gebhart/patrepeval huggingface dataset:
Effects of conjugated linoleic acids (CLA) on tissue response to homeostatic signals and plasma variables associated with lipid metabolism in lactating dairy cows (2002)

We conducted a series of experiments to evaluate the effects of conjugated linoleic acids (CLA) on lipid metabolism and energy homeostasis in lactating dairy cows. In all experiments, multiparous Holstein cows in mid to late lactation were abomasally infused with CLA for 5 d. The initial study established that trans-10, cis-12 CLA markedly reduced milk fat yield whereas cis-9, trans-11 CLA, the predominant CLA isomer in milk fat, had no effect. Across the three investigations, infusions of the pure trans-10, cis-12 CLA isomer (3.5 to 14.0 g/d) resulted in a 25 to 50% decrease in milk fat yield and this was energetically equivalent to 6 to 11% of net energy intake. Effects were specific for milk fat as there were little or no changes in feed intake and the yield of milk or milk protein. In Exp. 1, infusing trans-10, cis-12 CLA had no effect on circulating plasma concentrations of glucose, insulin, or leptin. Basal NEFA concentrations were also unaffected, but lipolytic response to an epinephrine challenge was reduced (33%) when cows received trans-10, cis-12 CLA; this minor change in lipolytic response would be consistent with the slightly more positive net energy balance when cows received trans-10, cis-12 CLA. In Exp. 2, infusing differing amounts of trans-10, cis-12 CLA had only minor effects on basal NEFA concentrations, but again cows receiving trans-10, cis-12 CLA tended to have reduced (24%) lipolytic response to trans-10, cis-12 CLA compared to the control period. In Exp. 3, infusing trans-10, cis-12 CLA had no effect on basal glucose concentrations or glucose response to an insulin challenge. The fractional rate of glucose clearance in response to insulin was also not altered by treatment. In summary, the effects of trans-10, cis-12 CLA in lactating dairy cows appear to be specific for the mammary gland, resulting in reduced milk fat synthesis; adipose tissue response to a homeostatic signal regulating lipolysis (epinephrine), whole-body response to a homeostatic signal regulating glucose homeostasis (insulin), and plasma variables associated with lipid metabolism and energy homeostasis were relatively unaffected by treatment with trans-10, cis-12 CLA.
A Novel Positive Allosteric Modulator of the α7 Neuronal Nicotinic Acetylcholine Receptor:<i>In Vitro</i>and<i>In Vivo</i>Characterization (2005)

Several lines of evidence suggest a link between the alpha7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. In contrast, PNU-120596 produced no detectable change in currents mediated by alpha4beta2, alpha3beta4, and alpha9alpha10 nAChRs. PNU-120596 increased the channel mean open time of alpha7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect was suppressed by TTX, suggesting that PNU-120596 modulated the function of alpha7 nAChRs located on the somatodendritic membrane of hippocampal interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward currents in these interneurons. Systemic administration of PNU-120596 to rats improved the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. Together, these results suggest that PNU-120596 represents a new class of molecule that enhances alpha7 nAChR function and thus has the potential to treat psychiatric and neurological disorders.
The effects of the photomask on multiphase shift test monitors (2006)

A series of chromeless multiple-phase shift lithographic test monitors have been previously introduced. This paper investigates various effects that impact the performance of these monitors, focusing primarily on PSM Polarimetry, a technique to monitor illumination polarization. The measurement sensitivities from a variety of scalar and rigorous electromagnetic simulations are compared to experimental results from three industrial quality multi-phase test reticles. This analysis enables the relative importance of the various effects to be identified and offers the industry unique insight into various issues associated with the photomask. First, the unavoidable electromagnetic interaction as light propagates through the multiple phase steps of the mask topography appears to account for about 10 to 20% of the lost sensitivity, when experimental results are compared to an ideal simulated case. The polarization dependence of this effect is analyzed, concluding that the 4-phase topography is more effective at manipulating TM polarization. Second, various difficulties in the fabrication of these complicated mask patterns are described and likely account for an additional 60-80% loss in sensitivity. Smaller effects are also described, associated with the photoresist, mask design and subtle differences in the proximity effect of TE and TM polarization of off-axis light at high numerical aperture. Finally, the question: "How practical is PSM polarimetry?" is considered. It is concluded that, despite many severe limiting factors, an accurately calibrated test reticle promises to monitor polarization in state-of-the-art lithography scanners to within about 2%.
Fabrication of a Glass Capillary Electrophoresis Microchip With Integrated Electrodes (2006)

