gebhart/patrepeval huggingface dataset:
Highly variable expression of tissue‐restricted self‐antigens in human thymus: Implications for self‐tolerance and autoimmunity (2007)

Induction of T cell tolerance in the thymus (central tolerance) is essential for preventing organ-specific autoimmunity. This apparent paradox is in part explained by promiscuous expression of numerous tissue-restricted self-antigens (TRA) in medullary thymic epithelial cells (mTEC), which is highly conserved between mice and man. In animal models, the threshold of central tolerance towards such TRA is surprisingly sensitive towards minor shifts in antigen expression levels and this might also be the case in humans. To precisely assess the inter-individual variability of TRA expression in man, we determined the level of transcription of several auto-antigens in purified human mTEC and subsets thereof by quantitative RT-PCR. We detected two expression patterns: first, high variability (>20-fold) correlated with autoimmune regulator (Aire) expression and mTEC differentiation, and secondly, non-correlated low variability. Importantly, our approach revealed a significantly higher Aire-correlated insulin transcription in mTEC of carriers of the protective insulin-dependent diabetes mellitus locus 2 haplotype compared to the non-protective haplotype. The considerable, yet selective variability in thymic expression levels of target auto-antigen expression might constitute a hitherto underestimated risk factor for the susceptibility of autoimmune diseases in man.
Pharmacotherapies for sleep disturbances in Alzheimer's disease (2014)

We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in AD. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in AD, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin is beneficial to AD patients with moderate to severe dementia and sleep problems. There is some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in AD. Systematic assessment of adverse effects is essential.
Inhibition of p53 attenuates ischemic stress-induced activation of astrocytes (2015)

In cerebral ischemia, studies of cell death have focused primarily on neurons, but recent work indicates that ischemia also causes damage to astrocytes. Activation of astrocytes is a typical brain response to stress stimuli and is evidenced by changes in cellular function and morphology, as well as upregulation of glial fibrillary acidic protein. The tumor-suppressor transcription factor p53 has recently been implicated as a mediator of ischemia-induced neuronal death, but very little is known about its role in the activation or the death of astrocytes. The present study investigated the role of p53 in astrocyte and neuronal toxicity using in-vitro and in-vivo ischemic stroke models. We showed that p53 is activated in ischemic brains and in oxygen-glucose deprivation (OGD)-induced cell death in neurons and astrocytes. Inhibition of p53 activity using either pifithrin-α or small interference RNA interference reduced OGD-induced cell death and pifithrin-α reversed OGD-induced impairment of glutamate uptake in astrocytes, suggesting that p53 might play a key role in mediating neurotoxicity and gliotoxicity in ischemic brain injury. This study shows that p53 is activated in astrocytes during ischemia and that inhibition of the activity of this molecule prevents not only OGD-induced neuronal and astrocytic death but also astrocyte activation and impaired glutamate uptake. These findings suggest that p53 may be a valuable therapeutic target in ischemic brain injury.
Improved High-Pressure Liquid Chromatographic Assay of Serum 25-Hydroxycholecalciferol and 25-Hydroxyergocalciferol After Reverse-Phase Sep-Pak C<sub>18</sub>Cartridge Preparation of Sample (1981)

Abstract A simplified method is described for extracting and purifying 25-hydroxycholecalciferol and 25-hydroxyergocalciferol from serum for quantitation by high-pressure liquid chromatography. The method involves extracting and purifying these metabolites from serum (1–10 ml) with a reverse-phase octadecylsilane bonded silica cartridge (Sep-Pak C18). This method is faster than a previously described method involving extraction with dichloromethane and purification by Sephadex LH-20 chromatography. The correlation between the two methods was excellent (r2 = 0.96, p≤0.0001). The coefficient of variation for the new method is 4.3%. The new method allows measurement of 25-hydroxyergocalciferol from human serum since both 25-hydroxycholecalciferol and 25-hydroxyergocalciferol are extracted equally. This allows the use of [3H] 25-hydroxycholecalciferol to monitor the recovery of both the D2 and the D3 forms of the metabolite.
Desmosomes are unaltered during infections by attaching and effacing pathogens (2007)

