138 research outputs found
Effect of rotation in lubrication problems: Existence of more fundamental solutions
AbstractA generalized Reynolds equation is derived in the present paper by taking into account the effect of rotation in lubrication problems. The existence of certain fundamental solutions is shown in this extended framework which is not allowed in the classical Reynolds theory. Results concerning the pressure and the load capacity of the resulting bearing system are obtained and interpreted in the respective cases when the film thickness is a linear or an exponential functions of the coordinate along the bearing length. One of the important results is that while the load capacity decreases with increasing values of α for an exponentially inclined slider in the classical Reynolds theory, it increases with increasing values of α in the present context
Morphine for the treatment of pain in sickle cell disease.
Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia
Mast Cell Neural Interactions in Health and Disease
Mast cells (MCs) are located in the periphery as well as the central nervous system (CNS). Known for sterile inflammation, MCs play a critical role in neuroinflammation, which is facilitated by their close proximity to nerve fibers in the periphery and meninges of the spinal cord and the brain. Multifaceted activation of MCs releasing neuropeptides, cytokines and other mediators has direct effects on the neural system as well as neurovascular interactions. Emerging studies have identified the release of extracellular traps, a phenomenon traditionally meant to ensnare invading pathogens, as a cause of MC-induced neural injury. In this review article, we will discuss mechanisms of MC interaction with the nervous system through degranulation, de novo synthesis, extracellular vesicles (EVs), tunneling nanotubes, and extracellular traps with implications across a variety of pathological conditions
TarGEN: Targeted Data Generation with Large Language Models
The rapid advancement of large language models (LLMs) has sparked interest in
data synthesis techniques, aiming to generate diverse and high-quality
synthetic datasets. However, these synthetic datasets often suffer from a lack
of diversity and added noise. In this paper, we present TarGEN, a multi-step
prompting strategy for generating high-quality synthetic datasets utilizing a
LLM. An advantage of TarGEN is its seedless nature; it does not require
specific task instances, broadening its applicability beyond task replication.
We augment TarGEN with a method known as self-correction empowering LLMs to
rectify inaccurately labeled instances during dataset creation, ensuring
reliable labels. To assess our technique's effectiveness, we emulate 8 tasks
from the SuperGLUE benchmark and finetune various language models, including
encoder-only, encoder-decoder, and decoder-only models on both synthetic and
original training sets. Evaluation on the original test set reveals that models
trained on datasets generated by TarGEN perform approximately 1-2% points
better than those trained on original datasets (82.84% via syn. vs. 81.12% on
og. using Flan-T5). When incorporating instruction tuning, the performance
increases to 84.54% on synthetic data vs. 81.49% on original data by Flan-T5. A
comprehensive analysis of the synthetic dataset compared to the original
dataset reveals that the synthetic dataset demonstrates similar or higher
levels of dataset complexity and diversity. Furthermore, the synthetic dataset
displays a bias level that aligns closely with the original dataset. Finally,
when pre-finetuned on our synthetic SuperGLUE dataset, T5-3B yields impressive
results on the OpenLLM leaderboard, surpassing the model trained on the
Self-Instruct dataset by 4.14% points. We hope that TarGEN can be helpful for
quality data generation and reducing the human efforts to create complex
benchmarks.Comment: 10 pages, 6 tables, 5 figures, 5 pages references, 17 pages appendi
Selective Control of Conductance Modes in Multi-terminal Josephson Junctions
The Andreev bound state spectra of multi-terminal Josephson junctions form an
artificial band structure, which is predicted to host tunable topological
phases under certain conditions. However, the number of conductance modes
between the terminals of multi-terminal Josephson junction must be few in order
for this spectrum to be experimentally accessible. In this work we employ a
quantum point contact geometry in three-terminal Josephson devices. We
demonstrate independent control of conductance modes between each pair of
terminals and access to the single-mode regime coexistent with the presence of
superconducting coupling. These results establish a full platform on which to
realize tunable Andreev bound state spectra in multi-terminal Josephson
junctions.Comment: 15 pages, 4 figure
Gate-tunable Superconducting Diode Effect in a Three-terminal Josephson Device
The phenomenon of non-reciprocal critical current in a Josephson device,
termed the Josephson diode effect, has garnered much recent interest.
Realization of the diode effect requires inversion symmetry breaking, typically
obtained by spin-orbit interactions. Here we report observation of the
Josephson diode effect in a three-terminal Josephson device based upon an InAs
quantum well two-dimensional electron gas proximitized by an epitaxial aluminum
superconducting layer. We demonstrate that the diode efficiency in our devices
can be tuned by a small out-of-plane magnetic field or by electrostatic gating.
We show that the Josephson diode effect in these devices is a consequence of
the artificial realization of a current-phase relation that contains higher
harmonics. We also show nonlinear DC intermodulation and simultaneous
two-signal rectification, enabled by the multi-terminal nature of the devices.
Furthermore, we show that the diode effect is an inherent property of
multi-terminal Josephson devices, establishing an immediately scalable approach
by which potential applications of the Josephson diode effect can be realized,
agnostic to the underlying material platform. These Josephson devices may also
serve as gate-tunable building blocks in designing topologically protected
qubits
Mast Cells Induce Blood Brain Barrier Damage in SCD by Causing Endoplasmic Reticulum Stress in the Endothelium
Endothelial dysfunction underlies the pathobiology of cerebrovascular disease. Mast cells are located in close proximity to the vasculature, and vasoactive mediators released upon their activation can promote endothelial activation leading to blood brain barrier (BBB) dysfunction. We examined the mechanism of mast cell-induced endothelial activation via endoplasmic reticulum (ER) stress mediated P-selectin expression in a transgenic mouse model of sickle cell disease (SCD), which shows BBB dysfunction. We used mouse brain endothelial cells (mBECs) and mast cells-derived from skin of control and sickle mice to examine the mechanisms involved. Compared to control mouse mast cell conditioned medium (MCCM), mBECs incubated with sickle mouse MCCM showed increased, structural disorganization and swelling of the ER and Golgi, aggregation of ribosomes, ER stress marker proteins, accumulation of galactose-1-phosphate uridyl transferase, mitochondrial dysfunction, reactive oxygen species (ROS) production, P-selectin expression and mBEC permeability. These effects of sickle-MCCM on mBEC were inhibited by Salubrinal, a reducer of ER stress. Histamine levels in the plasma, skin releasate and in mast cells of sickle mice were higher compared to control mice. Compared to control BBB permeability was increased in sickle mice. Treatment of mice with imatinib, Salubrinal, or P-selectin blocking antibody reduced BBB permeability in sickle mice. Mast cells induce endothelial dysfunction via ER stress-mediated P-selectin expression. Mast cell activation contributes to ER stress mediated endothelial P-selectin expression leading to increased endothelial permeability and impairment of BBB. Targeting mast cells and/or ER stress has the potential to ameliorate endothelial dysfunction in SCD and other pathobiologies
(E)-N′-{7-MethÂoxyÂspiroÂ[chromeno[4,3-d]thiaÂzole-4,1′-cycloÂhexaÂn]-2-yl}-N,N-dimethylÂacetimidamide
In the chromenothiaÂzole ring system of the title molÂecule, C20H25N3O2S, the pyran ring is in a half-chair conformation. The dihedral angle between the thiaÂzole and benzene rings is 14.78 (6)°. The cycloÂhexane ring is in a chair conformation. The crystal structure is stabilized by weak interÂmolecular C—H⋯N and C—H⋯O hydrogen bonds
"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire
Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work
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