gebhart/patrepeval huggingface dataset:
Identification of Niemann-Pick C1 disease biomarkers through sphingolipid profiling (2013)

Niemann-Pick type C (NPC)1 is a rare neurodegenerative disease for which treatment options are limited. A major barrier to development of effective treatments has been the lack of validated biomarkers to monitor disease progression or serve as outcome measures in clinical trials. Using targeted metabolomics to exploit the complex lipid storage phenotype that is the hallmark of NPC1 disease, we broadly surveyed Npc1(-/-) mouse tissues and identified elevated species across multiple sphingolipid classes that increased with disease progression. There was a striking accumulation of sphingoid bases, monohexosylceramides (MCs), and GM2 gangliosides in liver, and sphingoid bases and GM2 and GM3 gangliosides in brain. These lipids were modestly decreased following miglustat treatment, but markedly decreased in response to treatment with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), two drugs that have shown efficacy in NPC1 animal models. Extending these studies to human subjects led to identification of sphingolipid classes that were significantly altered in the plasma of NPC1 patients. Plasma MCs and ceramides were elevated, whereas sphingoid bases were reduced in NPC1 subjects. Intervention with miglustat in NPC1 patients was accompanied by striking alterations in plasma (reductions in GM1 and GM3 gangliosides) and cerebrospinal fluid (CSF) (increased MCs) sphingolipids. Similar alterations were observed in the CSF from the NPC1 feline model following HP-β-CD treatment. Our findings suggest that these lipid biomarkers may prove useful as outcome measures for monitoring efficacy of therapy in clinical trials.
A real-time, practical sensor fault-tolerant module for robust EMG pattern recognition (2015)

This paper presented a real-time, lightweight, and automatic SFTM, which paved the way for reliable and robust EMG PR for prosthesis control.
The EM Algorithm and Extensions, 2E (2008)

The EM algorithm and extensions 2008 , The EM algorithm and extensions 2008 , کتابخانه دیجیتال جندی شاپور اهواز
Mild Hypothermia Has Minimal Effects on the Tolerance to Severe Progressive Normovolemic Anemia in Swine (2002)

During progressive normovolemic hemodilution in pigs, hypothermia did not significantly change Hgb(CRIT), but it decreased the Hgb at death, i.e., short-term survival was prolonged.
VSE++: Improved Visual-Semantic Embeddings. (2017)

This paper investigates the problem of image-caption retrieval using joint
visual-semantic embeddings. We introduce a very simple change to the loss
function used in the original formulation by Kiros et al. (2014), which leads
to drastic improvements in the retrieval performance. In particular, the
original paper uses the rank loss which computes the sum of violations across
the negative training examples. Instead, we penalize the model according to the
hardest negative examples. We then make several additional modifications
according to the current best practices in image-caption retrieval. We showcase
our model on the MS-COCO and Flickr30K datasets through comparisons and
ablation studies. On MS-COCO, we improve caption retrieval by 21% in R@1 with
respect to the original formulation. Our results outperform the
state-of-the-art results by 8.8% in caption retrieval and 11.3% in image
retrieval at R@1. On Flickr30K, we more than double R@1 as reported by Kiros et
al. (2014) in both image and caption retrieval, and achieve near
state-of-the-art performance. We further show that similar improvements also
apply to the Order-embeddings by Vendrov et al. (2015) which builds on a
similar loss function.
Arterial Hypertension Induced by Erythropoietin and Erythropoiesis-Stimulating Agents (ESA) (2009)

This review summarizes the evidence for a hypertensinogenic effect of Erythropoietin (Epo) in normal human subjects and predialysis, hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD) patients. The possible mechanisms of Epo-induced hypertension are examined with in vivo animal and in vitro data, as well as pathophysiological human studies in both normal subjects and CKD patients. The evidence for a hypertensinogenic effect of erythropoiesis-stimulating agents (ESAs) in normal subjects, predialysis CKD, hemodialysis, and CAPD patients is compelling. Epo increases BP directly and notably independently of its erythropoietic effect and its effect on blood rheology. The potential for the development of future agents that might act as specific stimulators of erythropoiesis, devoid of direct hemodynamic side effects is underscored.
MicroRNA 135 Regulates HOXA10 Expression in Endometriosis (2011)

