gebhart/patrepeval huggingface dataset:
Effects of Hepatic Expression of the High-Density Lipoprotein Receptor SR-BI on Lipoprotein Metabolism and Female Fertility (2006)

The etiology of human female infertility is often uncertain. The sterility of high-density lipoprotein (HDL) receptor-negative (SR-BI(-/-)) female mice suggests a link between female infertility and abnormal lipoprotein metabolism. SR-BI(-/-) mice exhibit elevated plasma total cholesterol [with normal-sized and abnormally large HDL and high unesterified to total plasma cholesterol (UC:TC) ratio]. We explored the influence of hepatic SR-BI on female fertility by inducing hepatic SR-BI expression in SR-BI(-/-) animals by adenovirus transduction or stable transgenesis. For transgenes, we used both wild-type SR-BI and a double-point mutant, Q402R/Q418R (SR-BI-RR), which is unable to bind to and mediate lipid transfer from wild-type HDL normally, but retains virtually normal lipid transport activities with low-density lipoprotein. Essentially wild-type levels of hepatic SR-BI expression in SR-BI(-/-) mice restored to nearly normal the HDL size distribution and plasma UC:TC ratio, whereas approximately 7- to 40-fold overexpression dramatically lowered plasma TC and increased biliary cholesterol secretion. In contrast, SR-BI-RR overexpression had little effect on SR-BI(+/+) mice, but in SR-BI(-/-) mice, it substantially reduced levels of abnormally large HDL and normalized the UC:TC ratio. In all cases, hepatic transgenic expression restored female fertility. Overexpression in SR-BI(-/-) mice of lecithin:cholesterol acyl transferase, which esterifies plasma HDL cholesterol, did not normalize the UC:TC ratio, probably because the abnormal HDL was a poor substrate, and did not restore fertility. Thus, hepatic SR-BI-mediated lipoprotein metabolism influences murine female fertility, raising the possibility that dyslipidemia might contribute to human female infertility and that targeting lipoprotein metabolism might complement current assisted reproductive technologies.
Nutrition, inflammation and oxidative stress - CKD 5D (2012)

Introduction and Aims: Higher creatinine levels in dialysis patients are associated with higher muscle mass, insufficient dialysis adequacy or a decline in residual renal function (RRF). We aimed to understand association between changes in creatinine levels and patient outcomes in incident hemodialysis patients with no RRF. Methods: We studied all incident hemodialysis (HD) patients treated in RRI clinics who had their first in-center treatment between 1/2000 and 12/2010. Only patients who survived the first 12 months on HD were included. Patients' baseline serum creatinine was computed as an average over the first 3 months. Slope of serum creatinine was computed on a per patient basis using simple linear regression of available creatinine values between months 4 and 12 from the start of treatment. Patients were stratified based on (a) their baseline creatinine (group 1: < 5 mg/dL; group 2: 5 to 8 mg/dL; group 3: > 8 mg/dL) and (b) the average rate of change in creatinine computed by simple linear regression (declined: < -2 mg/dL/year; stable: -2 to 2 mg/dL/year; increased: > 2 mg/dL/year). Patients were then stratified into 9 groups of baseline creatinine levels and creatinine changes. Only patients with no RRF at the start of dialysis were included. Further, for patients whose creatinine increased or declined, only patients with a significant p-value for the slope were included. Patient survival was assessed in months 13 to 18 from the start of dialysis. Cox proportional hazards model adjusted for age, gender, race, ethnicity, diabetic status, access type, BMI, albumin, systolic blood pressure, body temperature, nPCR, eKt/V, interdialytic weight gain, urea distribution volume, and slope of interdialytic weight gain in months 4 to 12 were constructed to compute associations of creatinine as well as creatinine changes and survival. Results: We studied 2333 patients. In a Cox model that includes only the baseline creatinine levels and not its trend, patients with creatinine < 5 ml/dL had a borderline significant association with poorest survival (HR = 1.43, 95% CI: 0.99-2.06, p = 0.06) compared to reference group (creatinine 5 to 8 mg/dL); no difference between creatinine 5 to 8 mg/dL and > 8 mg/dL was observed. In a model that includes the creatinine trend but not the baseline values, an increase of creatinine in months 4 to 12 was borderline significantly associated with improved survival (HR = 0.67, 95% CI: 0.45-1.02, p = 0.06) compared to the reference group (stable creatinine); no difference between declining and stable levels was observed.
Cancer-Associated Fibroblasts Induce Matrix Metalloproteinase–Mediated Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cells (2012)

