gebhart/patrepeval huggingface dataset:
Electrochemical protection of thin film electrodes in solid state nanopores (2011)

Solid state nanopores are a core element of next-generation single molecule tools in the field of nano-biotechnology. Thin film electrodes integrated into a pore can interact with charges and fields within the pore. In order to keep the nanopore open and thus functional electrochemically induced surface alteration of electrode surfaces and bubble formation inside the pore have to be eliminated. This paper provides electrochemical analyses of nanopores drilled into TiN membranes which in turn were employed as thin film electrodes. We studied physical pore integrity and the occurrence of water decomposition yielding bubble formation inside pores by applying voltages between -4.5 and +4.5 V to membranes in various protection stages continuously for up to 24 h. During potential application pores were exposed to selected electrolyte-solvent systems. We have investigated and successfully eliminated electrochemical pore oxidation and reduction as well as water decomposition inside nanopores of various diameters ranging from 3.5 to 25 nm in 50 nm thick TiN membranes by passivating the nanopores with a plasma-oxidized layer and using a 90% solution of glycerol in water as KCl solvent. Nanopore ionic conductances were measured before and after voltage application in order to test for changes in pore diameter due to electrochemical oxidation or reduction. TEM imaging was used to confirm these observations. While non-passivated pores were electrochemically oxidized, neither electrochemical oxidation nor reduction was observed for passivated pores. Bubble formation through water decomposition could be detected in non-passivated pores in KCl/water solutions but was not observed in 90% glycerol solutions. The use of a protective self-assembled monolayer of hexadecylphosphonic acid (HDPA) was also investigated.
Rapid simultaneous identification and quantitation of Staphylococcus aureus and Pseudomonas aeruginosa directly from bronchoalveolar lavage specimens using automated microscopy (2013)

Diagnosis of ventilator-assisted pneumonia (VAP) requires pathogen quantitation of respiratory samples. Current quantitative culture methods require overnight growth, and pathogen identification requires an additional step. Automated microscopy can perform rapid simultaneous identification and quantitation of live, surface-immobilized bacteria extracted directly from patient specimens using image data collected over 3 h. Automated microscopy was compared to 1 μL loop culture and standard identification methods for Staphylococcus aureus and Pseudomonas spp. in 53 remnant bronchoalveolar lavage specimens. Microscopy identified 9/9 S. aureus and 7/7 P. aeruginosa in all specimens with content above the VAP diagnostic threshold. Concordance for specimens containing targets above the diagnostic threshold was 13/16, with concordance for sub-diagnostic content of 86/90. Results demonstrated that automated microscopy had higher precision than 1 μL loop culture (range ~0.55 log versus ≥1 log), with a dynamic range of ~4 logs (~10(3) to 10(6) CFU/mL).
NGF/TrkA Signaling as a Therapeutic Target for Pain (2015)

Nerve growth factor (NGF) was first discovered approximately 60 years ago by Rita Levi-Montalcini as a protein that induces the growth of nerves. It is now known that NGF is also associated with Alzheimer's disease and intractable pain, and hence, it, along with its high-affinity receptor, tropomyosin receptor kinase (Trk) A, is considered to be 1 of the new targets for therapies being developed to treat these diseases. Anti-NGF antibody and TrkA inhibitors are known drugs that suppress NGF/TrkA signaling, and many drugs of these classes have been developed thus far. Interestingly, local anesthetics also possess TrkA inhibitory effects. This manuscript describes the development of an analgesic that suppresses NGF/TrkA signaling, which is anticipated to be 1 of the new methods to treat intractable pain.
Origins of the specificity of tissue-type plasminogen activator. (1995)

The role of subsite interactions in defining the stringent substrate specificity of tissue-type plasminogen activator (t-PA) has been examined by using an fd phage library that displayed random hexapeptide sequences and contained 2 x 10(8) independent recombinants. Forty-four individual hexapeptides were isolated and identified as improved substrates for t-PA. A peptide containing one of the selected amino acid sequences was cleaved by t-PA 5300 times more efficiently than a peptide that contained the primary sequence of the actual cleavage site in plasminogen. These results suggest that small peptides can mimic determinants that mediate specific proteolysis, emphasize the importance of subsite interactions in determining protease specificity, and have important implications for the evolution of protease cascades.
Measurement of Coal Cleat Porosity and Relative Permeability Characteristics (1991)

