gebhart/patrepeval huggingface dataset:
Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis (2018)

Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-SOD1 ALS, we performed a blinded histological and biochemical analysis of post mortem brain and spinal cord tissues from 19 sporadic ALS, compared with a SOD1 A4V patient as well as Alzheimer's disease (AD) and non-neurological controls. Multiple conformation- or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
Polymeric endoluminal paving (2004)

Symptoms of upper urinary tract dilatation during pregnancy Upper urinary tract dilatation during pregnancy is usually painless, asymptomatic and without renal damage.7,20-22 However, some pregnant women describe various symptoms, the most common (more than 80%), with or without urinary tract dilatation and with or without stone confirmation being flank pain (ref. 2 and authors’ own data). Many women also complain of dysuria, haematuria and/or fever due to urinary tract infection (pyelonephritis, cystitis). It may be very difficult to distinguish between those symptoms due to urological changes and those related to pregnancy; many of the presenting signs and symptoms may be masked by the pregnancy.
Preventive Effect of Biodegradable Stents On Biliary Stricture And Fibrosis After Biliary Anastomosis In A Porcine Model (2021)

Abstract The aim of this animal study was to evaluate the preventive effect of novel biodegradable stents (BS) on biliary stricture and fibrosis after duct-to-duct (DD) biliary anastomosis. Ten mini-pigs were allocated to the control group (n = 5) and or the stent group (n = 5). The common bile duct was exposed through surgical laparotomy, and then resected transversely. In the stent group, a 4 mm or 6 mm polydioxanone/magnesium sheath core BS was inserted according to the width of the bile duct, followed by DD biliary anastomosis. In the control group, DD biliary anastomosis was performed without BS insertion. In the stent group, stents were observed without deformity for up to four weeks in all animals. Eight weeks later, histopathologic examination revealed that the common bile duct of the anastomosis site was relatively narrower in circumference in the control group compared to the stent group. The degree of fibrosis in the control group was more marked than in the stent group (3.84 mm vs. 0.68 mm, respectively, p &lt; 0.05). Our study showed that novel BS maintained their original shape and radial force for an adequate time and then disappeared without adverse events.
A High-$Q$ Widely Tunable Gigahertz Electromagnetic Cavity Resonator (2006)

This paper describes the design, fabrication and testing of a quasi-static electromagnetic cavity resonator fabricated using potassium-hydroxide (KOH) etching, shallow reactive-ion etching (RIE), metalization and wafer bonding. The resonator is distinguished by its simultaneous high-Q near 200, and wide high-frequency tuning range, 2.5-4.0 GHz for the experimental resonator presented here. When combined with an integrated actuator, it should be suitable for use in electronically tunable radio-frequency (RF) bandpass filters and oscillators. The experimental resonator, however, is tuned with an external piezoelectric actuator for simplicity
Doppler Lidar Measurements of Tropospheric Wind Profiles Using the Aerosol Double Edge Technique (2000)

The development of a ground based direct detection Doppler lidar based on the recently described aerosol double edge technique is reported. A pulsed, injection seeded Nd:YAG laser operating at 1064 nm is used to make range resolved measurements of atmospheric winds in the free troposphere. The wind measurements are determined by measuring the Doppler shift of the laser signal backscattered from atmospheric aerosols. The lidar instrument and double edge method are described and initial tropospheric wind profile measurements are presented. Wind profiles are reported for both day and night operation. The measurements extend to altitudes as high as 14 km and are compared to rawinsonde wind profile data from Dulles airport in Virginia. Vertical resolution of the lidar measurements is 330 m and the rms precision of the measurements is a low as 0.6 m/s.
Super-resolution applied to Distributed Video Coding with Spatial Scalability (2008)

Distributed Video Coding is a new video coding paradigm that enables video codecs with reversed complexity. It is well-known that the performance of any distributed video coder is heavily dependent on the quality of the side information generated by motion-estimation at the decoder. As a continuation of previous works, in this paper we propose to use a super-resolution method to up-sample the non-key frames using the key frames as reference, in order to improve the side information generation in a distributed video coding scheme with spatial scalability. The framework, proposed in previous works, enables reduced encoding complexity by reduced spatial-resolution encoding of the non-reference frames, followed by Wyner-Ziv coding of the Laplacian residue. The side information generation is iterative, in the first iteration the high-frequency data of matching blocks from the key frames are added to the low-resolution blocks of the interpolated downsampled frames. Results are presented using the state-of-the-art video coding standard H.264/AVC.
Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B‐cell lymphoma (2021)