In this chapter, a detailed outline delineating the processing steps for microfabricating capillary electrophoresis (CE) with integrated electrochemical detection (ECD) platforms for performing analyte separation and detection is presented to enable persons familiar with microfabrication to enter a cleanroom and fabricate a fully functional Lab-on-a-Chip (LOC) microdevice. The processing steps outlined are appropriate for the production of LOC prototypes using easily obtained glass substrates and common microfabrication techniques. Microfabrication provides a major advantage over existing macro-scale systems by enabling precise control over electrode placement, and integration of all required CE and ECD electrodes directly onto a single substrate with a small footprint. In the processing sequences presented, top and bottom glass substrates are photolithographically patterned and etched using wet chemical processing techniques. The bottom substrate contains seven electrodes required for CE/ECD operation, whereas the top substrate contains the microchannel network. The flush planar electrodes are created using sputter deposition and lift-off processing techniques. Finally, the two glass substrates are thermally bonded to create the final LOC device.
Partial synthesis of the 15β-hydroxygibberellins A<sub>67</sub>and A<sub>68</sub>and of 15β-hydroxygibberellins A<sub>1</sub>and A<sub>3</sub> (1985)

The structures of two new higher plant gibberellins, A67(7) and A68(4), have been established by their partial synthesis from gibberellin A3(2). In addition, 15β-hydroxyGA1(8) and 15β-hydroxyGA3(3) have also been prepared from GA3(2). The preparation of GA68(4) from GA3(2) involves the novel displacement of a bridgehead hydroxy group by chlorine under the conditions of the Swern oxidation in which di-isopropylethylamine is replaced by triethylamine.
Design of high-efficiency dielectric reflection gratings (1997)

We discuss examples of designs for all-dielectric reflection gratings that tolerate high intensity and are potentially capable of placing up to 99% of the incident light into a single diffraction order, such as are needed for contemporary high-power lasers utilizing chirped-pulse amplification. The designs are based on placing a dielectric transmission grating atop a high-reflectivity (HR) multilayer dielectric stack. We comment on the connection between transmission gratings and reflection gratings and note that the grating and the HR stack can, to a degree, be treated independently. Because many combinations of gratings and multilayer stacks offer high efficiency, it is possible to attain secondary objectives in the design. We describe examples of such designs aimed toward improving fabrication and lowering the susceptibility to laser-induced damage. We present examples of the dependence of grating efficiency on grating characteristics. We describe examples of high-efficiency (95%) gratings that we have fabricated by using hafnia and silica multilayers.
Optical Phase Conjugation for Tissue Turbidity Suppression (2009)

We will discuss our recent findings on the use of optical-phase-conjugation to undo optical tissue scatterings. Amongst other results, we discovered that light scattered hundreds of times still retains sufficient memory to enable path retracing.
Effects of Artificial Small Defect and Corrosive Environment on Torsional Fatigue Strength of High Strength Spring Steel (2007)

Torsional fatigue tests were conducted for spring steels whose Vickers hardness were 430, 480, 550, and 620. The effects of corrosive environment and surface artificial pits on the fatigue strength were studied. The fatigue strength of smooth specimens was maximum at 550HV for fatigue in air and 480HV for corrosion fatigue. Intergranular fracture surfaces were observed on the fatigue fracture surface corresponded to the decrease in the fatigue strength of the high-hardness materials. The fatigue fracture of smooth specimens was generated from shear crack for fatigue in air and from corrosion pit in corrosion fatigue. The stress intensity factor for crack initiation from corrosion pit was nearly the same for all materials. The fatigue strength reduction factor was constant under fatigue loading in air, while decreased with increasing fatigue life and hardness in corrosion fatigue. For the case of long of the material with 620HV in corrosive environment, a significant influence of the artificial pit on the fatigue strength was not seen. Many small cracks were observed at the sites except for artificial pit on the surface of the 620HV specimens fatigued at low stress levels.
Efficient sodium/sulfur battery. [S-impregnated C matrix has resistivity varying with location] (1978)

Improved sodium/sulfur batteries are provided by enhancing the utilization of active positive-electrode material. In sodium/sulfur batteries, employing a liquid sodium electrode separated from a liquid sulfur electrode by a solid ..beta..-alumina electrolyte separator, where the sulfur is impregnated in an electronically conducting matrix such as porous carbon, enhanced utilization of active electrode material is achieved during the charging--discharging cycling by enhancing the electronic resistivity adjacent the ..beta..-alumina in the sulfur electrode. This can be achieved in a variety of ways, particularly by employing porous carbon of higher resistivity adjacent the ..beta..-alumina as compared to the porous carbon distant from the ..beta..-alumina. 2 figures.
Thickness Measurements of Epitaxial Layers of Double Epitaxial Silicon Wafers by Far‐Infrared Reflection (1998)