The human attaching and effacing (A/E) intestinal pathogens enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and the murine A/E pathogen Citrobacter rodentium cause serious diarrhea in their hosts. These bacteria alter numerous host cell components, including organelles, the host cell cytoskeleton, and tight junctions during the infectious process. One of the proteins that contribute to the intermediate filament network in host cells, cytokeratin-18, is extensively altered during EPEC infections. Based on this, we tested the hypothesis that desmosomes, the only intercellular junctions that interact with intermediate filaments, are also influenced by A/E pathogen infections. We found that the desmosomal transmembrane proteins desmoglein and desmocollin, as well as the desmosome plaque protein desmoplakin, all remain unchanged during EPEC infection in vitro. This evidence is corroborated by the unaltered localization of desmoglein and desmoplakin in vivo in mice infected with C. rodentium for 7 days. Electron microscopic analysis of 7-day C. rodentium-infected murine colonocytes also show no observable differences in the desmosomes when compared to uninfected controls. Our data suggest that, unlike tight junctions, the desmosome protein levels and localization, as well as desmosome morphology, are unaltered during A/E pathogenesis.
How Can I Safely Dispose Of Excess Pesticides, Including Herbicides, And Their Containers? Part 1 (2002)

Pesticide use requires disposal of either excess pesticides or empty pesticide containers.You can reduce the pesticides
Bernard Routh et la mort de Montesquieu (1949)

Journal Article BERNARD ROUTH ET LA MORT DE MONTESQUIEU Get access O. R. TAYLOR O. R. TAYLOR ABERYSTWYTH Search for other works by this author on: Oxford Academic Google Scholar French Studies, Volume III, Issue 2, April 1949, Pages 101–121, https://doi.org/10.1093/fs/III.2.101 Published: 01 April 1949
Chemotherapy of Non Small Cell Lung Cancer. A Prospectively Randomized Study of Cisplatin-Etoposide versus Cisplatin-Mitomycin-Vinblastine (1997)

Based on preclinical studies showing synergism between cisplatin and etoposide, we randomized patients with non small cell lung cancer (NSCLC) to receive either the above combination (cisplatin 100 mg/m2 day 1, etoposide 130 mg/m2 days 1-3) or the combination of cisplatin-mitomycin-c and vinca drugs (MVP) (cisplatin 100 mg/m2, vinblastine 6 mg/m2, mitomycin 10 mg/m2 day 1), a regimen with a steady response rate. Partial responses were achieved in 12/44 (27%) of the cisplatin-etoposide group and in 11/43 (26%) of the MVR group. No difference in median survival could be demonstrated between the two groups (36 weeks versus 38 weeks). Myelotoxicity and alopecia were more severe in the cisplatin-etoposide group. Compared to international experience both regimens exhibited a relatively low response rate. It seems that for NSCLC new agents are required.
Design, implementation, and applications of a B-ISDN simulation testbed (2002)

We describe the need and desired features for broadband ISDN (B-ISDN) simulation environments and present the design and implementation details of a simulation testbed prototype. The simulation testbed is designed to be highly flexible for network topology/traffic descriptions and provide a friendly graphical user interface. We also show that interesting simulation results can be easily observed via the use of this testbed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Continuing evaluation of the Queen's University tactile vocoder. I: Identification of open set words. (1986)

Identification of open set words, by an experienced normal hearing subject using the tactile vocoder developed at Queen's University, was examined. The tactile vocoder filters and processes the acoustic waveform into 16 filter channels, each of which controls a vibrator on the skin surface. After acquiring a 250-word vocabulary through the tactile vocoder, the subject was presented with three sets of 1000 different open set words in three reception conditions. The percentages of words correctly identified in the tactile vocoder (TV), lipreading (L), and lipreading plus tactile vocoder (L + TV) conditions were 8.8, 39.4, and 68.7 percent respectively. Phonemic analysis of stimulus/response pairs revealed that 36.7, 64.9 and 85.5 percent of the phonemes were correctly identified in TV, L, and L + TV conditions, respectively, indicating that incorrect-response words often contained many correct phonemes. Also, syllabic stress of stimulus and response words was identical 88 percent of the time in the TV condition. Important information about speech was transmitted through the tactile vocoder.
Learning Sensorimotor Abstractions (2011)

