gebhart/patrepeval huggingface dataset:
Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors (2002)

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/ D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photoreceptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist L-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.
Combining Shape Memory Alloys and Microfluidic Chips on Printed Circuit boards (2008)

Integrated multi-layer fluidic chips, with hundreds of elastomeric valves, are useful in immunoassays, protein crystallization, cell culture and several other applications. Although the devices are micro-scale, because valves are actuated pneumatically, each chip requires a relatively large pneumatic control system for operation. Fulfilling the great promise of microfluidics, for instance building throwaway, portable, massively parallel, point-of-care diagnostic systems is unlikely until there is a solution for actuating micro-valves electrically. We introduce a combination of materials—shape memory alloys (SMAs) and elastomersto solve this problem. SMAs offer among the highest work per unit volume of any actuator, and elastomers have the ability to absorb the energy and return the SMA to its original configuration, while providing electric and thermal insulation. Using this marriage of materials, with PDMS (elastomer) and Ni/Ti wires (SMA), we built electrically activated micro-fluidic valves, peristaltic pumps and multiplexers. The first generation valve design needs 50 to 250 mA current in the on state, with power requirements of about 0.5 W. It can hold back &gt;1 atmosphere of pressure and run for thousands of cycles, actuating at sub-second speeds. The dead volume is &lt;1 nano-liter. Crucially, these devices are assembled on printed circuit boards, like conventional electronic components. Thus, the technology used in assembling electronics is applicable to assembling fluidic chips, and both electronics and fluidics can be integrated on one platform for biomedical applications.
Capacitor bank design for wide tuning range LC VCOs: 850MHz-7.1GHz (157%) (2010)

This paper describes novel design techniques for optimizing the switched-capacitor array in a wide tuning range LC VCO. The switches in the capacitor array are optimally sized to maximize the tuning range. Additionally, parasitic interconnect inductance inherent in the capacitor array is used for increasing the equivalent capacitance value. Based on these proposed techniques, an LC VCO that achieves 157% frequency tuning range from 850MHz to 7.1GHz with phase noise between -107.1 and -119.1 dBc/Hz at 1MHz offset and power dissipation between 3 and 15 mW is designed. The power and phase noise performance of this VCO is at par with the best wideband solutions. However, this is, by far, the largest tuning range obtained for CMOS LC VCOs till date.
IN-VIVO EFFECT OF THE COMBINATION OF TNF AND ADRIAMYCIN AGAINST A HUMAN BREAST CELL-LINE EXPRESSING THE MDR-PHENOTYPE (1995)

The combined effect of tumor necrosis factor alpha (TNF) and adriamycin (ADR) on tumor cell killing was investigated in vivo. The human breast adenocarcinoma ADR-resistant MDA/ADR cells found to be resistant to in vitro TNF lysis and with an apparent index of resistance to ADR of 23 have been used. Treatment of MDA/ADR subcutaneous tumor bearing mice with PBS, TNF, ADR or the combination of TNF/ADR indicate that the combination of TNF and ADR treatment leads to a significant decrease in tumor growth while treatment with TNF was inactive and treatment with ADR was moderately active. Tumor cells were collected from mice treated with TNF/ADR combination and analysed by PCR for MnSOD and TNF ne expression. No induction of the expression of these genes, known to be involved in the regulation of TNF-induced cell killing, was noted following TNF/ADR combination treatment, suggesting that their products were not involved in the observed resistance.
ChemInform Abstract: Some Baeyer‐Villiger Oxidations Using a Monooxygenase Enzyme from Pseudomonas putida NCIMB 10007. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Rapid Injection NMR in Mechanistic Organocopper Chemistry. Preparation of the Elusive Copper(III) Intermediate (2007)

