gebhart/patrepeval huggingface dataset:
Safety of Intradiaphragmatic Delivery of Adeno-Associated Virus-Mediated Alpha-Glucosidase (rAAV1-CMV- <i>hGAA</i> ) Gene Therapy in Children Affected by Pompe Disease (2017)

A first-in-human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory and neural dysfunction in early-onset Pompe disease was conducted. The primary objective of this study was to assess the safety of rAAV1-CMV-hGAA vector delivered to the diaphragm muscle of Pompe disease subjects with ventilatory insufficiency. Safety was assessed by measurement of change in serum chemistries and hematology, urinalysis, and immune response to GAA and AAV, as well as change in level of health. The data demonstrate that the AAV treatment was safe and there were no adverse events related to the study agent. Adverse events related to the study procedure were observed in subjects with lower baseline neuromuscular function. All adverse events were resolved before the end of the study, except for one severe adverse event determined not to be related to either the study agent or the study procedure. In addition, an anti-capsid and anti-transgene antibody response was observed in all subjects who received rAAV1-CMV-hGAA, except for subjects who received concomitant immunomodulation to manage reaction to enzyme replacement therapy, as per their standard of care. This observation is significant for future gene therapy studies and serves to establish a clinically relevant approach to blocking immune responses to both the AAV capsid protein and transgene product.
Bridge the Gap between Neural Networks and Neuromorphic Hardware with a Neural Network Compiler (2018)

Different from developing neural networks (NNs) for general-purpose processors, the development for NN chips usually faces with some hardware-specific restrictions, such as limited precision of network signals and parameters, constrained computation scale, and limited types of non-linear functions. This paper proposes a general methodology to address the challenges. We decouple the NN applications from the target hardware by introducing a compiler that can transform an existing trained, unrestricted NN into an equivalent network that meets the given hardware's constraints. We propose multiple techniques to make the transformation adaptable to different kinds of NN chips, and reliable for restrict hardware constraints. We have built such a software tool that supports both spiking neural networks (SNNs) and traditional artificial neural networks (ANNs). We have demonstrated its effectiveness with a fabricated neuromorphic chip and a processing-in-memory (PIM) design. Tests show that the inference error caused by this solution is insignificant and the transformation time is much shorter than the retraining time. Also, we have studied the parameter-sensitivity evaluations to explore the tradeoffs between network error and resource utilization for different transformation strategies, which could provide insights for co-design optimization of neuromorphic hardware and software.
Suppression of Th17 Cell Response in the Alleviation of Dextran Sulfate Sodium-Induced Colitis by <i>Ganoderma lucidum</i> Polysaccharides (2018)

GLP prevented inflammation, maintained intestinal homeostasis, and regulated the intestinal immunological barrier functions in mice with DSS-induced colitis.
A gene from Alcaligenes denitrificans that confers albicidin resistance by reversible antibiotic binding (1995)

Albicidin antibiotics specifically block prokaryote DNA replication. The albicidin resistance gene (albB) cloned from a soil isolate of Alcaligenes denitrificans encodes a 23 kDa protein capable of detoxifying albicidin by reversible binding. This mechanism operates intracellularly to protect DNA replication in albicidin-sensitive Escherichia coli expressing the cloned resistance gene, which can be induced fivefold in the presence of 1.5 micrograms albicidin ml-1 in the surrounding medium. The coding region of 621 bp has regions with partial DNA sequence homology to an albicidin resistance gene (albA) from Klebsiella oxytoca, but with rearrangements and frame-shifts resulting in loss of protein homology. There is a short region of N-terminal homology between the albicidin resistance (Albr) proteins from A. denitrificans and K. oxytoca, although the two genes use different codons for shared amino acids. The N-terminal homology suggested a common functional domain; this was confirmed by deletion analysis, translational fusions and albicidin binding by a synthetic oligopeptide. Antibiotic binding provides a high level of albicidin resistance in E. coli. The gene appears to be a useful candidate for transfer to plants to protect plastid DNA replication from inhibition by albicidin phytotoxins involved in sugarcane leaf scald disease.
Betulinic Acid Inhibits Aminopeptidase N Activity (1998)

