gebhart/patrepeval huggingface dataset:
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments (2014)

SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.
Vertical Addressing of 1‐Plane Electrodes for Digital Microfluidics (2021)

Abstract Digital microfluidics (DMF) has become a mainstay in the microfluidics and microelectromechanical communities. Many users rely on simple DMF devices featuring a small number of rows and columns of electrodes that can be rapidly manufactured using “one plane” lithographic or printing techniques. But as the popularity of DMF grows, there are increasing needs for larger devices that can facilitate multiplexed handling of many samples and reagents in parallel. One option for scaling DMF devices is to use “vertical addressing” techniques such as printed circuit boards (PCBs), but PCBs formed using standard techniques exhibit topography that is not ideal for smooth and reliable droplet movement. A new method to produce DMF devices using vertical addressing of 1‐plane electrodes (VAPE‐DMF) is introduced. This method, which separates devices into “covers” (bearing 1‐plane electrodes) and “sub‐substrates” (for vertical addressing), enables rapid and inexpensive manufacture of devices with arbitrarily large driving electrode arrays. This work describes how to manufacture VAPE‐DMF devices and demonstrates a proof‐of‐concept device with an array of 336 electrodes to handle 48 droplets to run 24 reactions in parallel. It is proposed that VAPE‐DMF represents a useful new development for the growing community of users and innovators of digital microfluidics and related methods.
Derivation of a Retinoid X Receptor Scaffold from Peroxisome Proliferator‐Activated Receptor γ Ligand 1‐Di(1H‐indol‐3‐yl)methyl‐4‐trifluoromethylbenzene (2009)

PPARgamma agonist DIM-Ph-4-CF(3), a template for RXRalpha agonist (E)-3-[5-di(1-methyl-1H-indol-3-yl)methyl-2-thienyl] acrylic acid: DIM-Ph-CF(3) is reported to inhibit cancer growth independent of PPARgamma and to interact with NR4A1. As both receptors dimerize with RXR, and natural PPARgamma ligands activate RXR, DIM-Ph-4-CF(3) was investigated as an RXR ligand. It displaces 9-cis-retinoic acid from RXRalpha but does not activate RXRalpha. Structure-based direct design led to an RXRalpha agonist.1-Di(1H-indol-3-yl)methyl-4-trifluoromethylbenzene (DIM-Ph-4-CF(3)) is reported to inhibit cancer cell growth and to act as a transcriptional agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear receptor 4A subfamily member 1 (NR4A1). In addition, DIM-Ph-4-CF(3) exerts anticancer effects independent of these receptors because PPARgamma antagonists do not block its inhibition of cell growth, and the small pocket in the NR4A1 crystal structure suggests no ligand can bind. Because PPARgamma and NR4A1 heterodimerize with retinoid X receptor (RXR), and several PPARgamma ligands transcriptionally activate RXR, DIM-Ph-4-CF(3) was investigated as an RXR ligand. DIM-Ph-4-CF(3) displaces 9-cis-retinoic acid from RXRalpha but does not transactivate RXRalpha. Structure-based design using DIM-Ph-4-CF(3) as a template led to the RXRalpha transcriptional agonist (E)-3-[5-di(1-methyl-1H-indol-3-yl)methyl-2-thienyl]acrylic acid. Its docked pose in the RXRalpha ligand binding domain suggests that binding is stabilized by interactions of its carboxylate group with arginine 316, its indoles with cysteines 269 and 432, and its 1-methyl groups with hydrophobic residues lining the binding pocket. As is expected of a selective activator of RXRalpha, but not of RARs and PPARgamma, this RXRalpha agonist, unlike DIM-Ph-4-CF(3), does not appreciably decrease cancer cell growth or induce apoptosis at pharmacologically relevant concentrations.
Reactive Intermediates Involved in Cobalt Corrole Catalyzed Water Oxidation (and Oxygen Reduction) (2017)

