gebhart/patrepeval huggingface dataset:
Novel Binding Mode of a Potent and Selective Tankyrase Inhibitor (2012)

Tankyrases (TNKS1 and TNKS2) are key regulators of cellular processes such as telomere pathway and Wnt signaling. IWRs (inhibitors of Wnt response) have recently been identified as potent and selective inhibitors of tankyrases. However, it is not clear how these IWRs interact with tankyrases. Here we report the crystal structure of the catalytic domain of human TNKS1 in complex with IWR2, which reveals a novel binding site for tankyrase inhibitors. The TNKS1/IWR2 complex provides a molecular basis for their strong and specific interactions and suggests clues for further development of tankyrase inhibitors.
Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock (2007)

SaPIs are a family of homologous phage-related pathogenicity islands in staphylococci that carry superantigen and other virulence genes, and are responsible for a wide variety of superantigen-related diseases. SaPIs are induced to excise and replicate by particular staphylococcal phages and are encapsidated in infectious, small-headed, phage-like particles, which are transmitted at very high frequency among staphylococcal strains and species. SaPI2 is a prototypical member of this family that was identified in a typical menstrual toxic shock syndrome (TSS) strain of Staphylococcus aureus, the so-called Harrisburg strain, and found to be mobilizable by typing phage 80. Most menstrual TSS strains belong to a highly uniform agr group III clone of electrophoretic type (ET) 41, and this study was undertaken to determine whether such strains typically carry SaPI2, and whether it has spread beyond the ET41 clone. We report here the complete sequence of SaPI2, describe its relation to other known SaPIs, and show that it, or a very similar element, is carried by most ET41 strains but that it has disseminated to other strains that have also been implicated in TSS. We show additionally, that SaPIs are widespread among the staphylococci and that most TSS strains carry two or more, including SaPI2.
Gonadotroph Adenomas in Men Produce Biologically Active Follicle-Stimulating Hormone* (1990)

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men. In addition, three adenoma patients received TRH (400 micrograms, iv). The mean basal serum FSH level (international units per L), as measured by both bio- and immunoassays, and the FSH B/I ratios were significantly higher (P less than 0.02, by Kolmogorov-Smirnov test) in the adenoma patients than in normal men (mean +/- SEM; adenoma patients: bioactivity, 68.8 +/- 10.4; immunoreactivity, 34.8 +/- 13.7; B/I ratio, 3.4 +/- 0.6; normal men: bioactivity, 5.8 +/- 1.2; immunoreactivity, 6.4 +/- 0.8; B/I ratio, 0.90 +/- 0.1). Both bio- and immunoactive FSH rose after TRH injection, resulting in maintenance of the B/I (mean +/- SEM; pre-TRH: bio-FSH, 63.7 +/- 22.4; immuno-FSH, 28.0 +/- 14.1; B/I ratio, 2.8 +/- 1.2; post-TRH: bio-FSH, 125.6 +/- 42.7; immuno-FSH, 45.8 +/- 21.8; B/I ratio, 3.5 +/- 1.6). When gonadotroph adenoma cells from three separate patients were cultured and their conditioned media (n = 3) studied, relatively large amounts of both bio- and immuno-FSH were detected. Furthermore, the major isoelectric profile of bio-FSH (pH 4.9-3.0) in the conditioned medium from two such adenomas was shown by chromatofocusing to be comparable to that of purified human pituitary FSH (pH 5.2-3.6). We conclude that gonadotroph adenomas in men secrete FSH that is biologically active, both basally and in response to TRH.
Optical processing for self-cohering of phased-array imaging signals (1992)

We describe three real-time optical processing systems, for imaging radar, that form the array phase function and produce the radar image from the incoming signals. The first is an implementation of the Steinberg algorithm where we have modified the data format by frequency multiplexing the range information to allow for the data from all range bins to be present simultaneously. The second implementation uses this same input format, but provides hysteresis on the point scatterer used to calibrate the array. This allows for moving radar arrays where the point used to calibrate the array may be time varying. Finally we describe a self oscillating phase conjugate resonator, with a coherent optical to RF converter inside the cavity. This is a hybrid optical-microwave oscillator that adapts to the incoming signal.
Exosome-dependent immune surveillance at the metastatic niche requires BAG6 and CBP/p300-dependent acetylation of p53 (2019)

