gebhart/patrepeval huggingface dataset:
Genome‐wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations (2008)

Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P-values with a magnitude less than 10(-5), are discussed in this manuscript. Seventeen of these candidate genes had association P-values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P-values lower than 0.01 and multiple association P-values at a magnitude of 10(-5) in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD.
Short-wavelength free-electron laser sources and science: a review (2017)

This review is focused on free-electron lasers (FELs) in the hard to soft x-ray regime. The aim is to provide newcomers to the area with insights into: the basic physics of FELs, the qualities of the radiation they produce, the challenges of transmitting that radiation to end users and the diversity of current scientific applications. Initial consideration is given to FEL theory in order to provide the foundation for discussion of FEL output properties and the technical challenges of short-wavelength FELs. This is followed by an overview of existing x-ray FEL facilities, future facilities and FEL frontiers. To provide a context for information in the above sections, a detailed comparison of the photon pulse characteristics of FEL sources with those of other sources of high brightness x-rays is made. A brief summary of FEL beamline design and photon diagnostics then precedes an overview of FEL scientific applications. Recent highlights are covered in sections on structural biology, atomic and molecular physics, photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A short industrial perspective is also included to emphasise potential in this area.
AirLand Battle Management Program decision aids for battle management planning (2002)

The AirLand Battle Management (ALBM) Program is a prototype demonstration project sponsored by DARPA and the US Army. Its goal is to demonstrate that advanced computer processing and artificial intelligence techniques, particularly cooperating expert systems, can be used to accelerate and improve the development of US Army manoeuver and fire support plans for airland battle forces. The program is providing a decision support environment that helps commanders and staff officers reason about complex situations represented by large amounts of information. There are two major components, FORCES and STAR. FORCES is a collection of prototype cooperating expert systems which support the commander and staff in performing the decision-making process. STAR is a collection of computer programs (tools) which provide the foundation for FORCES, enabling developers to build additional application programs rapidly, and enabling soldiers to add new knowledge.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
ET-1-induced bronchoconstriction is mediated via ET<sub>B</sub> receptor in mice (1997)

Endothelin (ET)-1 is one of the most potent agonists of airway smooth muscle and can act via two different ET receptor subtypes, i.e., ETA and ETB. To determine the effects of ET-1 on in vivo pulmonary function and which ET receptors are involved in murine lungs, we investigated 1) the effects of ET and sarafotoxin S6c (S6c), a selective ETB agonist, on pulmonary function and 2) the effects of BQ-123 and BQ-788, specific ETA- and ETB-receptor antagonists, on ET-1-induced bronchoconstriction. ICR mice were anesthetized and mechanically ventilated (frequency = 2.5 Hz, tidal volume = 8 ml/kg, positive end-expiratory pressure = 3 cmH2O). Intravenous ET-1, ET-2, and ET-3 increased lung resistance similarly and equipotently, whereas S6c elicited a greater degree of bronchoconstriction. Mice were then pretreated with saline (Sal), BQ-123 (0.2, 1, and 5 mg/kg), or BQ-788 (0.2, 1, and 5 mg/kg) before administration of ET-1 (10(-7) mol/kg iv). No dose of BQ-123 blocked ET-1-induced constriction, whereas pretreatment with each dose of BQ-788 significantly inhibited ET-1-induced responses. There were significant differences in morphometrically assessed airway constriction between Sal and BQ-788 and between BQ-123 and BQ-788, whereas no significant difference was observed between Sal and BQ-123. There were no significant morphometric differences in the airway wall area among the three groups. These observations suggest that the ETB- but not ETA-receptor subtype may mediate the changes in murine pulmonary function in response to ET-1. In addition, the ETB-receptor antagonist reduces ET-1-induced airway narrowing by affecting airway smooth muscle contraction in mice.
Drones for parcel and passenger transportation: A literature review (2020)

Delivery drones and ‘air taxis’ are currently among the most intensely discussed emerging technologies, likely to expand mobility into the ‘third dimension’ of low-level airspace. This paper presents a systematic literature review of 111 interdisciplinary publications (2013 - 03/2019). The review systematizes the current socio-technical debate on civil drones for transportation purposes allowing for a (critical) interim assessment. To guide the review process four dimensions of analysis were defined. A total of 2581 relevant quotations were subdivided into anticipated barriers (426), potential problems (1037), proposed solutions (737) and expected benefits (381). We found that the debate is characterized by predominantly technical and regulatory problems and barriers which are considered to prevent or impede the use of drones for parcel and passengers transportation. At the same time, definite economic expectations are juxtaposed with quite complex and differentiated concerns regarding societal and environmental impacts. Scrutinizing the most prevalent transportation-related promises of traffic reduction, travel time saving and environmental relief we found that there is a strong need to provide scientific evidence for the promises linked to the use of drones for transportation. We conclude that the debate on drones for transportation needs further qualification, emphasizing societal benefits and public involvement more strongly.
Photodynamic Therapy for Treatment of Solid Tumors — Potential and Technical Challenges (2008)