Projecte final de carrera fet en col.laboracio amb Aalto University. School of Science and Technology. Faculty of Information and Natural Sciences
Increase in GLUT1 in Smooth Muscle Alters Vascular Contractility and Increases Inflammation in Response to Vascular Injury (2010)

In summary, these findings suggest that increased glucose uptake in VSMCs impairs vascular contractility and accelerates a proinflammatory, neutrophil-rich lesion in response to injury, as well as medial hypertrophy, which is associated with enhanced transforming growth factor-β activity.
Baseball's John Fowler: The 1887 Season in Binghamton, New York (1992)

In order to explore the genetic diversity within Echinococcus multilocularis (E. multilocularis), the cestode responsible for the alveolar echinococcosis (AE) in humans, a microsatellite, composed of (CA) and (GA) repeats and designated EmsB, was isolated and characterized in view of its nature and potential field application. PCR-amplification with specific primers exhibited a high degree of size polymorphism between E. multilocularis and Echinococcus granulosus sheep (G1) and camel (G6) strains. Fluorescent-PCR was subsequently performed on a panel of E. multilocularis isolates to assess intra-species polymorphism level. EmsB provided a multi-peak profile, characterized by tandemly repeated microsatellite sequences in the E. multilocularis genome. This "repetition of repeats" feature provided to EmsB a high discriminatory power in that eight clusters, supported by bootstrap p-values larger than 95%, could be defined among the tested E. multilocularis samples. We were able to differentiate not only the Alaskan from the European samples, but also to detect different European isolate clusters. In total, 25 genotypes were defined within 37 E. multilocularis samples. Despite its complexity, this tandem repeated multi-loci microsatellite possesses the three important features for a molecular marker, i.e. sensitivity, repetitiveness and discriminatory power. It will permit assessing the genetic polymorphism of E. multilocularis and to investigate its spatial distribution in detail.
Mirror Bisulfite Sequencing: A Method for Single-Base Resolution of Hydroxymethylcytosine (2018)

Although the role of 5-methylcytosine has been well studied, the biological role of 5-hydroxymethylcytosine still remains unclear because of the limited methods available for single-base detection of 5-hydroxymethylcytosine (5hmC). Here, we present mirror bisulfite sequencing for 5hmC detection at a single CpG site by synthesizing a DNA strand to mirror the parental strand. This semiconservative duplex is sequentially treated with β-glucosyltransferase and M.SssI methylase. The glucosyl-5hmCpG in the parental strand inhibits methylation of the mirroring CpG site, and after bisulfite conversion, a thymine in the mirroring strand indicates a 5hmCpG site in the parental strand, whereas a cytosine indicates a non-5hmC site. Using this method, the 5hmC levels of various human tissues and paired liver tissues were mapped genomewide.
In Vitro Studies with 5-Fluorocytosine (1969)

5-Fluorocytosine, an antifungal agent with potential value as a chemotherapeutic agent, is being evaluated in the treatment of human cryptococcosis. In vitro studies with this agent have been hindered by the fact that it is inhibited significantly in the presence of partially degraded biological substances. This loss of activity is presumed to result from a competitive inhibition between the agent and its natural analogues. Procedures are described for in vitro studies with 5-fluorocytosine. These include methods for susceptibility testing and a bioassay for 5-fluorocytosine in biological fluids. Minimal inhibitory and minimal fungicidal concentrations of 5-fluorocytosine for Cryptococcus neoformans were usually in the range of 0.46 to 3.9 mug/ml and 3.9 to 15.6 mug/ml, respectively. Corresponding values for Candida albicans were 0.46 to 3.9 mug/ml and 15.6 mug/ml or greater, respectively. Strains of C. neoformans and C. albicans resistant to greater than 1,000 mug/ml were encountered both after exposure to the drug and in the absence of any known exposure. Bioassays of specimens from patients treated with 5-fluorocytosine indicated that serum and cerebrospinal fluid concentrations of 10 to 30 mug/ml and 8 to 20 mug/ml, respectively were readily achieved with a dosage of 100 mg per kg per day.
Modified multiband excitation model at 2400 bps (2002)

