gebhart/patrepeval huggingface dataset:
Sequence information can be obtained from single DNA molecules (2003)

The completion of the human genome draft has taken several years and is only the beginning of a period in which large amounts of DNA and RNA sequence information will be required from many individuals and species. Conventional sequencing technology has limitations in cost, speed, and sensitivity, with the result that the demand for sequence information far outstrips current capacity. There have been several proposals to address these issues by developing the ability to sequence single DNA molecules, but none have been experimentally demonstrated. Here we report the use of DNA polymerase to obtain sequence information from single DNA molecules by using fluorescence microscopy. We monitored repeated incorporation of fluorescently labeled nucleotides into individual DNA strands with single base resolution, allowing the determination of sequence fingerprints up to 5 bp in length. These experiments show that one can study the activity of DNA polymerase at the single molecule level with single base resolution and a high degree of parallelization, thus providing the foundation for a practical single molecule sequencing technology.
[Corneal burns and matrix metalloproteinases (MMP-2 and -9): the effects of human amniotic membrane transplantation]. (2002)

The results support a role for MMP-2 and MMP-9 in corneal burn neovascularization. Amniotic membrane transplantation can play a protective role by up-regulation of their biological expression.
Assessment of Hepatic Steatosis in Patients Undergoing Liver Resection: Comparison of US, CT, T1-weighted Dual-Echo MR Imaging, and Point-resolved1H MR Spectroscopy (2010)

In contrast to US and CT, T1-weighted MR imaging and (1)H MR spectroscopy strongly correlate with histopathologic steatosis assessment and are able to demonstrate differences across steatosis grades. T1-weighted dual-echo MR imaging and (1)H MR spectroscopy had the best diagnostic accuracy in depicting hepatic steatosis.
Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene (1986)

We have isolated the human prointerleukin 1 (proIL-1) beta gene from leukocyte and fetal liver libraries. The nucleotide sequence and its gene organization reveals that the proIL-1 beta gene is composed of seven exons with a primary transcription product length of 7,008 nucleotides. The exon sequence agrees well with that of the human proIL-1 beta cDNA. Features of interest within the transcriptional unit include positioned TATA, CAT, and poly-adenylation signals for gene regulation, as well as the signatures of gene duplication via retrotransposition in the form of flanking direct repeats and a genomic poly A tail. The genomic organization of the proIL-1 beta gene with respect to the number and position of exon boundaries is strikingly similar to that of the recently reported human proIL-1 alpha gene. Therefore, we hypothesize that the proIL-1 beta may have arisen by a reverse transcriptase mediated duplication of the related alpha gene.
DNA as a Force Sensor in an Aptamer-Based Biochip for Adenosine (2009)

Without prior signal amplification, small molecules are difficult to detect by current label-free biochip approaches. In the present study, we developed a label-free capture biochip based on the comparative measurement of unbinding forces allowing for direct detection of small-molecule-aptamer interactions. The principle of this assay relies on increased unbinding forces of bipartite aptamers due to complex formation with their cognate ligands. The bipartite aptamers are immobilized on glass support via short DNA duplexes that serve as references to which unbinding forces can be compared. In a simple model system, adenosine is captured from solution by an adenosine-selective aptamer. Linking the molecular chains, each consisting of a short DNA reference duplex and a bipartite aptamer, between glass and a poly(dimethylsiloxane) (PDMS) surface and subsequently separating the surfaces compares the unbinding forces of the two bonds directly. Fluorescence readout allows for quantification of the fractions of broken aptamer and broken reference bonds. The presence of micromolar adenosine concentrations reliably resulted in a shift toward larger fractions of broken reference bonds. Because of the force-based design, the interactions between the bipartite aptamer and the target, rather than the presence of the target, are detected and no washing step disturbing the equilibrium state prior to probing and no reporter aptamer or antibody is required. The assay exhibits excellent selectivity against other nucleotides and detects adenosine in the presence of a complex molecular background. Multiplexing was demonstrated by performing whole titration experiments on a single chip revealing an effective half-maximal concentration of 124.8 microM agreeing well with literature values.
Nitinol medical devices and implants (2000)