Extracellular vesicles released by tumor cells contribute to the reprogramming of the tumor microenvironment and interfere with hallmarks of cancer including metastasis. Notably, melanoma cell-derived EVs are able to establish a pre-metastatic niche in distant organs, or on the contrary, exert anti-tumor activity. However, molecular insights into how vesicles are selectively packaged with cargo defining their specific functions remain elusive. <b>Methods</b>: Here, we investigated the role of the chaperone Bcl2-associated anthogene 6 (BAG6, synonym Bat3) for the formation of pro- and anti-tumor EVs. EVs collected from wildtype cells and BAG6-deficient cells were characterized by mass spectrometry and RNAseq. Their tumorigenic potential was analyzed using the B-16V transplantation mouse melanoma model. <b>Results</b>: We demonstrate that EVs from B-16V cells inhibit lung metastasis associated with the mobilization of Ly6C<sup>low</sup> patrolling monocytes. The formation of these anti-tumor-EVs was dependent on acetylation of p53 by the BAG6/CBP/p300-acetylase complex, followed by recruitment of components of the endosomal sorting complexes required for transport (ESCRT) via a P(S/T)AP double motif of BAG6. Genetic ablation of BAG6 and disruption of this pathway led to the release of a distinct EV subtype, which failed to suppress metastasis but recruited tumor-promoting neutrophils to the pre-metastatic niche. <b>Conclusion</b>: We conclude that the BAG6/CBP/p300-p53 axis is a key pathway directing EV cargo loading and thus a potential novel microenvironmental therapeutic target.
Biological roles of ionic zinc. (1983)

We tentatively conclude from our work that intracellular calcium acts as a second messenger to affect membrane function through activation of calmodulin. This activation, if too great, leads to pathological erythrocyte adherence and aggregation phenomena. We have shown that calmodulin inhibitors can prevent some of these calcium-induced abnormalities. Since some of this work involves a very specific anticalmodulin antibody, it appears very likely that calmodulin is involved in producing membrane effects. Zinc appears to act upon the membrane in part, at least, through the inhibition of calmodulin action. Our work leads us to believe that zinc regulates copper absorption from the gastrointestinal tract in a somewhat complex manner. That is, direct zinc-copper antagonism within the lumen of the gastrointestinal tract is not adequate to explain the effects of zinc on inhibiting copper absorption in man. It appears from our work that tissues must become loaded with zinc before an effect on copper absorption is observed. This produces a lag effect during which zinc administration does not produce a negative copper balance. However, after this lag effect, zinc has produced a negative to neutral copper balance in 5 of 5 Wilson's disease patients studied. At this time, therefore, we believe that zinc therapy can be offered as an alternative to penicillamine therapy in previously decoppered patients or patients who are not yet symptomatic. However, we recommend that this therapy only be used at this time in accordance with the one zinc therapy regimen we have tested.
The Challenge of Communicating Computational Research (2013)

Computational approaches to scholarship have revolutionized how research is done but have at the same time complicated the process of disseminating the results of that research. Conclusions may be produced using mathematical models or custom software that are not easily accessible to, or reproducible by, those outside the research team. And in some fields, a lack of understanding of computational approaches may lead to skepticism about their use. The panel considers urgent questions faced by researchers across the range of academic disciplines. How can scientists and social scientists address the lack of access to the software and code used to produce many research results, which has led to a crisis of verifiability and concern about the accuracy of the scientific record? How can digital humanists approach discussions of computational methods, which may not fit into traditional forms of scholarship and can be viewed with suspicion in disciplines that prize the art of scholarly analysis? Computational researchers are examining communication practices, policies, and tools that promise to more effectively convey their research process and the results it produces. The panelists are: Neil Chue Hong, Director of the Software Sustainability Institute; Matthew L. Jockers, Assistant Professor of English at the University of Nebraska-Lincoln; and Daniel P. W. Ellis, Associate Professor of Electrical Engineering at Columbia University.
A zero-overhead self-timed 160-ns 54-b CMOS divider (1991)