A growing body of evidence suggests that components of the tumor microenvironment, including cancer-associated fibroblasts (CAF), may modulate the treatment sensitivity of tumor cells. Here, we investigated the possible influence of CAFs on the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to cetuximab, an antagonistic epidermal growth factor receptor (EGFR) antibody. Cetuximab treatment caused a reduction in the proliferation rate of HNSCC cell lines, whereas the growth of HNSCC-derived CAF cultures was unaffected. When tumor cells were cocultured with CAFs in a transwell system, the cetuximab-induced growth inhibition was reduced, and a complete protection from growth inhibition was observed in one of the tumor cell lines investigated. Media that had been conditioned by CAFs offered protection from cetuximab treatment in a concentration-dependent manner, suggesting that the resistance to treatment was mediated by CAF-derived soluble factors. The coculture of HNSCC cell lines with CAFs resulted in an elevated expression of matrix metalloproteinase-1 (MMP-1) in both the tumor cells and CAFs. Moreover, the CAF-induced resistance was partly abolished by the presence of an MMP inhibitor. However, CAFs treated with siRNA targeting MMP-1 still protected tumor cells from cetuximab treatment, suggesting that several MMPs may cooperate to facilitate resistance or that the protective effect is mediated by another member of the MMP family. These results identify a novel CAF-dependent modulation of cetuximab sensitivity and suggest that inhibiting MMPs may improve the effects of EGFR-targeted therapy.
Identification of indirubin derivatives as anti-trypanosomal agents (2014)

Trypanosoma brucei has been identified as the parasite responsible for the sleeping sickness encountered in sub-Saharan Africa, resulting in severe damages in the central nervous system and various organs, and is life-threatening if not timely treated. The population at high and moderate risk of being infected rises to more than 20 million, whereas the lack of effective vaccines and the serious limitations of current chemotherapy, makes the discovery of new antiparasitics an urgent need. Indirubins represent a class of compounds offering great possibilities for the treatment of parasite infections like leishmaniasis, while their activity has been associated with the inhibition of parasitic kinases and specifically Leishmania donovani (Ld) GSK-3 s [1, 2]. In addition, the T. brucei l orthologue of GSK-3, TbGSK-3 s has been identified as a promising drug target as it is essential for parasite viability [3]. In this context, we proceeded to the screening of sixty-nine 5-, 6-, 7- and 5, 6- substituted indirubin derivatives in order to assess their antiparasitic potential against T. brucei bloodstream forms. Moreover, the inhibition of TbGSK-3 s was tested in combination with cytotoxicity on J774.1 murine macrophage cell line. Compound 1 showed a significant inhibitory activity towards trypanosomal GSK-3 while retaining low toxicity on macrophages, thus pointing to a new substitution pattern for indirubin derivatives to be further developed as antitrypanosomal agents.
Real-Time Determination of OBM Filtrate Contamination During Openhole Wireline Sampling (2001)

E&amp;P Exchange - SPE 70479
High-Power Tunable FDD Front-End Employing a Balanced CMOS N-Path Receiver and Evanescent-Mode Cavity Filters (2023)

A single-antenna, frequency-tunable FDD front-end supporting simultaneous transmit (TX) and receive (RX) operation with high power handling capabilities and low TX and RX losses is presented. The system comprises a balanced CMOS N-path receiver in series with tunable evanescent-mode filters, and leverages frequency-selective reflectivity and matching for quadrature signal construction and self-interference cancellation at corresponding ports of interest. A measured 65 nm CMOS receiver prototype with manufactured cavity filters demonstrated 38 dBm blocker tolerance (B1dB) around 1 GHz at 100 MHz TX−RX spacing with no RX EVM degradation, < 0.4 dB TX insertion loss, and 3.5−4.5 dB RX NF over 0.9−1.8 GHz tunable frequency range.
Biochemical characterization of Drosophila γ‐glutamyl carboxylase and its role in fly development (2006)

To investigate structure-function relationships in gamma-glutamyl carboxylases, the enzyme from Drosophila melanogaster was characterized. Four cysteine residues were shown to be important determinants for enzymatic activity. Native Drosophila substrates have not yet been identified, but propeptides of human prothrombin and factor IX are recognized by the Drosophila enzyme. The presence of the propeptide region increased apparent affinity by approximately 200-fold, and mutation of a hydrophobic residue of factor IX propeptide (F-16A) decreased carboxylation by 90%, as in the human enzyme. Substrate recognition appears to be highly conserved between the human and Drosophila gamma-glutamyl carboxylases. Inactivation of Drosophila gamma-glutamyl carboxylase by non-sense mutations or insertional mutagenesis by P-element insertion have no apparent effects on growth and fertility under laboratory conditions.
Carbogen breathing significantly enhances the penetration of red light in murine tumoursin vivo (2004)

We report results of experiments that evaluated the influence of oxygenation on the penetration of red light in tissue, with particular emphasis on 630 and 650 nm laser wavelengths commonly used in photodynamic therapy (PDT) of solid tumours. Direct measurements in tissue-simulating phantoms comprised of intact human erythrocytes suspended in a scattering emulsion demonstrated significant enhancements in fluence rate at depths of 0.5-2 cm from the irradiated surface when the cells were fully oxygenated versus fully deoxygenated. The 630 and 650 nm fluence rates at depth in the homogeneous phantoms continued to increase when examined over a continuous range of oxygen partial pressures from 0 to 160 Torr. When considered as a function of haemoglobin oxygen saturation, the largest increases in fluence rate were observed as the saturation increased beyond 70%. Dramatic increases in optical fluence rate were measured at the base of 1-cm-thick subcutaneous EMT6 mammary carcinomas in vivo when the tumour-bearing mouse was subjected to carbogen through a nose cone. These results indicate that improved tumour oxygenation is important in PDT not only for the maintenance of the oxygen-dependent photochemistry but, through the effects reported here, may also enable more efficient treatment of thicker lesions.
Ballistic Electron Emission Microscopy Study of p-Type 4H-SiC (2004)

Ballistic electron emission microscopy (BEEM) measurements have been performed on Pt/p-type 4H-SiC Schottky contacts to probe the metal/semiconductor (M/S) interface and the valence band structure of the semiconductor. The Schottky barrier height (SBH) is found to be 1.45 eV, compared with 1.55 eV for Pt on n-type 4H-SiC measured under identical conditions with BEEM. A second threshold is also observed in the BEEM spectrum on Pt/p-type 4H-SiC contacts, which is possibly related to a lower-energy valence band. The sum of the measured p-type and n-type SBH's is slightly less than the 4H-SiC bandgap, which suggests the existence of an interfacial oxide layer and rather weak Fermi level pinning, consistent with prior measurements of SBH vs. metal work function.
Test structure design for model-based electromigration (2018)

As VLSI technology features are pushed to the limit with every generation and with the introduction of new materials and increased current densities to satisfy performance demands, failure risk due to Electromigraton (EM) is ever-increasing. In this paper, we present experimental results using a novel set of test structures to validate a new model-based EM risk assessment approach. In this method, EM risk can be assessed for any interconnect geometry through an exact solution of the fundamental stress equations. This approach eliminates the need for complex look-up tables for different geometries and can be implemented in CAD tools very easily as we demonstrate on real design examples.
Haswell: The Fourth-Generation Intel Core Processor (2014)

Haswell, Intel's fourth-generation core processor architecture, delivers a range of client parts, a converged core for the client and server, and technologies used across many products. It uses an optimized version of Intel 22-nm process technology. Haswell provides enhancements in power-performance efficiency, power management, form factor and cost, core and uncore microarchitecture, and the core's instruction set.
Analysis and modeling of a DC hybrid power system testbed for power management strategy development (2009)

This paper presents the analysis and modeling results of a DC hybrid power system testbed. Hybrid power systems combine multiple complementary power generation and energy storage technologies to achieve a level of system performance that is not possible for those involving a single technology. Complicated dynamic interactions of the hybrid power system elements, coupled with stringent safety, power quality and efficiency requirements, impose challenging coordinating control and dynamic optimization problems. To facilitate optimization and power management strategy development for system level design, an experimental testbed was developed at the University of Michigan by the authors. A large signal dynamic model of the DC hybrid power system testbed is developed and validated by experimental results. This model will enable a model based design approach for control development and system integration.
Optimization of multiplexed CRISPR/Cas9 system for highly efficient genome editing in Setaria viridis (2020)

In recent years, Setaria viridis has been developed as a model plant to better understand the C4 photosynthetic pathway in major crops. With the increasing availability of genomic resources for S. viridis research, highly efficient genome editing technologies are needed to create genetic variation resources for functional genomics. Here, we developed a protoplast assay to rapidly optimize the multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas9) system in S. viridis. Targeted mutagenesis efficiency was further improved by an average of 1.4-fold with the exonuclease, Trex2. Distinctive mutation profiles were found in the Cas9_Trex2 samples, with 94% of deletions larger than 10 bp, and essentially no insertions at all tested target sites. Further analyses indicated that 52.2% of deletions induced by Cas9_Trex2, as opposed to 3.5% by Cas9 alone, were repaired through microhomology-mediated end joining (MMEJ) rather than the canonical non-homologous end joining DNA repair pathway. Combined with a robust Agrobacterium-mediated transformation method with more than 90% efficiency, the multiplex CRISPR/Cas9_Trex2 system was demonstrated to induce targeted mutations in two tightly linked genes, svDrm1a and svDrm1b, at a frequency ranging from 73% to 100% in T0 plants. These mutations were transmitted to at least 60% of the transgene-free T1 plants, with 33% of them containing bi-allelic or homozygous mutations in both genes. This highly efficient multiplex CRISPR/Cas9_Trex2 system makes it possible to create a large mutant resource for S. viridis in a rapid and high throughput manner, and has the potential to be widely applicable in achieving more predictable and deletion-only MMEJ-mediated mutations in many plant species.
Functionalized random copolymers from versatile one-pot click chemistry (2009)

International audience
Pulmonary microvascular endothelial cell contractility on silicone rubber substrate (1989)

Endothelial cell (EC) motility may contribute to the regulation of microvascular perfusion and/or paracellular permeability. The experiments reported herein demonstrate that bovine pulmonary microvessel EC can reversibly deform a silicone substrate in response to agents known to contract and relax smooth muscle cells. Contracting pulmonary microvessel EC exerted a tension that created wrinkles in the underlying deformable substrate. Relaxation and loss of tension were revealed by the disappearance of these wrinkles without loss of cell adhesion to the substratum. Angiotensin II (Ang II) and bradykinin stimulated pulmonary microvessel EC to contract within 3 to 8 min in a Ca2+-dependent fashion. The peak of contraction at 10 to 20 min was followed by relaxation. Forskolin and sodium nitroprusside (SNP) initiated relaxation of the microvessel EC within 3 to 10 min respectively. Relaxed EC contracted following the addition of Ang II, also within 3 min. Dibutyryl cAMP, dibutyryl cGMP, and the photoactivated internalized "caged" cAMP and cGMP promoted EC relaxation in a manner similar to forskolin and SNP. Increases in the intracellular concentration of inositol triphosphate (IP3) with the photoactivated IP3 complex promoted EC contraction in 2 min with a peak at 7 min. The contraction was followed by relaxation, which occurred at 20-25 min. Neither bovine pulmonary artery nor retinal microvessel EC, used as controls, contracted under these experimental conditions. One could speculate that this unique contractile property of pulmonary microvessel EC as observed in vitro may play a regulatory role in vivo, in local perfusion and/or in intercellular gap regulation.
Highly Sensitive and Durable Organic Photodiodes Based on Long-Term Storable NiOx Nanoparticles (2022)

