gebhart/patrepeval huggingface dataset:
ARTIFICIAL INTELLIGENCE-SUPPORTED WEATHER PREDICTION FOR HIGHWAY OPERATIONS (1992)

This study proves the feasibility of a numerical weather prediction system that accounts for local geography and incorporates interaction betweeen user-supplied weather and road surface conditions, and numerical weather predictions. The study involved the design of a new concept, that of hybrid modeling, which combines aspects of numerical weather prediction with those of artificial intelligence-based, symoblic object manipulation. The report outlines the results of the user-friendly, artificial intelligence-supported weather prediction software which integrates historical and current local weather information for use in state highway departments' snow and ice control operations. The software tailors user-supplied road and weather conditions with graphic modeling to predict range, type and magnitude of approaching storms.
Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains (1994)

The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase-positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions.
Short-chain fatty acids: bacterial mediators of a balanced host-microbial relationship in the human gut. (2002)

The luminal compartment of the gastrointestinal tract is colonized by a large and highly complex microflora providing not only nutritional advances, but also representing a potential immunological challenge for the host. Under physiological conditions, the immune cells of the colonic mucosa do not defeat the microflora. In contrast, in cases of inflammatory bowel disease (IBD), the intestinal microflora appears to be the target of immune reactivity as demonstrated in various genetic studies and animal models of mucosal inflammation. The mechanisms responsible for the maintenance of this immunological unresponsiveness in the mucosal compartment are still largely enigmatic though recent studies indicate that luminal components might control this peculiar state. The bacterial fermentation product n-butyrate has been identified as such as critical molecule. Apart from its essential nutritional function for colonocytes, an anti-inflammatory activity of this short-chain fatty acid (SCFA) has been recognized in vitro and in vivo. Regarding its molecular mode of action, an interference with transcription factors critical for the production of pro-inflammatory cytokines has been found. This overview discusses the physiological functions of this bacterial metabolite and its emerging role as a potent regulator of mucosal homeostasis. Special emphasis is laid on potential therapeutic implications of SCFA in the treatment of several forms of colitis.
Human Hepatocyte Nuclear Factor 4 Isoforms Are Encoded by Distinct and Differentially Expressed Genes (1996)

Hepatocyte nuclear factor 4 (HNF4) was first identified as a DNA binding activity in rat liver nuclear extracts. Protein purification had then led to the cDNA cloning of rat HNF4, which was found to be an orphan member of the nuclear receptor superfamily. Binding sites for this factor were identified in many tissue-specifically expressed genes, and the protein was found to be essential for early embryonic development in the mouse. We have now isolated cDNAs encoding the human homolog of the rat and mouse HNF4 splice variant HNF4 alpha 2, as well as a previously unknown splice variant of this protein, which we called HNF alpha 4. More importantly, we also cloned a novel HNF4 subtype (HNF4 gamma) derived from a different gene and showed that the genes encoding HNF 4 alpha and HNF4 gamma are located on human chromosomes 20 and 8, respectively. Northern (RNA) blot analysis revealed that HNF4 GAMMA is expressed in the kidney, pancreas, small intestine, testis, and colon but not in the liver, while HNF4 alpha RNA was found in all of these tissues. By cotransfection experiments in C2 and HeLa cells, we showed that HNF4 gamma is significantly less active than HNF4 alpha 2 and that the novel HNF4 alpha splice variant HNF4 alpha 4 has no detectable transactivation potential. Therefore, the differential expression of distinct HNF4 proteins may play a key role in the differential transcriptional regulation of HNF4-dependent genes.
Discovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties (2018)

A novel series of CXCR4 antagonists with piperidinyl and piperazinyl alkylamine side chains designed as butyl amine replacements are described. Several of these compounds showed similar activity to the parent compound TIQ-15 (<b>5</b>) in a SDF-1 induced calcium flux assay. Preliminary structure-activity relationship investigations led us to identify a series containing <i>N</i>-propyl piperazine side chain analogs exemplified by <b>16</b> with improved off-target effects as measured in a muscarinic acetylcholine receptor (mAChR) calcium flux assay and in a limited drug safety panel screen. Further efforts to explore SAR and optimize drug properties led to the identification of the <i>N</i>'-ethyl-<i>N</i>-propyl-piperazine tetrahydroisoquinoline derivative <b>44</b> and the <i>N</i>-propyl-piperazine benzimidazole compound <b>37</b>, which gave the best overall profiles with no mAChR or CYP450 inhibition, good permeability in PAMPA assays, and metabolic stability in human liver microsomes.
Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation (2016)

Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5, indicating that residual C5 activity may derogate the drug's therapeutic benefit under certain conditions. By using eculizumab and the tick-derived C5 inhibitor coversin, we determined conditions ex vivo in which C5 inhibition is incomplete. The degree of such residual lytic activity depended on the strength of the complement activator and the resulting surface density of the complement activation product C3b, which autoamplifies via the alternative pathway (AP) amplification loop. We show that at high C3b densities required for binding and activation of C5, both inhibitors reduce but do not abolish this interaction. The decrease of C5 binding to C3b clusters in the presence of C5 inhibitors correlated with the levels of residual hemolysis. However, by employing different C5 inhibitors simultaneously, residual hemolytic activity could be abolished. The importance of AP-produced C3b clusters for C5 activation in the presence of eculizumab was corroborated by the finding that residual hemolysis after forceful activation of the classical pathway could be reduced by blocking the AP. By providing insights into C5 activation and inhibition, our study delivers the rationale for the clinically observed phenomenon of residual terminal pathway activity under eculizumab treatment with important implications for anti-C5 therapy in general.
CA125 based diagnosis and therapy in recurrent ovarian cancer. (1997)

Approximately 85% of patients with advanced ovarian cancer will experience recurrence of the disease. In 311 patients CA125 serum levels were determined at follow up investigation in our department. A sensitivity of 92% and specificity of 89% were calculated. Reflecting the further course of disease, specificity could be increased up to 97%. Using 25 U/ml/month as the upper limit of grade of CA125 increase, a 100% specificity for detecting recurrence could be achieved. In conclusion, recurrence diagnosis and even therapy should be started in cases of either significantly raised CA125 levels or elevated grade of CA125 increase.
Wild‐type p53‐induced apoptosis in a Burkitt lymphoma cell line is inhibited by interferon gamma (1996)

The tumor suppressor p53 plays a central role in negative growth control, including growth arrest and apoptosis. Interferons (IFNs) are capable of modulating a variety of cellular responses, including apoptosis. In this study, we have evaluated the influence of γ- and α-interferon (IFN) on wild-type (wt) p53-induced apoptosis using a Burkitt lymphoma cell line, BL41, transfected with a temperature-sensitive p53 construct. γ-IFN, but not α-IFN, was found to protect cells from wt p53-induced apoptosis. The γ-IFN-dependent protection was due neither to down-regulation of p53, nor to the p53-induced genes, p21 (WAF-I) and bax, nor to up-regulation of bcl-2 or bcl-xL. Expression of the proto-oncogene c-myc, implicated in the control of both proliferation and apoptosis, was not affected by γ-IFN. We conclude that γ-IFN can suppress p53-induced apoptosis, and that the cytokine microenvironment may be decisive in the cellular response to wt p53 expression. © 1996 Wiley-Liss, Inc.
HLA‐A*0201‐restricted Cytotoxic T‐cell Epitopes in Three PE/PPE Family Proteins of Mycobacterium tuberculosis (2008)

CD8+ T cells are thought to play an important role in protective immunity against tuberculosis. We report the identification of three peptides derived from Rv1818c, Rv3812 and Rv3018c proteins of Mycobacterium tuberculosis that bound to HLA-A*0201 molecules and their ability to induce in vitro T-cell response in peripheral blood lymphocytes from HLA-A*0201-positive healthy individuals (PPD+) and patients with TB. The peptide-specific cytotoxic T lymphocytes (CTL) generated were capable of recognizing peptide pulsed targets. Three 9-mer peptides bound with high affinity to HLA-A*0201 and displayed low dissociation rates of the bound peptide from HLA. Epitope-specific recognition was demonstrated by the release of perforin and gamma-interferon. Overall, our results demonstrate the presence of HLA class I-restricted CD8+ CTL against proteins from PE and PPE proteins of M. tuberculosis and identify epitopes that are strongly recognized by HLA-A*0201-restricted CD8+ T cells in humans. These epitopes thus represent potential subunit components for the design of vaccines against tuberculosis.
Functional Mitochondria Are Required for α-Synuclein Toxicity in Aging Yeast (2008)

alpha-Synuclein is one of the principal toxic triggers of Parkinson disease, an age-associated neurodegeneration. Using old yeast as a model of alpha-synuclein expression in post-mitotic cells, we show that alpha-synuclein toxicity depends on chronological aging and results in apoptosis as well as necrosis. Neither disruption of key components of the unfolded protein response nor deletion of proapoptotic key players (including the yeast caspase YCA1, the apoptosis-inducing factor AIF1, or the serine protease OMI) did prevent alpha-synuclein-induced cell killing. However, abrogation of mitochondrial DNA (rho(0)) inhibited alpha-synuclein-induced reactive oxygen species formation and subsequent apoptotic cell death. Thus, introducing an aging yeast model of alpha-synuclein toxicity, we demonstrate a strict requirement of functional mitochondria.
Primary Care Medicine (1987)