A detailed investigation of the cobalt corrole Co(tpfc) as molecular catalyst for electrochemical water oxidation uncovered many important mechanism-of-action details that are crucial for the design of optimally performing systems. This includes the identification of the redox states that do and do not participate in catalysis and very significant axial ligand effects on the activity of the doubly oxidized complex. Specifics deduced for the electrocatalysis under homogeneous conditions include the following: the one-electron oxidation of the cobalt(III) corrole is completely unaffected by reaction conditions; catalysis coincides with the second oxidation event; two catalytic waves develop in the presence of OH<sup>-</sup>, and the one at lower overpotential is dominant under more basic conditions. Comparative spectroelectrochemical measurements performed for Co(tpfc) and Al(tpfc), the analogous corrole chelated by the nonredox active aluminum, revealed that the second oxidation process of Co(tpfc) is much more significantly metal-centered than the first one. EPR studies revealed that shift from fully corrole-centered to partially metal-centered in the singly oxidized complex [Co(tpfc)]<sup>+</sup> is achievable with fluoride as axial ligand. The analogous experiment, but with hydroxide instead of fluoride, could not be performed because of a surprising phenomenon: formation of a cobalt-superoxide complex that is actually relevant to oxygen reduction rather than to water oxidation. Nevertheless, fluoride and hydroxide induce very similar effects in terms of the appearance of two catalytic waves, lowering of onset potentials, and increasing the catalytic activity. The main conclusions from the accumulated data are that the apparent pH effect is actually due to hydroxide binding to the cobalt center and that π-donating axial ligands play pivotal and beneficial roles regarding the main factors that are important for facilitating the oxidation of water.
Novel Types of Carborane‐Carrier Hyaluronan Derivatives via “Click Chemistry” (2008)

Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells.
A Laser-cooled Cesium Fountain Frequency Standard and a Measurement of the Frequency Shift due to Ultra-cold Collisions (1993)

In our Cs atomic fountain, we laser cooled and trapped 10(exp 10) Cs atoms in 0.4 s. By shifting the frequencies of the laser beams, the atoms were launched upwards at 2.5 m/s and a fraction of the atoms were optically pumped into the F=3 ground state. The unwanted atoms in the F=4 ground state were removed from the fountain with radiation pressure from a laser beam tuned to excite only those atoms. The Cs atoms in the F=3 state traveled ballistically upwards, were excited by the microwave cavity, and then returned back through the same cavity in the atomic fountain configuration.
Diffraction of Coupled Waves and Determination of Phase Mismatch Between Holographic Grating and Fringe Pattern (1979)

Coupled-wave analysis is used to calculate the diffraction of two light beams on a volume phase hologram. The complex amplitudes of the diffracted beams depend strictly on the spatial mismatch of the holographic grating with respect to the interference pattern; this gives the possibility of determining the grating phase shift. Measurements of energy and phase redistribution between two light beams passing through the hologram were used to determine the grating phse shift for DCG gratings and for dynamic gratings in pure reduced LiNbO3 crystals.
Quantum dot laser diodes (1999)

Recently, semiconductor quantum dot (QD) laser diodes have been successfully demonstrated. The emphasis in this paper is on the recent progresses at our institute, towards the understanding the physics of such zero-dimensional heterostructures and pointing out the benefits and challenges associated with incorporating these nanostructures in the active layers of practical devices such as laser diodes.
Use of the Site of Subcutaneous Insulin Administration for the Measurement of Glucose in Patients With Type 1 Diabetes (2009)

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g). As controls, the further two MP catheters were perfused with an insulin-free solution (5% mannitol) and used for glucose sampling only. Plasma glucose was measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter was adequate to achieve and maintain normoglycemia during fasting and after glucose ingestion. Tissue glucose concentrations derived with the insulin-perfused catheter agreed well with plasma glucose levels. Median correlation coefficient and median absolute relative difference values were found to be 0.93 (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis indicated that the percentage number of tissue values falling in the clinically acceptable range is 99.6%. Comparable analysis results were obtained for the two mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of plasma glucose concentrations from the glucose levels directly observed at the site of subcutaneous insulin infusion is feasible and its quality is comparable to that of estimating plasma glucose concentrations from glucose levels measured in insulin-unexposed subcutaneous tissue.
Adaptation of the electric machines learning process to the european higher education area (2010)