A “copper(III) intermediate” has been proposed to be crucially involved in many reactions of organocopper reagents, for example, with α-enones, alkyl halides, and allylic carboxylates. By using rapid injection NMR (RI-NMR), we have been able to prepare the first example of this elusive species under conditions where it is stable for extended periods of time. Extensive NMR investigations establish its structure and include two-bond 13C−13C coupling constants 2J across copper, measured on 13C-labeled material. Especially noteworthy is the extremely deshielded nature of the methyl C atoms attached to Cu, as indicated by the downfield 13C NMR shifts of 12.43 and 25.31 ppm. Large trans couplings, 2J = 38.1 Hz (upfield methyl−ring methine) and 2J = 35.4 Hz (downfield methyl−cyano), are consistent with a square planar complex.
Accurate in vitro transcriptional initiation of the chick alpha 2 (Type I) collagen gene. (1981)

Chick genomic DNA containing the extreme 5' end of the alpha 2 (type I) collagen gene has been used as template in an in vitro HeLa cell transcription system. RNA polymerase II-dependent transcription initiates from a specific site on this DNA. The precise location of this site was determined by three types of experiments: sizing of in vitro-synthesized RNA runoff transcripts, comparing the sequence of the in vitro-made RNA transcripts with the structure of the DNA template, and identifying the first and second nucleotides of the in vitro-synthesized transcripts. Transcription was found to initiate 33 base pairs downstream from a canonical Goldberg-Hogness sequence (TATAAATA). This in vitro start site is the same as the initiation site of in vivo-synthesized collagen RNA.
Stochastic Resolution of Identity for Real-Time Second-Order Green's Function: Ionization Potential and Quasi-particle Spectrum (2019)

We develop a stochastic resolution of identity approach to the real-time second-order Green's function (real-time sRI-GF2) theory, extending our recent work for imaginary-time Matsubara Green's function {\em J. Chem. Phys.} {\bf 151}, 044114 (2019)). The approach provides a framework to obtain the quasi-particle spectra across a wide range of frequencies as well as predict ionization potentials and electron affinities. To assess the accuracy of the real-time sRI-GF2, we study a series of molecules and compare our results to experiments and to a many-body perturbation approach based on the GW approximation, where we find that the real-time sRI-GF2 is as accurate as self-consistent GW. The stochastic formulation reduces the formal scaling to $O(N_e^3)$, where $N_e$ is the number of electrons. This is illustrated for a chain of hydrogen dimers, where we observe a slightly lower than cubic scaling for systems containing up to $N_e \approx 1000$.
Leakage Current Suppression on Metal-Induced Laterally Crystallized Polycrystalline Silicon Thin-Film Transistors by Asymmetrically Deposited Nickel (2013)

The electrical performance of low-temperature polycrystalline silicon (LTPS) thin-film transistors (TFTs) fabricated by metal-induced lateral crystallization (MILC) is greatly affected by metal catalyst contaminations, such as Ni and Ni silicide trapped in the channel, since they concentrate in front of laterally grown crystallites. In the present work, the effect of the MILC/MILC boundary (MMB) on MILC polycrystalline silicon (poly-Si) TFTs is investigated by the comparison of MILC poly-Si TFTs with MMB at the center of the channel, and equivalent TFTs with MMB at a position ejected from the channel. The MMB location was controlled by the Ni catalyst position. Both a low off-state leakage current and a free from short channel effect (kink effect) were observed in high electric-field conditions. Furthermore, the field-effect mobility and drain current noise were drastically improved by ejecting the MILC boundary in the source direction.
Myelomastocytic leukemia: histopathological features, diagnostic criteria and differential diagnosis (2014)

Myelomastocytic leukemia (MML) is an extremely rare myeloid overlap-neoplasm that belongs to the group of tryptase-positive (T+) myeloid neoplasms. Main differential diagnoses include aggressive systemic mastocytosis (ASM), in particular ASM in transformation; mast cell leukemia; T+ acute myeloid leukemia (T+ AML); acute basophilic leukemia and chronic basophilic leukemia. MML exhibits both proliferative and dysplastic features and is characterized by prominent differentiation into the mast cell lineage in an advanced myeloid neoplasm, usually primary or secondary AML. While the histological key feature of MML is a diffuse increase in neoplastic cells expressing mast cell-related antigens like tryptase and CD117 (KIT), the most important cytomorphological finding in bone marrow (BM) and peripheral blood (PB) is the metachromatically granulated blast cell (= metachromatic blast). In contrast to systemic mastocytosis (SM), MML neither shows activating point mutations at codon 816 of KIT nor the aberrant expression of CD25 by mast cells is seen. MML can only be diagnosed when tryptase-staining is performed on BM biopsy specimens, PB and BM smears are investigated for presence of metachromatic blasts and other T+ leukemias have been excluded.
Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D (2017)

