gebhart/patrepeval huggingface dataset:
Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders (2008)

Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders.
MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity (2018)

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene <i>ORF4b</i> Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking <i>ORF4b</i> elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, <i>ORF4b</i> deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal-human interface.
Binding of Mn-deoxyribonucleoside triphosphates to the active site of the DNA polymerase of bacteriophage T7 (2011)

Divalent metal ions are crucial as cofactors for a variety of intracellular enzymatic activities. Mg<sup>2+</sup>, as an example, mediates binding of deoxyribonucleoside 5'-triphosphates followed by their hydrolysis in the active site of DNA polymerase. It is difficult to study the binding of Mg<sup>2+</sup> to an active site because Mg<sup>2+</sup> is spectroscopically silent and Mg<sup>2+</sup> binds with low affinity to the active site of an enzyme. Therefore, we substituted Mg<sup>2+</sup> with Mn<sup>2+</sup>:Mn<sup>2+</sup> that is not only visible spectroscopically but also provides full activity of the DNA polymerase of bacteriophage T7. In order to demonstrate that the majority of Mn<sup>2+</sup> is bound to the enzyme, we have applied site-directed titration analysis of T7 DNA polymerase using X-ray near edge spectroscopy. Here we show how X-ray near edge spectroscopy can be used to distinguish between signal originating from Mn<sup>2+</sup> that is free in solution and Mn<sup>2+</sup> bound to the active site of T7 DNA polymerase. This method can be applied to other enzymes that use divalent metal ions as a cofactor.
Target Privacy Threat Modeling for COVID-19 Exposure Notification Systems (2020)

The adoption of digital contact tracing (DCT) technology during the COVID-19pandemic has shown multiple benefits, including helping to slow the spread of infectious disease and to improve the dissemination of accurate information. However, to support both ethical technology deployment and user adoption, privacy must be at the forefront. With the loss of privacy being a critical threat, thorough threat modeling will help us to strategize and protect privacy as digital contact tracing technologies advance. Various threat modeling frameworks exist today, such as LINDDUN, STRIDE, PASTA, and NIST, which focus on software system privacy, system security, application security, and data-centric risk, respectively. When applied to the exposure notification system (ENS) context, these models provide a thorough view of the software side but fall short in addressing the integrated nature of hardware, humans, regulations, and software involved in such systems. Our approach addresses ENSsas a whole and provides a model that addresses the privacy complexities of a multi-faceted solution. We define privacy principles, privacy threats, attacker capabilities, and a comprehensive threat model. Finally, we outline threat mitigation strategies that address the various threats defined in our model
Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis (2020)

&lt;p&gt;We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with [&lt;sup&gt;18&lt;/sup&gt;F]KF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.&lt;/p&gt;
Phonological Markers of Oxytocin and MDMA Ingestion (2017)

Speech data has the potential to become a powerful tool to provide quantitative information about emotion beyond that achieved by subjective assessments. Based on this concept, we investigate the use of speech to identify effects in subjects under the influence of two different drugs: Oxytocin (OT) and 3, 4-methylenedioxymethamphetamine (MDMA), also known as ecstasy. We extract a set of informative phonological features that can characterize emotion. Then, we perform classification to detect if the subject is under the influence of a drug. Our best results show low error rates of 13% and 17% for the subject classification of OT and MDMA vs. placebo, respectively. We also analyze the performance of the features to differentiate the two levels of MDMA doses, obtaining an error rate of 19%. The results indicate that subtle emotional changes can be detected in the context of drug use.
An enhanced topology for reliability of a high performance 3.3V I/O buffer in a single-well bulk CMOS 1.8v-oxide low voltage process (2009)

The aggressive scaling of CMOS process is central to the continued performance enhancement of microprocessors. While the process scales every generation the I/O interface standards do not change at the same rate. This introduces a host of reliability issues. One not only needs to design for performance, but should also meet the reliability goals in the scaled technology for these standards. This paper presents a 3.3 V I/O buffer designed using 1.8 V transistors in a 65 nm bulk CMOS process. Proposed I/O uses a novel differential amplifier based pre-driver topology, which has excellent gate-oxide reliability, runs at 200 MHz and has comparative area and static power of an equivalent I/O in 65 nm 3.3 V CMOS process.
Approaches in CMOS to sub-THz systems and applications (2014)

As wavelengths shrink to the mm and sub-mm range new capabilities from material sensing to imaging become possible, in addition to the larger bandwidths possible for large data communication. These new application possibilities from below 100GHz towards 1THz will be outlined in this talk. Paths of how to build cost effectively entire systems operating in the sub-THz frequency range using CMOS will be shown. An overview will be given of a fully integrated 160GHz RF Pulsed Radar Transceiver in 65nm CMOS with fully package integrated antennas.
ESTIMATION OF DRY WEIGHT (DW) IN HEMODIALYSIS PATIENTS (HDP) BY MEASURING INTERSTITIAL (IT) HYDRATION USING SEGMENTAL BIOIMPEDANCE (2001)

The correct DW is dependent on an appropriate ratio of fluid volume in the IT compartment to extracellular volume (ECV= IT+Blood volume). We investigated the ratio of IT compartment to ECV conductivity (σT/σE) in 24 HDP compared to 24 normals (NS). Electrodes were placed on the calf to measure resistance (R) and a BP cuff was placed over these to produce a pressure (P) for squeezing blood volume out of the studied segment in 1–2 seconds. Regional ECV resistance R0 (P=0 mmHg) and IT resistance Rp (P=240 mmHg) were measured by segmental bioimpedance (Xitron 4200S) at the end of HD. Resistivity was calculated by ρ = R×A/L (Ω°Cm). The ratio (λ) of σT to σE was calculated by λ = σT/σE. Results: There were significant differences between NS and HDP (P<0.01). The patients' post weight (PW) did not reach their clinical DW (CDW) as shown by the lower ρ and higher λ compared to that of NS (Table 1).TableIn previous studies, we have shown that resistivity (ρ = 1/σ) could be used to assess DW. However, accurate measurement of ρ could be affected by individual difference in fat. Therefore, use of Δ (a ratio which removes fat as a variable) may be able, together with measurement of ρ, to improve accuracy of dry weight estimation.
Sur des aspects algébriques et combinatoires de l'Analyse Relationnelle. (2007)

L’Analyse Relationnelle est un ensemble de methodes qui s’interesse a l’etude des relations
binaires et aux applications faisant intervenir ces dernieres. La particularite de la theorie pre-
sentee ici et proposee initialement par J.F. Marcotorchino et P. Michaud, est de representer ces
relations binaires sous la forme de matrices de comparaisons par paires d’objets sur lesquels
portent ces relations. Par ailleurs, elle fait appel a diverses branches mathematiques que sont
la theorie des graphes, la statistique et la programmation lineaire. Deux des applications clas-
siques de l’Analyse Relationnelle sont la classification automatique et l’agregation multicritere
qui correspondent respectivement a l’etude des relations d’equivalence et des relations d’ordre.
Nous avons cherche a enrichir l’Analyse Relationnelle de differents outils provenant de l’al-
gebre relationnelle, de la logique multivalente, de l’analyse combinatoire et de l’optimisation
combinatoire. Cette approche nous a permis d’etendre la theorie et les champs d’application
de l’Analyse Relationnelle. Outre les applications classiques citees precedemment, nous nous
sommes interesses a l’axiomatique issue de la theorie du choix social et a la theorie des tresses.
Les contributions que nous avons pu obtenir finalement dans le cadre de ce memoire de these
sont les suivantes :
• Definition d’un nouvel algorithme de classification automatique ne necessitant pas la
fixation d’un nombre de classes
• Presentation unifiee de certains indices de similarite entre vecteurs numeriques (issus de
variables binaires, qualitatives ou quantitatives), de certains criteres d’association entre
variables qualitatives et de certains criteres d’association entre variables ordonnees
• Definition d’une methode d’agregation appelee calcul consensuel, fondee sur une regle
majoritaire et qui se base sur les formules combinatoires de H. Poincare et de Ch. Jordan
• Generalisation des resultats de D. Black, de K. Inada et de A.K. Sen en theorie du choix
social aboutissant a des conditions necessaires et suffisantes pour que la preference col-
lective issue de plusieurs preferences individuelles soit transitive
• Modelisation originale des tresses permettant de definir de maniere generique des mou-
vements isotopiques de brins et d’aborder les problemes algorithmiques autour du groupe
des tresses et celui des noeuds sous l’angle de l’optimisation combinatoire
Scalable Purification of Plasmid DNA Nanoparticles by Tangential Flow Filtration for Systemic Delivery (2021)