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors.
Lessons from gene knockouts (1998)

The authors describe the technique for the application of homologous recombination in embryonic stem cells, which is now widely used to engineer mice which carry specific knockouts of genes. A summary is given of some of the knowledge of the pathogenesis of and resistance to infections with parasites, bacteria, or viruses which has accumulated during recent years, based on the investigation of knockout mice. Special emphasis is placed on knockout animals which lack components of the cytokine network, lack genes which are critical for the correct presentation of antigens or are deficient in different immune cell subsets. In addition, a brief explanation is offered of the possibilities for inducing targeted deletions or mutations in genes of livestock species (e.g., by nuclear transfer or by mutagenesis using the alkylating agent N-ethyl-N-nitrosourea) which could lead to the breeding of animals which are resistant to infectious diseases in the future.
Electrophoretic mobility for peptides with post‐translational modifications in capillary electrophoresis (2003)

Several semiempirical models for peptide electrophoretic mobility have been tested for capillary electrophoresis (CE) separation with a positively charged capillary using on-line CE combined with electrospray ionization-mass spectrometry (ESI-MS). In the current system with pH 2.7, the expression q/M(0.56) provided the best correlation with the electrophoretic mobility in the analysis of a set of 18 standard samples, where q is the calculated net charge and M is the molecular weight. The peptides resulting from various digests of horse heart myoglobin or bovine hemoglobin were used to demonstrate the validity of this correlation. Post-translationally modified peptides from tryptic digest of human myelin basic protein were also investigated and were found to provide excellent correlation with the linear plot when the total charge of the peptide was correctly calculated. If the total charge was not properly calculated then the post-translationally modified peptides fell off the linear plot. Using this method five arginine residues (residues 5, 49, 54, 97 and 130) were found to be partially citrullinated, four glutamine residues (residues 8, 103, 121 and 147) were found to be partially deamidated and both methionines at residues 21 and 167 were found to be partially oxidized. Three peptides were found with phosphorylation; TPPPSQGK (residue 98 to 105), FSWGAEGQR (residue 114 to 122), and SGSPMAR (residue 163 to 169) and Arginine at 107 was found to be partially monomethylated or dimethylated. The method may provide an excellent means of identifying the presence of peptides with post-translational modifications in conjunction with MS.
Prolonged nasal eosinophilia in all_ergic patients after common cold (2001)

Prolonged nasal eosinophil influx was observed in allergic patients after common cold. What immunologic factors can induce prolonged eosinophil influx and whether this may increase the risk of subsequent allergen-induced hypersensitivity reactions must be studied further.
[Acute hypoxia induce free radicals generation in rat's cortex and hippocampus]. (1995)

Anesthetized rats were ventilated artificially to 10.5%-11.0% O2 in N2 (equivalent to altitude about 5 000 m). PBN (alpha-phenyl-ter-butylnitrone) was injected intravenously 5 min before hypoxia. The experiment results showed that the ESR (electron spin resonance) signal intensity of PBN-spin adduct in cortex and hippocampus both increased significantly during hypoxia (15 min) as compared with normoxia group (n = 5, P < 0.01). In the third group of rats injected with MPEG-SOD (monomethoxy-polyethylene glycol-superoxide dismutase) intravenously 20 min before hypoxia, the ESR signal intensity of PBN-spin adduct in cortex and hippocampus did not decrease significantly under hypoxia for 15 min (compared with hypoxia group, n = 5, P > 0.05). This may be due to the fact that MPEG-SOD could not pass the blood-brain barrier owing to its large molecular weight. The enzyme activity of SOD (superoxide dismutase. EC 1.15.1.1), GSH-Px (Glutathione peroxidase, EC 1.11.1.9) and content of MDA (malondialdehyde) was also determined. The results showed that the hypoxia had no effect on the SOD, GSH-Px activity and MDA content (n = 7 or n = 8, P > 0.05). The above results suggested that ventilation to 10.5%-11.0% O2 in N2 15 min induced free radical generation in rat's cortex and hippocampus, but this generation was not due to decrease of SOD, GSH-Px activity in cortex and hippocampus.
Intelligent robust control of a robotic unicycle based on a new physical measure for mechanical controllability (1997)

