gebhart/patrepeval huggingface dataset:
Phosphatidylinositol 3-kinase and mTOR mediate lipopolysaccharide-stimulated nitric oxide production in macrophages via interferon-β (2000)

Bacterial lipopolysaccharide (LPS) elicits responses by macrophages that help the body repel infections. Recent evidence indicates that phosphatidylinositol 3-kinase (PI 3-kinase) may mediate some of these responses. Here, we show that exposing macrophages to LPS rapidly increased membrane-associated PI 3-kinase activity and also elevated p70 S6 kinase activity. Inhibitors of PI 3-kinase or the mammalian target of rapamycin (mTOR) fully blocked p70 S6 kinase activation, implying that this kinase is controlled by PI 3-kinase and mTOR. These inhibitors also substantially reduced LPS-induced nitric oxide (NO) production. This inhibition was, in part, attributable to impaired LPS-stimulated secretion of interferon-beta, an autocrine co-factor for NO production. However, the addition of exogenous interferon-beta did not fully restore NO production, indicating that the NO response was being inhibited by another mechanism as well. Together, these data suggest that PI 3-kinase, mTOR, and possibly p70 S6 kinase mediate LPS-induced NO production by regulating the secretion of interferon-beta and by a second undefined mechanism.
EVIDENCE FOR EPITOPE SPREADING AND ACTIVE SUPPRESSION IN SKIN GRAFT TOLERANCE AFTER DONOR-SPECIFIC TRANSFUSION1 (1999)

(1) Pretransplantation infusion of Ld-mismatched lymphocytes in the presence or absence of multiple mH mismatches induces permanent survival of donor-specific skin allografts. (2) CsA abrogates DST-induced transplantation tolerance.
Soluble VCAM-1 binding to α4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells (2000)

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is generated during inflammation and can alter lymphocyte functions. The authors report that the binding of sVCAM-1 to alpha4 integrin-bearing cells is a dynamically regulated, active cellular process. Binding of recombinant sVCAM-1 to alpha4 integrins on peripheral blood mononuclear cells was cell-type specific. Circulating CD16+ NK cells constitutively bound sVCAM-1 with high affinity, whereas a subpopulation of T-lymphocytes, primarily CD45RO+ (memory), bound sVCAM-1 only after phorbol ester stimulation. sVCAM-1 binding to homogenous stable cell lines was also cell-type specific, and required active cellular processes because it was blocked by the inhibition of ATP synthesis and by Fas-induced apoptosis. Indeed, the loss of high-affinity VCAM-1 binding was an early event in apoptosis. Furthermore, an H-Ras/Raf-initiated signaling pathway also suppressed sVCAM-1 binding to alpha4beta1 integrins. Collectively, these results showed that the capacity of alpha4 integrins to bind VCAM-1 is actively regulated and that this regulation may control alpha4 integrin-dependent cellular functions. (Blood. 2000;95:602-609)
1918 Influenza Virus Hemagglutinin (HA) and the Viral RNA Polymerase Complex Enhance Viral Pathogenicity, but Only HA Induces Aberrant Host Responses in Mice (2013)

The 1918 pandemic influenza virus was the most devastating infectious agent in human history, causing fatal pneumonia and an estimated 20 to 50 million deaths worldwide. Previous studies indicated a prominent role of the hemagglutinin (HA) gene in efficient replication and high virulence of the 1918 virus in mice. It is, however, still unclear whether the high replication ability or the 1918 influenza virus HA gene is required for 1918 virus to exhibit high virulence in mice. Here, we examined the biological properties of reassortant viruses between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001 [K173]) in a mouse model. In addition to the 1918 influenza virus HA, we demonstrated the role of the viral RNA replication complex in efficient replication of viruses in mouse lungs, whereas only the HA gene is responsible for lethality in mice. Global gene expression profiling of infected mouse lungs revealed that the 1918 influenza virus HA was sufficient to induce transcriptional changes similar to those induced by the 1918 virus, despite difference in lymphocyte gene expression. Increased expression of genes associated with the acute-phase response and the protein ubiquitination pathway were enriched during infections with the 1918 and 1918HA/K173 viruses, whereas reassortant viruses bearing the 1918 viral RNA polymerase complex induced transcriptional changes similar to those seen with the K173 virus. Taken together, these data suggest that HA and the viral RNA polymerase complex are critical determinants of Spanish influenza pathogenesis, but only HA, and not the viral RNA polymerase complex and NP, is responsible for extreme host responses observed in mice infected with the 1918 influenza virus.
Globally Feedback Linearizable Time-Invariant Systems: Optimal Solution for Mayer’s Problem (1998)