This paper presents the modified multiband excitation model used for speech coding. In many MBE model coders, speech quality is degraded when incorrect voicing decisions are made, particularly for high-pitched female speakers. The MMBE addresses this issue with a modified voiced/unvoiced decision algorithm and a more robust pitch estimate. The listening quality of speech produced using the MMBE model is superior to the FS-1016 CELP coder and is at least comparable with the new 2400 bps MELP coder chosen as the new 2400 bps Federal Standard.
Studies on Fluoride Concentrations in Human Submandibular/Sublingual Saliva and their Relation to Flow Rate and Plasma Fluoride Levels (1989)

Submandibular/sublingual saliva and blood were collected from five subjects after ingestion of 1 mg fluoride as NaF. An individual collection device, made from a silicone impression material, was used to collect the saliva in 10-minute samples, before and during 2 hr after the fluoride intake. In two separate experiments on each individual, submandibular/sublingual saliva was collected continuously at different flow rates: without stimulation and with gustatory stimulation. Blood was also collected at intervals throughout the experiments. The concentration of fluoride in the submandibular/sublingual saliva was less than that in the plasma but independent of salivary flow rate. The ratio between the saliva and plasma fluoride concentrations at the peak of the mean plasma fluoride concentrations was 0.55 +/- 0.13 and 0.69 +/- 0.11 in the experiments on unstimulated and stimulated salivary, flow rate, respectively. The total amount of the ingested fluoride dose that was excreted through the submandibular/sublingual glands during 130 min was highly correlated with the salivary flow rate. The fraction of the ingested fluoride dose excreted in 2 hr was 0.04 +/- 0.02% in the unstimulated saliva and 0.15 +/- 0.09% in the stimulated saliva.
The Prepatent Period of Some Horse Nematodes Determined by Experimental Infection (1969)

Experimental infections with strongyles were carried out using ponies reared worm-free. Infection with Strongylus vulgaris was produced by artificially administering larvae to housed ponies. Infection with small strongyles was produced both by this method and also by exposing hitherto worm free ponies to heavily infested pasture. The shortest prepatent periods found were: S. vulgaris , 149–156 days; Triodontophorus spp. and Poteriostomum spp., 63–70 days and trichonemid species 35–42 days.
All-optical switch for TDM and WDM/TDM systems demonstrated in a 640 Gbit/s demultiplexing experiment (1998)

A novel interferometric switch is presented that exhibits high linearity, high switching contrast, low noise, wide bandwidth and low crosstalk. The switching principle, which is based on refractive index modulation in a wavelength band far from the gain region of a semiconductor-optical amplifier, is successfully demonstrated in an error-free 640 Gbit/s demultiplexing experiment.
A study of collaboration in software design (2004)

This paper presents a study of collaboration in software design at a large software company. Ethnographic studies of development teams in the field are relatively rare, so this paper contributes to a small, but growing, body of knowledge about the collaborative activities involved in such design work. Five separate development groups were studied over a six-week period. The methodology included shadowing, interviews and communication event logging. A novel LPDA-based application was used for real-time data collection. The results of the study indicate that designers communicate frequently, using a wide variety of communication and collaboration modalities. Designers prefer general-purpose tools to domain-specific applications. In support of communication, designers frequently change their physical location throughout the day. Finally, designers frequently change the ways in which they communicate, changing their communication modalities and styles.
Central Regulation of Respiration by Endogenous Neurotransmitters and Neuromodulators (1981)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Determining the differences among cost savings, cost avoidance, and cost reduction. (1999)