The triterpene betulinic acid inhibits the activity of aminopeptidase N (EC 3.4.11.2) in a dose-dependent manner. An IC50 of 7.3 +/- 1.4 microM was determined for betulinic acid. This inhibitory activity is higher than that of bestatin' (IC50 = 16.9 +/- 4.1 microM), a well known inhibitor of this enzyme. The finding supports the idea that betulinic acid acts as anti-melanoma agent via inhibition of aminopeptidase N activity.
Octacalcium phosphate carboxylates (1994)

Kinetic and thermodynamic studies of octacalcium phosphate succinate (OCP-SUCC), Ca8(HPO4)2-x(succ)x(PO4)4h. yH2O, where 0.8 < x < 1.0 and 5.5 < y < 6.5, broaden the present knowledge in the chemistry of octacalcium phosphate carboxylates. The kinetics of formation of OCP-SUCC by conversion of α-tricalcium phosphate (α-TCP), α-Ca3(PO4)2, in ammonium succinate solutions was followed at varied initial pH, I ≈0.5 mol dm-3, 37°C. The changes in the liquid phase were monitored by pH measurements. Solid phases were characterized by means of chemical analyses, X-ray diffraction and infrared spectroscopy. The rate of conversion decreased with increasing initial pH. In the solubility experiments the concentrations of calcium, phosphate, succinate, ammonium and pH were determined in solutions equilibrated with OCP-SUCC (6.1< pH <7.4). Utilizing these data and association constants of phosphoric and succinic acid and stability constants of the soluble complexes, the solubility product of OCP-SUCC, Ks = c8(Ca2+)c1.07(H+)c0.93(succ2-)c5.07(PO3-4), was determined: pKs(OCP-SUCC) = 68.4 − 0.9 at I = 0.5 mol dm3-, 37°C.
EDTA effect on creatine kinase (CK) and on the SCE reagent (1979)

The inclusion of EDTA in the creatine kinase reagent recommended by the Scandinavian Committee on Enzymes was shown to increase reagent stability from less than 24 h to 5 days. Part of this effect can be explained by the fact that EDTA delays the formation of inhibitory products formed when N-acetyl cysteine is oxidized. The addition of EDTA to the reagent also results in increased measured CK activity. This effect is more pronounced for CK-BB than for CK-MM. Calcium and ferric ions are shown to inhibit the enzyme and the chelation of these ions can partly explain the observed increase of CK acitivity.
The preparation, antischistosomal and antitumor activity of hycanthone and some of its congeners. Evidence for the mode of action of hycanthone (1988)

The synthesis of a series of esters of hycanthone (HC) and 7-hydroxyhycanthone, their antitumor activity, and their antischistosomal effects on HC-sensitive and HC-resistant schistosomes are reported. Binding studies using tritium-labeled HC and hycanthone N-methylcarbamate (HNMC) with calf thymus DNA provided evidence that HNMC but not HC alkylated the DNA. Tritiated HNMC also bound to the DNA of intact HeLa cells exposed to the drug while very little tritiated HC bound to DNA under the same conditions. The mechanism proposed previously to account for the antischistosomal action of HC, namely, drug esterification followed by alkylation of DNA, applies also to the antitumor action of the drug as shown in Scheme I.
Ideal Brittle Fracture of Silicon Studied with Molecular Dynamics (1998)

Dynamic fracture experiments measure crack velocity versus energy flux to the tip. We report here the first calculation of this quantity in a realistic setting, using molecular dynamics to study silicon. The results require relating the short length and time scales of simulations to the long length and time scales of experiments.
Methane production, digestion, ruminal fermentation, nitrogen balance, and milk production of cows fed corn silage- or barley silage-based diets (2013)

