gebhart/patrepeval huggingface dataset:
Peptidomimetic Growth Hormone Secretagogues. Design Considerations and Therapeutic Potential (1998)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTPeptidomimetic Growth Hormone Secretagogues. Design Considerations and Therapeutic PotentialRavi P. Nargund, Arthur A. Patchett, Mark A. Bach, M. Gail Murphy, and Roy G. SmithView Author Information Departments of Medicinal Chemistry, Clinical Pharmacology, Clinical Sciences, and Biochemistry and Physiology, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065 Cite this: J. Med. Chem. 1998, 41, 17, 3103–3127Publication Date (Web):July 17, 1998Publication History Received23 May 1997Published online17 July 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/jm970342ohttps://doi.org/10.1021/jm970342oreview-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views680Altmetric-Citations61LEARN 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 SUBJECTS:Agonists,Peptides and proteins,Peptidomimetics,Receptors,Rodent models Get e-Alerts
Separation of the Infectious Ribonucleic Acid of Potato Spindle Tuber Virus from Double-Stranded Ribonucleic Acid of Plant Tissue Extracts (1971)

The infectious ribonucleic acid (RNA) of potato spindle tuber virus (PSTV) can be separated by hydroxyapatite chromatography from double-stranded RNA detectable in low amounts in both infected and uninfected plant tissue extracts. The chromatographic behavior of ribonuclease-sensitive PSTV RNA resembles that of transfer RNA.
Detection of 91 potential conserved plant microRNAs in Arabidopsis thaliana and Oryza sativa identifies important target genes (2004)

MicroRNAs (miRNAs) are an extensive class of tiny RNA molecules that regulate the expression of target genes by means of complementary base pair interactions. Although the first miRNAs were discovered in Caenorhabditis elegans, >300 miRNAs were recently documented in animals and plants, both by cloning methods and computational predictions. We present a genome-wide computational approach to detect miRNA genes in the Arabidopsis thaliana genome. Our method is based on the conservation of short sequences between the genomes of Arabidopsis and rice (Oryza sativa) and on properties of the secondary structure of the miRNA precursor. The method was fine-tuned to take into account plant-specific properties, such as the variable length of the miRNA precursor sequences. In total, 91 potential miRNA genes were identified, of which 58 had at least one nearly perfect match with an Arabidopsis mRNA, constituting the potential targets of those miRNAs. In addition to already known transcription factors involved in plant development, the targets also comprised genes involved in several other cellular processes, such as sulfur assimilation and ubiquitin-dependent protein degradation. These findings considerably broaden the scope of miRNA functions in plants.
Urinary Peptidome May Predict Renal Function Decline in Type 1 Diabetes and Microalbuminuria (2009)

One third of patients with type 1 diabetes and microalbuminuria experience an early, progressive decline in renal function that leads to advanced stages of chronic kidney disease and ESRD. We hypothesized that the urinary proteome may distinguish between stable renal function and early renal function decline among patients with type 1 diabetes and microalbuminuria. We followed patients with normal renal function and microalbuminuria for 10 to 12 yr and classified them into case patients (n = 21) with progressive early renal function decline and control subjects (n = 40) with stable renal function. Using liquid chromatography matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we identified three peptides that decreased in the urine of patients with early renal function decline [fragments of alpha1(IV) and alpha1(V) collagens and tenascin-X] and three peptides that increased (fragments of inositol pentakisphosphate 2-kinase, zona occludens 3, and FAT tumor suppressor 2). In renal biopsies from patients with early nephropathy from type 1 diabetes, we observed increased expression of inositol pentakisphosphate 2-kinase, which was present in granule-like cytoplasmic structures, and zona occludens 3. These results indicate that urinary peptide fragments reflect changes in expression of intact protein in the kidney, suggesting new potential mediators of diabetic nephropathy and candidate biomarkers for progressive renal function decline.
Thrombopoietin expands erythroid, granulocyte-macrophage, and megakaryocytic progenitor cells in normal and myelosuppressed mice. (1996)

Thrombopoietin (Tpo), the ligand for the proto-oncogene receptor c-Mpl, increases megakaryocyte size, ploidy, and surface expression of platelet-specific glycoproteins, is inversely related to platelet mass, and is a potent in vivo stimulus of platelet production. However, several features of c-mpl biology, and that of its viral counterpart v-mpl, suggest that the action of Tpo may not be strictly limited to megakaryocytopoiesis. To investigate the possibility that Tpo might affect a multitude of cell lineages, we studied the effects of in vivo administration of the hormone on multiple types of marrow and splenic clonogenic hematopoietic progenitors. We report that Tpo acts to expand BFU-E, CFU-GM, and CFU-Mk and redistribute CFU-E in normal mice and to hasten the recovery of all of these progenitor cell types in myelosuppressed animals. These findings argue that the hematopoietic progenitor cell compartment responds to Tpo as a whole and that the in vivo effects of Tpo administration may be more wide-ranging than previously anticipated.
Tensional forces in fibrillar extracellular matrices control directional capillary sprouting (1999)