As part of an ongoing effort at Amgen to develop a disease-modifying therapy for Alzheimer's disease, we have previously used the aminooxazoline xanthene (AOX) scaffold to generate potent and orally efficacious BACE1 inhibitors. While AOX-BACE1 inhibitors demonstrated acceptable cardiovascular safety margins, a retinal pathological finding in rat toxicological studies demanded further investigation. It has been widely postulated that such retinal toxicity might be related to off-target inhibition of Cathepsin D (CatD), a closely related aspartyl protease. We report the development of AOX-BACE1 inhibitors with improved selectivity against CatD by following a structure- and property-based approach. Our efforts culminated in the discovery of a picolinamide-substituted 3-aza-AOX-BACE1 inhibitor absent of retinal effects in an early screening rat toxicology study.
Perturbations of Time Shifts in Signal Apparition (2018)

In the field of exploration geophysics, the method known as “signal apparition” offers a different perspective on how to separate signals acquired from simultaneously fired seismic sources. The method uses a periodic sequence of small time shift variations to encode the different sources, and this choice leads to exact separation of signals in diamond-shaped regions of the frequency-wavenumber domain which are twice as large compared to those recovered by other methods. In this paper we investigate the signal apparition method's sensitivity to perturbations of the periodic time shift sequence. We model (measured or unknown) perturbations in a stochastic fashion and prove that the resulting inverse problem of separating the data is still well-posed, and we demonstrate the stability by numerical simulations on a finite-difference synthetic data set generated over a complex salt model.
Biosynthesis of Medium-Chain ω-Hydroxy Fatty Acids by AlkBGT of Pseudomonas putida GPo1 With Native FadL in Engineered Escherichia coli (2019)

Hydroxy fatty acids (HFAs) are valuable compounds that are widely used in medical, cosmetic and food fields. Production of ω-HFAs <i>via</i> bioconversion by engineered <i>Escherichia coli</i> has received a lot of attention because this process is environmentally friendly. In this study, a whole-cell bio-catalysis strategy was established to synthesize medium-chain ω-HFAs based on the AlkBGT hydroxylation system from <i>Pseudomonas putida</i> GPo1. The effects of blocking the β-oxidation of fatty acids (FAs) and enhancing the transportation of FAs on ω-HFAs bio-production were also investigated. When <i>fadE</i> and <i>fadD</i> were deleted, the consumption of decanoic acid decreased, and the yield of ω-hydroxydecanoic acid was enhanced remarkably. Additionally, the co-expression of the FA transporter protein, FadL, played an important role in increasing the conversion rate of ω-hydroxydecanoic acid. As a result, the concentration and yield of ω-hydroxydecanoic acid in NH03(pBGT-<i>fadL</i>) increased to 309 mg/L and 0.86 mol/mol, respectively. This whole-cell bio-catalysis system was further applied to the biosynthesis of ω-hydroxyoctanoic acid and ω-hydroxydodecanoic acid using octanoic acid and dodecanoic acid as substrates, respectively. The concentrations of ω-hydroxyoctanoic acid and ω-hydroxydodecanoic acid reached 275.48 and 249.03 mg/L, with yields of 0.63 and 0.56 mol/mol, respectively. This study demonstrated that the overexpression of AlkBGT coupled with native FadL is an efficient strategy to synthesize medium-chain ω-HFAs from medium-chain FAs in <i>fadE</i> and <i>fadD</i> mutant <i>E. coli</i> strains.
Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma (2016)