Thickness evaluation of epitaxial layers of double epitaxial silicon wafers is studied by infrared reflection, with respect to the resistivity of the first epitaxial layers just on the substrates. It has been shown that the thickness of the epitaxial layers can be measured nondestructively by far‐infrared reflection and maximum entropy frequency analysis.
2-Aminothiazole Derivative as a New Class of TrkA Kinase Inhibitor (2011)

Cancer (also called a malignant neoplasm) is a class of diseases in which a group of cells show uncontrolled cell growth, invasion and occasionally metastasis, and is a major public health problem worldwide. However, drug discovery and the development of cancer therapeutics take many years before a patient can benefit from a new drug. This time period is too long and needs to be shortened so patients can benefit quickly from new technologies and product development ideas. Combinatorial chemistry is a widely used technique for accelerating drug discovery and development, in which tools and technologies from biology and chemistry are used in a parallel manner. It was reported that many 2-aminothiazoles exhibit antitumor activity through the inhibition of kinases, 1-3 Therefore, in the course of searching for anticancer agents, 2-aminothiazole derivatives were recently prepared by varying the 2-amino position and 5-substituted group in a high-speed parallel format according to the literature procedure, as shown in Scheme 1. 4 Among synthesized, compound H154 exhibited significant cell growth inhibition against Hep3B cells with an IC50 value of 0.040 µM by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. However, the specific cellular mechanism of action of this compound is unclear. 5
Fish population dynamics revealed by instantaneous continental-shelf scale acoustic imaging (2005)

Video images of fish population densities over vast areas of the New Jersey continental shelf have been produced from acoustic data collected on a long range bistatic sonar system during the Acoustic Clutter 2003 experiment. Areal fish population densities were obtained after correcting the acoustic data for two-way transmission loss modeled using the range-dependent parabolic equation, spatially varying beampattern of the array, source level and mean target strength per fish. The wide-area fish density images reveal the temporal evolution of fish school distributions, their migration, as well as shoal formation and fragmentation at 50 s interval. Time series of the fish population within various density thresholds were made over the period of a day in an area containing millions of fish that at some instances formed a massive shoal extending over 12 km. The analysis shows that fish population in the area can be decomposed into a stable ambient population from lower-fish-density regions and a time-varying population composed from higher-density regions. Estimates of the differential speed between population centers of various shoals show that the average speed is on the order of a slow-moving surface vessel or submarine.
Serotonin Regulates Osteoclast Differentiation Through Its Transporter (2004)

Taken together, these data suggest that the 5-HT system plays an important role in bone homeostasis through effects on osteoclast differentiation and implies that commonly used antidepressive agents may affect bone mass.
Fullerene-Coated Beads as Reusable Catalysts (2002)

New heterogeneous catalysts that use oxygen and light to generate singlet oxygen ((1)O2) have been prepared. The catalysts facilitate various types of singlet oxygenation reactions including the Ene reaction, the Diels-Alder reaction, and others. The catalysts are made by stirring a heterogeneous mixture of fullerene-C(60) (dissolved in toluene) with aminomethylated poly(styrene-co-divinylbenzene) beads. Also, catalysts for aqueous photooxidations are made by reacting the initial catalysts with poly(allylamine) to create an outer layer that is more hydrophilic.
“M-AAA-Thrombin”, a New Thrombin Mutant with Potent Anticoagulant and Antiplatelet Properties. (2005)

Abstract Thrombosis is a major cause of morbidity and mortality, and thrombin is a major inducer of thrombus formation. Thus several antithrombotic agents targeting thrombin have been developed. We previously reported an anticoagulant and antiplatelet thrombin derivative, ‘M-anhydrothrombin’ prepared by chemical modifications. In this study, we prepared a new thrombin mutant, specificity of which was highly modulated with substantially improved antithrombotic efficacy. The thrombin mutant designated “AAA-Thrombin” in which Lys65, His43 and Ser205 in B-chain have been replaced by Ala revealed higher affinity and specificity for factor VIII with no enzymatic activity. AAA-Thrombin prolonged APTT much more than anhydrothrombin in a dose dependent manner without affecting PT and TT. Platelet aggregation induced by activation of PAR-1 was also effectively suppressed by AAA-Thrombin. “M-AAA-Thrombin” prepared by further chemical modification of carboxyl groups in AAA-Thrombin enhanced its antithrombotic efficacy. M-AAA-Thrombin (250nM) prolonged APTT approx. two times, and suppressed platelet aggregation by PAR-1 activation, while AAA-Thrombin did not at the same concentration. M-AAA-Thrombin also suppressed ristocetin-induced platelet aggregation. In vivo experiments, M-AAA-Thrombin demonstrated significant antithrombotic property in the arterio-venous shunt thrombosis model and the FeCl3-induced carotid artery thrombosis model in guinea pigs. These results indicate that M-AAA-Thrombin would be a candidate for quite an innovative anticoagulant and antiplatelet agent for both arterial and venous thromboses. Further optimization of mutagenesis and modification, in terms of efficacy and safety is in progress in our laboratory.
Identification of steroid derivatives that function as potent antiandrogens (2005)