HOXA10 was aberrantly regulated in the endometrium of women with endometriosis by both miR135a and miR135b. Increased microRNA expression likely suppresses genes required for implantation.
GPR98 mutations cause Usher syndrome type 2 in males (2009)

Mutations in the large GPR98 gene underlie Usher syndrome type 2C (USH2C), and all patients described to date have been female. It was speculated that GPR98 mutations cause a more severe, and eventually lethal, phenotype in males. We describe for the first time two male patients with USH2 with novel GPR98 mutations. Clinical characterization of a male patient and his affected sister revealed a typical USH2 phenotype in both. GPR98 may have been excluded from systematic investigation in previous studies, and the proportion of patients with USH2C probably underestimated. GPR98 should be considered in patients with USH2 of both sexes.
A Limited Number of Transducible Hepatocytes Restricts a Wide-Range Linear Vector Dose Response in Recombinant Adeno-Associated Virus-Mediated Liver Transduction (2002)

Recombinant adeno-associated virus (rAAV) vectors are promising vehicles for achieving stable liver transduction in vivo. However, the mechanisms of liver transduction are not fully understood, and furthermore, the relationships between rAAV dose and levels of transgene expression, total number of hepatocytes transduced, and proportion of integrated vector genomes have not been well established. To begin to elucidate the liver transduction dose response with rAAV vectors, we injected mice with two different human factor IX or Escherichia coli lacZ-expressing AAV serotype 2-based vectors at doses ranging between 4.0 x 10(8) and 1.1 x 10(13) vector genomes (vg)/mouse, in three- to sixfold increments. A 2-log-range linear dose-response curve of transgene expression was obtained from 3.7 x 10(9) to 3.0 x 10(11) vg/mouse. Vector doses above 3.0 x 10(11) vg/mouse resulted in disproportionately smaller increases in both the number of transduced hepatocytes and levels of transgene expression, followed by saturation at doses above 1.8 x 10(12) vg/mouse. In contrast, a linear increase in the number of vector genomes per hepatocyte was observed up to 1.8 x 10(12) vg/mouse concomitantly with enhanced vector genome concatemerization, while the proportion of integrated vector genomes was independent of the vector dose. Thus, the mechanisms that restrict a wide-range linear dose response at high doses likely involve decreased functionality of vector genomes and restriction of transduction to fewer than 10% of total hepatocytes. Such information may be useful to determine appropriate vector doses for in vivo administration and provides further insights into the mechanisms of rAAV transduction in the liver.
N‐linked glycan profiling of GGTA1/CMAH knockout pigs identifies new potential carbohydrate xenoantigens (2013)

We provide for the first time a comparison of the serum protein glycomes of the human, domestic pig, and genetically modified pigs important to xenotransplantation.
An in vitro assay for frameshift mutations: hotspots for deletions of 1 bp by Klenow-fragment polymerase share a consensus DNA sequence. (1988)

The fidelity of in vitro DNA synthesis catalyzed by the large fragment of DNA polymerase I was examined. The templates, specifically designed to detect shifts to the +1 or to the -1 reading frame, are composites of M13mp8 and bacteriophage T4 rIIB DNA and were designed to assist in the identification of the types of frameshifts that are the specific consequence of DNA polymerization errors. In vitro polymerization by the Klenow fragment produced only deletions, rather than the mixture of duplications and deletions characteristic of in vivo frameshifts. The most frequent frameshifts were deletions of 1 bp opposite a template purine base. Hotspots for these deletions occurred when the template purine immediately preceded the template sequence TT. The highest mutation frequencies were seen when the TTPu consensus sequence was adjacent to G:C rich sequences in the 3' direction. The nature of the consensus sequence itself distinguishes this 1-bp deletion mechanism from those operating in DNA repeats and attributed to the misalignment of DNA primers during synthesis. Deletions that were larger than 1 or 2 bp isolated after in vitro replication were consistent with the misalignment of the primer. Deletions of 2 bp and complex frameshifts (the replacement of AA by C) were also found. Mechanisms that may account for these mutations are discussed.
Field emitter-array development for microwave applications (1995)