This study evaluated the effects of replacing barley silage (BS) with corn silage (CS) in dairy cow diets on enteric CH4 emissions, ruminal fermentation characteristics, digestion, milk production, and N balance. Nine ruminally cannulated lactating cows were used in a replicated 3 × 3 Latin square design (32-d period) and fed (ad libitum) a total mixed ration (TMR; forage:concentrate ratio 60:40; dry matter basis) with the forage portion consisting of either barley silage (0% CS; 0% CS and 54.4% BS in the TMR), a 50:50 mixture of both silages (27% CS; 27.2% CS and 27.2% BS in the TMR), or corn silage (54% CS; 0% BS and 54.4% CS in the TMR). Increasing the CS proportion (i.e., at the expense of BS) also involved increasing the proportion of corn grain (at the expense of barley grain). Intake and digestibility of dry matter and milk production increased linearly as the proportion of CS increased in the diet. Increasing dietary CS proportion decreased linearly the acetate molar proportion and increased linearly that of propionate. Daily CH4 emissions tended to respond quadratically to increasing proportions of CS in the diet (487, 540, and 523 g/d for 0, 27, and 54% CS, respectively). Methane production adjusted for dry matter or gross energy intake declined as the amount of CS increased in the diet; this effect was more pronounced when cows were fed the 54% CS diet than the 27% CS diet. Increasing the CS proportion in the diet improved N utilization, as reflected by decreases in ruminal ammonia concentration and urinary N excretion and higher use of dietary N for milk protein secretion. Total replacement of BS with CS in dairy cow diets offers a strategy to decrease CH4 energy losses and control N losses without negatively affecting milk performance.
Active Remodeling in Idiopathic Interstitial Pneumonias: Evaluation of Collagen Types XII and XIV (2006)

Fibril-associated collagens with interrupted triple helices (FACITs) XII and XIV act as fibril organizers and assist in the maintenance of uniform fibril size. We investigated the spatial expression patterns of collagens XII and XIV in cryptogenic organizing pneumonia (COP)/organizing pneumonia (OP) and in idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) and compared them to normal human lung. Study subjects included 10 patients with COP/OP, 10 patients with IPF/UIP, and 8 control subjects. Immunostaining for collagens XII and XIV was carried out in paraffin-embedded human lung tissue sections. Picrosirius red histochemical staining for collagen I expression and electron microcopy to evaluate fibril diameter were also performed. In normal lung, collagens XII and XIV were expressed in perivascular and subpleural connective tissue. In COP/OP, both collagens showed intense staining in perivascular connective tissue, thickened alveolar septae, and subpleural areas. In IPF/UIP, XII and XIV were expressed in perivascular connective tissue, in areas of established fibrosis, and in areas of subpleural thickening. Only collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblastic foci in IPF/UIP. Collagen type I was overexpressed in fibrotic areas. Electron micrographs revealed obvious fibril diameter alteration and fusion in the same areas. FACITs XII and XIV are expressed in normal and fibrotic lung. Unlike collagen XIV, collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblast foci in IPF/UIP. This may suggest a possible distinct role for both collagens in the modulation of the extracellular matrix during the onset of fibrotic process.
Electrical Performance Advancement in SiC Power Module Package Design With Kelvin Drain Connection and Low Parasitic Inductance (2018)

Silicon carbide (SiC) power modules are promising for high-power applications because of the high breakdown voltage, high operation temperature, low ON-resistance, and fast switching speed. However, the large parasitic inductance in existing package designs results in compromised performance, i.e., long blanking time in the desaturation protection scheme and large overvoltage spikes during the switching transient. Consequently, the benefits of SiC devices are often not fully utilized in practical applications. This paper deals with these two issues and aims at improving the electrical performance of the existing SiC module package. Specifically, a package design with Kelvin drain-to-source connection is first proposed to minimize the blanking time. More than 99% reduction of blanking time is achieved experimentally compared to the conventional package design. Second, a low parasitic inductance package with double-side cooling is proposed to allow the fast switching speed of SiC devices without sacrificing the thermal performance. A power loop inductance of 1.63 nH is realized from Q3D simulation. Verified by the experiment, more than 60% reduction of power loop inductance is achieved in comparison to a previously designed baseline module. At 0- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\Omega $ </tex-math></inline-formula> external gate resistance, the turn-off voltage spike is less than 9% of the dc-link voltage under the rated load condition.
NMR Methods for Characterizing the Pore Structures and Hydrogen Storage Properties of Microporous Carbons (2010)