We observed a drastic negative shift of methylation levels in miRNA cluster regions. Changes in methylation status of miRNAs were more indicative of target gene expression and pathological diagnosis than respective miRNA expression changes, suggesting the importance of genome-wide miRNA methylation for tumor development. Our study dynamically summarized global miRNA hypomethylation and its genome-wide scale consequence in NBNC-HCC.
Synthesis of deep-cavity fluorous calix[4]arenes as molecular recognition scaffolds (2008)

Several lower-rim perfluoroalkylated (fluorous) calix[4]arenes have been synthesized by O-alkylation of the parent calix[4]arene. The compounds are formed in the cone conformation. They are soluble in several fluorous solvents and show promise for use in sensing, selective extractions and other applications.
Neurotoxicity fingerprinting of venoms using on-line microfluidic AChBP profiling (2018)

Venoms from snakes are rich sources of highly active proteins with potent affinity towards a variety of enzymes and receptors. Of the many distinct toxicities caused by envenomation, neurotoxicity plays an important role in the paralysis of prey by snakes as well as by venomous sea snails and insects. In order to improve the analytical discovery component of venom toxicity profiling, this paper describes the implementation of microfluidic high-resolution screening (HRS) to obtain neurotoxicity fingerprints from venoms that facilitates identification of the neurotoxic components of envenomation. To demonstrate this workflow, 47 snake venoms were profiled using the acetylcholine binding protein (AChBP) to mimic the target of neurotoxic proteins, in particular nicotinic acetylcholine receptors (nAChRs). In the microfluidic HRS system, nanoliquid chromatographic (nanoLC) separations were on-line connected to both AChBP profiling and parallel mass spectrometry (MS). For virtually all neurotoxic elapid snake venoms tested, we obtained bioactivity fingerprints showing major and minor bioactive zones containing masses consistent with three-finger toxins (3FTxs), whereas, viperid and colubrid venoms showed little or no detectable bioactivity. Our findings demonstrate that venom interactions with AChBP correlate with the severity of neurotoxicity observed following human envenoming by different snake species. We further, as proof of principle, characterized bioactive venom peptides from a viperid (Daboia russelli) and an elapid (Aspidelaps scutatus scutatus) snake by nanoLC-MS/MS, revealing that different toxin classes interact with the AChBP, and that this binding correlates with the inhibition of α7-nAChR in calcium-flux cell-based assays. The on-line post-column binding assay and subsequent toxin characterization methodologies described here provide a new in vitro analytic platform for rapidly investigating neurotoxic snake venom proteins.
Development of a Method to Test Anti-LH-RH Activity in Rats (1974)

A method for testing anti-LH-RH activity wasdevised. The substance to be investigated was infused for 2 h i.e. in ovariectomized, estrogen- and progesterone-pretreated rats, followed by an acute injection of synthetic LH-RH into the jugular vein. The serum LH concentration was investigated be-fore and 20 min after the injection of LH-RH. Among all the peptides investigated, des-His-2-LH-RH was the only one that did not modify the response to LH-RH. The infusion with (pyro)Glu-His-Trp-NH2, Leu-3-LH-RH, and des-Trp-3-des-Gly-10-LH-RH only partially inhibited the response to LH-RH, whereas comparatively lower doses of des-His-2-des-Gly-10-LH-RH-ethylamide significantly blocked the LH release after the administration of LH-RH.
120 channel AM-VSB transmission by two wavelengthmultiplexed signalsusing gain flattened hybrid erbium-doped fibre amplifier (1995)

By using a hybrid EDFA with a flat gain over 17 nm, two wavelength multiplexed 120 channel AM-VSB signals were successfully transmitted, for the first time, without significant degradation of distortions. This was also realised with the help of a newly developed BPF which had a flat transmittance around the peak wavelength.
Dynamic publication model for neurophysiology databases (2001)