Abstract After several trials and errors, an acceptable procedure has been formulated for cutting, handling, preparing, and selecting coal core samples for laboratory tests. The unsteady-state method for relative permeability measurement has been found to provide satisfactory results when applied to whole core samples of coal. Furthermore, a novel nondestructive and simple laboratory technique has been developed to estimate the porosity and irreducible water saturation associated with the coal cleat network. In this paper, examples are presented using results obtained with coal core samples from the San Juan and Warrior Basin. Laboratory measured relative permeability curves, porosity, and irreducible water saturation of coal cleats have proven valuable in numerical simulation and other engineering studies of coalbed methane recovery.
Evidence for diurnal periodicity in human cholesterol synthesis. (1990)

Diurnal variation in human cholesterol synthesis in the rapidly exchangeable pool was studied in six healthy normolipidemic individuals by measurement of deuterium incorporation from body water into plasma cholesterol. After oral administration of D2O, free and de-esterified plasma cholesterol and plasma water were sampled over 48 h, converted to hydrogen, and deuterium enrichment was determined by isotope ratio mass spectrometry. Deuterium enrichment changes over 4-h intervals were used to calculate fractional synthetic rate (FSR). No significant time effects were observed on plasma total cholesterol levels over the 48-h study. The highest rate of deuterium incorporation into free cholesterol occurred during early morning, whereas during afternoon and early evening incorporation rates were lower. Free cholesterol FSR values were lowest at 14:00 to 18:00 h and peaked at 06:00 h. The periodicity across timepoints was not significantly different from that of a derived sine function equation. For cholesteryl ester, FSR data showed less distinct variation over time, peaking during early morning, indicative of maximal efflux of free cholesterol to the ester pool during this period. These findings offer direct evidence for diurnal patterns in human cholesterol synthesis.
Induction of the Acyl-Coenzyme A Synthetase Gene by Fibrates and Fatty Acids Is Mediated by a Peroxisome Proliferator Response Element in the C Promoter (1995)

The long-chain acyl-coenzyme A synthetase (ACS) gene gives rise to three transcripts containing different first exons preceded by specific regulatory regions A, B, and C. Exon-specific oligonucleotide hybridization indicated that only A-ACS mRNA is expressed in rat liver. Fibrate administration induced liver C-ACS strongly and A-ACS mRNA to a lesser extent. B-ACS mRNA remained undetectable. In primary rat hepatocytes and Fa-32 hepatoma cells C-ACS mRNA increased after treatment with fenofibric acid, alpha-bromopalmitate, tetradecylthioacetic acid, or alpha-linolenic acid. Nuclear run-on experiments indicated that fenofibric acid and alpha-bromopalmitate act at the transcriptional level. Transient transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic acid, respectively. Unilateral deletion and site-directed mutagenesis identified a peroxisome proliferator activator receptor (PPAR)-responsive element (PPRE) mediating the responsiveness to fibrates and fatty acids. This ACS PPRE contains three imperfect half sites spaced by 1 and 3 oligonucleotides and binds PPAR.retinoid X receptor heterodimers in gel retardation assays. In conclusion, the regulation of C-ACS mRNA expression by fibrates and fatty acids is mediated by PPAR.retinoid X receptor heterodimers interacting through a PPRE in the C-ACS promoters. PPAR therefore occupies a key position in the transcriptional control of a pivotal enzyme controlling the channeling of fatty acids into various metabolic pathways.
Epidemiology of obstructive sleep apnea: a population-based perspective (2008)

