gebhart/patrepeval huggingface dataset:
Alternative splicing of GluN1 gates glycine-primed internalization of NMDA receptors (2020)

Summary N-methyl-D-aspartate receptors (NMDARs), a principal subtype of excitatory neurotransmitter receptor, are composed as tetrameric assemblies of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. Gating of the NMDARs requires binding of four co-agonist molecules, but the receptors can signal non-ionotropically through binding of glycine, alone, to its cognate site on GluN1. A consequence of this signalling by glycine is that NMDARs are primed such that subsequent gating, produced by glycine and glutamate, drives receptor internalization. The GluN1 subunit is not a singular molecular species in the CNS, rather there are 8 alternatively spliced isoforms of this subunit produced by including or excluding the N1 and the C1, C2 or C2’ polypeptide cassettes. Whether alternative splicing affects glycine priming signalling is unknown. Here, using recombinant NMDARs expressed heterologously we discovered that glycine priming of NMDARs critically depends on alternative splicing: the four splice isoforms lacking the N1 cassette, encoded in exon 5, are primed by glycine whereas glycine priming is blocked in the four splice variants containing the N1 cassette. On the other hand, the C-terminal cassettes – C1, C2 or C2’ – had no effect on glycine priming signalling. Nor was glycine priming affected by the GluN2 subunit in the receptor. In wild-type mice we found that glycine primed internalization of synaptic NMDARs in CA1 hippocampal pyramidal neurons. With mice we engineered such that GluN1 obligatorily contained the N1 cassette, glycine did not prime synaptic NMDARs in pyramidal neurons. In contrast to pyramidal neurons, we discovered that in wild-type mice, synaptic NMDARs in CA1 inhibitory interneurons were resistant to glycine priming. But we recapitulated glycine priming in inhibitory interneurons in mice engineered such that GluN1 obligatorily lacked the N1 cassette. Our findings reveal a previously unsuspected molecular function for alternative splicing of GluN1 in controlling non-ionotropic signalling of NMDAR by glycine and the consequential cell surface dynamics of the receptors.
Somatic cell genetic analysis of human cell surface antigens: chromosomal assignments and regulation of expression in rodent-human hybrid cells. (1984)

The expression of 13 newly defined human cell surface antigens identified by monoclonal antibodies was studied in a panel of reduced rodent-human somatic cell hybrid clones. For each antigenic system the segregation of antibody reactivity was concordant with the segregation of a specific human chromosome, permitting the chromosomal assignment of 13 gene loci determining antigen expression. The antigens can be placed in four groups on the basis of their patterns of control in the hybrid cells. (i) Presence of a single human chromosome is necessary and sufficient for antigen expression; L230 (assigned to chromosome 2), AJ425, K15 (chromosome 3), SR84 (chromosome 5), JF23, Q14 (chromosome 11), SV13 (chromosome 15), and F10 (chromosome 19). (ii) AJ2 (chromosome 10) and J143 (chromosome 17); two antigens coded for by separate human chromosomes but associated as a molecular complex on the surface of AJ2+/J143+ human cells. (iii) F8 (chromosome 19); antigen expression dependent on the growth characteristics of hybrid cells: substrate-adherent cells are F8+, whereas cells growing in suspension are F8-. (iv) AO122 and F23 (chromosome 15); antigen expression controlled by the permissive/inducing vs. nonpermissive/noninducing nature of the rodent fusion partner. Hybrids derived from both antigen-positive and antigen-negative human cells can express AO122 and F23 but only when specific rodent cell types are used for hybridization: N4TG-1 neuroblastoma and L cells, but not RAG renal carcinoma cells, permit AO122 expression, whereas RAG and L cells, but not N4TG-1 cells, permit F23 expression. The rapidly expanding list of monoclonal antibodies defining human cell surface molecules provides a range of markers to probe the genetic regulation of antigen diversity in somatic cells.
Supplementary Legends from Investigation of Antigen-Specific T-Cell Receptor Clusters in Human Cancers (2023)

&lt;p&gt;Legends for supplementary figures, tables and datasets.&lt;/p&gt;
Monte Carlo Simulations Of The Response Of Shielded SNM To A Pulsed Neutron Source (2011)