Plasmid DNA (pDNA) nanoparticles synthesized by complexation with linear polyethylenimine (lPEI) are one of the most effective non-viral gene delivery vehicles. However, the lack of scalable and reproducible production methods and the high toxicity have hindered their clinical translation. Previously, we have developed a scalable flash nanocomplexation (FNC) technique to formulate pDNA/lPEI nanoparticles using a continuous flow process. Here, we report a tangential flow filtration (TFF)-based scalable purification method to reduce the uncomplexed lPEI concentration in the nanoparticle formulation and improve its biocompatibility. The optimized procedures achieved a 60% reduction of the uncomplexed lPEI with preservation of the nanoparticle size and morphology. Both <i>in vitro</i> and <i>in vivo</i> studies showed that the purified nanoparticles significantly reduced toxicity while maintaining transfection efficiency. TFF also allows for gradual exchange of solvents to isotonic solutions and further concentrating the nanoparticles for injection. Combining FNC production and TFF purification, we validated the purified pDNA/lPEI nanoparticles for future clinical translation of this gene nanomedicine.
AZP-3813, a bicyclic 16-amino acid peptide antagonist of the human growth hormone receptor as a potential new treatment for acromegaly (2022)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
Defining the core essential genome of Pseudomonas aeruginosa (2018)

Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. It is becoming clear that a major limitation was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both genetic background and growth condition. We thus developed a strategy for more rigorously defining the core essential genome of a bacterial species by studying many pathogen strains and growth conditions. We assessed how many strains must be examined to converge on a set of core essential genes for a species. We used transposon insertion sequencing (Tn-Seq) to define essential genes in nine strains of Pseudomonas aeruginosa on five different media and developed a novel statistical model, FiTnEss , to classify genes as essential versus non-essential across all strain-media combinations. We defined a set of 321 core essential genes, representing 6.6% of the genome. We determined that analysis of 4 strains was typically sufficient in P. aeruginosa to converge on a set of core essential genes likely to be essential across the species across a wide range of conditions relevant to in vivo infection, and thus to represent attractive targets for novel drug discovery.
Electrostatic Control and Entanglement of CMOS Position-Based Qubits (2020)

In this paper we demonstrate electrostatic control and feasibility of entanglement in CMOS qubits. We present both single particle and multi-particle methodologies to describe quantum transport using a time-dependent Hamiltonian assuming one spatial degree of freedom. The developed models predict maximally entangled states of electrons controlled electrostatically by external driving fields and interacting via the Coulomb force.
Questioning teachers about their use of portable computers (1999)

This paper analyses case studies from the ‘Multimedia Portables for Teachers’ pilot project where two teachers in more than 500 English schools received portable computers to use at home and at school for one year to develop confidence and competence. In‐depth interviews with a representative sample of 60 of the teachers revealed a disparate range of uses that reflected teachers’ needs and interests, and often were imaginative and innovative. For nearly all the teachers the project was successful on a number of criteria: they gave time and commitment, they gained confidence, they increased their number of IT (information technology) skills, and certain IT activities became a natural and regular part of their work. Gains were evident regardless of the baseline from which they were starting. Issues discussed include the use of email and WWW, prior access to computers, use by the teacher's family, the value of portability, and the relationship with colleagues. Some practical recommendations are made for future schemes of this kind.
SiC and GaN Wide Bandgap Device Technology Overview (2007)