This paper discusses the optimal solution of Mayer’s problem for globally feedback linearizable time-invariant systems subject to general nonlinear path and actuator constraints. This class of problems includes the minimum time problem, important for engineering applications. Globally feedback linearizable nonlinear systems are diffeomorphic to linear systems that consist of blocks of integrators. Using this alternate form, it is proved that the optimal solution always lies on a constraint arc. As a result of this optimal structure of the solution, efficient numerical procedures can be developed. For a single input system, this result allows to characterize and build the optimal solution. The associated multi-point boundary value problem is then solved using direct solution techniques. [S0022-0434(00)02002-5]
Changes of Norepinephrine Levels, Tyrosine Hydroxylase and Dopamine-Beta-Hydroxylase Activities after Castration and Testosterone Treatment in Vas Deferens of Adult Rats1 (1989)

Norepinephrine levels and tyrosine hydroxylase and dopamine-beta-hydroxylase activities have been used to evaluate the effect of castration and testosterone treatment on the sympathetic innervation of the adult vas deferens. Castration was followed by a decrease in both norepinephrine content and tyrosine hydroxylase activity, even though the changes were not concomitant. Treatment of castrated animals with testosterone reversed the effect of castration on organ weight and norepinephrine content, but only a short-lasting increase in tyrosine hydroxylase activity occurred at the beginning of testosterone treatment. In contrast, the testosterone-induced recovery of norepinephrine content observed at this time was accompanied by a marked increase in dopamine-beta-hydroxylase activity. The results suggest that in rat vas deferens, norepinephrine levels are under androgenic control and that this regulation mainly involves changes in dopamine-beta-hydroxylase activity rather than a modulation of tyrosine hydroxylase.
Ambler: an autonomous rover for planetary exploration (1989)

The authors are building a prototype legged rover, called the Ambler (loosely an acronym for autonomous mobile exploration robot) and testing it on full-scale, rugged terrain of the sort that might be encountered on the Martian surface. They present an overview of their research program, focusing on locomotion, perception, planning, and control. They summarize some of the most important goals and requirements of a rover design and describe how locomotion, perception, and planning systems can satisfy these requirements. Since the program is relatively young (one year old at the time of writing) they identify issues and approaches and describe work in progress rather than report results. It is expected that many of the technologies developed will be applicable to other planetary bodies and to terrestrial concerns such as hazardous waste assessment and remediation, ocean floor exploration, and mining.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A conserved mechanism regulates reversible amyloids via pH-sensing regions (2022)

Abstract Amyloids were long viewed as irreversible, pathological aggregates, often associated with neurodegenerative diseases 1 . However, recent insights challenge this view, providing evidence that reversible amyloids can form upon stress conditions and fulfil crucial cellular functions 2 . Yet, the molecular mechanisms regulating functional amyloids and the differences to their pathological counterparts remain poorly understood. Here we investigate the conserved principles of amyloid reversibility by studying the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that PK forms stress-dependent reversible amyloids through a pH-sensitive amyloid core. Stress- induced cytosolic acidification promotes aggregate formation via protonation of specific glutamate (in yeast) or histidine (in human) residues within the amyloid core. Our work thus unravels a conserved and potentially widespread mechanism underlying amyloid functionality and reversibility, fine-tuned to the respective physiological cellular pH range.
Nested objects in a Byzantine quorum-replicated system (2004)