This review summarizes the recent literature on the epidemiology of adult obstructive sleep apnea (OSA) from various population-based studies. Despite methodologic differences, comparisons have yielded similar prevalence rates of the OSA syndrome in various geographic regions and amongst a number of ethnic groups. Risk factors for OSA including obesity, aging, gender, menopause, and ethnicity are analyzed. We also provide discussion on adverse medical conditions associated with OSA including hypertension, stroke, congestive heart failure, coronary artery disease, cardiovascular mortality, insulin resistance, and neurocognitive dysfunction. Finally with the progression of the global obesity epidemic, we focus on the economic health care burden of OSA and the importance of recognizing the largely undiagnosed OSA population with emphasis on strategies to improve access to diagnostic resources.
Novel type of in situ extraction: Use of solvent containing microcapsules for the bioconversion of 2‐phenylethanol from L‐phenylalanine by Saccharomyces cerevisiae (2003)

A novel in situ product removal (ISPR) method that uses microcapsules to extract inhibitory products from the reaction suspension is introduced into fermentation technology. More specifically, L-phenylalanine (L-Phe) was transformed by Saccharomyces cerevisiae to 2-phenylethanol (PEA), which is inhibitory toward the yeast. In order to continuously remove PEA from the vicinity of the cells, the reaction suspension was brought into contact with capsules of 2.2-mm diameter that had a hydrophobic core of dibutyl sebacate and an alginate-based wall. This novel process combines the advantages of a normal in situ extraction process (fast mass transfer and simple process set-up) with the benefits of a membrane-based process (reduction of the solvent toxicity and avoidance of stable emulsions). In particular, the microbial cells are shielded from the phase toxicity of the organic solvent by a hydrogel layer surrounding the organic core. By placing the microcapsules into the fermenter, the final overall concentration of PEA in a fed-batch culture was increased from 3.8 to 5.6 g/L because a part of the inhibitory product dissolved in the dibutyl sebacate core. In another fermentation experiment, the capsules were placed in a fluidized bed that was connected via a loop to the fermenter. In addition, the fluidized bed was connected via a second loop to a back-extractor to regenerate the capsules. By alternating the extraction and back-extraction cycles, it was possible to limit the PEA concentration of the fed-batch culture in the fermenter to 2.4 g/L while producing important quantities of PEA that accumulated in an external reservoir.
Effect of Bilateral Carotid-Body Resection on Ventilatory Control at Rest and during Exercise in Man (1971)

Abstract To investigate the role of the carotid bodies in the control of ventilation during rest and moderate exercise, seven asthmatic subjects who had undergone bilateral carotid-body resection (the barostatic reflexes remained intact) were studied while they were breathing air and hypoxic, hypercapnic, and hyperoxic gas. During breathing of air and 25 per cent oxygen, ventilation was not different between this group and control subjects either at rest or during exercise. The hyperpnea of hypoxia was absent, and the ventilatory response to increased arterial carbon dioxide tension was reduced 30 per cent after carotid-body resection. These studies indicate that ventilation with the subject breathing air during rest and steady-state exercise is not affected by the operation, the carotid bodies appear to be responsible for the hyperpnea of hypoxia, and this response is not enhanced by moderate exercise, and the ventilatory response to increased arterial carbon dioxide tension is reduced after bilateral ca...
Use of Lambda Phage S and R Gene Products in an Inducible Lysis System for Vibrio cholerae - and Salmonella enterica Serovar Typhimurium-Based DNA Vaccine Delivery Systems (2000)

Novel methods for adapting DNA vaccine technology to the prevention of mucosal diseases are greatly needed. Here we show that regulated expression of phage lambda lysis genes S and R causes dramatic lysis of both Vibrio cholerae and Salmonella enterica serovar Typhimurium cells with concomitant release of plasmid DNA into the surrounding media. We also used single and double DNase mutant strains to show that secreted V. cholerae DNases can adversely affect the integrity of DNA molecules released upon lysis. These results suggest that incorporation of lambda SR-mediated lysis constructs and DNA stabilizing mutations into candidate live attenuated bacterial vaccines offers a promising approach for the development of effective mucosal DNA delivery vectors for humans.
Linear optical properties of gold nanoshells (1999)