Organic optoelectronic devices that can be fabricated at low cost have attracted considerable attention because they can absorb light over a wide frequency range and have high conversion efficiency, as well as being lightweight and flexible. Moreover, their performance can be significantly affected by the choice of the charge-selective interlayer material. Nonstoichiometric nickel oxide (NiO<sub><i>x</i></sub>) is an excellent material for the hole-transporting layer (HTL) of organic optoelectronic devices because of the good alignment of its valence band position with the highest occupied molecular orbital level of many p-type polymers. Herein, we report a simple low-temperature process for the synthesis of NiO<sub><i>x</i></sub> nanoparticles (NPs) that can be well dispersed in solution for long-term storage and easily used to form thin NiO<sub><i>x</i></sub> NP layers. NiO<sub><i>x</i></sub> NP-based organic photodiode (OPD) devices demonstrated high specific detectivity (<i>D</i>*) values of 10<sup>12</sup>-10<sup>13</sup> jones under various light intensities and negative biases. The <i>D</i>* value of the NiO<sub><i>x</i></sub> NP-based OPD device was 4 times higher than that of a conventional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-based device, an enhancement that originated mainly from the 16 times decreased leakage current. The NiO<sub><i>x</i></sub> NP-based OPD device demonstrated better reliability over a wide range of light intensities and operational biases in comparison to a device with a conventional sol-gel-processed NiO<sub><i>x</i></sub> film. More importantly, the NiO<sub><i>x</i></sub> NP-based OPD showed long-term device stability superior to those of the PEDOT:PSS and sol-gel-processed NiO<sub><i>x</i></sub>-based devices. We highlight that our low-temperature solution-processable NiO<sub><i>x</i></sub> NP-based HTL could become a crucial component in the fabrication of stable high-performance OPDs.
Dynamic speckle illumination wide-field reflection phase microscopy (2014)

We demonstrate a quantitative reflection-phase microscope based on time-varying speckle-field illumination. Due to the short spatial coherence length of the speckle field, the proposed imaging system features superior lateral resolution, 520 nm, as well as high-depth selectivity, 1.03 Âµm. Off-axis interferometric detection enables wide-field and single-shot imaging appropriate for high-speed measurements. In addition, the measured phase sensitivity of this method, which is the smallest measurable axial motion, is more than 40 times higher than that available using a transmission system. We demonstrate the utility of our method by successfully distinguishing the motion of the top surface from that of the bottom in red blood cells. The proposed method will be useful for studying membrane dynamics in complex eukaryotic cells.
Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments (2021)

The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid-based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood-brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support. The outcomes of these efforts will also benefit patients with "common" diseases by improving diagnostics, developing the widely applicable NBT technology platforms, and promoting deeper understanding of biological mechanisms that underlie disease pathogenesis. Furthermore, with successes in genetic research, a growing proportion of "common" disease cases can now be attributed to mutations in particular genes, essentially extending the orphan disease field. Together, the developments occurring in orphan diseases are building the foundation for the future of personalized medicine. In this review, we will focus on recent achievements in developing therapies for orphan neurological disorders.
Welcome to the First Anniversary Issue of ACS Sensors (2017)

TEST 02 - Elsevier's Scopus, the largest abstract and citation database of peer-reviewed literature. Search and access research from the science, technology, medicine, social sciences and arts and humanities fields.
9,000-km transmission of 32 × 42.7 Gb/s dense-WDM signals using 195-µm2-Aeff fiber and inverse double-hybrid span configuration (2002)

We demonstrate the first transpacific distance transmission of 40-Gb/s-based dense-WDM signals. This result was obtained by using an inverse double-hybrid span configuration that was optimized for a newly developed I 95-µm2-Aeff fiber and distnbuted all-Raman amplification.