A NEW ASPIRINLIKE, nonnarcotic drug may be more effective than morphine in relieving postoperative pain, according to researchers at Chicago's Northwestern University. The new agent, ketorolac tromethamine, is currently undergoing randomized, double-blind clinical trials to assess its safety and effectiveness as a pain reliever. The compound belongs to the same class of drugs as indomethacin, which provides relief of inflammation and fever as well as easing pain. "It [ketorolac] may prove to be a very important pain reliever, for it is at least as effective as morphine, lasts much longer when given by injection, and has few side effects," said Dorene A. O'Hara, MD, of Northwestern University, Chicago. O'Hara reported the study findings at the annual meeting of the American Society of Anesthesiologists in Las Vegas on Oct 19,1986. Since ketorolac is a nonnarcotic drug, it may not possess the addictive potential of morphine, she said. Previous studies have demonstrated
An enhanced direct anonymous attestation scheme with mutual authentication for network-connected UAV communication systems (2018)

In network-connected UAV (NC-UAV) communication systems, user authentication is replaced by platform identity authentication and integrity check because many NC-UAVs are operated without human intervention. Direct anonymous attestation (DAA) is an attractive cryptographic scheme that provides an elegant balance between platform authentication and anonymity. However, because of the low-level computing capability and limited transmission bandwidth in UAV, the existing DAA schemes are not suitable for NC-UAV communication systems. In this paper, we propose an enhanced DAA scheme with mutual authentication (MA-DAA scheme), which meets the security requirements of NC-UAV communication systems. The proposed MA-DAA scheme, which is based on asymmetric pairings, bundles the identities of trusted platform module (TPM) and Host to solve the malicious module changing attacks. Credential randomization, batch proof and verification, and mutual authentication are realized in the MA-DAA scheme. The computational workload in TPM and Host is reduced in order to meet the low computation and resource requirements in TPM and Host. The entire scheme and protocols are presented, and the security and efficiency of the proposed MA-DAA scheme are proved and analyzed. Our experiment results also confirm the high efficiency of the proposed scheme.
A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy (2019)

The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy.
A process for the combined fabrication of ion sensors and CMOS circuits (1988)

A novel process for the fabrication of ion-selective field-effect transistors (ISFETs) together with CMOS circuits on the same chip is reported. The process is based on a standard 2- mu m, n-well, CMOS process, which is only modified starting at the metal interconnect step. The interconnect layer used is tungsten silicide. ISFETs are fabricated with floating polysilicon gates, which are exposed to photolithographic masking and HF etching before silicon nitride is deposited on the wafer. This layer of Si/sub 3/N/sub 4/ acts both as the pH-sensitive insulator for the ISFETs and as a protection layer for the on-chip circuitry buried beneath it. A source-follower circuit is described that provides an output voltage dependent on the threshold-voltage variations of the sensing transistor.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New consensus nomenclature for mammalian keratins (2006)

Keratins are intermediate filament-forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human keratins, it offers the flexibility needed to incorporate additional keratins from other mammalian species.
A generic intron increases gene expression in transgenic mice. (1991)

To investigate the role of splicing in the regulation of gene expression, we have generated transgenic mice carrying the human histone H4 promoter linked to the bacterial gene for chloramphenicol acetyltransferase (CAT), with or without a heterologous intron in the transcription unit. We found that CAT activity is 5- to 300-fold higher when the transgene incorporates a hybrid intron than with an analogous transgene precisely deleted for the intervening sequences. This hybrid intron, consisting of an adenovirus splice donor and an immunoglobulin G splice acceptor, stimulated expression in a broad range of tissues in the animal. Although the presence of the hybrid intron increased the frequency of transgenics with significant CAT activity, it did not affect the integration site-dependent variation commonly seen in transgene expression. To determine whether the enhancement is a general outcome of splicing or is dependent on the particular intron, we also produced equivalent transgenics carrying the widely used simian virus 40 small-t intron. We found that the hybrid intron is significantly more effective in elevating transgene expression. Our results suggest that inclusion of the generic intron in cDNA constructs may be valuable in achieving high levels of expression in transgenic mice.
Segmentation of Dual-Axis Swallowing Accelerometry Signals in Healthy Subjects With Analysis of Anthropometric Effects on Duration of Swallowing Activities (2009)