During angiogenesis, anastomosing capillary sprouts align to form complex three-dimensional networks of new blood vessels. Using an endothelial cell spheroid model that was developed to study endothelial cell differentiation processes, we have devised a novel collagen gel-based three-dimensional in vitro angiogenesis assay. In this assay, cell number-defined, gel-embedded endothelial cell spheroids act as a cellular delivery device, which serves as a focal starting point for the sprouting of lumenized capillary-like structures that can be induced to form complex anastomosing networks. Formation of capillary anastomoses is associated with tensional remodeling of the collagen matrix and directional sprouting of outgrowing capillaries towards each other. To analyze whether directional sprouting is dependent on cytokine gradients or on endothelial cell-derived tractional forces transduced through the extracellular matrix, we designed a matrix tension generator that enables the application of defined tensional forces on the extracellular matrix. Using this matrix tension generator, causal evidence is presented that tensional forces on a fibrillar extracellular matrix such as type I collagen, but not fibrin, are sufficient to guide directional outgrowth of endothelial cells. RGD peptides but not control RAD peptides disrupted the integrity of sprouting capillary-like structures and induced detachment of outgrowing endothelial cells cultured on top of collagen gels, but did not inhibit primary outgrowth of endothelial cells. The data establish the endothelial cell spheroid-based three-dimensional angiogenesis technique as a standardized, highly reproducible quantitative assay for in vitro angiogenesis studies and demonstrate that integrin-dependent matrix tensional forces control directional capillary sprouting and network formation.
Monoclonal antibodies to myeloid differentiation antigens: in vivo studies of three patients with acute myelogenous leukemia. (1983)

Three patients with acute myelogenous leukemia (AML) in relapse were treated with intravenous infusions of one or more purified murine monoclonal antibodies (MoAbs) specific for differentiation antigens on normal and malignant myeloid cells. Three of the MoAbs used were IgM immunoglobulins that react with glycolipids, while the fourth, an IgG2b, reacts with a protein antigen. Peripheral blood leukemia cell counts decreased significantly, but transiently, during treatment. Evidence of in vivo binding of each MoAb to leukemia cells was obtained, although two of the four MoAbs could not be detected in the plasma following infusion, perhaps due to circulating blocking factors. Antigenic modulation was not encountered in these studies. However, the induction of human antibody to murine MoAb was observed in one patient who was treated over a 70-day period. Toxicities encountered were minimal and included fever (3 patients), back pain (1 patient), and arthralgias and myalgias (1 patient). This is the first reported clinical trial of (1) IgM MoAbs, (2) MoAb therapy in patients with AML, (3) combinations of MoAbs directed toward different myeloid differentiation antigens, and (4) MoAbs directed to glycolipids. The relative lack of toxicity and the positive effects of MoAb treatment in the reduction of leukemia cell counts permit the continued study of more innovative approaches to the treatment of AML with MoAbs.
Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of Hepatic Nuclear Factor 4 Alpha (2010)

In summary, our study using a combination of alignment, statistical and network analysis tools to examine deep sequencing data of microRNAs in hES-MSC has led to a result that (i) identifies intracellular and exosome microRNA expression profiles of hES-MSC with a possible mechanism of miRNA mediated intercellular regulation by these cells and (ii) placed HNF4A within the cross roads of regulation by the let-7 family of microRNAs.
Vision assisted control for manipulation using virtual fixtures: experiments at macro and micro scales (2003)

We present the design and implementation of a vision-based system for micron-scale, cooperative manipulation of a surgical tool. The system is based on a control algorithm that implements a broad class of guidance modes called virtual fixtures. A virtual fixture, like a real fixture, limits the motion of a tool to a prescribed class or range. The implemented system uses vision as a sensor for providing a reference trajectory, and the control algorithm then provides haptic feedback involving direct, shared manipulation of a surgical tool. We have tested this system on the JHU Steady Hand robot and provide experimental results for path following and positioning on structures at both macroscopic and microscopic scales.
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders (2011)