Summary form only given. In order to make microfabricated field-emitters useful for microwave operation it is necessary to maximize the transconductance of the emitter array. The parameters that determine the transconductance are the emitter tip's work function; the field-enhancement factor at the tip, /spl beta/ (E=/spl beta/V); and the packing density of the emitter array. The work function depends on the tip material and the condition of the tip's surface resulting from processing and operating environment. Control of these parameters can be rather limited in practical applications. It is shown that the most direct way to increase the transconductance is by increasing the packing density of the emitter array. With emerging lithography techniques it is possible to increase the packing density by about two orders of magnitude over what was available at the start of the microwave development effort. Updated details of how these improvements have been implemented and their impact on cathode performance are presented.
Elevated Tumor Necrosis Factorα Production Concomitant to Elevated Prostaglandin E2 Production by Trauma Patients' Monocytes (1990)

The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median = 5.93 ng/10(6) monocytes per milliliter). Increases in patients' total monocyte TNF alpha levels greater than 30 ng/10(6) monocytes per milliliter correlated with septic episodes. In patients with sepsis, the total monocyte TNF alpha levels were increased despite a concomitant increase in their prostaglandin E2 levels in both stimulated (interferon gamma plus muramyl dipeptide) and unstimulated in vitro assays (9 patients: stimulated prostaglandin E2 range, 30.1 to 123.6 ng/10(6) monocytes per milliliter). Massively elevated monocyte TNF alpha and prostaglandin E2 production occurred simultaneously in patients with sepsis.
Synthesis of well-defined hydrogel networks using Click chemistry (2006)

New PEG-based hydrogel materials have been synthesized by Click chemistry and shown to result in well-defined networks having significantly improved mechanical properties; the selectivity of the azide/acetylene coupling reaction also allows for the incorporation of various additives and functional groups leading to chemical tailoring of the hydrogels.
"Wright-Patterson Air Force Base: Ohio's Economic Opportunity" Speech (1988)

A speech given by Charles Horn on how Wright-Patterson Air Force Base's technology initiatives could be used to create more civilian jobs in Ohio. Horn was heavily involved in many projects with WPAFB.
Hypotensive Effects of Adenosine and Adenosine Triphosphate Compared with Sodium Nitroprusside (1982)

Hypotensive effects of the intravenous injection of adenine compounds [adenosine triphosphate (ATP), adenosine] were compared with those of sodium nitroprusside (SNP) in rabbits during light, stable halothane anesthesia. ATP and adenosine were almost equipotent in their effects on blood pressure and heart rate. The hypotensive potencies of ATP and adenosine were approximately 1/6 (bolus injection) and 1/40 (continuous infusion) that of SNP, but the adenine compounds had a more rapid onset of action and shorter recovery times than SNP. With bolus injection, SNP invariably caused a baroreceptor-mediated reflex increase in heart rate. In contrast, ATP and adenosine caused a dose-related decrease in heart rate and hypotension. With continuous infusion, ATP and adenosine produced immediate onset of hypotension without tachycardia. Blood pressure remained remarkably stable throughout the infusion; neither tachyphylaxis nor rebound hypertension were observed. Thus, the adenine compounds offer possible advantages over SNP as they are physiologic agents with little or no acute toxicity and may be devoid of tachycardia, tachyphylaxis, and rebound hypertension.
agr-Mediated Dispersal of Staphylococcus aureus Biofilms (2008)

The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing from a biofilm have been observed displaying an active agr system. Here, we report that repression of agr is necessary to form a biofilm and that reactivation of agr in established biofilms through AIP addition or glucose depletion triggers detachment. Inhibitory AIP molecules did not induce detachment and an agr mutant was non-responsive, indicating a dependence on a functional, active agr system for dispersal. Biofilm detachment occurred in multiple S. aureus strains possessing divergent agr systems, suggesting it is a general S. aureus phenomenon. Importantly, detachment also restored sensitivity of the dispersed cells to the antibiotic rifampicin. Proteinase K inhibited biofilm formation and dispersed established biofilms, suggesting agr-mediated detachment occurred in an ica-independent manner. Consistent with a protease-mediated mechanism, increased levels of serine proteases were detected in detaching biofilm effluents, and the serine protease inhibitor PMSF reduced the degree of agr-mediated detachment. Through genetic analysis, a double mutant in the agr-regulated Aur metalloprotease and the SplABCDEF serine proteases displayed minimal extracellular protease activity, improved biofilm formation, and a strongly attenuated detachment phenotype. These findings indicate that induction of the agr system in established S. aureus biofilms detaches cells and demonstrate that the dispersal mechanism requires extracellular protease activity.
The High-Fat Diet–Fed Mouse (2004)