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory large B-cell lymphoma (R/R LBCL). To reduce axi-cel-related toxicity, several exploratory safety management cohorts were added to ZUMA-1 (NCT02348216), the pivotal phase 1/2 study of axi-cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 10<sup>6</sup> anti-CD19 CAR T cells/kg after conditioning chemotherapy. Forty-one patients received axi-cel. Incidences of any-grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone-equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA-1 cohorts. With a median follow-up of 14·8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi-cel.
Perfluorocarbon-based Oxygen Delivery (2006)

The basic properties of perfluorocarbons (PFCs) and PFC emulsions relevant to their use as oxygen delivery systems are briefly reviewed. The key issues related to the selection of an appropriate, readily excretable PFC and the engineering of a stable injectable PFC emulsion are discussed. Oxygent, a terminally heat-sterilized, injectable 60% w/v PFC emulsion made primarily of F-octyl bromide and a few percent of F-decyl bromide, with egg phospholipids as an emulsifier, has been developed. Its efficacy in avoiding and reducing red cell transfusion during surgery has been established during a Phase III clinical evaluation. Another Phase III clinical trial in cardiopulmonary bypass surgery, with a protocol that included both augmented-acute normovolemic hemodilution and intraoperative autologous donation, has, however, been interrupted following the observation of adverse events. Data analysis assigned these events to an inappropriate study protocol. A search for possible interactions between Oxygent and fluids present during cardiopulmonary bypass surgery detected no effect of the emulsion on hemostasis, hemolysis and blood rheology.
45-Gb/s SiGe BiCMOS PRBS Generator and PRBS Checker (2003)

A 2'-l pseudorandom bit sequence (PRBS) generator chip set that operates up to 45Gh/s was fabricated and tested. The circuits are implemented using bipolar transistors in a SiGe BiCMOS technology and operate from a single -3.3V power supply. The PRBS generator, which consumes 1.32W, uses a high speed 4:l multiplexer to produce the final output from four quarter-rate streams. The automatic synchronizing PRBS checker consumes 1.2W and uses a half-rate architecture, demultiplexing the full-rate data stream to lower rate streams that are checked io parallel.
490-km transmission in a "single-fiber" 2.488 Gb/s repeaterless system with remote pre-amplifier and dispersion compensation (1996)

A cost-effective repeaterless system with remote pumping in a single fiber is reported. Omitting dedicated pump fibers, 490 km transmission is demonstrated at 2.488 Gb/s with a fiber loss of 87.4 dB. The system employs a remote pre-amplifier and dispersion-compensating fiber but no remote post-amplifier.
Reconfigurable disruption tolerant routing via Reinforcement Learning (2009)

This paper shows packet delivery rate can be improved by adopting learning-based hybrid routing strategies when a wired network suffers from severe link disruption. The dynamics of the link disruptions complicate the routing problem; successful and stable routing operations of conventional routing approaches are hindered as the level of disruption increases. The target is to develop a robust and efficient routing approach in a single structure. A robust routing approach means a packet should be delivered to a destination even under severe disruptions. Efficient routing should deliver a packet with the shortest path at no disruption. These goals should be achieved with the maximum utilization of preexisting network components and with the minimal human intervention once installed. Therefore, we chose a popular conventional routing scheme, link state, and add-ons that can learn changing network environment. Our approach is to add a learning agent and a simple routing scheme to link state in order to automatically select a better routing scheme at an arbitrary level of disruption. Markov decision process is employed to model this problem. The simulation results show robustness and packet delivery rate are increased up to 35% at acceptable cost of computational and architectural complexity even when link state approach is close to be collapsed.
Beta 2-adrenoceptor density in fibroblast culture correlates with human NaCl sensitivity (1992)

To study salt sensitivity in humans and its relation to expression of adrenoceptors, 20 male normotensive Caucasians were investigated on a diet of 180 mmol NaCl/day followed by 60 mmol NaCl/day over 2 wk and again by 180 mmol NaCl/day over 2 wk, and blood pressure changes were assessed by long-term oscillatory blood pressure monitoring under basal conditions. Individual cell cultures of skin fibroblasts from skin biopsies were also established, and alpha 2- and beta 2-adrenoceptors were measured. Seven subjects were salt sensitive, and the remainder were salt resistant. Cultured skin fibroblasts in salt-sensitive subjects express less than half the number of beta 2-adrenoceptors compared with salt-resistant subjects (65 +/- 12.7 vs. 173 +/- 14.8 fmol/mg, P less than 0.001), and there is a correlation between the absolute rise of blood pressure on a high-salt diet and the density of beta 2-adrenoceptors (r = -0.67, P less than 0.01). It remains to be established whether a reduced in vitro density of beta 2-adrenoceptors in cultured cells is causally related to salt sensitivity in normotensive humans.
Novel Tunable Millimeter-Wave Grating-Gated Plasmonic Detectors (2010)