Active interrogation (AI) has been used as a technique for the detection and identification of Special Nuclear Material (SNM) for both proposed and field-tested systems. Idaho National Laboratory (INL) has been studying this technique for systems ranging from small systems employing portable electronic neutron generators (ENGs) 1 to larger systems employing linear accelerators as high-energy photon sources for assessment of vehicles and cargo2. In order to assess the feasibility of new systems, INL has undertaken a campaign of Monte Carlo simulations of the response of a variety of masses of SNM in multiple shielding configurations to a pulsed neutron source using the MCNPX3 code, with emphasis on the neutron and photon response of the system as a function of time after the initial neutron pulse. We present here some preliminary results from these calculations. 1. D.L. Chichester and E.H. Seabury, “ Using Electronic Neutron Generators in Active Interrogation to Detect Shielded Nuclear Material,” IEEE Transactions on Nuclear Science 56 (2009) pp 441-447. 2. J.L. Jones et al., “Photonuclear-based, nuclear material detection system for cargo containers,” Nuclear Instruments and Methods in Physics Research B 241 (2005) pp 770-776. 3. D.B. Pelowitz, “MCNPXTM User’s Manual version 2.6.0,” Los Alamos National Laboratory Report LA-CP-07-1473 (2008).
Lightweight UAV-based Measurement System for Air-to-Ground Channels at 28 GHz (2021)

Wireless communication at millimeter wave frequencies is an attractive option for high-bit-rate connectivity to unmanned aerial vehicles (UAVs). However, conducting the channel measurements necessary to assess the communication performance at these frequencies has been challenging due to the severe payload and power restrictions in commercial UAVs. This work presents a novel lightweight (approximately 1.3kg) channel measurement system at 28GHz installed on a commercially available UAV. A ground transmitter equipped with a horn antenna conveys sounding signals to a UAV equipped with a lightweight spectrum analyzer. We demonstrate that the measurements can be highly influenced by the onboard antenna pattern as shaped by the UAV's frame. A calibration procedure is presented to correct for the resulting angular variations in antenna gain. The measurement setup is then validated on real flights from an airstrip at distances in excess of 300m.
Prolactin Secretion Abnormalities in Patients with the "Syndrome of Spotty Skin Pigmentation, Myxomas, Endocrine Overactivity and Schwannomas" (Carney Complex) (2000)

Carney complex is a multiple neoplasia and lentiginosis syndrome. Acromegaly due to growth hormone (GH)-producing adenomas has been considered the only pituitary-related manifestation of the complex. In the present study, seven patients with Carney complex, who belonged to three unrelated kindreds and had relatives with acromegaly, were investigated for the presence of GH and prolactin (PRL) secretion abnormalities (familial cases). In addition, four patients with the complex and no family history of the complex were studied (sporadic cases). Seven of the patients were female and four were male; their mean age was 24.27 +/- 4.34 years. Sampling every 20 min for one hour in the morning and under fasting and unstimulated conditions was performed in all patients, for determination of serum PRL levels. Insulin-like growth factor-I (IGF-I) levels and magnetic resonance imaging (MRI) of the pituitary were also obtained. Patients who had elevated IGF-I levels underwent investigation for acromegaly by oral glucose tolerance test and thyrotropin-releasing hormone. Seven of the 11 patients (63.6%) had moderately high PRL levels (mean Z score value 2.12 +/- 0.66); three of these patients also had elevated IGF-I levels but a negative investigation for acromegaly. All patients had negative pituitary MRI. The patient with the highest PRL levels underwent 24-hour sampling every 20 min, which demonstrated a higher baseline secretion of this hormone with preservation of its circadian pulsatility. Hyperprolactinemia was present in two siblings and a parent-child pair. We conclude that prolactin hypersecretion, albeit mild, appears to be frequent in patients with Carney complex, is inherited in an autosomal dominant manner in kindreds with the syndrome, and may be associated with elevated IGF-I levels in some, but not all, patients.
Nanostructured Magnéli-Phase W18O49 Thin Films for Photoelectrochemical Water Splitting (2020)

Converting water into hydrogen through the photo-electrochemical (PEC) process is one of the most exciting approaches in this field, and there is a quest to design or search for new electro-photo-catalytic materials. In this work, simple steps for fabrication and transformation of metallic tungsten thin film into the photo-active Magnéli-phase (W18O49) of tungsten oxide thin film is demonstrated. The post-annealing temperature has a significant impact on the phase evolution of tungsten film into W18O49. The film thickness of W18O49 is controlled by controlling the sputtering time (or deposition time) of W film. The PEC performance of the as-prepared electrodes is evaluated by monitoring the water oxidation reaction under visible radiation. The PEC findings reveal a correlation between PEC performance and phase, morphology, and thickness of the film. The as-derived W18O49 can efficiently catalyze the water oxidation reaction at neutral solution pH, generating 0.6 and 1.4 mA cm−1 photo-current at 0.6 and 0.8 V vs. Saturated calomel electrode (SCE), respectively, in addition to excellent stability. The electrical conductivity and the charge transfer kinetics are investigated employing the electrochemical impedance spectroscopic (EIS) technique.
Controlling microstructure in deposits fabricated using powder blown direct energy deposition technique (2018)