(1)H NMR spectroscopy is used to investigate a series of microporous activated carbons derived from a poly(ether ether ketone) (PEEK) precursor with varying amounts of burnoff (BO). In particular, properties relevant to hydrogen storage are evaluated such as pore structure, average pore size, uptake, and binding energy. High-pressure NMR with in situ H(2) loading is employed with H(2) pressure ranging from 100 Pa to 10 MPa. An N(2)-cooled cryostat allows for NMR isotherm measurements at both room temperature ( approximately 290 K) and 100 K. Two distinct (1)H NMR peaks appear in the spectra which represent the gaseous H(2) in intergranular pores and the H(2) residing in micropores. The chemical shift of the micropore peak is observed to evolve with changing pressure, the magnitude of this effect being correlated to the amount of BO and therefore the structure. This is attributed to the different pressure dependence of the amount of adsorbed and non-adsorbed molecules within micropores, which experience significantly different chemical shifts due to the strong distance dependence of the ring current effect. In pores with a critical diameter of 1.2 nm or less, no pressure dependence is observed because they are not wide enough to host non-adsorbed molecules; this is the case for samples with less than 35% BO. The largest estimated pore size that can contribute to the micropore peak is estimated to be around 2.4 nm. The total H(2) uptake associated with pores of this size or smaller is evaluated via a calibration of the isotherms, with the highest amount being observed at 59% BO. Two binding energies are present in the micropores, with the lower, more dominant one being on the order of 5 kJ mol(-1) and the higher one ranging from 7 to 9 kJ mol(-1).
Tridimensional-Temporal-Thematic Hydroclimate Modeling of Distributed Parameters for the San Miguel River Basin (2013)

A geographic database (GDB) for the San Miguel river basin has been built by integrating data from multiple sources for analysis and graphical representation of diverse physiographic features and hydroclimate phenomena such as rainfall, temperature, soil-evaporation and topography, among others. This database allowed us to combine digital maps and images along with thematic information and spatially- referenced vector data. Moreover, further geographical referencing and validating processes enabled us to accurately represent continuous data through discrete data structures which fit the mathematical models used in representing the physical phenomena at the study site. In this paper we discuss some significant progress on models generated for the analysis of existing records for a season with measurable rainfall at the San Miguel river basin during the period from June 1st to September 30th of 2005.
Hypocalcemic Effect of Osteoclastogenesis Inhibitory Factor/Osteoprotegerin in the Thyroparathyroidectomized Rat (1998)

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprotegerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect on serum calcium level remains to be determined. In this study we examined the acute effect of OCIF on thyroparathyroidectomized rats whose serum calcium concentrations were raised either by exogenous PTH or 1,25-(OH)2D3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was administered into rats with established hypercalcemia, it decreased serum calcium rapidly (within 2 hr) and dramatically. OCIF did not increase urinary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the formation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.
Neurokinin 3 (NK3) Receptor Modulators for the Treatment of Psychiatric Disorders (2008)

The neurokinin-3 (NK(3)) is one of the tachykinin peptide neurotransmitter / neuromodulator receptor family. NK(3) receptors are predominantly expressed in neurons of both the peripheral and central nervous systems and in particular, in many of the forebrain areas, such as frontal, parietal and cingulate cortices, and basal ganglia structures implicated in psychiatric disease states. Consistent with this localization pattern, NK(3) receptors appear to modulate monoaminergic and amino acid neurotransmission within these structures. Taken together these observations have lead to the speculation that modulators of NK(3) receptor activity may have therapeutic utility in psychiatric diseases such as schizophrenia and affective disorders. This speculation has recently gained clinical credence through a number of reports of efficacy in placebo controlled studies. In this article, the authors review the recent patent literature highlighting the various NK(3) receptor modulation strategies for potential therapeutic utility in psychiatric disease indications.
A Non-infringing Route for Enantioselective Synthesis of Antiepileptic Agent Lacosamide (2013)

