methods for specific tasks in clinical genomics, including variant calling, genome annotation and variant classification, and phenotype-to-genotype correspondence. Finally, we end with a discussion on the future potential of AI in individualized medicine applications, especially for risk prediction in common complex diseases, and the challenges, limitations, and biases that must be carefully addressed for the successful deployment of AI in medical applications, particularly those utilizing human genetics and genomics data.
Biosynthesis of hydrocarbons in Anabaena variabilis. Incorporation of [methyl-14C] and [methyl-2H2] Methionine into 7- and 8-methyl-heptadecanes (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiosynthesis of hydrocarbons in Anabaena variabilis. Incorporation of [methyl-14C] and [methyl-2H2] Methionine into 7- and 8-methyl-heptadecanesSteven W. G. Fehler and Robley J. LightCite this: Biochemistry 1970, 9, 2, 418–422Publication Date (Print):January 20, 1970Publication History Published online1 May 2002Published inissue 20 January 1970https://pubs.acs.org/doi/10.1021/bi00804a032https://doi.org/10.1021/bi00804a032research-articleACS PublicationsRequest reuse permissionsArticle Views178Altmetric-Citations63LEARN 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-Alertsclose Get e-Alerts
Optical properties of rolled-up tubular microcavities from shaped nanomembranes (2009)

Tubular optical microcavities have been fabricated by releasing prestressed SiO/SiO2 bilayer nanomembranes from polymer sacrificial layers, and their geometrical structure is well controlled by defining the shape of nanomembranes via photolithography. Optical measurements at room temperature demonstrate that resonant modes of microtubular cavities rolled up from circular shapes can be tuned in peak energy and relative intensity along the tube axes compared to those from square patterns. The resonant modes shift to higher energy with decreasing number of tube wall rotations and thickness, which fits well to finite-difference time-domain simulations. Polarization resolved measurements of the resonant modes indicate that their polarization axes are parallel to the tube axis, independent of the polarization of the excitation laser.
Beyond JAK inhibitor therapy in myelofibrosis (2013)

Myelofibrosis (MF), including primary MF, postpolycythemia vera MF, and postessential thrombocythemia MF, is a clonal stem cell disorder characterized by BM fibrosis, extramedullary hematopoiesis, and a variable propensity to transform into acute leukemia. Allogeneic stem cell transplantation is the only known cure for MF, but its applicability is limited by the advanced age of most patients and by comorbid conditions. In the past decade, there has been an explosion of information on the molecular-genetic features associated with these diseases, fueled recently by the discovery of the JAK2V617F mutation. The development of JAK inhibitors has represented a significant therapeutic advance for these diseases; however, their use in MF has not yet been associated with eradication or a significant suppression of the malignant clone. In this era, much remains to be understood about MF, but it is likely that the identification of key pathogenetic drivers of the disease, coupled with the availability of novel molecularly targeted agents, will result in the discovery of new agents that significantly alter the natural history of the disease. This review focuses on recent and ongoing efforts in the development of novel agents in MF that go beyond the field of JAK inhibitors.
Glibenclamide Reduces Inflammation, Vasogenic Edema, and Caspase-3 Activation after Subarachnoid Hemorrhage (2008)

Subarachnoid hemorrhage (SAH) causes secondary brain injury due to vasospasm and inflammation. Here, we studied a rat model of mild-to-moderate SAH intended to minimize ischemia/hypoxia to examine the role of sulfonylurea receptor 1 (SUR1) in the inflammatory response induced by SAH. mRNA for Abcc8, which encodes SUR1, and SUR1 protein were abundantly upregulated in cortex adjacent to SAH, where tumor-necrosis factor-alpha (TNFalpha) and nuclear factor (NF)kappaB signaling were prominent. In vitro experiments confirmed that Abcc8 transcription is stimulated by TNFalpha. To investigate the functional consequences of SUR1 expression after SAH, we studied the effect of the potent, selective SUR1 inhibitor, glibenclamide. We examined barrier permeability (immunoglobulin G, IgG extravasation), and its correlate, the localization of the tight junction protein, zona occludens 1 (ZO-1). SAH caused a large increase in barrier permeability and disrupted the normal junctional localization of ZO-1, with glibenclamide significantly reducing both effects. In addition, SAH caused large increases in markers of inflammation, including TNFalpha and NFkappaB, and markers of cell injury or cell death, including IgG endocytosis and caspase-3 activation, with glibenclamide significantly reducing these effects. We conclude that block of SUR1 by glibenclamide may ameliorate several pathologic effects associated with inflammation that lead to cortical dysfunction after SAH.
Learning Subjective Adjectives from Corpora (2000)