We present the development of tunable, narrow-band plasmonic millimeter wave detectors. The current generation of this class of detector monolithically integrates a 2-D plasmonic absorber and a bolometric sensor in a GaAs/AlGaAs HEMT located at the vertex of a broad-band antenna. Response and transport measurements demonstrate absorption by high-order plasmon modes sensed by the integrated bolometer and with a two order of magnitude improvement in sensitivity and noise equivalent power over prior generations of 2-D plasmonic detectors. We compare these recent results with the state of the art in millimeter and submillimeter wave-detection technology.
39-OR: Pancreatic Beta Cell SERCA2 Deficiency Impacts ER-Golgi Vesicle Trafficking and Ceramide Metabolism (2021)

Alterations in endoplasmic reticulum (ER) calcium (Ca2+) levels arising from reduced activity of the Sarcoendoplasmic Reticulum Ca2+ ATPase (SERCA) pump are associated with impaired insulin secretion and reduce β-cell survival in both major forms of diabetes. However, at present, the mechanisms of how reduced ER Ca2+ impairs β-cell function remain incompletely understood. To test this, we analyzed mice with β-cell specific SERCA2 deletion (βS2KO mice) and S2KO INS1 cells. βS2KO mice exhibited age-dependent glucose intolerance, reduced glucose-stimulated insulin secretion, and increased proinsulin secretion without evidence of impaired insulin sensitivity. Immunoblot analysis of βS2KO islets and S2KO INS-1 cells revealed reduced active forms of the proinsulin processing enzymes, PC1/3, PC2, and CPE, while immunofluorescence analysis suggested impaired ER-Golgi trafficking of the convertase enzymes and proinsulin. Because the ER serves as the main site of cellular lipid synthesis and changes in the β-cell lipidome have been linked with diabetes pathophysiology, we hypothesized that ER Ca2+ loss may alter protein trafficking in the secretory pathway through changes in ER lipid content. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on the ER fractions of control and S2KO INS1 cells and revealed increased levels of 16:0, 24:0, 24:1, and total ceramides in S2KO cells. SERCA2 restoration partially rescued convertase enzyme expression, proinsulin processing, and ceramide content. Consistent with these findings, RNA sequencing analysis of βS2KO islets revealed changes in pathways related to vesicle transport, protein processing, and lipid metabolism. We conclude that SERCA2 in the β-cell plays a central role in the maintenance of insulin biosynthesis as well as ceramide metabolism. Disclosure T. Kono: None. H. Iida: None. C. Lee: None. P. Krishnan: None. P. Arvan: None. I. Lindberg: None. C. Evans-molina: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; Dompe, Other Relationship; Self; Bristol-Myers Squibb Company, Nimbus Pharmaceuticals, Pfizer Inc. Funding National Institutes of Health (R01DK093954)
Functional Characterization of Nuclear Localization and Export Signals in Hepatitis C Virus Proteins and Their Role in the Membranous Web (2014)

The hepatitis C virus (HCV) is a positive strand RNA virus of the Flavivirus family that replicates in the cytoplasm of infected hepatocytes. Previously, several nuclear localization signals (NLS) and nuclear export signals (NES) have been identified in HCV proteins, however, there is little evidence that these proteins travel into the nucleus during infection. We have recently shown that nuclear pore complex (NPC) proteins (termed nucleoporins or Nups) are present in the membranous web and are required during HCV infection. In this study, we identify a total of 11 NLS and NES sequences in various HCV proteins. We show direct interactions between HCV proteins and importin α5 (IPOA5/kapα1), importin β3 (IPO5/kap β3), and exportin 1 (XPO1/CRM1) both in-vitro and in cell culture. These interactions can be disrupted using peptides containing the specific NLS or NES sequences of HCV proteins. Moreover, using a synchronized infection system, we show that these peptides inhibit HCV infection during distinct phases of the HCV life cycle. The inhibitory effects of these peptides place them in two groups. The first group binds IPOA5 and inhibits infection during the replication stage of HCV life cycle. The second group binds IPO5 and is active during both early replication and early assembly. This work delineates the entire life cycle of HCV and the active involvement of NLS sequences during HCV replication and assembly. Given the abundance of NLS sequences within HCV proteins, our previous finding that Nups play a role in HCV infection, and the relocation of the NLS double-GFP reporter in HCV infected cells, this work supports our previous hypothesis that NPC-like structures and nuclear transport factors function in the membranous web to create an environment conducive to viral replication.
Magnetic Measurements of SPIONs using NVs in Diamond. (2021)

Abstract not provided.
Gap Junction Assembly: Multiple Connexin Fluorophores Identify Complex Trafficking Pathways (2001)