A metal nanoshell consists of a nanometer-scale dielectric core surrounded by a thin metallic shell. The plasmon resonance of metal nanoshells displays a geometric tunability controlled by the ratio of the core radius to the total radius. For gold-coated Au2S this ratio varies from 0.6 to 0.9, yielding a plasmon resonance tunable from 600 to greater than 1000 nm. Mie scattering theory for the nanoshell geometry quantitatively accounts for the observed plasmon resonance shifts and linewidths. In addition, the plasmon linewidth is shown to be dominated by electron surface scattering.
PROLONGATION OF IN VIVO MOUSE ISLET ALLOGRAFT SURVIVAL BY MODULATION OF MHC CLASS I ANTIGENs (1994)

Major histocompatibility complex class I-deficient islets from beta-2 microglobulin-deficient mice have been shown to have prolonged in vivo islet allograft survival. Additionally in vitro studies using the mixed lymphocyte islet coculture system have demonstrated a reduction in cytotoxic T lymphocyte activity against alloislets that have been pretreated with an antibody directed against MHC class I antigen. The clinical applicability of these findings are examined in this study, which evaluates the ability of MHC class I blocking antibody to prevent the in vivo destruction of alloislets. Recipients of allogenic islet transplants treated with phosphate-buffered saline or control F(ab')2 fragments rejected the transplanted alloislets in median times of 11.5 days and 11 days, respectively. Recipient mice treated with a monoclonal antibody or F(ab')2 fragments specific to the donor MHC class I antigen had significant prolongation in allograft survival (median allograft survival for both groups was 21 days) when compared with mice treated with PBS or control F(ab')2 fragment. These results demonstrate that treating recipients of alloislets with donor-specific MHC class I monoclonal antibody or the respective F(ab')2 fragments prolongs islet allograft survival. This confirms the importance of MHC class I antigen in the rejection of pancreatic islet allografts and suggests that blocking different domains on the MHC class I molecule could be used therapeutically in the protection of allografts from the immune system.
Maxwell - a 64 FPGA Supercomputer (2007)

We present the initial results from the FHPCA Supercomputer project at the University of Edinburgh. The project has successfully built a general-purpose 64 FPGA computer and ported to it three demonstration applications from the oil, medical and finance sectors. This paper describes in brief the machine itself - Maxwell - its hardware and software environment and presents very early benchmark results from runs of the demonstrators.
Fragmentation studies on the antibiotic avilamycin A using ion trap mass spectrometry (2004)

A comprehensive study on the fragmentation pattern of the antimicrobial growth promoter avilamycin A was conducted in a quadrupole ion trap mass spectrometer equipped with an electrospray ionization (ESI) source. Performing multiple-stage experiments on the deprotonated molecule (m/z 1401) and its principal product ions showed that a sequential shortening of the oligosaccharide backbone took place, which can be attributed to the localization of the negative charge in the terminal dichloroisoeverninic acid. Under (+)-ESI conditions, avilamycin A readily formed an intense sodium-cationized molecule, [M + Na](+) (m/z 1425). Structural elucidation of the second-, third- and fourth-generation fragment ions revealed that all of the structures shared a common molecular portion comprising a central monosaccharide. This observation allowed us to assign confidently the complexation site of the alkali metal cation. In addition to the monosodiated molecule, the full-scan mass spectral acquisition also yielded a less abundant disodiated molecule, [M - H + 2Na](+) (m/z 1447). Multiple-stage experiments on this ion indicated that the second sodium ion compensates for the negative charge located at either of two positions within the molecule. While deprotonation of the phenolic hydroxyl group in the dichloroisoeverninic acid moiety was suggested to be driven by charge stabilization in the aromatic ring (in analogy with the deprotonated molecule in the (-)-ESI mode), the deprotonation at an alpha-carbon of an ester side-chain substituent in the oligosaccharide part was believed to provide a stable chelation-like coordination site for the cation.
Active surface cooling protocol to induce mild therapeutic hypothermia after out-of-hospital cardiac arrest: A retrospective before-and-after comparison in a single hospital* (2009)