Modern distributed, object-based systems support nested method invocations, whereby one object can invoke methods on another. In this paper we present a framework that supports nested method invocations among Byzantine fault-tolerant, replicated objects that are accessed via quorum systems. A challenge in this context is that client object replicas can induce unwanted method invocations on server object replicas, due either to redundant invocations by client replicas or Byzantine failures within the client replicas. At the core of our framework are a new quorum-based authorization technique and a novel method invocation protocol that ensure the linearizability and failure atomicity of nested method invocations despite Byzantine client and server replica failures. We detail the implementation of these techniques in a system called Fleet, and give preliminary performance results for them.
Self-Assembly of ABC Bottlebrush Triblock Terpolymers with Evidence for Looped Backbone Conformations (2018)

Bottlebrush block copolymers offer rich opportunities for the design of complex hierarchical materials. As consequences of the densely grafted molecular architecture, bottlebrush polymers can adopt highly extended backbone conformations and exhibit unique physical properties. A recent report has described the unusual phase behavior of ABC bottlebrush triblock terpolymers bearing grafted poly(<sub>D,L</sub>-lactide) (PLA), polystyrene (PS), and poly(ethylene oxide) (PEO) blocks (LSO). In this work, a combination of resonant soft X-ray reflectivity (RSoXR), near edge X-ray absorption fine structure spectroscopy (NEXAFS), and self-consistent field theory (SCFT) was used to provide insight into the phase behavior of LSO and underlying backbone chain conformations. Consistent with SCFT calculations, RSoXR measurements confirm a unique mesoscopic ACBC domain connectivity and <i>decreasing</i> lamellar periods (<i>d</i> <sub>0</sub>) with increasing backbone length of the PEO block. RSoXR and NEXAFS demonstrate an additional unusual feature of brush LSO thin films: when the overall film thickness is ~3.25<i>d</i> <sub>0</sub>, the film-air interface is majority PS (>80%). Since PS is the midblock, the triblocks must adopt looping configurations at the surface, despite the preference for the backbone to be extended. This result is supported by backbone concentrations calculated through SCFT, which suggest that looping midblocks are present throughout the film. Collectively, this work provides evidence for the flexibility of the bottlebrush backbone and the consequences of low-<i>χ</i> block copolymer design. We propose that PEO blocks localize at the PS/PLA domain interfaces in order to screen the highest-<i>χ</i> contacts in the system, driving the formation of loops. These insights introduce a potential route to overcome the intrinsic penalties to interfacial curvature imposed by the bottlebrush architecture, enabling the design of unique self-assembled materials.
A robust low phase noise K<inf>u</inf> band VCO with 23.3% tuning range for E-band and V-band backhaul transceivers (2015)

This paper presents a K <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</sub> band G <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> boosted Colpitts VCO designed in IBM 0.13μm SiGe BiCMOS8hp technology for E-Band and V-band backhaul transceivers. The VCO achieves 23.3% tuning range, covering 15.2 - 19.2 GHz while maintaining low phase noise. Measured phase noise at 10 MHz is lower than -133 dBc/Hz at 25°C. The VCO shows robust behaviour to temperature variations, with a measured frequency drift of less than 15 ppm/°C. The power consumption is 51.4mW and calculated FOM is -183.5 dBc/Hz.
Epstein-Barr virus and telomerase: from cell immortalization to therapy (2014)

Overcoming cellular senescence is strictly required for virus-driven tumors, including those associated with Epstein-Barr virus (EBV). This critical step is successfully accomplished by EBV through TERT expression and telomerase activation in infected cells. We herein review the complex interplay between EBV and TERT/telomerase in EBV-driven tumorigenesis. Evidence accumulated so far clearly indicates that elucidation of this issue may offer promising opportunities for the design of innovative treatment modalities for EBV-associated malignancies. Indeed, several therapeutic strategies for telomerase inhibition have been developed and are being investigated in clinical trials. In this respect, our recent finding that TERT inhibition sensitizes EBV+ lymphoma cells to antivirals through activation of EBV lytic replication is particularly promising and provides a rationale for the activation of clinical studies aimed at assessing the effects of combination therapies with TERT inhibitors and antivirals for the treatment of EBV-associated malignancies.
Data from Persistence of CTL Clones Targeting Melanocyte Differentiation Antigens Was Insufficient to Mediate Significant Melanoma Regression in Humans (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) can mediate durable cancer regression in selected patients with metastatic melanoma. However, the tumor antigens associated with these favorable responses remain unclear. We hypothesized that a clinical strategy involving the iterative adoptive transfer of selected autologous antigen-specific T-cell clones could help systematically define immunologic targets associated with successful cancer therapy, without the interpretative ambiguity of transferring polyclonal populations. Here, we evaluated the clinical efficacy of CD8&lt;sup&gt;+&lt;/sup&gt; T-cell clones specific for the melanocyte differentiation antigens (MDA), gp100 and MART-1, respectively.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We conducted two consecutive phase II clinical trials involving the adoptive transfer of highly selected autologous antigen-specific CD8&lt;sup&gt;+&lt;/sup&gt; T-cell clones against gp100 and MART-1, respectively. Fifteen patients with HLA-A2&lt;sup&gt;+&lt;/sup&gt; treatment-refractory metastatic melanoma received highly avid MDA-specific CD8&lt;sup&gt;+&lt;/sup&gt; T-cell clones specific for either gp100 (&lt;i&gt;n&lt;/i&gt; = 10) or MART-1 (&lt;i&gt;n&lt;/i&gt; = 5) with or without intravenous interleukin-2 (IL2) after a lymphodepleting myeloablative preparative regimen.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of the 15 treated patients, we observed immune-mediated targeting of skin melanocytes in 11 patients (73%) and clonal engraftment in eight patients (53%) after cell transfer. There were only transient minor tumor regressions observed, but no objective tumor responses based on Response Evaluation Criteria in Solid Tumor (RECIST) criteria.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Despite successful clonal repopulation and evidence of &lt;i&gt;in vivo&lt;/i&gt; antigen targeting, the poor therapeutic efficacy after the adoptive transfer of autologous MDA-specific T cells raises significant concerns regarding future immunotherapy efforts targeting this class of tumor antigens. &lt;i&gt;Clin Cancer Res; 21(3); 534–43. ©2014 AACR.&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Heat and fire resistance of polyurethane‐polydimethylsiloxane hybrid material (2006)

Abstract This work examines the synthesis of polyurethane (PU)—polydimethylsiloxane (PDMS) hybrid in order to provide low flammability to PU. Chemical characterization of PU/PDMS hybrid by solid state NMR of carbon and FT‐IR shows that some PDMS segments are incorporated in the macromolecular chains of PU. Heat stability of PU (thermo‐oxidative decomposition) is not enhanced by the incorporation of PDMS except that the amount of the high temperature residue is improved and depends on the amount of PDMS incorporated in the PU chains. It is explained by the formation and the accumulation of silica. On the contrary, thermal stabilization (charring) occurs in the pyrolytic conditions when incorporating PDMS. The accumulation of silica as well as charring enhancement enables the flammability properties of the PU/PDMS hybrid to form a protective layer limiting heat transfer between the flame and the substrate. The heat release rate measured by cone calorimetry of PU/PDMS hybrid is significantly decreased compared to virgin PU and temperature of the back of the sample is comparatively low compared to virgin PU. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Quercetin, but not Its Glycosides, Is Absorbed from the Rat Stomach (2001)