The overall goal of this collaboration is to develop technologies to control grain morphology and microstructures of Inconel 718 components additively manufactured through the Direct Energy Deposition (DED) process (Identical to the LENS (laser engineered net shaping) processes) and to achieve equiaxed or near equiaxed grain structures. The phase1 technical collaboration was used to fabricate Inconel 718 builds with different process parameters, pre heat and scan strategies. The results were then rationalized using computational heat transfer and solidification models. Microstructural characterization showed that the aspect ratio of the grains can be reduced to less than 1.5, and that control of the grain sizes to within 50-100 μm could be potentially obtained by using an external source to preheat the substrate to 400 ̊C. Heat transfer models coupled with solidification models were used to rationalize the results which show that preheating lowered the temperature gradient thereby resulting in moving towards the equiaxed region of the columnar to equiaxed transition (CET) curve. The results demonstrate that higher preheat temperatures could be potentially used to obtain a truly equiaxed structure.
Electrical carrier-injection and transport characteristics of photochromic diarylethene films (2003)

Electrical carrier-injection and transport characteristics of photochromic diarylethene thin films were investigated. Injected and transported carriers (injected current) to the diarylethene film were increased with the existence ratio of the closed-ring form, which was one isomerization state of the diarylethene molecule. A dramatic increase was observed at a 12-percent existence ratio of the closed-ring molecules. A lowering effect of the potential barrier, which is caused by a Poole–Frenkel-like effect with a short distance interaction potential for hole transportation by increasing the existence ratio of the closed-ring molecules is proposed as the mechanism behind this phenomenon.
Retrieving similar images in an image database using a relational matrix (2003)

The definition of perceptual similarity between two images is a function of the distance between image features, i.e, shape, color and texture features of dominant image regions. We propose a relational matrix based distance measure that can be used to measure the similarity between images in a given image database. A relational matrix, individualized for an image, describes the spatial and functional relations between neighboring image segments in the image intensity matrix. Automated image segmentation using agglomerative clustering generates the relational matrix. We propose a distance measure between corresponding relational matrices representing any two images that can be used in content based image retrieval. Simulation results are given to demonstrate the potential of the relational matrix in the digital library application.
The Differential Expression of Kiss1, MMP9 and Angiogenic Regulators across the Feto-Maternal Interface of Healthy Human Pregnancies: Implications for Trophoblast Invasion and Vessel Development (2013)

Genes involved in invasion of trophoblast cells and angiogenesis are crucial in determining pregnancy outcome. We therefore studied expression profiles of these genes in both fetal and maternal tissues to enhance our understanding of feto-maternal dialogue. We investigated the expression of genes involved in trophoblast invasion, namely Kiss1, Kiss1 Receptor (Kiss1R) and MMP9 as well as the expression of angiogenic ligands Vascular Endothelial Growth Factor-A (VEGF-A) and Prokineticin-1 (PROK1) and their respective receptors (VEGFR1, VEGFR2 and PROK1R) across the feto-maternal interface of healthy human pregnancies. The placenta, placental bed and decidua parietalis were sampled at elective caesarean delivery. Real-time RT-PCR was used to investigate transcription, while immunohistochemistry and western blot analyses were utilized to study protein expression. We found that the expression of Kiss1 (p<0.001), Kiss1R (p<0.05) and MMP9 (p<0.01) were higher in the placenta compared to the placental bed and decidua parietalis. In contrast, the expression of VEGF-A was highest in the placental bed (p<0.001). While VEGFR1 expression was highest in the placenta (p<0.01), the expression of VEGFR2 was highest in the placental bed (p<0.001). Lastly, both PROK1 (p<0.001) and its receptor PROK1R (p<0.001) had highest expression in the placenta. Genes associated with trophoblast invasion were highly expressed in the placenta which could suggest that the influence on invasion capacity may largely be exercised at the fetal level. Furthermore, our findings on angiogenic gene expression profiles suggest that angiogenesis may be regulated by two distinct pathways with the PROK1/PROK1R system specifically mediating angiogenesis in the fetus and VEGFA/VEGFR2 ligand-receptor pair predominantly mediating maternal angiogenesis.
Discovery of Reversible Covalent Bruton’s Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib) (2022)

Bruton's tyrosine kinase (BTK), a Tec family tyrosine kinase, is critical in immune pathways as an essential intracellular signaling element, participating in both adaptive and immune responses. Currently approved BTK inhibitors are irreversible covalent inhibitors and limited to oncology indications. Herein, we describe the design of covalent reversible BTK inhibitors and the discoveries of PRN473 (<b>11</b>) and rilzabrutinib (PRN1008, <b>12</b>). These compounds have exhibited potent and durable inhibition of BTK, in vivo efficacy in rodent arthritis models, and clinical efficacy in canine pemphigus foliaceus. Compound <b>11</b> has completed phase 1 trials as a topical agent, and <b>12</b> is in phase 3 trials for pemphigus vulgaris and immune thrombocytopenia.
Switching transport through nanopores with pH-responsive polymer brushes for controlled ion permeability (2012)