The therapeutic hypothermia period was associated with a significant improvement in neurologic outcomes in patients whose initial rhythm was ventricular fibrillation, but not in patients with other rhythms.
Molecular Cloning and Analysis of a Putative Siderophore ABC Transporter from Staphylococcus aureus (2000)

From a mass-excised Staphylococcus aureus lambdaZapII expression library, we cloned an operon encoding a novel ABC transporter with significant homology to bacterial siderophore transporter systems. The operon encodes four genes designated sstA, -B, -C, and -D encoding two putative cytoplasmic membrane proteins (sstA and sstB), an ATPase (sstC), and a membrane-bound 38-kDa lipoprotein (sstD). The sst operon is preceded by two putative Fur boxes, which indicated that expression of the sst operon was likely to be iron dependent. SstD was overexpressed in Escherichia coli, purified by Triton X-114 phase partitioning, and used to generate monospecific antisera in rats. Immunoblotting studies located SstD in the membrane fraction of S. aureus and showed that expression of the lipoprotein was reduced under iron-rich growth conditions. Triton X-114 partitioning studies on isolated membranes provided additional biochemical evidence that SstD in S. aureus is a lipoprotein. Immunoreactive polypeptides of approximately 38 kDa were detected in a wide range of staphylococcal species, but no antigenic homolog was detected in Bacillus subtilis. Expression of SstD in vivo was confirmed by immunoblotting studies with S. aureus recovered from a rat intraperitoneal chamber implant model. To further define the contribution of SstD in promoting growth of S. aureus in vitro and in vivo, we used antisense RNA technology to modulate expression of SstD. Expression of antisense sstD RNA in S. aureus resulted in a decrease in SstD expression under both iron-rich and iron-restricted growth conditions. However, this reduction in SstD levels did not affect the growth of S. aureus in vitro in an iron-limited growth medium or when grown in an intraperitoneal rat chamber implant model in vivo.
TNFα and IL‐6 are mediators in the blistering process of pemphigus (2001)

Inflammatory cytokine expression around the blister could play a mediator role in pemphigus lesions by increasing epithelial damage.
Dietary salt and blood pressure. A perspective. (1991)

Although dietary salt restriction is often valuable as sole or adjunctive therapy of hypertensive disorders, it is abundantly clear that hypertensive patients comprise a heterogeneous group with regard to salt sensitivity of blood pressure. This is apparent despite the many methodological obstacles to defining salt sensitivity in an individual patient. Currently, dietary trial is the only sure means of defining a given patient as responsive to salt restriction. Easily definable markers of salt sensitivity would allow appropriate targeting of this rather ponderous therapy. Promising leads include the assessment of membrane ion transporters such as sodium-lithium exchange and of the activity of the renin-angiotensin system, including the phenomenon of "non-modulating" hypertension and other volume regulatory hormones such as atrial natriuretic factor. Although less intensively studied than in hypertensive patients, the blood pressure response of normal subjects to salt restriction is also marked by great variability. Given the possibility of deleterious consequences of population-wide salt restriction for at least some people in a setting such as the United States, it seems imprudent to recommend such a policy before its proven worth has been demonstrated by clinical trial. Pending such evidence and the development of markers, salt restriction should be reserved for those in whom it is of demonstrated efficacy.
Optical coherence tomography based angiography [Invited] (2017)

Optical coherence tomography (OCT)-based angiography (OCTA) provides <i>in vivo</i>, three-dimensional vascular information by the use of flowing red blood cells as intrinsic contrast agents, enabling the visualization of functional vessel networks within microcirculatory tissue beds non-invasively, without a need of dye injection. Because of these attributes, OCTA has been rapidly translated to clinical ophthalmology within a short period of time in the development. Various OCTA algorithms have been developed to detect the functional micro-vasculatures <i>in vivo</i> by utilizing different components of OCT signals, including phase-signal-based OCTA, intensity-signal-based OCTA and complex-signal-based OCTA. All these algorithms have shown, in one way or another, their clinical values in revealing micro-vasculatures in biological tissues <i>in vivo</i>, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential pre-clinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography.