gebhart/patrepeval huggingface dataset:
1078 Conditionally activatable interferon-alpha 2b improves tolerability and exhibits preferential activity in tumors (2022)

<h3>Background</h3> Despite its potential, the toxicity of interferon alpha has limited its clinical use. CytomX proprietary Probody® Therapeutics (Pb-Tx) technology allowed us to create a conditionally active IFN-a2b (Pb-IFN-a2b) with minimal activity in its prodrug form. The prodrug is activated in the tumor microenvironment (TME), leading to preferential activity in the TME but not in healthy tissues. Pb-IFN-a2b demonstrated a substantially enhanced tolerability profile compared to standard IFN therapy without compromising its antitumor effects. <h3>Methods</h3> The Pb-Tx platform technology attenuates activity of a molecule by blocking its active regions through affinity or steric interference. Such blockade, termed masking, is reversed upon proteolytic cleavage of a linker between the molecule and the mask by tumor associated proteases. <h3>Results</h3> Pb-IFN-a2b demonstrated considerable reduction (1000-fold or more) of interferon signaling in vitro and significantly reduced immune cell activation. Exposure to viable tumor tissues or tumor-associated proteases in vitro fully restored its bioactivity, including the ability of Pb-IFN to stimulate tumor-infiltrating immune cells. Antitumor activity of the Pb-IFN-a2b in xenograft studies is equal to or greater than Peg-IFN-α2b. In syngeneic mouse tumor models, Pb-IFN demonstrated significant antitumor activity that was further enhanced by PD-(L)1 blockade. Activation of lymphocytes by the molecule was observed in tumors but not in secondary lymphoid organs. Toxicology studies performed in hamsters demonstrated enhanced tolerability of the molecule compared to its unmasked control. In addition, Pb-IFN-a2b suppressed growth of hamster melanoma tumor model RPMI1846 at dose levels that were above the tolerated dose of the unmasked control. Biomarkers of IFN signaling were greatly attenuated in non-human primates compared to the unmasked control. In cynomolgus monkey, Pb-IFN-a2b demonstrated linear pharmacokinetics, extended half-life, and was well tolerated at weekly doses up to 60 mg/kg. <h3>Conclusions</h3> Pb-IFN-a2b shows improved tolerability and antitumor activity in preclinical studies compared to traditional IFN treatment. These data support Probody cytokine therapeutics as a promising addition to current immunotherapy regimens, potentially expanding their benefits to patients with typically unresponsive tumors. <h3>Ethics Approval</h3> All animal experiments were reviewed and approved by CytomX’s Institutional Animal Care and Use Committee (IACUC Protocol AP303).
Synthesis and preliminary characterization of radioiodinated benzofuran‐3‐yl‐(indol‐3‐yl)maleimide derivatives as potential SPECT imaging probes for the detection of glycogen synthase kinase‐3β (GSK‐3β) in the brain (2016)

We report on the synthesis and preliminary characterization of two radioiodinated benzofuran-3-yl-(indol-3-yl)maleimides, 3-(benzofuran-3-yl)-4-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione ([(125) I]5), and 3-(5-[(125) I]iodo-1-methyl-1H-indol-3-yl)-4-(6-methoxybenzofuran-3-yl)-1H-pyrrole-2,5-dione ([(125) I]6), as the first potential SPECT imaging probes targeting glycogen synthase kinase-3β (GSK-3β). In this study, we used (125) I as a surrogate of (123) I because of its ease of use. The radioiodinated ligands were prepared from the corresponding tributyltin precursors through an iododestannylation reaction using hydrogen peroxide as an oxidant with a radiochemical yield of 10-30%. In vitro binding experiments suggested that both compounds show high affinity for GSK-3β at a level similar to a known GSK-3β inhibitor. Biodistribution studies with normal mice revealed that the radioiodinated compounds display sufficient uptake into (1.8%ID/g at 10 min postinjection) and clearance from the brain (1.0%ID/g at 60 min postinjection). These preliminary results suggest that the further optimization of radioiodinated benzofuran-3-yl-(indol-3-yl)maleimide derivatives may facilitate the development of clinically useful SPECT imaging probes for the in vivo detection of GSK-3β.
Design and Optimization of a Mechanism for Out of Plane Insect Wing Like Motion With Twist (2004)

A mechanism is presented that can generate insect wing like motion. This motion includes both flapping out of the stroke plane in addition to twist of the wing. The mechanism has a single degree-of-freedom and employs a five bar mechanism in addition to an auxiliary four bar mechanism. The parameters in the mechanism were optimized to generate a prescribed motion of the wing taken from a hawk moth kinematic flight data. A scaled model of the mechanism was fabricated to verify practical feasibility of the design. In future we will miniaturize this mechanism on our flying bird prototypes.
A New Triggering Receptor Expressed on Myeloid Cells (TREM) Family Member, TLT-6, is Involved in Activation and Proliferation of Macrophages (2015)