This study characterizes the high-fat diet-fed mouse as a model for impaired glucose tolerance (IGT) and type 2 diabetes. Female C57BL/6J mice were fed a high-fat diet (58% energy by fat) or a normal diet (11% fat). Body weight was higher in mice fed the high-fat diet already after the first week, due to higher dietary intake in combination with lower metabolic efficiency. Circulating glucose increased after 1 week on high-fat diet and remained elevated at a level of approximately 1 mmol/l throughout the 12-month study period. In contrast, circulating insulin increased progressively by time. Intravenous glucose challenge revealed a severely compromised insulin response in association with marked glucose intolerance already after 1 week. To illustrate the usefulness of this model for the development of new treatment, mice were fed an orally active inhibitor of dipeptidyl peptidase-IV (LAF237) in the drinking water (0.3 mg/ml) for 4 weeks. This normalized glucose tolerance, as judged by an oral glucose tolerance test, in association with augmented insulin secretion. We conclude that the high-fat diet-fed C57BL/6J mouse model is a robust model for IGT and early type 2 diabetes, which may be used for studies on pathophysiology and development of new treatment.
A Computer Alert System to Prevent Injury From Adverse Drug Events (1998)

Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.
Structural and Binding Characteristics of the Carboxyl Terminal Fragment of Apolipophorin III from Manduca sexta (1994)

The molecular basis of the interaction of apolipophorin III (apoLp-III), an exchangeable apolipoprotein from hemolymph of the sphinx moth. Manduca sexta, with lipoprotein surfaces and phospholipids was studied by investigating the structural and binding properties of the C-terminal fragment of the native protein. A 4K peptide, corresponding to the terminal helical segment of the native protein, was generated by cyanogen bromide treatment, purified by gel filtration and reverse-phase HPLC, and characterized by N-terminal sequencing and amino acid and mass spectrometric analysis. Circular dichroism (CD) spectroscopy of the peptide in buffer indicated a predominantly unstructured state while addition of trifluoroethanol (TFE), a helix-inducing agent, resulted in an alpha-helical structure. Sedimentation equilibrium studies revealed that the 4K peptide was monomeric in buffer. The 4K peptide assumed an alpha-helical conformation in the presence of sodium dodecyl sulfate (SDS) and lysolecithin, but was unstructured in the presence of dimyristoylphosphatidylcholine, either when added to preformed vesicles or upon cosonication, indicating an ability to bind to detergent micelles but not to phospholipid bilayers. Unlike native apoLp-III, the 4K peptide did not confer protection against turbidity development to human low density lipoprotein upon incubation with phospholipase C, indicating an inability to interact with the surface of lipoproteins. Upon interaction with SDS micelles, both the 4K peptide and apoLp-III were resistant to urea-induced denaturation when compared to free apoLp-III, as evaluated by CD spectroscopy. The structural stability conferred upon interaction with detergents was similar for both the peptide and the native protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertensive Retinal Vessel Wall Signs in a General Older Population (2003)