In this paper the basic lines of a complete teaching methodology that has been developed to adapt the electric machines learning process to the European Higher Education Area (EHEA) are presented. New teaching materials that are specific to Electric Machines have been created (textbooks, self-learning e-books, guidelines for achieving teamwork research, etc.). Working in groups has been promoted, as well as problem solving and self-learning exercises, all of which are evaluated in a way that encourages students' participation. Finally, the students' learning process in the lab has been improved by the development both of a new methodology to follow in the lab and new workbenches with industrial machines that are easier to use and also enable the lab experiments to be automated. Finally, the first results obtained as a result of applying the proposed methodology are presented.
A Germination-Specific Endo-β-Mannanase Gene Is Expressed in the Micropylar Endosperm Cap of Tomato Seeds (2000)

Endo-beta-mannanase (EC 3.2.1.78) is involved in hydrolysis of the mannan-rich cell walls of the tomato (Lycopersicon esculentum Mill.) endosperm during germination and post-germinative seedling growth. Different electrophoretic isoforms of endo-beta-mannanase are expressed sequentially in different parts of the endosperm, initially in the micropylar endosperm cap covering the radicle tip and subsequently in the remaining lateral endosperm surrounding the rest of the embryo. We have isolated a cDNA from imbibed tomato seeds (LeMAN2) that shares 77% deduced amino acid sequence similarity with a post-germinative tomato mannanase (LeMAN1). When expressed in Escherichia coli, the protein encoded by LeMAN2 cDNA was recognized by anti-mannanase antibody and exhibited endo-beta-mannanase activity, confirming the identity of the gene. LeMAN2 was expressed exclusively in the endosperm cap tissue of tomato seeds prior to radicle emergence, whereas LeMAN1 was expressed only in the lateral endosperm after radicle emergence. LeMAN2 mRNA accumulation and mannanase activity were induced by gibberellin in gibberellin-deficient gib-1 mutant seeds but were not inhibited by abscisic acid in wild-type seeds. Distinct mannanases are involved in germination and post-germinative growth, with LeMAN2 being associated with endosperm cap weakening prior to radicle emergence, whereas LeMAN1 mobilizes galactomannan reserves in the lateral endosperm.
Reactivation of silent rRNA genes by simian virus 40 in human-mouse hybrid cells. (1979)

Mouse-human hybrid cells were used to study the ability of simian virus 40 to regulate the expression of rRNA genes in vivo. In these hybrid cells, only the rRNA genes of the dominant species are expressed; the genes for the rRNA of the recessive species are silent. Simian virus 40 infection of these hybrids led to the production of two distinct 28S rRNA species as analyzed by agarose/2.4% polyacrylamide gel electrophoresis. These species were identified as human and mouse rRNAs. This result was confirmed by histochemical studies which indicated that the nucleolus organizer regions of both mouse and human chromosomes were actively synthesizing rRNA in the virus-infected hybrid cells. These results indicate that simian virus 40 infection can induce the expression of otherwise silent rRNA genes.
Gamma radiation sterilization of N95 respirators leads to decreased respirator performance (2021)

In response to personal protective equipment (PPE) shortages in the United States due to the Coronavirus Disease 2019, two models of N95 respirators were evaluated for reuse after gamma radiation sterilization. Gamma sterilization is attractive for PPE reuse because it can sterilize large quantities of material through hermetically sealed packaging, providing safety and logistic benefits. The Gamma Irradiation Facility at Sandia National Laboratories was used to irradiate N95 filtering facepiece respirators to a sterilization dose of 25 kGy(tissue). Aerosol particle filtration performance testing and electrostatic field measurements were used to determine the efficacy of the respirators after irradiation. Both respirator models exhibited statistically significant decreases in particle filtering efficiencies and electrostatic potential after irradiation. The largest decrease in capture efficiency was 40-50% and peaked near the 200 nm particle size. The key contribution of this effort is correlating the electrostatic potential change of individual filtration layer of the respirator with the decrease filtration efficiency after irradiation. This observation occurred in both variations of N95 respirator that we tested. Electrostatic potential measurement of the filtration layer is a key indicator for predicting filtration efficiency loss.
Bacterial protein microarrays for identification of new potential diagnostic markers for Neisseria meningitidis infections (2005)