The triggering receptor expressed on myeloid cells (TREM) family, which is abundantly expressed in myeloid lineage cells, plays a pivotal role in innate and adaptive immune response. In this study, we aimed to identify a novel receptor expressed on hematopoietic stem cells (HSCs) by using in silico bioinformatics and to characterize the identified receptor. We thus found the TREM-like transcript (TLT)-6, a new member of TREM family. TLT-6 has a single immunoglobulin domain in the extracellular region and a long cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motif-like domains. TLT-6 transcript was expressed in HSCs, monocytes and macrophages. TLT-6 protein was up-regulated on the surface of bone marrow-derived and peritoneal macrophages by lipopolysaccharide stimulation. TLT-6 exerted anti-proliferative effects in macrophages. Our results demonstrate that TLT-6 may regulate the activation and proliferation of macrophages.
A Biomechanical Definition of Spinal Segmental Instability Taking Personal and Disc Level Differences Into Account (1993)

The biomechanical definition of spinal segmental instability has not been clarified sufficiently, because of the great personal and level differences in intervertebral disc deformation. This article proposes a new method of judging spinal segmental instability regardless of these differences, using lateral functional radiographs. The linear relationship between the disc geometry and the disc deformation was confirmed in the normal intervertebral discs. The degree of spinal segmental instability could be evaluated statistically by calculating a regression residual from the regression line of the normal discs. Strain distributions of an intervertebral disc in the sagittal plane also were investigated to make sure of the differences in the deformation behaviors between normal spines and unstable lumbar spines. Although normal lumbar spines showed the consistent deformation pattern, the patterns of the unstable lumbar spines were different.
Surface sampling concentration and reaction probe (2023)

A method of analyzing a chemical composition of a specimen is described. The method can include providing a probe comprising an outer capillary tube and an inner capillary tube disposed co-axially within the outer capillary tube, where the inner and outer capillary tubes define a solvent capillary and a sampling capillary in fluid communication with one another at a distal end of the probe; contacting a target site on a surface of a specimen with a solvent in fluid communication with the probe; maintaining a plug volume proximate a solvent-specimen interface, wherein the plug volume is in fluid communication with the probe; draining plug sampling fluid from the plug volume through the sampling capillary; and analyzing a chemical composition of the plug sampling fluid with an analytical instrument. A system for performing the method is also described.
Adversarial Heart Attack: Neural Networks Fooled to Segment Heart\n Symbols in Chest X-Ray Images (2021)

Adversarial attacks consist in maliciously changing the input data to mislead\nthe predictions of automated decision systems and are potentially a serious\nthreat for automated medical image analysis. Previous studies have shown that\nit is possible to adversarially manipulate automated segmentations produced by\nneural networks in a targeted manner in the white-box attack setting. In this\narticle, we studied the effectiveness of adversarial attacks in targeted\nmodification of segmentations of anatomical structures in chest X-rays.\nFirstly, we experimented with using anatomically implausible shapes as targets\nfor adversarial manipulation. We showed that, by adding almost imperceptible\nnoise to the image, we can reliably force state-of-the-art neural networks to\nsegment the heart as a heart symbol instead of its real anatomical shape.\nMoreover, such heart-shaping attack did not appear to require higher\nadversarial noise level than an untargeted attack based the same attack method.\nSecondly, we attempted to explore the limits of adversarial manipulation of\nsegmentations. For that, we assessed the effectiveness of shrinking and\nenlarging segmentation contours for the three anatomical structures. We\nobserved that adversarially extending segmentations of structures into regions\nwith intensity and texture uncharacteristic for them presented a challenge to\nour attacks, as well as, in some cases, changing segmentations in ways that\nconflict with class adjacency priors learned by the target network.\nAdditionally, we evaluated performances of the untargeted attacks and targeted\nheart attacks in the black-box attack scenario, using a surrogate network\ntrained on a different subset of images. In both cases, the attacks were\nsubstantially less effective. We believe these findings bring novel insights\ninto the current capabilities and limits of adversarial attacks for semantic\nsegmentation.\n
FPGA based predictive deadbeat control for high switching frequency SEPIC (2012)

This paper presents the application of predictive deadbeat control to the high switching frequency DC/DC Single-Ended Primary Inductor Converter (SEPIC). An extended Kalman observer with load variation estimation is designed to achieve current sensorless operation of the controller. A hybrid Delta-Sigma (Δ-Σ) Digital Pulse Width Modulation (DPWM) is used to effectively achieve 11-bit resolution at high-frequency and reduce the system clock frequency. The proposed DPWM along with the predictive deadbeat control algorithm is validated by using a Virtex-II FPGA. Experimental studies are conducted for a laboratory prototype with switching frequency of 500kHz. Simulation and experimental results prove the performance of the proposed solution.
USE OF AN ALUMINA-ON-ALUMINA BEARING SYSTEM IN TOTAL HIP ARTHROPLASTY FOR OSTEONECROSIS OF THE HIP (2006)