To describe cross-sectional relations between hypertension and retinal vessel wall signs in an older white population. These signs were defined from fundus photographs in 3654 Blue Mountains Eye Study participants > or =49 years of age. Focal arteriolar narrowing and arteriovenous nicking were graded through the use of standard protocol. Photographs were digitized to measure retinal vessel diameters. Average arteriolar diameter, summarized as central retinal arteriolar equivalent and arteriole-to-venule ratio, were used as indexes of generalized arteriolar narrowing. Blood pressure was measured with the use of a mercury sphygmomanometer. Hypertension was defined through the use of antihypertensive medications, systolic blood pressure > or =160 mm Hg, or diastolic blood pressure > or =95 mm Hg. Hypertension was categorized as controlled (using medication, normal blood pressure), uncontrolled (using medication, high blood pressure), or untreated (not using medication). Hypertensive subjects had higher prevalence of all retinal microvascular signs. After adjusting for age, gender, body mass index, and smoking, persons with controlled (18.2%), uncontrolled (13.8%), or untreated hypertension (13.8%) were significantly more likely than normotensive subjects (54.2%) to have (a) lower central retinal arteriolar equivalent: adjusted odds ratios 1.5, (95% CI, 1.1 to 1.9), 2.1 (1.6 to 2.7), and 2.1 (1.6 to 2.7), respectively, and lower arteriole-to-venule ratio: 1.3 (1.0 to 1.6), 1.4 (1.1 to 1.8), and 1.7 (1.3 to 2.2), respectively; (b) focal arteriolar narrowing: 1.3 (0.9 to 1.9), 2.2 (1.5 to 3.2), and 2.5 (1.8 to 3.6), respectively; and (c) arteriovenous nicking: 1.3 (0.9 to 1.8), 2.3 (1.6 to 3.2), and 1.9 (1.3 to 2.7), respectively. Our findings demonstrate a strong relation between presence and severity of hypertension and retinal microvascular structural changes.
Intravenous Human Plasma-Derived Augmentation Therapy in α1-Antitrypsin Deficiency: From Pharmacokinetic Analysis to Individualizing Therapy (2008)

AAT augmentation therapy can be effectively individualized on a pharmacokinetic basis with a simple, easily executed method.
Mutation-adapted U1 snRNA corrects a splicing error of the dopa decarboxylase gene (2016)

Aromatic l-amino acid decarboxylase (AADC) deficiency is an inborn error of monoamine neurotransmitter synthesis, which results in dopamine, serotonin, epinephrine and norepinephrine deficiencies. The DDC gene founder mutation IVS6 + 4A > T is highly prevalent in Chinese patients with AADC deficiency. In this study, we designed several U1 snRNA vectors to adapt U1 snRNA binding sequences of the mutated DDC gene. We found that only the modified U1 snRNA (IVS-AAA) that completely matched both the intronic and exonic U1 binding sequences of the mutated DDC gene could correct splicing errors of either the mutated human DDC minigene or the mouse artificial splicing construct in vitro. We further injected an adeno-associated viral (AAV) vector to express IVS-AAA in the brain of a knock-in mouse model. This treatment was well tolerated and improved both the survival and brain dopamine and serotonin levels of mice with AADC deficiency. Therefore, mutation-adapted U1 snRNA gene therapy can be a promising method to treat genetic diseases caused by splicing errors, but the efficiency of such a treatment still needs improvements.
Single-growth-step GaAs/AlGaAs distributed Braggreflector lasers with holographically-defined recessedgratings (1994)

A ridge waveguide GaAs/AlGaAs quantum well DBR laser fabricated with a simplified grating recess-technology and a third order grating is described. The reflector is fabricated on top of a recessed waveguide using holographic exposure followed by reactive ion etching. The laser operates on a single longitudinal and lateral mode with threshold current as low as 20 mA, output power 5 mW per facet and is intended for monolithically integrated interferometer applications.
Cardiac Systolic Function Recovery After Hemorrhage Determines Survivability During Shock (2010)

The unique advantage of the pressure-volume methodology over all other available approaches to measure cardiac function is that it enables more specific measurement of the left ventricle performance independently from loading conditions and heart rate. Our findings demonstrated that failure to recover cardiac systolic function after hemorrhage, is a major determinant of mortality during hypovolemic shock.
A Method for Detecting Chaos in Canine Myocardial Microcirculatory Red Cell Flux (2000)

Capillary red cell flux (movement of red cells in capillaries) is nonlinear, (i.e., chaotic). This complexity suggests that the primary control for oxygen delivery to cardiac myocytes by red blood cells resides in the microcirculation. Also, capillary red cell flux is bifractal, suggesting an ordering of control.