The development of a biosensor for high throughput screening of membrane proteins is a major challenge in drug development. Our aim is to chemically functionalize supported nanoporous films and nanosieves, so that they can be used as platforms for membrane protein assays. For this we use pH-responsive poly(methacrylic acid) (PMAA) brushes.
Broadband 200-nm second-harmonic generation in silicon in the telecom band (2020)

Silicon is well known for its strong third-order optical nonlinearity, exhibiting efficient supercontinuum and four-wave mixing processes. A strong second-order effect that is naturally inhibited in silicon can also be observed, for example, by electrically breaking the inversion symmetry and quasi-phase matching the pump and the signal. To generate an efficient broadband second-harmonic signal, however, the most promising technique requires matching the group velocities of the pump and the signal. In this work, we utilize dispersion engineering of a silicon waveguide to achieve group velocity matching between the pump and the signal, along with an additional degree of freedom to broaden the second harmonic through the strong third-order nonlinearity. We demonstrate that the strong self-phase modulation and cross-phase modulation in silicon help broaden the second harmonic by 200 nm in the O-band. Furthermore, we show a waveguide design that can be used to generate a second-harmonic signal in the entire near-infrared region. Our work paves the way for various applications, such as efficient and broadband complementary-metal oxide semiconductor based on-chip frequency synthesizers, entangled photon pair generators, and optical parametric oscillators.
An Ultra Low Power 180-Degree, 1-Bit Phase Shifter using MOSFETS (2009)

Abstract : An ultra low power 180-degree, 1-bit phase shifter has been designed using Agilent's Advanced Design Software (ADS) co-simulation. Silicon-on-Insulator (SOI). MOSFETs were used as the switching elements because of their low current draw and low capacitance. A 1-bit 0, 180-degree phase shift has been realized with only two MOSFETs, simplifying manufacture and decreasing power.
The application of lithography defect simulation to submicron CMOS yield improvement efforts (2002)

Yield improvement efforts traditionally involve extensive experimental work aimed at diagnosing defects. This paper proposes supplementing such experimental work with defect simulation. An example of identifying a defect in the top antireflective coating (TARC) on photoresist illustrates yield improvement efforts involving both defect simulations and experimentation.
Nachlese : motion, drive & automation (2003)

Boldt, Torsten; Breit, Holger; Deeken, Michael; Görres, Martin; Hantke, Patrick; Hoppermann, Andreas; Jansen, Roman J.; Meindorf, Thomas; Meuser, Marcell Josef; Schultz, Albert W.; Stammen, Christian; Theissen, Heino
Cryopreservation of pronuclear stage human embryos (2010)

For several decades, attempts to cryopreserve human oocytes have been performed in many in vitro fertilization (IVF) centers worldwide, with variable results. Ice-free cryopreservation is an attempt to circumvent the hazards of water crystallization as ice. Three key factors influence the probability of successful vitrification: cooling and warming rates, the composition of the cryoprotectants (CPA) solution, and the sample volume. Pressure is another factor that increases the chance of vitrification but this has had very little, if any, application in the clinical assisted reproductive technology (ART) arena. The osmotic stress during removal of CPAs was initially reduced in slow cooling by a stepwise dilution (using reduced concentration of CPAs progressively), allowing enough time for the cell to return to an equilibrium volume. Two of the dangers of cryopreservation are solution effects and intracellular ice formation. Other factors causing damage are extracellular ice and intracellular dehydration.
64‐1: Modeling the Mechanical Performance of a Foldable Display Panel Bonded by 3M Optically Clear Adhesives (2017)

Among the multiple design goals for foldable displays to perform under repeated folding and unfolding is to reduce bending stress and various failure modes induced by bending of the film stack. In this work, we demonstrate, through modeling the folding of simplified display film stacks, that the optically clear adhesives (OCA) in a display can be leveraged not only to provide a secure bond between the functional layers, but also to improve the overall folding performance and mechanical durability of the display. Specifically, we discuss these OCA advantages through three topics commonly encountered in designing a flexible display: • reducing the bending stresses by neutral plane management, • facilitating large shear strains between layers to reduce shear coupling between the layers, • improving buckling resistance.
Lessons From a Systematic Literature Search on Diagnostic DNA Methylation Biomarkers for Colorectal Cancer: How to Increase Research Value and Decrease Research Waste? (2022)

This systematic literature search revealed that major requirements to develop clinically relevant diagnostic CRC DNA methylation markers are often lacking. To avoid the resulting research waste, clinical needs, intended biomarker use, and independent validation should be better considered before study design. In addition, improved reporting quality would facilitate meta-analysis, thereby increasing the level of evidence and enabling clinical translation.
Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX‐2 (2013)

A series of 3,4-diarylpyrazole-1-carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single-dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase-2 inhibition and ERK pathway inhibition.