Background: The results of total hip arthroplasty in patients with osteonecrosis of the femoral head are not always optimal. The use of alumina-on-alumina interfaces in young and active patients may decrease wear and lower the rate of aseptic loosening of the implant and appears to be an attractive alternative to the use of conventional cobalt-chromium-on-polyethylene bearings. The purpose of this study was to evaluate the safety and efficacy of the alumina-on-alumina bearing in patients with osteonecrosis and to compare this group of patients to a group of similarly treated patients with osteoarthritis and a group of patients who received conventional cobalt-chromium-on-polyethylene bearings. Methods: Patients were selected from a United States Investigational Device Exemption multicenter prospective randomized clinical study that was initiated in 1996. Seventy patients with osteonecrosis of the femoral head (seventy-nine hips) received a cementless alumina-on-alumina bearing system and were directly matched to seventy-six patients with osteoarthritis of the hip (seventy-nine hips) who were managed with the same implant. Both groups were compared with twenty-five patients (twenty-six hips) with osteonecrosis and twenty-five patients (twenty-six hips) with osteoarthritis who were managed with a cementless cobalt-chromium-on-polyethylene bearing system. All patients received a cementless hydroxyapatite-coated femoral stem and were followed both clinically and radiographically. Results: The clinical outcomes for alumina-on-alumina bearings were similar for both osteonecrotic and osteoarthritic hips. The seven-year survival probability was 95.5% for the osteonecrotic hips and 89.4% for the osteoarthritic hips in the alumina-on-alumina bearing group and 92.3% for the osteonecrotic hips and 92.9% for the osteoarthritic hips in the cobalt-chromium-on-polyethylene bearing group. At the time of the most recent follow-up, the mean Harris hip score was 96 points for both the osteonecrotic and the osteoarthritic hips in the alumina-on-alumina group and 96 points for the osteonecrotic hips and 97 points for the osteoarthritic hips in the cobalt-chromium-on-polyethylene bearing group. Conclusions: The results of the use of alumina-on-alumina and cobalt-chromium-on-polyethylene bearings in cementless standard total hip implants in patients with osteonecrosis and osteoarthritis were comparable. The low revision rate for the alumina-on-alumina bearing is encouraging and offers a promising option for younger, more active patients who have this challenging disease. Level of Evidence: Therapeutic Level III. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.
Mice Humanized for Major Histocompatibility Complex and Angiotensin-Converting Enzyme 2 with High Permissiveness to SARS-CoV-2 Omicron Replication (2022)

Abstract Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike glycoprotein. The murine ACE2 ortholog does not interact efficiently with SARS-CoV-2 Spike and therefore the conventional laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in C57BL/6 “HHD-DR1” background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. Compared to the previously available B6.K18-ACE2 2Prlmn/JAX mice, which have limited permissiveness to SARS-CoV-2 Omicron replication, these three new hACE2 transgenic strains display higher levels of hACE2 mRNA expression, associated with high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral vector-based COVID-19 vaccine candidate.
Phase-sensitive amplification and deamplification of noise and the noise rise in period-doubling systems near a bifurcation (1988)

We have observed in experiments with a driven nonlinear electrical resonator that the fluctuations in the ``noisy precursor'' to a period-doubling bifurcation are phase dependent and that the noise is deamplified in one of the phases. This is a classical effect analogous to ``squeezing'' which normally refers to deamplification of quantum noise. Preceding the period-doubling bifurcation a ``noise rise'' similar to that observed in Josephson-junction parametric amplifiers evolves and the noise deamplification ceases. This phenomenon and the ``noise rise'' appear to be related as successive stages in the development of bifurcation in a nonlinear system in the presence of noise.
Field observations of ecoacoustic dynamics of a Japanese bush warbler using an open-source software for robot audition HARK (2018)

We report on a simple and practical application of HARK, an easily available and portable system for bird song localization using an open-source software for robot audition HARK, to a deeper understanding of ecoacoustic dynamics of bird songs, focusing on a fine-scaled temporal analysis of song movement — song type dynamics in playback experiments. We extended HARKBird and constructed a system that enables us to conduct automatic playback and interactive experiments with different conditions, with a real-time recording and localization of sound sources. We investigate how playback of conspecific songs and playback patterns can affect vocalization of two types of songs and spatial movement of an individual of Japanese bush-warbler, showing quantitatively that there exist strong relationships between song type and spatial movement. We also simulated the ecoacoustic dynamics of the singing behavior of the focal individual using a software, termed Bird song explorer, which provides users a virtual experience of acoustic dynamics of bird songs using a 3D game platform Unity. Based on experimental results, we discuss how our approach can contribute to ecoacoustics in terms of two different roles of sounds: sounds as tools and subjects.
Root-knot nematode perineal pattern development: a reconsideration (2001)