Superelastic Nitinol is now a common and well-known engineering material in the medical industry. While the greater flexibility of the alloy drives many of its applications, there are also a large number of lesser-known advantages of Nitinol in medical devices. This paper reviews 7 of these less-obvious but very important reasons for Nitinol's success, both past and future. Several new medical applications will be used to exemplify these points, including the quickly-growing and technologically-demanding stent applications. Stents are particularly interesting because they take advantage of the thermoelastic hysteresis of Nitinol.
MAPK-activated Protein Kinase 2 Differentially Regulates Plasmodium falciparum Glycosylphosphatidylinositol-induced Production of Tumor Necrosis Factor-α and Interleukin-12 in Macrophages (2009)

Proinflammatory responses induced by Plasmodium falciparum glycosylphosphatidylinositols (GPIs) are thought to be involved in malaria pathogenesis. In this study, we investigated the role of MAPK-activated protein kinase 2 (MK2) in the regulation of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12, two of the major inflammatory cytokines produced by macrophages stimulated with GPIs. We show that MK2 differentially regulates the GPI-induced production of TNF-alpha and IL-12. Although TNF-alpha production was markedly decreased, IL-12 expression was increased by 2-3-fold in GPI-stimulated MK2(-/-) macrophages compared with wild type (WT) cells. MK2(-/-) macrophages produced markedly decreased levels of TNF-alpha than WT macrophages mainly because of lower mRNA stability and translation. In the case of IL-12, mRNA was substantially higher in MK2(-/-) macrophages than WT. This enhanced production is due to increased NF-kappaB binding to the gene promoter, a markedly lower level expression of the transcriptional repressor factor c-Maf, and a decreased binding of GAP-12 to the gene promoter in MK2(-/-) macrophages. Thus, our data demonstrate for the first time the role of MK2 in the transcriptional regulation of IL-12. Using the protein kinase inhibitors SB203580 and U0126, we also show that the ERK and p38 pathways regulate TNF-alpha and IL-12 production, and that both inhibitors can reduce phosphorylation of MK2 in response to GPIs and other toll-like receptor ligands. These results may have important implications for developing therapeutics for malaria and other infectious diseases.
Light and Electron Microscopic Study of Port-Wine Stains after Flashlamp Dye Laser Treatment (1991)

Selective photothermolysis of port-wine stains induced by Candela model SPTL-1P (577nm) and SPTL-1 (585nm) flashlamp pumped pulsed dye lasers were examined light and electron microscopically. Immediately after irradiation, red blood cells agglutination and heat necrosis were found at the dilated vessels in the dermis, and perivascular collagen fibrils necrosis was minimum. Twenty-four hours after irradiation, a lot of inflammatory cells were infiltrated around the necrotic vessels. One month after irradiation, the area in which dilated vessels had showed necrosis was replaced by granulation tissue. No recurrence or scar formation was observed in the dermis 6 months after irradiation. Comparing to SPTL-1P (577nm), SPTL-1 (585nm) showed deeper penetration in the dermis while the selectivity of vessel necrosis was not different between them. In the cases with epidermal hyperpigmentation, epidermal necrosis and reepithelization was found after irradiation. The reepithelized epidermis showed the state of pigment blockade for several weeks, and returned to normal pigmentation within 6 months.
25‐Hydroxycholesterol sulfation regulates lipid metabolism in vivo in mice (2011)