We have implemented a pair of database projects, one serving cortical electrophysiology and the other invertebrate neurones and recordings. The design for each combines aspects of two proven schemes for information interchange. The journal article metaphor determined the type, scope, organization and quantity of data to comprise each submission. Sequence databases encouraged intuitive tools for data viewing, capture, and direct submission by authors. Neurophysiology required transcending these models with new datatypes. Time-series, histogram and bivariate datatypes, including illustration-like wrappers, were selected by their utility to the community of investigators. As interpretation of neurophysiological recordings depends on context supplied by metadata attributes, searches are via visual interfaces to sets of controlled-vocabulary metadata trees. Neurones, for example, can be specified by metadata describing functional and anatomical characteristics. Permanence is advanced by data model and data formats largely independent of contemporary technology or implementation, including Java and the XML standard. All user tools, including dynamic data viewers that serve as a virtual oscilloscope, are Java-based, free, multiplatform, and distributed by our application servers to any contemporary networked computer. Copyright is retained by submitters; viewer displays are dynamic and do not violate copyright of related journal figures. Panels of neurophysiologists view and test schemas and tools, enhancing community support.
Interactions between Proxy Mobile IPv6 (PMIPv6) and Mobile IPv6 (MIPv6): Scenarios and Related Issues (2012)

The use of Proxy Mobile IPv6 (PMIPv6) and Mobile IPv6 (MIPv6) in the same network requires some care. This document discusses scenarios where such mixed usage is appropriate and points out the need for interaction between the two mechanisms. Solutions and recommendations to enable these scenarios are also described.
Suspended InGaAs membrane waveguide devices with subwavelength gratings and photonic crystal structures for ammonia sensing at lambda=6.15um (Conference Presentation) (2020)

Fully suspended InGaAs waveguide devices with holey photonic crystal waveguides (HPCWs) and Sub-wavelength waveguides (SWWs) are designed and fabricated for mid-infrared sensing at λ=6.15µm in the low index contrast InGaAs-InP platform. We experimentally detect 5 ppm ammonia in 1 mm long suspended HPCW and 3 mm long suspended SWW with propagation loss of 39.1 dB/cm and 4.1 dB/cm, respectively. This result emphasizes the advantage of SWWs which can utilize the longer devices by virtue of its low propagation loss to increase the gas sensing sensitivity compare to HPCWs.
BAG-1L Protein Enhances Androgen Receptor Function (1998)

BAG-1 is a regulator of heat shock protein (Hsp) 70/Hsc70 family proteins that interacts with steroid hormone receptors. The recently identified BAG-1 long (BAG-1L) protein, an isoform of BAG-1 that arises from translation initiation at a noncanonical CUG codon, was co-immunoprecipitated with androgen receptors (AR) from LNCaP prostate cancer cells and other cell lysates, whereas the shorter originally identified BAG-1 and BAG-1M (RAP 46) proteins were not. BAG-1L, but not BAG-1 or BAG-1M (RAP46), also markedly enhanced the ability of AR to transactivate reporter gene plasmids containing an androgen response element (ARE) in PC3 prostate cancer and other cell lines. A C-terminal region deletion mutant of BAG-1L failed to co-immunoprecipitate with AR and functioned as a trans-dominant inhibitor of BAG-1L, impairing AR-induced transactivation of ARE-containing reporter plasmids. In addition, BAG-1L significantly reduced the concentrations of 5alpha-dihydrotestosterone (DHT) required for AR activity but did not induce ligand-independent transactivation. BAG-1L also markedly improved the ability of AR to transactivate reporter genes when cells were cultured with DHT in combination with the anti-androgen cyproterone acetate. The effects of BAG-1L on AR could not be explained by detectable alterations in the DHT-induced translocation of AR from cytosol to nucleus, nor by BAG-1L-induced increases in the amounts of AR protein. These findings implicate BAG-1L in the regulation of AR function and may have relevance to mechanisms of prostate cancer resistance to hormone-ablative and anti-androgen therapy.
Numerical and Analytical Approaches for Non Contact Fluorescence Optical Tomography (2006)

A numerical and an analytical approach for the forward solver used in non contact fluorescence optical tomography have been considered. Experiments have been performed on a half cylinder like resin phantom with Alexa750 fluorophores inclusions.