The assembly of gap junction channels was studied using mammalian cells expressing connexin (Cx) 26, 32 and 43 in which the carboxyl terminus was fused to green, yellow or cyan fluorescent proteins (GFP, YFP, CFP). Intracellular targeting of Cx32-CFP and 43-GFP to gap junctions was disrupted by brefeldin A treatment and resulted in a severe loss of gap junctional intercellular communication reflected by low intercellular dye transfer. Cells expressing Cx43-GFP exposed to nocodazole showed normal targeting to gap junctions and dye transfer. Cx32 and 43 thus appear to be transported and assembled into gap junctions via the classical secretory pathway. In contrast, we found that assembly of Cx26-GFP into functional gap junctions was relatively unaffected by treatment of cells with brefeldin A, but was extremely sensitive to nocodazole treatment. Coexpression of Cx26-YFP and Cx32-CFP indicated a different intracellular distribution that was accentuated in the presence of brefeldin A, with the gap junctions in these cells constructed predominantly of Cx26-YFP. A site specific mutation in the first transmembrane domain that distinguished Cx32 from Cx26 (Cx32128L) resulted in the adoption of the trafficking properties of Cx26 as well as its unusual post-translational membrane integration characteristics. The results indicate that multiple intracellular connexin trafficking routes exist and provide a further mechanism for regulating the connexin composition of gap junctions and thus specificity in intercellular signalling.
Central Nervous System Safety And Tolerability Of DS-5565: A Randomized, Double-Blind, Placebo- And Active Comparator-Controlled Phase II Study In Diabetic Peripheral Neuropathic Pain (P7.296) (2014)

OBJECTIVE: To profile CNS safety/tolerability of DS-5565 (a potent, specific alpha2-delta ligand) in diabetic peripheral neuropathic pain (DPNP) BACKGROUND: Available alpha2-delta ligands are established as first-line treatments for DPNP. However, dosage and efficacy may be limited by frequent and significant central nervous system (CNS)-related side effects. New pharmacological treatments are needed. DESIGN/METHODS: 452 patients with DPNP were randomized (1:1:1:1:1:2:1 ratio) to DS-5565 (5mg qd, 10mg qd, 15mg qd, 10mg bid, 15mg bid), placebo, or pregabalin (150mg bid). DS-5565 15mg bid and pregabalin 150mg bid were titrated from half doses during week 1. The primary endpoint was weekly change in average daily pain score (ADPS) for DS-5565 versus placebo from baseline to week 5. Safety/tolerability was assessed based on incidence of treatment-emergent adverse events (TEAEs). The safety analysis set (N=435) included patients who received at least 1 dose of study medication. RESULTS: The primary endpoint was met. DS-5565 showed significant improvements in ADPS at week 5 versus placebo (P<0.05 for 15mg qd, 10mg bid, 15mg bid). For the DS-5565 combined (all dosages), placebo, and pregabalin groups, completion rates were 86.3%, 86.6% and 73.2%, respectively. No patients discontinued due to a drug-related serious TEAE. CNS adverse events (somnolence, dizziness, balance disorder, headache) were reported in 72(26.0%), 8(7.4%), and 11(22.0%) patients in the DS-5565 combined, placebo, and pregabalin groups, respectively, and were predominantly mild in severity and generally dose dependent. In the DS-5565 5mg qd, 10mg qd, 15mg qd, 10mg bid, 15mg bid, placebo, and pregabalin groups, somnolence was reported in 1(1.8%), 1(1.8%), 3(5.7%), 5(8.9%), 7(12.3%), 1(0.9%), and 4(8.0%) patients, respectively; dizziness was reported in 0(0.0%), 7(12.5%), 6(11.3%), 4(7.1%), 9(15.8%), 2(1.9%), and 3(6.0%) patients, respectively. CONCLUSIONS: DS-5565 demonstrated efficacy with a dose-response and had a balanced safety profile across all doses evaluated. Overall rates of TEAEs and CNS TEAEs of interest were low. Study Supported by: Daiichi Sankyo Inc.
Proceedings of the 9th SIGdial Workshop on Discourse and Dialogue (2008)

We are pleased to present in this volume, the Proceedings of the 9th SIGdial Workshop on Discourse and Dialogue. These proceedings could not have been produced without the assistance of this year's excellent program committee. The quality of the collection is a result of their efforts and we are indebted to them for donating their time and expertise. 19 of the 46 submissions were accepted as long papers and another 10 were accepted as short papers. This selection of papers follows the SIGdial tradition of providing a venue for work on theory, implemented systems, developed work and new approaches. The topics covered include generation for dialogue systems, dialogue system evaluation, opinions, persuasion, multi-party dialogue, probabilistic methods for dialogue, grounding and the use of dialogue features for improving speech processing. We are optimistic that the breadth and quality of the selected papers will contribute to a lively and interesting workshop event and will prove a valuable resource for the SIGdial readership.