Background Oxysterol sulfotransferase, SULT2B1b, catalyzes sulfation of 25‐hydroxycholesterol (25HC). The product 25‐hydroxycholesterol‐3‐sulfate (25HC3S) was found to decrease cellular lipids in human aortic endothelial cells, macrophages, and hepatocytes via inactivation of LXR/SREBP‐1c signaling. 25HC3S appears to be a potent regulator of lipid metabolism with regulatory properties opposite to those of its precursor 25‐HC. Hypothesis Oxysterol sulfation, by determining the balance between 25HC and 25HC3S, could play an important role in lipid homeostasis. Results Following transfection, the SULT2B1b gene was successfully overexpressed in liver, aorta and lung tissues, but not in heart or kidney. SULT2B1b overexpression significantly decreased hepatic triglycerides by 30%, total cholesterol by 28%, and free cholesterol by 18%, as compared to control, while fatty acids were unchanged. Gene expression analysis showed that increases in SULT2B1b expression were accompanied by reduction in key regulators and enzymes in lipid metabolism, including SREBP‐1, SREBP‐2, acetyl‐CoA carboxylase‐1 and fatty acid synthase. Conclusion Overexpression of SULT2B1b, accompanied by 25HC administration, suppresses SREBP‐1 and ‐2 and decreases serum and hepatic lipids in cholesterol‐fed mice. This finding supports the hypothesis that 25HC3S is an important endogenous regulator of lipid biosynthesis. This pathway may represent a novel target for pharmacological intervention in NAFLD.
Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes (2015)

Brown adipocytes (BAs) play important roles in body temperature regulation, energy balance, and carbohydrate and lipid metabolism. Activities of BAs are remarkably diminished in obese and diabetic patients, providing possibilities of transplanting functional BAs resulting in therapeutic benefit. Here, we show generation of functional BAs by cellular reprogramming procedures. Transduction of the PRDM16 gene into iPSC-derived embryoid bodies induced BA phenotypes (iBAs). Moreover, normal human fibroblasts were directly converted into BAs (dBAs) by C/EBP-β and C-MYC gene transduction. Approximately 90% of the fibroblasts were successfully converted within 12 days. The dBAs were highly active in mitochondrial biogenesis and oxidative metabolism. Mouse dBAs were induced by Prdm16, C/ebp-β, and L-myc genes, and after transplantation, they significantly reduced diet-induced obesity and insulin resistance in an UCP1-dependent manner. Thus, highly functional BAs can be generated by cellular reprogramming, suggesting a promising tailor-made cell therapy against metabolic disorders including type 2 diabetes mellitus.
Downregulating sphingosine kinase-1 for cancer therapy (2008)

The studies described provide strong evidence that strategies to kill cancer cells via sphingosine kinase-1 inhibition are valid and could have a favorable therapeutic index.
Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition (2013)

Antifolates, folate analogs that inhibit vitamin B9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.
A proteomic analysis of mammalian preimplantation embryonic development (2005)

Genetic studies on the mammalian preimplantation embryo are providing a wealth of information regarding gene expression. However, changes in the transcriptome do not always reflect cellular function or the complexity and diversity of the mammalian proteome with post-translational modifications or protein-protein interactions. To elucidate embryonic cellular function, a detailed understanding at the protein level is necessary. The aim of this study was to generate protein profiles of mammalian embryos throughout development, and to investigate the effects of oxygen concentration on the embryonic proteome. A protocol was developed to analyse small groups of embryos (n = 5) by time-of-flight mass spectrometry. F1 mice zygotes were cultured in G1/G2 sequential media with recombinant albumin (2.5 mg/ml) in 6% CO(2) and O(2) concentrations of either 5% or 20%. In vivo-developed embryos were flushed from the reproductive tract (day 4). Protein profiles were generated for all embryonic samples and statistical analysis revealed 32 potential proteins/biomarkers with significant changes (P < 0.05). Embryos generated under 5% O(2) more closely resembled in vivo-developed embryos. Under 20% O(2) conditions, embryos showed down-regulation of 10 proteins/biomarkers (masses between 4 to 20 kDa) (P < 0.05) confirming the pathological effects of oxygen during embryonic development. These data demonstrate for the first time the complexity of the mammalian preimplantation proteome. The unique protein profiles of in vivo-developed embryos and a panel of selected biomarkers represent optimal cellular function, against which comparisons can be made to facilitate improvements in mammalian assisted reproduction techniques procedures.
Manipulation of differential electron yields via autoionizing wave-packet control (2001)