A non-infringing route for enantioselective synthesis of lacosamide has been developed. The synthesis started from commercially available acrylic acid and was completed in eight steps using Sharpless asymmetric dihydroxylation as a key step with an overall yield of 29%. All the reactions were very clean with good yields.
Terahertz pulsed imaging and spectroscopy for biomedical and pharmaceutical applications (2003)

Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum. Advances in THz technology have opened up many opportunities in this scientifically and technologically important spectroscopic region. The THz frequency range excites large amplitude vibrational modes of molecules as well as probing the weak interactions between them. Here we describe two techniques that utilize THz radiation, terahertz pulsed imaging (TPI) and terahertz pulsed spectroscopy (TPS). Both have a variety of possible applications in biomedical imaging and pharmaceutical science. TPI, a non-invasive imaging technique, has been used to image epithelial cancer ex vivo and recently in vivo. The diseased tissue showed a change in absorption compared to normal tissue, which was confirmed by histology. To understand the origins of the differences seen between diseased and normal tissue we have developed a TPS system. TPS has also been used to study solids of interest in the pharmaceutical industry. One particularly interesting example is ranitidine hydrochloride, which is used in treatment of stomach ulcers. Crystalline ranitidine has two polymorphic forms known as form 1 and form 2. These polymorphs have the same chemical formula but different crystalline structure that give rise to different physiochemical properties of the material. Using TPS it is possible to rapidly distinguish between the two polymorphic forms.
The European Bioinformatics Institute Macromolecular Structure Database (E-MSD) (2002)

Obtaining good quality single crystals remains one of the major barriers to the study of protein structure. Cryocooling reduces radiation damage and is widely employed for data collection with synchrotron radiation. However, cryocooling frequently leads a reduction in crystal quality, motivating an in-situ powder diffraction study to understand the processes occurring during the freezing of a protein crystal.
Forced plumes (1959)

This paper describes an investigation of the turbulent forced plumes generated by steady release of mass, momentum and buoyancy from a source situated in an extensive region of uniform or stably stratified fluid. The treatment, which is an extension of earlier work on buoyant plumes, also brings out the relationship between the jet and the Plume as special cases of forced plumes. The analysis shows that the behaviour of a forced plume from a source of finite size which delivers buoyancy, mass and momentum can in a uniform environment be related to that from a virtual point source of buoyancy and momentum only, and a treatment is given for the latter type of forced plume. When the environment is weakly stratified it is inferred that forced plumes can be related to point definitely; but when the environment is stably stratified, increasing the release of mass and momentum from a given source of buoyancy has the effect at first of reducing the total height of the plume, and only for very large flux of momentum does the height increase again, without limit. A description is given for the behaviour of vertical jets in a stably stratified environment, and for forced plumes of fluid with negative buoyancy.
Compact and fast photonic crystal  silicon optical modulators (2012)

We demonstrate the first sub-100 μm silicon Mach-Zehnder modulators (MZMs) that operate at >10 Gb/s, by exploiting low-dispersion slow-light in lattice-shifted photonic crystal waveguides (LSPCWs). We use two LSPCW-MZM structures, one with LSPCWs in both arms of the MZM, and the other with an LSPCW in only one of the arms. Using the first structure we demonstrate 10 Gb/s operation with a operating bandwidth of 12.5 nm, in a device with a phase-shifter length of only 50 μm. Using the second structure, owing to a larger group index as well as lower spectral noise, we demonstrate 40 Gb/s operation with a phase-shifter length of only 90 μm, which is more than an order-of-magnitude shorter than most 40 Gb/s MZMs.