Wide bandgap (WBG) devices offer significant advantages for next generation military and commercial systems. SiC MESFETs currently achieve power densities of 4.0 W/mm with power added efficiencies in excess of 60% on a repeatable basis. They are commercially available in packaged or die formats and have been successfully designed into a number of systems. GaN is also extremely promising as a next generation wide bandgap device. Cree has demonstrated power densities higher than 25 watts per mm of gate periphery. With f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">tau</sub> 's > 40 GHz, GaN devices have the capability of satisfying system device requirements from UHF through millimeter-wave. Both technologies are now also offered through commercial MMIC foundry services using design rules and non-linear models provided for external designers. Significant progress has also been made in the development of 100-mm SiC substrates and WBG epitaxy (SiC and GaN) which is key for commercializing the technology and providing low costs. Micropipe densities as low as 2.5 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> have been demonstrated for 100-mm HPSI substrates and both SiC and GaN epitaxy with excellent intra-wafer sheet resistance uniformity have been demonstrated. With robust reliability for SiC MESFETs now established for several years, the latest results for GaN device reliability benchmarking are shown.
An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases the susceptibility of cancer patients to herpes viridae (2011)

Cyclin-dependent kinase (CDK) inhibitors have been considered as excellent drug candidates for cancer therapy owing to their potential capacity to restore cell cycle control. The first generation of CDK inhibitors showed modest clinical advantages that could be attributed to off-target effects preventing them from reaching therapeutic concentrations. A phase I dose-escalation study using the second generation multi-CDK inhibitor PHA-793887 was conducted on a total of 19 patients with advanced refractory malignancies in two sites in Europe: the University of Leeds and St. James's Institute of Oncology, Leeds, UK, and the Institut Gustave Roussy, Villeujf, France (IGR). Fifteen patients were treated at IGR. Six among these patients manifested the reactivation of herpes virus replication. In vitro experiments revealed that PHA-793887 severely impaired signaling by toll-like receptors (such as TLR3, TLR4 and TLR9) in dendritic cells (DC), thus suppressing the production of multiple cytokines (type 1 interferon, interleukin-6,-10, -12, and tumor necrosis factorα) by mature DC, as well as the DC-stimulated production of interferon-γ by natural killer cells. Pharmacological inhibition of glycogen synthase-3β (GSK-3β), one of the off-targets of PHA-793887, did not cause such immunological defects. Altogether, these data underscore a hitherto unsuspected immunosuppressive effect of PHA-793887.
A Novel Submodule Voltage Balancing Scheme for Modular Multilevel Cascade Converter—Double-Star Chopper-Cells (MMCC-DSCC) Based STATCOM (2019)

A novel capacitor voltage balancing scheme for modular multilevel cascade converter-double-star chopper-cells (MMCC-DSCC)-based STATCOM is proposed in this paper. Compared with the conventional software voltage balancing methods, the proposed scheme has three main advantages. First, only six voltage sensors are needed, and other voltage sensors have been removed. Then, the control framework can be simple without sort and select process, or some balancing control loops. Additional delay process caused by the sampling and control signals transmission is also mitigated. Finally, the faster capacitor balancing speed can be obtained. In addition, compared with some other hardware voltage balancing schemes, there are superior characteristics in terms of the reduced number of switches and only the popular power modules in the additional units are applied. For these additional modules, the parameters design guide of the proposed scheme has been discussed. Verified results from the 13-level simulated system and 9-level experimental platform for the MMCC-DSCC based STATCOM show the effectiveness of the proposed scheme. By the proposed scheme, both DC capacitor voltage balancing control and reactive power compensation are simultaneously realized for the MMCC-DSCC-based STATCOM even in balanced and unbalanced load.