Ultrashort laser pulses have been used to produce nonstationary Ca $4pnl$ autoionizing states via sudden isolated-core excitation of $4snl$ angular Rydberg wave packets. The angular distributions of the electrons ejected into the $4s\ensuremath{\epsilon}l$ and $3d\ensuremath{\epsilon}l$ continua are altered by varying the initial orientation of the $4snl$ angular wave packet. While the observed level of control is less than might be expected from an intuitive picture, it is in excellent agreement with R-matrix quantum-defect theory calculations.
Nocturnal desaturation in patients with stable heart failure (1998)

Nocturnal desaturation is common in patients with treated heart failure. Low ejection fraction was related to dip frequency. Lack of correlation between dips and ESS suggests that arousal from sleep is more important than hypoxia in the aetiology of daytime sleepiness in heart failure. Overnight oximetry is a useful screening test for Cheyne-Stokes respiration in patients with known heart failure.
Vitamin B6 biosynthesis: formation of pyridoxine 5′‐phosphate from 4‐(phosphohydroxy)‐l‐threonine and 1‐deoxy‐d‐xylulose‐5‐phosphate by PdxA and PdxJ protein (1999)

In Escherichia coli the coenzyme pyridoxal 5'-phosphate (PLP) is synthesised de novo by a pathway that is thought to involve the condensation of 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose, catalysed by the enzymes PdxA and PdxJ, to form either pyridoxine (vitamin B6) or pyridoxine 5'-phosphate (PNP). Here we show that incubation of PdxJ with PdxA, 4-(phosphohydroxy)-L-threonine, NAD and 1-deoxy-D-xylulose-5-phosphate, but not 1-deoxy-D-xylulose, results in the formation of PNP. The PNP formed was characterised by (i) cochromatography with an authentic standard, (ii) conversion to pyridoxine by alkaline phosphatase treatment, and (iii) UV and fluorescence spectroscopy. Furthermore, when [2-(14)C]1-deoxy-D-xylulose-5-phosphate was used as a substrate, the radioactivity was incorporated into PNP. These results clarify the previously unknown role of PdxJ in the de novo PLP biosynthetic pathway. The sugar used as substrate by PdxJ is 1-deoxy-D-xylulose-5-phosphate rather than the previously assumed 1-deoxy-D-xylulose. The first vitamin B6 vitamer synthesised is PNP, and not pyridoxine.
Development of a Syngeneic Rat Brain Tumor Model Expressing EGFRvIII and Its Use for Molecular Targeting Studies with Monoclonal Antibody L8A4 (2005)

Based on these data, we have concluded that the F98(npEGFRvIII) glioma should be a valuable animal model for therapy studies focusing on molecular targeting of EGFRvIII by receptor specific mAbs.
Flying head read/write characteristics using a monolithically integrated laser diode/photodiode at a wavelength of 1.3 μm (1991)

A feasibility study is shown for an optical disk drive using an optically switched laser (OSL) flying head. This head consists of an AlN slider and 1.3-micrometers wavelength InGaAsP laser diode monolithically integrated with a photodiode. The laser diode has a taper-ridged waveguide on the top of the facet facing the recording medium. The disk consists of an SiN dielectric protective layer, an SbTe Ge recording medium, and 1.5-micrometers -track pitch sampled servo format pits on the glass substrate. The lensless near-field flying head gives excellent read/write performance and head/medium reliability: a high-quality readout SNR of 35 dB, stable write operation with 16 mW of laser power, and a lifetime of 4.4 X 10<SUP>8</SUP> passes under experimental room conditions.
Nicotine-Derived Compounds as Therapeutic Tools Against Post-Traumatic Stress Disorder (2015)

Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in eliciting abnormal fear responses are urgently required. Cotinine, the main metabolite of nicotine, decreased anxiety and depressive-like behavior, and enhanced fear extinction in mouse models of PTSD. Cotinine, considered a positive modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), enhances fear extinction in rodents in a manner dependent on the activity of the αnAChRs. Cotinine stimulates signaling pathways downstream of α7nAChR including the protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway and the extracellular signal-regulated kinases (ERKs). The stimulation of these factors promotes synaptic plasticity and the extinction of fear. In this review, we discuss the hypothesis that cotinine relieves PTSD symptoms and facilitates fear memory extinction by promoting brain plasticity through the positive modulation of presynaptic nAChRs and its effectors in the brain.
Soluble CD23 (Fc epsilon RII) and interleukin 1 synergistically induce early human thymocyte maturation. (1990)

The ability of human thymus-derived CD7+CD2-CD3- cells to acquire mature T cell antigens was assessed. Purified CD7+ thymocytes were incubated with rIL-1, rIL-2, and/or recombinant soluble CD23 (rsCD23). Short-term incubation of these cells with only rsCD23 + rIL-1 induced mature T cell antigen expression on at least half of the cells. The induction of CD2 was functionally significant, as these cells became able to respond to CD2 triggering and could proliferate in response to IL-2. Possible sources of CD23 in the thymus are under investigation.
Learning from Protein Structure with Geometric Vector Perceptrons (2020)

Learning on 3D structures of large biomolecules is emerging as a distinct area in machine learning, but there has yet to emerge a unifying network architecture that simultaneously leverages the graph-structured and geometric aspects of the problem domain. To address this gap, we introduce geometric vector perceptrons, which extend standard dense layers to operate on collections of Euclidean vectors. Graph neural networks equipped with such layers are able to perform both geometric and relational reasoning on efficient and natural representations of macromolecular structure. We demonstrate our approach on two important problems in learning from protein structure: model quality assessment and computational protein design. Our approach improves over existing classes of architectures, including state-of-the-art graph-based and voxel-based methods. We release our code at https://github.com/drorlab/gvp.
DNA sequence and organization of genes in a 5{middle dot}5 kbp EcoRI fragment mapping in the short unique segment of Marek's disease virus (strain RB1B) (1991)

The DNA sequence of a 5.5 kbp EcoRI fragment located in the short unique region (US) of the 'highly oncogenic' strain RB1B of Marek's disease virus (MDV) was determined. The sequence contained six open reading frames (ORFs), four of which were homologous to proteins mapping in the US region of herpes simplex virus type 1 (HSV-1). These include the homologues of HSV-1 protein kinase, glycoprotein D (gD), glycoprotein I (gI) and US2 which is of unknown function. The MDV ORFs had a marked bias for A or T in the third codon position and analysis of the dinucleotide frequencies showed a marginal deficit in ApG/CpT but no overall deviation of CpG from random expectations. Comparison of genes in the US region of MDV to herpesvirus proteins confirmed and extended our previous observation that MDV is more closely related to alphaherpesviruses than to gamma-herpesviruses. We also showed that MDV possessed a homologue of HSV-1 gD which is lacking in varicella-zoster virus (VZV) but that MDV probably lacked homologues of US4 and US5 of HSV-1. These results show that in contrast to the genes in the long unique region which were grossly collinear in HSV, VZV and MDV, those mapping in US show greater diversity.
Subclavian-axillary vein thrombosis: successful treatment with streptokinase. (1984)

Proximal vein thrombosis has been associated with residual disability from the postphlebetic syndrome in patients receiving symptomatic therapy or heparin and sodium warfarin. This paper describes a man with painless swelling of the right arm secondary to subclavian-axillary vein thrombosis that was successfully treated with streptokinase and conventional anticoagulant therapy.