Subjectivity tagging is distinguishing sentences used to present opinions and evaluations from sentences used to objectively present factual information. There are numerous applications for which subjectivity tagging is relevant, including information extraction and information retrieval. This paper identifies strong clues of subjectivity using the results of a method for clustering words according to distributional similarity (Lin 1998), seeded by a small amount of detailed manual annotation. These features are then further refined with the addition of lexical semantic features of adjectives, specifically polarity and gradability (Hatzivassiloglou &amp;amp; McKeown 1997), which can be automatically learned from corpora. In 10-fold cross validation experiments, features based on both similarity clusters and the lexical semantic features are shown to have higher precision than features based on each alone.
Fast and faster: A designed variant of the B‐domain of protein A folds in 3 μsec (2004)

We have introduced the mutation glycine 29 to alanine, designed to increase the rate of protein folding, into the B-domain of protein A (BdpA). From NMR lineshape analysis, we find the G29A mutation increases the folding rate constant by threefold; the folding time is 3 microsec. Although wild-type BdpA folds extremely fast, simple-point mutations can still speed up the folding; thus, the folding rate is not evolutionarily maximized. The short folding time of G29A BdpA (the shortest time yet reported) makes it an attractive candidate for an all-atom molecular dynamics simulation that could potentially show a complete folding reaction starting from an extended chain. We also constructed a fluorescent variant of BdpA by mutating phenylalanine 13 to tryptophan, allowing fluorescence-based time-resolved temperature-jump measurements. Temperature jumps and NMR complement each other, and give a very complete picture of the folding kinetics.
Atomic Layer Deposition of Ultrathin Copper Metal Films from a Liquid Copper(I) Amidinate Precursor (2006)

We report a method for producing thin, completely continuous and highly conductive copper films conformally inside very narrow holes with aspect ratios over 35:1 by atomic layer deposition (ALD). Pure copper thin films were grown from a novel copper(I) amidinate precursor, copper(I) -di-sec-butylacetamidinate, and molecular hydrogen gas as the reducing agent. This copper precursor is a liquid during vaporization because its melting point is lower than its vaporization temperature . Thus, the transport of the precursor vapor is very reproducible and controllable. Carbon and oxygen impurities were below 1 atom %. The growth per cycle varied from on or surfaces but was only on metallic Ru, Cu, and Co surfaces. On oxide surfaces, copper atoms form isolated copper crystallites that merge into rough polycrystalline films after more deposition cycles. On Ru and Co metal surfaces ALD Cu nucleates densely, forming smooth and strongly adherent films that are continuous even for films as thin as 4 atomic layers. With Cu deposited on Ru substrates, the sheet resistance is below /◻, which is low enough for making seed layers for electroplating Cu interconnect wires.
Type II diabetes mellitus. (1998)

Type II diabetes is a common disorder whose prevalence is increasing in the United States and throughout the world. Type II diabetes is also associated with several other metabolic abnormalities such as central obesity, hypertension, and dyslipidemia, which contributes to the very high rate of cardiovascular morbidity and mortality. The main pathologic defects in diabetes consist of excessive hepatic glucose production, peripheral insulin resistance, and defective beta-cell secretory function. The duration and severity of the hyperglycemia dictate the microvascular complications, no matter what the etiology of the glucose intolerance, and the goals of therapy should be similar to those of insulin-dependent type I diabetic patients. Initiation of nonpharmacologic therapy should be started as soon as the diagnosis is made. Pharmacologic agents should be initiated if the glycemic goals are not met with a 3-month trial of diet and exercise. The cornerstone of therapy consists of a regular exercise routine along with a diet consisting of 40% to 50% complex carbohydrates, 10% to 20% protein, and monounsaturated fats such as canola oil and olive oil. If nonpharmacologic therapy does not achieve adequate glycemic control, initiation of an oral antidiabetic agent is warranted. In addition to the sulfonylureas, which work by stimulating insulin secretion, we now have metformin, which inhibits excessive hepatic glucose production; acarbose, which delays the absorption of carbohydrates in the gut; and troglitazone, which reduces insulin, resistance primarily in skeletal muscle. The selection of an initial oral antidiabetic agent depends on patient characteristics such as the presence of obesity and dyslipidemia, the duration of diabetes, and other concomitant conditions. Combination therapy with two or three of the different classes of oral antidiabetic agents is effective and has been used throughout the world. When maximum doses of oral antidiabetic agents do not adequately control glycemia, insulin therapy is necessary. In selected patients, combination therapy consisting of bedtime intermediate-acting insulin in addition to daytime oral antidiabetic agent(s) can be an effective method to normalize glucose control without the need for rigorous insulin regimens. When combination therapy fails, a split-mixed regimen using premixed 70/30 insulin prebreakfast and predinner can be very effective in obese subjects. In thin insulin-requiring subjects with type II diabetes, more intensive regimens may be required. In general, the risk of severe hypoglycemia is quite low in patients with type II diabetes, and the main adverse effect of insulin therapy is weight gain. Prevention and aggressive treatment of glucose intolerance and the other adverse metabolic conditions associated with type II diabetes will not only have a positive effect on the quality of life but also provide long-term cost savings.