We have hypothesized that some steroid derivatives bind to the androgen receptor (AR) with very low androgenic activity and therefore potentially function as better AR antagonists than clinically used antiandrogens, such as flutamide. Indeed, we previously found such a compound, 3beta-acetoxyandrosta-1,5-diene-17-one ethylene ketal (ADEK), with some estrogenic activity. Here we report the identification of 2 additional steroid derivatives, 3beta-hydroxyandrosta-5,16-diene (HAD) and androsta-1,4-diene-3,17-dione-17-ethylene ketal (OAK), as new potent antiandrogens. Like ADEK, HAD and OAK could interrupt androgen binding to the AR and suppress both dihydrotestosterone- and androstenediol-induced transactivations of wild-type and mutant ARs in prostate cancer cells. These 2 compounds also inhibited prostate-specific antigen expression in LNCaP as well as growth of different AR-positive prostate cancer cell lines stimulated by androgen. Significantly, HAD and OAK had only marginal agonist effects, as compared to hydroxyflutamide. More importantly, in contrast to ADEK, OAK was shown to possess marginal estrogenic activity. These results strengthen our hypothesis and suggest that selective steroid derivatives could be potent antiandrogenic drugs with less unfavorable effects for the treatment of prostate cancer.
Piezoelectric-based self-powered electronic adjustable impulse switches (2018)

Novel piezoelectric-based self-powered impulse detecting switches are presented. The switches are designed to detect shock loading events resulting in acceleration or deceleration above prescribed levels and durations. The prescribed acceleration level and duration thresholds are adjustable. They are provided with false trigger protection logic. The impulse switches are provided with electronic and logic circuitry to detect prescribed impulse events and reject events such as high amplitude but short duration shocks, and transportation vibration and similar low amplitude and relatively long duration events. They can be mounted directly onto electronics circuit boards, thereby significantly simplifying the electrical and electronic circuitry, simplifying the assembly process and total cost, significantly reducing the occupied volume, and in some applications eliminating the need for physical wiring to and from the impulse switches. The design of prototypes and testing under realistic conditions are presented.
Prospective schemes for next generation x-ray lasers (2009)

Two novel schemes for efficient x-ray laser generation from laser-produced plasma and
capillary discharge-driven plasmas are described. The combination of nano-structured targets with the
high energy ultrashort pulse lasers can result in the generation of laser-produced plasmas that could lead
to high brightness sources of incoherent multi-KeV radiation and x-ray lasers of short pulse duration at
shorter wavelengths. The generation of 0.5-1 keV x-ray laser radiation from a Ni-like U plasma created
using excitation from a Petawatt laser is analyzed. The efficient excitation of capillary discharge plasmas
in micro-capillary discharge channels is discussed.
A Methylation Density Binary Classifier for Predicting and Optimizing the Performance of Methylation Biomarkers in Clinical Samples (2019)

Aberrant DNA methylation is commonly heralded as a promising cancer biomarker; however, its inherently stochastic nature often leads to variable methylation patterns that can complicate the use of methylation biomarkers for clinical diagnostics, particularly in dilute samples such as liquid biopsies. Here, we present a methylation density binary classifier, a statistical method for leveraging differential heterogeneous methylation to predict and optimize the performance of methylation biomarkers for clinical applications. We first developed and tested the classifier using methylation density profiles derived from reduced representation bisulfite sequencing reads of ovarian carcinoma at ZNF154, a recurrently methylated locus in multiple cancer types. We then used in silico simulations to predict the performance of the classifier in liquid biopsies and validated these predictions using quasi-digital melt curve analysis (DREAMing) of circulating cell-free DNA from individuals with versus without ovarian carcinoma. We found good agreement between predicted and observed classifier performance, and further demonstrated that implementation of this approach with ZNF154 outperformed CA-125 for use in etiologically-diverse ovarian cancer types. Our results indicate that methylation density profiles can be exploited to predict and facilitate implementation of methylation biomarkers for clinical applications, and that ZNF154 methylation shows promise as a clinically-useful biomarker for ovarian cancer.