Abstract The perineal pattern, a unique and complex structure located at the female posterior body region, comprises the vulva-anus area, tail terminus, phasmids, lateral lines and surrounding cuticular striae. Little is known about the development of this important but variable character complex. Published information together with scanning electron and light microscopical observations on female development and perineal patterns were used to explain in detail the perineal pattern. The basic pattern, with fine striae, is formed just after the last moult when the vulva is induced above the anus at the posterior ventral body side. This process is likely to be influenced by the previous feeding stage. The vulva-anus region moves posteriorly, while the female is still enclosed by the old cuticle layers. After resuming feeding, the female diameter increases rapidly and pattern striae become folded and coarser. The role of the expanding rectal glands and perineal pattern structures as lateral lines, anus, tail terminus and punctations are discussed in detail. Major origins for pattern variation are developmental and aging factors in both feeding stages, a vulva-anus shift and the observation of patterns of different age, in combination with variable interpretation and description.
In situ High-Field Dynamic Nuclear Polarization-Direct and Indirect Polarization of [superscript 13]C nuclei (2010)

In situ High-Field Dynamic Nuclear Polarization: Direct and indirect polarization of [superscript 13]C nuclei by DNP is investigated (see graphic). The field-dependent enhancement profile for both processes are investigated and the bulk polarization build-up time constants τ[C over B] and τ[H over B] for direct and indirect [superscript 13]C polarization are compared.
Averaged subtracted polarization imaging for endoscopic diagnostics of surface microstructures on translucent mucosae (2015)

An endoscopic image processing technique for enhancing the appearance of microstructures on translucent mucosae is described. This technique employs two pairs of co- and cross-polarization images under two different linearly polarized lights, from which the averaged subtracted polarization image (AVSPI) is calculated. Experiments were then conducted using an acrylic phantom and excised porcine stomach tissue using a manual experimental setup with ring-type lighting, two rotating polarizers, and a color camera; better results were achieved with the proposed method than with conventional color intensity image processing. An objective evaluation method that uses texture analysis was developed and used to evaluate the enhanced microstructure images. This paper introduces two types of online, rigid-type, polarimetric endoscopic implementations using a polarized ring-shaped LED and a polarimetric camera. The first type uses a beam-splitter-type color polarimetric camera, and the second uses a single-chip monochrome polarimetric camera. Microstructures on the mucosa surface were enhanced robustly with these online endoscopes regardless of the difference in the extinction ratio of each device. These results show that polarimetric endoscopy using AVSPI is both effective and practical for hardware implementation.
Asymmetric Frontal Response across the Gulf of Mexico Front in Winter 2016 (2021)

The interaction of cold-vertically stratified (CVS) Mississippi River water with warm-horizontally stratified (WHS) Gulf of Mexico water resulted in a front that affected the oceanic surface layer. Our cross-frontal observations demonstrated two vertical layers. The cross-frontal deep layer (9–30 m) averaged a temperature dissipation rate (TD) varied by a factor of 1000 and was larger on the CVS side. The near-surface layer (0–9 m) averaged TD did not vary significantly across the front. The deep layer frontal asymmetry coincided with depths where the Thorpe scale was large. The situation was similar for the layer averaged turbulent kinetic energy dissipation rate (TKED). Within both layers, the averaged-TKED values were 10–30 times larger on the CVS side. The surface turbulent heat flux was up to 4 times larger on the WHS side. The observed asymmetric response of the turbulence across the front could play a significant role in the ocean-atmosphere climate system.
Fast Volume Deformation Using Inverse-Ray-Deformation and FFD (2001)

In this paper we present a new approach for free-formdeformation of volume object. Free-form-deformation (FFD) is used as method for calculating the deformation. Rendering is based on the inverse deformation of viewing rays using approaches adapted from Barr [1] and Kurzion [10]. Thus this new approach doesn’t suffer from the overhead of the intermediate step to reconstruct the deformed volume as traditional approaches do. Compared to these earlier methods we integrated algorithmic optimization like distance-coding based space-leaping and early-ray-termination. This is achieved by approximating the deformed viewing rays with polylines and by treating the linear segments as conventional rays. The performance of this optimized rendering method depends on the length of the ray segments. The higher the local curvature, the smaller the segment length which is determined automatically during rendering. For semi-transparent volumes we thus achieve speedups of the optimized algorithm vs. the non-optimized algorithm between 3.13 and 4.43. In the case of opaque objects and empty space in-between the speedup decreases from 14.16 of non-deformed volumes to 4.52 for severely deformed volumes. Thereby the decrease of speedup is mainly determined by less efficient space-leaping due to shorter segments in the polylines.