Dysphagia (swallowing difficulty) is a serious and debilitating condition that often accompanies stroke, acquired brain injury, and neurodegenerative illnesses. Individuals with dysphagia are prone to aspiration (the entry of foreign material into the airway), which directly increases the risk of serious respiratory consequences such as pneumonia. Swallowing accelerometry is a promising noninvasive tool for the detection of aspiration and the evaluation of swallowing. In this paper, dual-axis accelerometry was implemented since the motion of the hyolaryngeal complex occurs in both anterior-posterior and superior-inferior directions during swallowing. Dual-axis cervical accelerometry signals were acquired from 408 healthy subjects during dry, wet, and wet chin tuck swallowing tasks. The proposed segmentation algorithm is based on the idea of sequential fuzzy partitioning of the signal and is well suited for long signals with nonstationary variance. The algorithm was validated with simulated signals with known swallowing locations and a subset of 295 real swallows manually segmented by an experienced speech language pathologist. In both cases, the algorithm extracted individual swallows with over 90% accuracy. The time duration analysis was carried out with respect to gender, body mass index (BMI), and age. Demographic and anthropometric variables influenced the duration of these segmented signals. Male participants exhibited longer swallows than female participants (p=0.05). Older participants and participants with higher BMIs exhibited swallows with significantly longer (p=0.05) duration than younger participants and those with lower BMIs, respectively.
Vasopressin in the treatment of vasodilatory shock in children (2005)

Vasopressin deficiency may occur in catecholamine-resistant hypotension of pediatric patients due to various causes including central nervous system disturbance, drug induced hypotension and sepsis. Small doses of vasopressin administration seems to be very effective in such conditions by increasing blood pressure and urinary output.
Glycosylation of G-protein-coupled receptors for hormones central to normal reproductive functioning: its occurrence and role (1999)

Many hormones that are central to normal reproductive functioning mediate their physiological effects by activating a receptor which belongs to the large family of G-protein-coupled receptors (GPCR). Members of this family of receptor proteins are usually glycosylated on extracellular domains. In recent years the role of this glycosylation in cell surface expression/protein folding, ligand recognition and receptor-effector coupling has been investigated. This review summarises current knowledge of the role of glycosylation in the functioning of the receptors for gonadotrophin-releasing hormone (GnRH), luteinizing hormone/human chorionic gonadotrophin (LH/HCG), follicle stimulating hormone (FSH), oxytocin (OT) and vasopressin (AVP).
Partial Reduction of BACE1 Has Dramatic Effects on Alzheimer Plaque and Synaptic Pathology in APP Transgenic Mice (2007)

The aspartyl protease beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates processing of amyloid precursor protein (APP) into amyloid beta (Abeta) peptide, the major component of Alzheimer disease (AD) plaques. To determine the role that BACE1 plays in the development of Abeta-driven AD-like pathology, we have crossed PDAPP mice, a transgenic mouse model of AD overexpressing human mutated APP, onto mice with either a homozygous or heterozygous BACE1 gene knockout. Analysis of PDAPP/BACE(-/-) mice demonstrated that BACE1 is absolutely required for both Abeta generation and the development of age-associated plaque pathology. Furthermore, synaptic deficits, a neurodegenerative pathology characteristic of AD, were also reversed in the bigenic mice. To determine the extent of BACE1 reduction required to significantly inhibit pathology, PDAPP mice having a heterozygous BACE1 gene knock-out were evaluated for Abeta generation and for the development of pathology. Although the 50% reduction in BACE1 enzyme levels caused only a 12% decrease in Abeta levels in young mice, it nonetheless resulted in a dramatic reduction in Abeta plaques, neuritic burden, and synaptic deficits in older mice. Quantitative analyses indicate that brain Abeta levels in young APP transgenic mice are not the sole determinant for the changes in plaque pathology mediated by reduced BACE1. These observations demonstrate that partial reductions of BACE1 enzyme activity and concomitant Abeta levels lead to dramatic inhibition of Abeta-driven AD-like pathology, making BACE1 an excellent target for therapeutic intervention in AD.
Safety-Aware Optimal Control of Stochastic Systems Using Conditional Value-at-Risk (2018)

In this paper, we consider a multi-objective control problem for stochastic systems that seeks to minimize a cost of interest while ensuring safety. We introduce a novel measure of safety risk using the conditional value-at-risk and a set distance to formulate a safety risk-constrained optimal control problem. Our reformulation method using an extremal representation of the safety risk measure provides a computationally tractable dynamic programming solution. A useful byproduct of the proposed solution is the notion of a risk-constrained safe set, which is a new stochastic safety verification tool. We also establish useful connections between the risk-constrained safe sets and the popular probabilistic safe sets. The tradeoff between the risk tolerance and the mean performance of our controller is examined through an inventory control problem.