Absorption and metabolism of quercetin, isoquercitrin (quercetin 3-O-glucose), and rutin (quercetin 3-O-glucose-rhamnose) were investigated in rats after in situ gastric administration (15 micromol/L) for 30 min. At the end of the experiment, 38% of the initial dose of quercetin had disappeared. Quercetin was rapidly absorbed by the stomach, and was recovered in the bile 20 min after infusion (4.07 +/- 0.10 micromol/L). The administration of rutin and isoquercitrin indicated that these glycosides were not hydrolyzed nor absorbed by this tissue. In conclusion, when flavonols are present in the diet as aglycons, they could be partly absorbed in the stomach, in contrast to their glycosidic forms which are not absorbed.
Probing the limits of optical cycling in a predissociative diatomic molecule (2023)

Molecular predissociation is the spontaneous, nonradiative bond breaking process that can occur upon excitation. In the context of laser cooling, predissociation is an unwanted consequence of molecular structure that limits the ability to scatter a large number of photons required to reach the ultracold regime. Unlike rovibrational branching, predissociation is irreversible since the fragments fly apart with high kinetic energy. Of particular interest is the simple diatomic molecule, CaH, for which the two lowest electronically excited states used in laser cooling lie above the dissociation threshold of the ground potential. In this work, we present measurements and calculations that quantify the predissociation probabilities affecting the cooling cycle. The results allow us to design a laser cooling scheme that will enable the creation of an ultracold and optically trapped cloud of CaH molecules. In addition, we use the results to propose a two-photon pathway to controlled dissociation of the molecules, in order to gain access to their ultracold fragments, including hydrogen.
Disposition of digoxin immune fab in patients with kidney failure (1993)

Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free digoxin were studied in five digoxin-toxic patients with end-stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (+/- SD) serum creatinine of 5.9 +/- 1.2 mg/dl (four patients were receiving long-term hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration-time profile of Fab appeared to be similar to the concentration-time profile of total digoxin. The mean (+/- SD) half-lives of the alpha and beta disposition phases of Fab were 13 +/- 5 hours and 96 +/- 31 hours, respectively, which were similar to the alpha and beta parameter estimates of total digoxin (14 +/- 4 and 123 +/- 16 hours, respectively). Steady-state volume of distribution and systemic clearance of Fab were 0.29 +/- 0.11 L/kg and 0.057 +/- 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total digoxin are markedly delayed in patients with end-stage renal disease, which may necessitate prolonged clinical monitoring.
[Techology of pharmaceutical powders: granulometric tests of powders]. (1977)

Data set comprising interviews with a range of stakeholders including: care-based hairdressers, people with dementia, informal carers, care workers and other practitioners and key informants. This research will explore the role that hairdressing plays in the lives of older people who are high-level users of health and social care. This will include investigating the formal/paid services provided by hairdressers, and the styling and management of hair undertaken by care workers. There are four main aims to this research: to describe the experience of hairdressing and explore the significance it holds for older service users to describe the workplace experience of care-based hairdressers and care workers to scrutinise and document the constituent elements of hairdressing encounters to consider patterns of provision, access and affordability of hairdressing services to older service users. This ethnographic study will be conducted over three types of setting: care received at home, long-stay hospital care settings and care homes. It will include observations and filming in care-based salons as well as interviews with care workers, hairdressers and older service users. The findings will inform policy and practices in care and raise the profile of body-work that is fundamental to well-being and the avoidance of decline, depression and neglect. The study addresses an aspect of care settings that is little understood and for which no evidence-base currently exists
Carbon Fibers Enhance the Propagation of High Loading Nanothermites: In Situ Observation of Microscopic Combustion (2021)

A major challenge in formulating and manufacturing energetic materials lies in the balance between total energy density, energy release rate, and mechanical integrity. In this work, carbon fibers are embedded into ∼90 wt % loading Al/CuO nanothermite sticks through a simple extrusion direct writing technique. With only ∼2.5 wt % carbon fiber addition, the burn rate and heat flux were promoted >2×. In situ microscopic observation of combustion shows that the carbon fiber intercept ejected hot agglomerates near the burning surface and enhanced heat feedback to the unreacted material. This study outlines how these approaches may enhance the propagation and reduce the two-phase flow losses.