The posture stability driving control of a human riding-type unicycle has been realized. The robotic unicycle is considered as a biomechanical system using an internal world representation with a description of emotion, instinct and intuition mechanisms. We introduced intelligent control methods based on soft computing, and confirmed that such an intelligent control and biological instinct as well as intuition together with a fuzzy inference is very important for emulating human behaviors or actions. For the fitness function of the generic algorithm, a new physical measure of the minimum entropy production for a description of the intelligent behavior in a biological model is introduced. The calculation of robustness and controllability of the robotic unicycle is presented. This paper provides a general measure to estimate the mechanical controllability both qualitatively and quantitatively, even if any control scheme is applied. The measure can be computed using a Lyapunov function coupled with the thermodynamic entropy change. Fuzzy simulation and experimental results of a robust intelligent control motion for the robotic unicycle are discussed.
Super Large Sn<sub>1–<i>x</i></sub>Se Single Crystals with Excellent Thermoelectric Performance (2019)

SnSe single crystals have drawn extensive attention for their ultralow thermal conductivity and outstanding thermoelectric performance. Here, we report super large Sn1–xSe single crystals with excellent thermoelectric properties, fabricated via an advanced horizontal Bridgman technique with great yield and high reproducibility. The obtained single crystals have a super large size of ∼70 × 50 × 15 mm with a considerable weight of 148 g, which leads to a record-high mass density of >6.1 g cm–3. Extensive chemical characterization demonstrates that ∼0.3% Sn vacancies are present, which results in a large concentration of holes, ∼1.2 × 1019 cm–3, and an enhanced power factor of ∼6.1 μW cm–1 K–2 at 793 K. Simultaneously, the Sn-vacancy-induced lattice distortions result in a low thermal conductivity of ∼0.39 W m–1 K–1 at 793 K, leading to a competitive ZT of ∼1.24. This work demonstrates that large-size off-stoichiometric SnSe single crystals hold promise to achieve high thermoelectric performance.
Human class 1 heparin-binding growth factor: structure and homology to bovine acidic brain fibroblast growth factor (1986)

The structure of the major class 1 heparin-binding growth factor from human brain has been analyzed. Edman degradation performed on the native mitogen and on fragments generated by chemical and enzymatic cleavage allows the sequence to be described by four nonoverlapping segments. The sum of the amino acids of the four segments is in excellent agreement with the experimentally determined amino acid composition of the mitogen itself, suggesting that, jointly, they account for the entire molecule. The four segments can be aligned into a presumptive complete sequence that shows 92% identity with that of bovine acidic brain fibroblast growth factor. The data indicate that the human mitogen has the following sequence: Phe1-Asn-Leu-Pro-Pro-Gly-Asn-Tyr-Lys-Lys-Pro-Lys-Leu-Leu-Try15+ ++-Cys- Ser-Asn-Gly-Gly-His-Phe-Leu-Arg-Ile-Leu-Pro-Asp-Gly-Thr30-Val-Asp- Gly-Thr-Arg- Asp-Arg-Ser-Asp-Gln-His-Ile-Gln-Leu-Gln45-Leu-Ser-Ala-Glu-Ser-Val- Gly-Glu-Val- Tyr-Ile-Lys-Ser-Thr-Glu60-Thr-Gly-Gln-Tyr-Leu-Ala- Met-Asp-Thr-Asp-Gly-Leu-Leu-Tyr-Gly75-Ser-Gin-Thr-Pro-Asn-Glu-Glu- Cys-Leu-Phe- Leu-Glu-Arg- Leu-Glu90-Glu-Asn-His-Tyr-Asn-Thr-Tyr-Ile-Ser-Lys-Lys-His-Ala-Glu- Lys105-Asn- Trp-Phe-Val-Gly- Leu-Lys-Lys-Asn-Gly-Ser-Cys-Lys-Arg-Gly120-Pro-Arg-Thr-His-Tyr-Gly -Gln-Lys-Ala- Ile-Leu-Phe-Leu- Pro-Leu135-Pro-Val-Ser-Ser-Asp140.
Tandem-genotypes: robust detection of tandem repeat expansions from long DNA reads (2019)

Tandemly repeated DNA is highly mutable and causes at least 31 diseases, but it is hard to detect pathogenic repeat expansions genome-wide. Here, we report robust detection of human repeat expansions from careful alignments of long but error-prone (PacBio and nanopore) reads to a reference genome. Our method is robust to systematic sequencing errors, inexact repeats with fuzzy boundaries, and low sequencing coverage. By comparing to healthy controls, we prioritize pathogenic expansions within the top 10 out of 700,000 tandem repeats in whole genome sequencing data. This may help to elucidate the many genetic diseases whose causes remain unknown.
Multi-mode microscopy using diffractive optical elements (2011)

This paper discusses a range of phase-diversity and tracking applications that have been demonstrated experimentally, and will present an analysis of experimental errors associated with the system used. Simultaneous imaging in multiple imaging modes is demonstrated and the use of wavefront-sensing techniques to achieve nanometric depth resolution is reviewed.
Inhibitor of H3K27 demethylase JMJD3/UTX GSK-J4 is a potential therapeutic option for castration resistant prostate cancer (2017)

Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC. Reduction of the repressive epigenetic modification H3K27me2/3 correlates with PCa aggressiveness, while corresponding demethylases JMJD3/UTX are overexpressed in PCa. We found that JMJD3/UTX inhibitor GSK-J4 reduced more efficiently proliferation of AR-ΔLBD cells (CRPC model) compared with isogenic AR-WT cells. Inhibition of JMJD3/UTX protects demethylation of H3K27Me2/3, thus reducing levels of H3k27Me1. We observed that the reduction dynamics of H3K27Me1 was faster and achieved at lower inhibitor concentrations in AR-ΔLBD cells, suggesting that inhibition of JMJD3/UTX diminished proliferation of these cells by hindering AR-driven transcription. In addition, we observed synergy between GSK-J4 and Cabazitaxel, a taxane derivative that is approved for CRPC treatment. Collectively, our results point at the H3K27 demethylation pathway as a new potential therapeutic target in CRPC patients.
In Vivo Anti-diabetic and Anti-oxidant Potential of Psoralea corylifolia Seeds in Streptozotocin Induced Type-2 Diabetic Rats (2011)

This study was made to investigate the anti-diabetic and antioxidant potential of ethanolic extract of seeds of Psoralea corylifolia L. in streptozotocin (STZ) nicotinamide induced type-2 diabetic rats. Male Albino Wistar rats (150-250 g) were taken for the study. The ethanolic extract of seeds of Psoralea corylifolia was prepared and the oral administration of this extract tested for anti-hyperglycemic activity in streptozotocin-nicotinamide induced diabetic rats showed significant effect on blood glucose level in acute and chronic study. The body weight, oral glucose tolerance test and biochemical parameter such as insulin level, liver glycogen contents, glycosylated hemoglobin, total plasma cholesterol and antioxidant parameters were estimated for all treated group and compared against diabetic control group. In oral glucose tolerance test both dose (200 and 400 mg/kg) intensively reduced external glucose level. After 28 days (chronic study) of treatment with extract the maximum reduction in blood glucose level were observed in streptozotocin-nicotinamide rats with ethanolic extract 400 mg/kg body weight per os. There were significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin level and total plasma cholesterol. However it also influences on the antioxidant parameters like decreases malondialdehyde (MDA) level and increases reduced glutathione (GSH) level. This investigation results that Psoralea corylifolia has significant antihyperglycemic and antioxidant activity.
Synthesis and Antiribosomal Activities of 4′-<i>O</i>-, 6′-<i>O</i>-, 4″-<i>O</i>-, 4′,6′-<i>O</i>- and 4″,6″-<i>O</i>-Derivatives in the Kanamycin Series Indicate Differing Target Selectivity Patterns between the 4,5- and 4,6-Series of Disubstituted 2-Deoxystreptamine Aminoglycoside Antibiotics (2015)

Chemistry for the efficient modification of the kanamycin class of 4,6-aminoglycosides at the 4'-position is presented. In all kanamycins but kanamycin B, 4'-O-alkylation is strongly detrimental to antiribosomal and antibacterial activity. Ethylation of kanamycin B at the 4″-position entails little loss of antiribosomal and antibacterial activity, but no increase of ribosomal selectivity. These results are contrasted with those for the 4,5-aminoglycosides, where 4'-O-alkylation of paromomycin causes only a minimal loss of activity but results in a significant increase in selectivity with a concomitant loss of ototoxicity.
Mapping eGFP Oligomer Mobility in Living Cell Nuclei (2009)

Movement of particles in cell nuclei can be affected by viscosity, directed flows, active transport, or the presence of obstacles such as the chromatin network. Here we investigate whether the mobility of small fluorescent proteins is affected by the chromatin density. Diffusion of inert fluorescent proteins was studied in living cell nuclei using fluorescence correlation spectroscopy (FCS) with a two-color confocal scanning detection system. We first present experiments exposing FCS-specific artifacts encountered in live cell studies as well as strategies to prevent them, in particular those arising from the choice of the fluorophore used for calibration of the focal volume, as well as temperature and acquisition conditions used for fluorescence fluctuation measurements. After defining the best acquisition conditions, we show for various human cell lines that the mobility of GFP varies significantly within the cell nucleus, but does not correlate with chromatin density. The intranuclear diffusional mobility strongly depends on protein size: in a series of GFP-oligomers, used as free inert fluorescent tracers, the diffusion coefficient decreased from the monomer to the tetramer much more than expected for molecules free in aqueous solution. Still, the entire intranuclear chromatin network is freely accessible for small proteins up to the size of eGFP-tetramers, regardless of the chromatin density or cell line. Even the densest chromatin regions do not exclude free eGFP-monomers or multimers.