The authors describe the design of a custom integrated circuit for the arithmetic operation of division. The chip uses self-timing to avoid the need for high-speed clocks and directly concatenates precharged function blocks without latches. Internal stages form a ring that cycles without any external signaling. The self-timed control introduces no serial overhead, making the total chip latency equal just the combinational logic delays of the data elements. The ring's data path uses embedded completion encoding and generates the mantissa of a 54-b (floating-point IEEE double-precision) result. Fabricated in 1.2- mu m CMOS, the ring occupies 7 mm/sup 2/ and generates a quotient and done indication in 45 to 160 ns, depending on the particular data operands.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A novel compact dual-mode bandpass filter using fractal shaped resonators (2006)

We present a miniaturization technique for square dual-mode resonators. By using the Minkowski fractal iteration it is possible to obtain compact resonators. Furthermore the second harmonic is highly attenuated, thus enhancing the rejection in the upper band. A 4 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> order filter using two dual-mode fractal resonators has been fabricated to illustrate these results. We use the suspended substrate technology to design these resonators but the results can be extended to other technologies.
A MEMS Rate Integrating Gyroscope Using Virtually Rotated Control and Demonstration of the Earth's Rotation Detection (2022)

This paper reports on a direct angle sensing rate integrating gyroscope (RIG) for high accuracy inertial navigation and automatic driving, which is characterized by high accuracy angle detection without the effect of integration error present in conventional rate gyros. On the other hand, asymmetry of frequency and damping due to manufacturing error causes two problems: detection limit of low speed rotation and cyclic angle error. In this paper, we present a method of low-speed rotation detection using "virtual rotation control," in which a constant rotation is applied by electrostatic force, as well as a correction method by modeling the angle error, and report the world's first detection of the earth's rotation using a 5 cm square module.
Self-propelled retrograde tethered capsule endomicroscopy (R-TCE) in the colon (2023)

We have developed a new self-propelled OCT imaging technology called retrograde Tethered Capsule Endomicroscopy (R-TCE) for colonic disease screening. We successfully demonstrated that the R-TCE device can be advanced over 1 meter in 5 swine colons in vivo. R-TCE with balloon pullback imaging enabled full circumferential OCT visualization of 95.94 % ± 0.13% of the colon wall. 3D reconstructed colon OCT images and 3D rendered flythroughs showed that R-TCE is feasible for OCT microscopic imaging of the entire colon in vivo. When translated to humans, this R-TCE technology may provide a less invasive and more efficient alternative to colonoscopy.
Effects of N doping in Ru-Ta alloy barrier on film property and reliability for Cu interconnects (2009)

RuTa(N) film has been prepared by doping N in Ru-Ta alloy and investigated its use as a barrier layer against Cu diffusion in Cu interconnects. It was found that RuTa(N) has a poor barrier property against Cu in the BEOL process, since N in Ru-Ta alloy is desorbed and RuTa(N) is recrystallized by heat treatment. It was also shown that RuTa(N) has inferior reliability due to its poor wettability with Cu compared to RuTa. On the other hand, RuTa has both good barrier property and superior reliability performance. It is possible to apply RuTa single film as a barrier layer for Cu interconnects.
Nonlinear pulse compression of mid-infrared pulses from a picosecond Ho:YLF laser in Kagome fibers (2016)

International audience
Generation of Porous Structures Using Fused Deposition (1998)

The Fused Deposition Modeling process uses hardware and software machine-level language that are very similar to that of a pen-plotter. Consequently, the·use of patterns with poly-lines as basic geometric features, instead of the current method based on filled polygons (monolithic models), can increase its efficiency. In the current study, various toolpath planning methods have been developed to fabricate porous structures. Computational domain decomposition methods can be applied to the physical or to slice-level domains to generate structured and unstructured grids. Also, textures can be created using periodic tiling of the layer with unit cells (squares, honeycombs, etc). Methods 'based on curves include fractal space filling curves and.change of effective road width Within a layer or within a continuous curve. Individual phases can also be placed in binary compositions. In present investigation, a custom software has been developed and implemented to generate build files (SML) and slice files (SSL) for the above-mentioned structures, demonstrating the efficient control ofthe size, shape, and distribution ofporosity.
Assessment of Target Engagement in a First‐in‐Human Trial with Sinbaglustat, an Iminosugar to Treat Lysosomal Storage Disorders (2020)

In this first-in-human study, the tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of sinbaglustat, a dual inhibitor of glucosylceramide synthase (GCS) and non-lysosomal glucosyl ceramidase (GBA2), were investigated in healthy subjects. The single-ascending dose (SAD) and multiple-ascending dose (MAD) studies were randomized, double-blind, and placebo-controlled. Single doses from 10 to 2,000 mg in men and multiple doses from 30 to 1,000 mg twice daily for 7 days in male and female subjects were investigated. Tolerability, PK, and PD data were collected up to 3 days after (last) treatment administration and analyzed descriptively. Sinbaglustat was well-tolerated in the SAD and MAD studies, however, at the highest dose of the MAD, three of the four female subjects presented a similar pattern of general symptoms. In all cohorts, sinbaglustat was rapidly absorbed. Thereafter, plasma concentrations decreased biphasically. In the MAD study, steady-state conditions were reached on Day 2 without accumulation. During sinbaglustat treatment, plasma concentrations of glucosylceramide (GlcCer), lactosylceramide, and globotriaosylceramide decreased in a dose-dependent manner, reflecting GCS inhibition. The more complex the glycosphingolipid, the more time was required to elicit PD changes. After treatment stop, GlcCer levels returned to baseline and increased above baseline at lowest doses, probably due to the higher potency of sinbaglustat on GBA2 compared to GCS. Overall, sinbaglustat was welltolerated up to the highest tested doses. The PK profile is compatible with b.i.d. dosing. Sinbaglustat demonstrated target engagement in the periphery for GCS and GBA2.
A cortical network underpinning the perceptual priority for rising intensity and auditory ‘‘looming.’’ (2002)

Relative motion between a sound source and a listener creates a change in acoustic intensity that can be used to anticipate the source’s approach. Humans have been shown to overestimate the intensity change of rising compared to falling intensity sounds and underestimate the time-to-contact of approaching sound sources. From an evolutionary perspective, this perceptual priority for looming sounds may represent an adaptive advantage that provides an increased margin of safety for responding to approaching auditory objects. Here, using functional magnetic resonance imaging, we show that the prioritization of rising contrasted with falling intensity sine-tones is grounded in a specific neural network. This network is predominantly composed of the superior temporal sulci, the middle temporal gyri, the right temporo-parietal junction, the motor and premotor cortices mainly on the right hemisphere, the left frontal operculum, and the left superior posterior cerebellar cortex. These regions are critical for the allocation of attention, the analysis of space, object recognition, and neurobehavioral preparation for action. Our results identify a widespread neural network underpinning the perceptual priority for looming sounds that can be used in translating sensory information into preparedness for adverse events and appropriate action. [Work supported by the Swiss and the American NSFs.]
Highly Miniaturized and Integrated Biosensor for Analysis of Whole Blood Samples (1999)

standard particle provides a measure of analyte concentration that is virtually independent of interfering factors. This ratio is therefore referred to a calibration curve to obtain the analyte concentration.
Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with 18F-Labeled Derivatives in Rats (2020)

The 3,4-dichloro-<i>N</i>-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for <sup>18</sup>F-positron emission tomography (<sup>18</sup>F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacological parameters of 15 candidates were investigated. Two promising compounds <b>3b</b> and <b>3e</b> with μ-OR (MOR) selective agonist activity in the moderate range (EC<sub>50</sub> = 1-100 nM) were subjected to <sup>18</sup>F-fluorination, autoradiography, and small-animal PET imaging. Radioligands [<sup>18</sup>F]<b>3b</b> and [<sup>18</sup>F]<b>3e</b> were obtained in activity yields of 21 ± 5 and 23 ± 4% and molar activities of 25-40 and 200-300 GBq/μmol, respectively. Displaceable binding matching MOR distribution in the brain was confirmed by imaging. Radioligands showed a rapid pharmacokinetic profile; however, metabolite-corrected, blood-based modeling was required for data analysis. Observed BP<sub>ND</sub> was low, although treatment with naloxone leads to a marked decrease in specific binding, confirming the discovery of a new template for <sup>18</sup>F-labeled OR-agonist PET ligands.
Anti-transferrin receptor antibody linked to Pseudomonas exotoxin as a model immunotoxin in human ovarian carcinoma cell lines. (1985)