Neisseria meningitidis is the most common cause of meningitis and causes epidemic outbreaks. One trait of N. meningitidis, which is associated with most of the currently recognized virulence determinants, is the presence of phase-variable genes that are suspected to enhance its ability to cause an invasive disease. To detect the immune responses to phase-variable expressed proteins, we applied protein microarray technology for the screening of meningitis patient sera. We amplified all 102 known phase-variable genes from N. meningitidis serogroup B strain MC58 by polymerase chain reaction and subcloned them for expression in Escherichia coli. With this approach, we were able to express and purify 67 recombinant proteins representing 66% of the annotated genes. These were spotted robotically onto coated glass slides to generate protein microarrays, which were screened using 20 sera of patients suffering from meningitis, as well as healthy controls. From these screening experiments, 47 proteins emerged as immunogenic, exhibiting a variable degree of seroreactivity with some of the patient sera. Nine proteins elicited an immune response in more than three patients, with one of them, the phase-variable opacity protein OpaV (NMB0442), showing responses in 11 patient sera. This is the first time that protein microarray technology has been applied for the investigation of genetic phase variation in pathogens. The identification of disease-specific proteins is a significant target in biomedical research, as such proteins may have medical, diagnostic, and commercial potential as disease markers.
An ultrasound research interface for a clinical system (2006)

Under a contract with the National Cancer Institute, we have developed a research interface to an ultrasound system. This ultrasound research interface (URI) is an optional feature providing several basic capabilities not normally available on a clinical scanner. The URI can store high-quality beamformed radio-frequency data to file for off-line processing. Also, through an integrated user interface, the user is provided additional control over the B-mode receive aperture and color flow ensemble size. A third major capability is the ability to record and playback macro files. In this paper, we describe the URI and illustrate its use on three research examples: elastography, computed tomography, and spatial compounding.
Investigation of temporal radiographic texture analysis for the detection of periprosthetic osteolysis (2006)

Periprosthetic osteolysis is a disease caused by the body's response to submicron polyethylene debris particles from the hip implant in total hip replacement (THR) patients. It leads to resorption of bone surrounding the implant and deterioration of the bone's trabecular texture, but this is difficult to detect until the later stages of disease progression. Radiographic texture analysis methods have shown promise in detecting this disease at an earlier stage; however, changes in texture over time may be more important than absolute texture measures. In this research, we investigated temporal radiographic texture analysis (tRTA) methods as possible aids in the detection of osteolysis. A database of 48 THR cases with images available from four different follow-up time intervals was used. ROIs were selected within the osteolytic region of the most recent follow-up image (or comparable region for normal cases) and visually matched on all previous images. Texture features were calculated from the ROIs and then trend analysis was performed using a simple linear regression method, an LDA method and a BANN method. The performance of these three methods was evaluated by ROC analysis. Maximum AUC values of 0.68, 0.78, and 0.88 for the task of distinguishing between osteolysis and normal cases were achieved for the respective tRTA features. These performances were superior to those of our prior stationary, non-temporal texture analysis. The results suggest that tRTA may have the potential to help detect osteolysis at an earlier, more treatable stage.
Simultaneous Multiple Pattern Correlation with <1 ns Reconfiguration Time (2012)

We demonstrate a data pattern correlator for OOK and BPSK signals that can simultaneously search for multiple patterns using optical sampling via wavelength conversion. We show reconfiguration times as low as 100 ps for the search pattern update in the correlator.
Mechanical and optical characterization of thermal microactuators fabricated in a CMOS process (1995)

Microelectromechanical actuators with large vertical deflections are desirable for microactuation and sensing applications, such as tactile stimulators for telerobotics, micropositioners, and microflaps for airflow control. Thermally actuated cantilever beams provide large deflections at low voltages and low power. Cantilever beams using silicon micromachining have been fabricated in a complementary metal-oxide-semiconductor process. The beams were tested using a microscope-based laser interferometer and a weight-balance force tester, both of which were specifically designed and built for analysis of microelectromechanical devices. Measurments were taken of cantilever beam deflection, maximum operating frequency, and operation under load. Cantilevers 300 micrometers long and 100 micrometers wide with a 2.6 K(Omega) polycrystalline silicon heating resistor were capable of deflecting loads of up to 15 mg with a 6 volt drive. The same cantilevers were tested for fatigue endurance under a 5 mg load, producing a 5 micrometers deflection that remained unchanged after 75 hours of continuous operation with a 6 volt peak, 0.33 Hz square wave drive signal.