Cost savings, cost avoidance, and cost reduction are important factors to measure when valuing clinical pharmacy services. Currently, there are no universally accepted definitions for these terms. The authors of this study evaluated 44 articles which claimed to measure cost savings, cost avoidance, or cost reduction associated with clinical pharmacy services, and offered recommendations for when it would be appropriate to use these terms. Based on the results of our analysis, it is evident that controversy exists in the literature when determining if services result in cost avoidance or cost reduction. Therefore, there is a need for universally accepted definitions of these terms so that future research may evaluate such factors uniformly.
In vitro structure-function studies of the Bacillus subtilis tyrS mRNA antiterminator: evidence for factor-independent tRNA acceptor stem binding specificity (2002)

Expression of many aminoacyl-tRNA synthetase, amino acid biosynthesis and transport genes in Bacillus subtilis is controlled at the level of transcription termination using the T box system and requires the formation of specific secondary structures in the mRNA leader region. One structure functions as a transcriptional terminator, while an alternate form, the antiterminator, is necessary for transcription of the downstream coding regions. We have investigated the interaction of antiterminator model RNAs, based on the B.subtilis tyrS antiterminator with tRNA(Tyr) and tRNA acceptor stem models, using a gel shift assay. Binding of the antiterminator RNA to tRNA(Tyr) was dependent on complimentarity with the acceptor end of the tRNA or microhelix; affinity for the microhelix RNA was reduced relative to the tRNA. Alteration of a conserved position in the non-base pairing region of the bulge greatly reduced tRNA binding, consistent with in vivo studies. Therefore, it appears that some of the antiterminator-tRNA binding specificity is dependent on the structure of the antiterminator bulge alone and the complex it forms with tRNA in the absence of additional trans-acting factors. During the course of these studies we also discovered that the antiterminator can form a 'kissing' bulge complex, a unique RNA motif. The ease of formation of this RNA homodimer illustrates the propensity for the bulge of the antiterminator to bind RNA.
Preparation of nano-crystalline diamonds using pulsed laser induced reactive quenching (1998)

Nano-crystalline diamond is prepared with a unique method in which a graphite target is etched by a high-power pulsed laser in water. Transmission electron microscopy (TEM) and high resolution electron microscopy (HREM) indicate nano-crystalline diamond is obtained, having a hexagonal lattice or cubic lattice.
Smart Fabrication Process of an Ir-IrO[sub x] Top-Electrode on a PZT Film for Reliable FeRAM (2004)

We have investigated the sputtering mechanism of films with regard to the fabrication of ferroelectric capacitors. The target surface was a stably metallic state, even when the reactive sputtering of was done in the reactive-gas system. The sputtered film phase, Ir or was determined by the dc power, essentially, the Ir-flux from the target into the plasma to react with oxygen radicals. The metallic Ir phase was deposited at high dc power with a large Ir-flux, while the oxide phase was obtained through a low Ir flux due to reacting well with oxygen radicals. This sputtering feature enabled us to obtain an -stacked top-electrode with a sharp interface by simply changing the sputtering power. This power-swing sputtering method is an effective way to form the stacked film when fabricating the top electrode of a (PZT) capacitor. We found that sputtering of the stacked top-electrode at a high oxygen pressure and low temperature suppressed damage to the PZT surface, achieving high-performance ferroelectric random access memory capacitors. © 2004 The Electrochemical Society. All rights reserved.
PocketNavigator (2010)

Pedestrian navigation systems are becoming popular but the currently dominant audio-visual interaction can have drawbacks. Tactile feedback is studied as a solution, but currently only available as research prototypes. With the PocketNavigator we propose a demonstrator that adds tactile feedback to a simple but robust map-based navigation system that runs on any Android Smartphone. Users can leave the device in the pocket, while being guided non-visually through vibration cues. Like a compass we "point at" the next waypoint by encoding its direction and distance in vibration patterns. As an advantage over previous approaches it allows giving continuous feedback instead of isolated turning instructions and it can be realized without custom-built tactile displays. Preliminary results from a field study show that pedestrian can effectively use this Tactile Compass to reach a destination without turn-by-turn instructions. Integrated into the PocketNavigator we can now deploy it at the Android Market to evaluate the Tactile Compass with a wide range of users.