The present in vitro study was performed to evaluate the potential usefulness of immunotoxins in treating human ovarian carcinomas. A monoclonal antibody against the human transferrin receptor was covalently linked to Pseudomonas exotoxin. The activity of this immunotoxin (anti-TFR-PE) was studied in five ovarian carcinoma cell lines, a breast carcinoma cell line (MCF-7), and in KB cells. The ovarian carcinoma cell lines included one previously established cell line (A1847) and four recent isolates obtained from the malignant ascites of patients with metastatic ovarian carcinoma (OVCAR cell lines). While all cell lines showed inhibition of protein synthesis by anti-TFR-PE, there were quantitative differences when the level of protein synthesis was assayed after a 12-hr incubation with the immunotoxin. These differences resulted from different kinetics of anti-TFR-PE activity in the various cell lines. Higher levels of cellular binding and internalization of anti-TFR were shown to contribute to increased toxicity of anti-TFR-PE. Verapamil increased the rate of protein synthesis inhibition and thus enhanced the toxicity of anti-TFR-PE in the OVCAR cell lines.
Humanitarian Mission in Pediatric Cardiothoracic Surgery: A Recipient's Perspective (2019)

Introduction : Paediatric Cardiac Surgical Mission programmes are deemed as common practice, especially in developing nations funded by international nongovernmental organizations (NGOs). This article presents and discusses the results and strategies implemented by this partnership, aiming at achieving the autonomy of the local centre by this collaboration. Materials and Methods : A retrospective review was conducted on patients with congenital heart disease who underwent surgical intervention from the beginning of NGOs collaboration (September 2015) until November 2018 in an existing cardiac centre. In between those visits, any congenital heart disease patient with Risk Adjustment Congenital Heart Surgery (RACHS)-1 Category 1-3 would be discussed in a local multi-disciplinary meeting with regards to the feasibility of the surgery being performed by the local members. Results: A total of 60 operations have been performed during the trips. Throughout the visit, 46% (28) of the operations were performed by the local surgeon, with or without assistance from the visiting surgeon. Between September 2015 until November 2018, 27 cases were also performed by local team independently. For the 27 cases performed by local team independently, the median age of patient was 42 days (ranging from 14 days to 20 years old), with median body weight of 3.2kg (ranging from 2.8-64kg). Conclusion : Humanitarian paediatric cardiac surgical missions are safe to be done for the population in need. In order to achieve autonomy, continuous efforts by both teams are crucial as the cooperation by the two parties ensures that the objectives are achieved.
X-ray Magnetic Circular Dichroism of Pseudomonas aeruginosa Nickel(II) Azurin (2004)

We show that X-ray magnetic circular dichroism (XMCD) can be employed to probe the oxidation states and other electronic structural features of nickel active sites in proteins. As a calibration standard, we have measured XMCD and X-ray absorption (XAS) spectra for the nickel(II) derivative of Pseudomonas aeruginosa azurin (NiAz). Our analysis of these spectra confirms that the electronic ground state of NiAz is high-spin (S = 1); we also find that the L(3)-centroid energy is 853.1(1) eV, the branching ratio is 0.722(4), and the magnetic moment is 1.9(4) mu(B). Density functional theory (DFT) calculations on model NiAz structures establish that orbitals 3d(x2-y2) and 3d(z2) are the two valence holes in the high-spin Ni(II) ground state, and in accord with the experimentally determined orbital magnetic moment, the DFT results also demonstrate that both holes are highly delocalized, with 3d(x2-y2) having much greater ligand character.