Autism spectrum disorders (ASDs) are a heterogeneous group of neuro-developmental disorders. While significant progress has been made in the identification of genes and copy number variants associated with syndromic autism, little is known to date about the etiology of idiopathic non-syndromic autism. Sanger sequencing of 21 known autism susceptibility genes in 339 individuals with high-functioning, idiopathic ASD revealed de novo mutations in at least one of these genes in 6 of 339 probands (1.8%). Additionally, multiple events of oligogenic heterozygosity were seen, affecting 23 of 339 probands (6.8%). Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1, TSC2 and UBE3A by the same sequencing technology revealed that controls were carriers of oligogenic heterozygous events at significantly (P < 0.01) lower rate, suggesting oligogenic heterozygosity as a new potential mechanism in the pathogenesis of ASDs.
Variation and infectivity neutralization in influenza (2006)

Worldwide epidemics of influenza are caused by viruses that normally infect other species, particularly waterfowl, and that contain haemagglutinin membrane glycoproteins (HAs) to which the human population has no immunity. Anti-HA immunoglobulins neutralize influenza virus infectivity. In this review we outline structural differences that distinguish the HAs of the 16 antigenic subtypes (H1-16) found in viruses from avian species. We also describe structural changes in HA required for the effective transfer to humans of viruses containing three of them, H1, H2 and H3, in the 1918 (Spanish), the 1957 (Asian) and the 1968 (Hong Kong) pandemics, respectively. In addition, we consider changes that may be required before the current avian H5 viruses could pass from human to human.
Pseudointima formation in woven and knitted dacron grafts. A comparative ultrastructural analysis. (1989)

Twelve specially designed crimped aortobifurcated grafts (aorta, woven 200 porosity; right limb, woven 500 porosity; left limb, knitted 1200 porosity) were implanted into mongrel dogs that were sacrificed at two, six, eight and twelve-month intervals. Pseudointima from the mid portion of each type of graft was studied with light (LM) and transmission electron microscopy (TEM). An ocular micrometer was used to determine the thickness of the pseudointima. A trilaminar cytoarchitecture resembling the wall of a medium-sized artery existed in the pseudointima. This was characterized by an inner cellular layer, outer fibrocollagenous layer, and multi-interlamination of cells and glycosaminoglycan in the middle layer. The cellular inner layer was thickest in the knitted and thinnest in the woven 200 porosity. A zone of acellularity separated the luminal cells from the underlying myoblasts and myofibroblasts. Specificity of varying types of cell distribution occurred in the pseudointima. Myoblasts and myofibroblasts were located near the lumen while fibroblasts and mesenchymoid cells were situated near the graft. The luminal cells had the combined features of endothelial cells and myofibroblasts. Collagen and glycosaminoglycans were the dominant extracellular matrix. Despite the difference of fluid permeability in high porosity woven and knitted dacron grafts, the pseudointima was well formed and revealed no striking general cytoarchitectural difference between these two types of grafts.
CCL22 is involved in the recruitment of CD4+CD25high T cells into tuberculous pleural effusions (2010)

CCL22 appeared to be increased in TPE compared with bacterial pleural effusions or transudates. CCL22 may be responsible for the infiltration of CD4(+)CD25(high) T cells into the pleural space of patients with tuberculous pleurisy.
Directional Discretized Occluders for Accelerated Occlusion Culling (2000)

We present a technique for accelerating the rendering of high depth‐complexity scenes. In a preprocessing stage, we approximate the input model with a hierarchical data structure and compute simple view‐dependent polygonal occluders to replace the complex input geometry in subsequent visibility queries. When the user is inspecting and visualizing the input model, the computed occluders are used to avoid rendering geometry which cannot be seen. Our method has several advantages which allow it to perform conservative visibility queries efficiently and it does not require any special graphics hardware. The preprocessing step of our approach can also be used within the framework of other visibility culling methods which need to pre‐select or pre‐render occluders. In this paper, we describe our technique and its implementation in detail, and provide experimental evidence of its performance. In addition, we briefly discuss possible extensions of our algorithm.
Changes of dipalmitoyl phosphatidyl choline after mechanical ventilation in patients with acute cerebral injury. (2006)

Mechanical ventilation can decrease the DPPC levels, decrease the lung compliance and increase the airway pressure, even impair the oxygenation function in patients with acute cerebral injury. Abnormal DPPC is one of the major causes of ventilator-associated lung injury.
Cooperativity between Cell Contractility and Adhesion (2004)

In living cells, the cytoskeleton connects to the extracellular environment through focal adhesions, multimolecular structures that can sense applied force. A model is presented that for the first time explains why the focal adhesions tend to high-curvature regions at the cell periphery. It is based on experimental evidence for positive feedback between adhesion formation and assembly of actomyosin bundles (stress fibers). The model predicts that the focal adhesions propagate by treadmilling with a velocity proportional to the integrin diffusion coefficient.
Solid-state circuit breakers for Medium Voltage DC power (2011)

How can the large power needs of future electric ships for propulsion, radar, and weapons systems be met given the prohibitive size and weight of the required number of standard 60 Hz AC generators and transformers? A solution may lie in a rugged, efficient, and compact solid-state, 10-20 kV Medium Voltage DC (MVDC) circuit breaker (Figure 1). In this paper, Diversified Technologies, Inc. will describe the architecture of a Medium Voltage DC (MVDC) circuit breaker. The solid-state, 10-20 kV class breaker is a breakthrough that establishes the viability of MVDC power distribution. It delivers extremely fast fault interruption, low peak currents, flexible and programmable coordination, and mechanical isolation; the keys to reliable and safe operation.
The Topology of Bulges in the Long Stem of the Flavivirus 3′ Stem-Loop Is a Major Determinant of RNA Replication Competence (2005)

All flavivirus genomes contain a 3'terminal stem-loop secondary structure (3'SL) formed by the most downstream approximately 100 nucleotides (nt) of the viral RNA. The 3'SL is required for virus replication and has been shown to bind both virus-coded and cellular proteins. Results of the present study using an infectious DNA for WN virus strain 956 initially demonstrated that the dengue virus serotype 2 (DEN2) 3'SL nucleotide sequence could not substitute for that of the WN 3'SL to support WN genome replication. To determine what WN virus-specific 3'SL nucleotide sequences were required for WN virus replication, WN virus 3'SL nucleotide sequences were selectively deleted and replaced by analogous segments of the DEN2 3'SL nucleotide sequence such that the overall 3'SL secondary structure was not disrupted. Top and bottom portions of the WN virus 3'SL were defined according to previous studies (J. L. Blackwell and M. A. Brinton, J. Virol. 71:6433-6444, 1997; L. Zeng, L., B. Falgout, and L. Markoff, J. Virol. 72:7510-7522, 1998). A bulge in the top portion of the long stem of the WN 3'SL was essential for replication of mutant WN RNAs, and replication-defective RNAs failed to produce negative strands in transfected cells. Introduction of a second bulge into the bottom portion of the long stem of the wild-type WN 3'SL markedly enhanced the replication competence of WN virus in mosquito cells but had no effect on replication in mammalian cells. This second bulge was identified as a host cell-specific enhancer of flavivirus replication. Results suggested that bulges and their topological location within the long stem of the 3'SL are primary determinants of replication competence for flavivirus genomes.
Electrical Recording from Hearts with Flexible Nanowire Device Arrays (2009)

We show that nanowire field-effect transistor (NWFET) arrays fabricated on both planar and flexible polymeric substrates can be reproducibly interfaced with spontaneously beating embryonic chicken hearts in both planar and bent conformations. Simultaneous recordings from glass microelectrode and NWFET devices show that NWFET conductance variations are synchronized with the beating heart. The conductance change associated with beating can be tuned substantially by device sensitivity, although the voltage-calibrated signals, 4-6 mV, are relatively constant and typically larger than signals recorded by microelectrode arrays. Multiplexed recording from NWFET arrays yielded signal propagation times across the myocardium with high spatial resolution. The transparent and flexible NWFET chips also enable simultaneous electrical recording and optical registration of devices to heart surfaces in three-dimensional conformations not possible with planar microdevices. The capability of simultaneous optical imaging and electrical recording also could be used to register devices to a specific region of the myocardium at the cellular level, and more generally, NWFET arrays fabricated on increasingly flexible plastic and/or biopolymer substrates have the potential to become unique tools for electrical recording from other tissue/organ samples or as powerful implants.
Measurement of heart rate variability and stress evaluation by using microwave reflectometric vital signal sensing (2010)

In this paper, we present two robust signal processing techniques for stress evaluation using a microwave reflectometric cardiopulmonary sensing instrument. These techniques enable the heart rate variability (HRV) to be recovered from measurements of body-surface dynamic motion, which is subsequently used for the stress evaluation. Specifically, two novel elements are introduced: one is a reconfiguration of the HRV from the cross-correlation function between a measurement signal and a template signal which is constructed by averaging periodic component over a measurement time. The other is a reconstruction of the HRV from the time variation of the heartbeat frequency; this is evaluated by a repetition of the maximum entropy method. These two signal processing techniques accomplish the reconstruction of the HRV, though they are completely different algorithms. For validations of our model, an experimental setup is presented and several sets of experimental data are analyzed using the two proposed signal processing techniques, which are subsequently used for the stress evaluation. The results presented herein are consistent with electrocardiogram data.
Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet (2020)

Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention.