gebhart/patrepeval huggingface dataset:
Impact of stoichiometry control in double junction memory on future scaling (2005)

We propose a new discrete trap memory with double tunnel junction where we can control trapped electron density by stoichiometry control of charge store part. This memory has less than 3 nm EOT tunnel oxide, and can retain a high trapped electron number density 10/sup 12/ cm/sup -2/, which is critical one for future scaling, for 10 years after low field w/e. It is concluded that stoichiometry control of charge store part in double junction memory is very promising method for future scaling.
Phosphorylation of p16 Correlates with Cdk4 Association (2003)

Progression through the eukaryotic cell cycle is driven by the activity of cyclin-dependent kinases. The cyclin D-dependent kinase Cdk4 promotes progression through the G(1) phase of the cell cycle and is deregulated in many human tumors. The tumor suppressor protein p16(INK4A) (p16) forms a complex with Cdk4 and inhibits kinase activity. Here we report that p16 is phosphorylated, and the phosphorylated form of p16 is preferentially associated with Cdk4 in normal human fibroblasts. We mapped phosphorylation sites on exogenously overexpressed p16 to serines 7, 8, 140, and 152 and found that endogenous p16 associated with Cdk4 is phosphorylated at serine 152. All mapped phosphorylation sites lie outside of the conserved kinase-binding domain of p16 but in regions of the protein affected by mutations in familial and sporadic cancer. Our results suggest a novel regulation of p16 activity.
On the definition of chronic cough and current treatment pathways: an international qualitative study (2014)

There is significant international variation in our understanding and management of chronic cough. Further work is required to bring forth clear guidance and effective medicines for these patients.
The role of water in host-guest interaction (2021)

One of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system’s degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding free energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail. © 2021, The Author(s).
Left Ventricular Unloading During Extracorporeal Membrane Oxygenation in Patients With Cardiogenic Shock (2019)

In observational studies, left ventricular unloading was associated with decreased mortality in adult patients with cardiogenic shock treated with VA-ECMO. In the absence of prospective randomized data, left ventricular unloading may be considered for appropriately selected patients undergoing VA-ECMO support.
Ground-State Depletion Microscopy: Detection Sensitivity of Single-Molecule Optical Absorption at Room Temperature (2010)

Optical studies of single molecules in ambient environments, which have led to broad applications, are primarily based on fluorescence detection. Direct detection of optical absorption with single-molecule sensitivity at room temperature is difficult because absorption is not a background-free measurement and is often complicated by sample scattering. Here we report ground-state depletion microscopy for ultrasensitive detection of absorption contrast. We image 20 nm gold nanoparticles as an initial demonstration of this microscopy. We then demonstrate the detection of an absorption signal from a single chromophore molecule at room temperature. This is accomplished by using two tightly focused collinear continuous-wave laser beams at different wavelengths, both within a molecular absorption band, one of which is intensity modulated at a high frequency (>MHz). The transmission of the other beam is found to be modulated at the same frequency due to ground state depletion. The signal of single chromophore molecules scanned across the common laser foci can be detected with shot-noise limited sensitivity. This measurement represents the ultimate detection sensitivity of nonlinear optical spectroscopy at room temperature.
Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: Sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau (1997)

The microtubule-associated protein (MAP) tau is abnormally hyperphosphorylated in Alzheimer disease and accumulates in neurons undergoing neurofibrillary degeneration. In the present study, the associations of the Alzheimer-hyperphosphorylated tau (AD P-tau) with the high molecular weight MAPs (HMW-MAPs) MAP1 and MAP2 were investigated. The AD P-tau was found to aggregate with MAP1 and MAP2 in solution. The association of AD P-tau to the MAPs resulted in inhibition of MAP-promoted microtubule assembly. However, unlike the coaggregation of AD P-tau and normal tau, the association between AD P-tau and the HMW-MAPs did not result in the formation of filaments/tangles. The affinity of the tau-AD P-tau association was higher than that of HMW-MAPs-AD P-tau because normal tau inhibited the latter binding. The association between AD P-tau and the HMW-MAPs also appeared to occur in situ because these proteins cosedimented from the Alzheimer brain extracts, and, in the sediment, the levels of the HMW-MAPs correlated with the levels of AD P-tau. These studies suggested that the abnormally phosphorylated tau can sequester both normal tau and HMW-MAPs and disassemble microtubules but, under physiological conditions, can form tangles of filaments only from tau.
Biochemical and Genetic Characterizations of a Novel Human Immunodeficiency Virus Type 1 Inhibitor That Blocks gp120-CD4 Interactions (2003)

BMS-378806 is a recently discovered small-molecule human immunodeficiency virus type 1 (HIV-1) attachment inhibitor with good antiviral activity and pharmacokinetic properties. Here, we demonstrate that the compound targets viral entry by inhibiting the binding of the HIV-1 envelope gp120 protein to cellular CD4 receptors via a specific and competitive mechanism. BMS-378806 binds directly to gp120 at a stoichiometry of approximately 1:1, with a binding affinity similar to that of soluble CD4. The potential BMS-378806 target site was localized to a specific region within the CD4 binding pocket of gp120 by using HIV-1 gp120 variants carrying either compound-selected resistant substitutions or gp120-CD4 contact site mutations. Mapping of resistance substitutions to the HIV-1 envelope, and the lack of compound activity against a CD4-independent viral infection confirm the gp120-CD4 interactions as the target in infected cells. BMS-378806 therefore serves as a prototype for this new class of antiretroviral agents and validates gp120 as a viable target for small-molecule inhibitors.
The Influenza A Virus M2Cytoplasmic Tail Is Required for Infectious Virus Production and Efficient Genome Packaging (2005)

The M2 integral membrane protein encoded by influenza A virus possesses an ion channel activity that is required for efficient virus entry into host cells. The role of the M2 protein cytoplasmic tail in virus replication was examined by generating influenza A viruses encoding M2 proteins with truncated C termini. Deletion of 28 amino acids (M2Stop70) resulted in a virus that produced fourfold-fewer particles but >1,000-fold-fewer infectious particles than wild-type virus. Expression of the full-length M2 protein in trans restored the replication of the M2 truncated virus. Although the M2Stop70 virus particles were similar to wild-type virus in morphology, the M2Stop70 virions contained reduced amounts of viral nucleoprotein and genomic RNA, indicating a defect in vRNP packaging. The data presented indicate the M2 cytoplasmic tail plays a role in infectious virus production by coordinating the efficient packaging of genome segments into influenza virus particles.
Understanding The Security of Discrete GPUs (2017)

GPUs have become an integral part of modern systems, but their implications for system security are not yet clear. This paper demonstrates both that discrete GPUs cannot be used as secure co-processors and that GPUs provide a stealthy platform for malware. First, we examine a recent proposal to use discrete GPUs as secure co-processors and show that the security guarantees of the proposed system do not hold on the GPUs we investigate. Second, we demonstrate that (under certain circumstances) it is possible to bypass IOMMU protections and create stealthy, long-lived GPU-based malware. We demonstrate a novel attack that compromises the in-kernel GPU driver and one that compromises GPU microcode to gain full access to CPU physical memory. In general, we find that the highly sophisticated, but poorly documented GPU hardware architecture, hidden behind obscure close-source device drivers and vendor-specific APIs, not only make GPUs a poor choice for applications requiring strong security, but also make GPUs into a security threat.
Optical absorption enhancement in silicon nanowire and nanohole arrays for photovoltaic applications (2010)

In this proceeding, we simulate the optical properties of vertically-aligned silicon nanowire and nanohole arrays using the transfer matrix method. We find that the optical absorption in both silicon nanowire and nanohole arrays improves with increasing lattice constant up to 600nm - 700nm. We attribute the observed optical absorption enhancement effect to an increase in the field concentration inside the active silicon region and the excitation of guided resonance modes. For optimized parameters, both structures can be more absorptive than an equally-thick silicon solid film with an optimal single layer Si<sub>3</sub>N<sub>4</sub> anti-reflection coating. This conclusion holds true for both optically thin (2.33&mu;m) and optically thick (100&mu;m) structures. For optically thin structures, the enhancement in the optimal nanohole array exceeds the conventional light trapping limit. For optically thick structures, the enhancement in both optimal nanohole and nanowire arrays exceeds the light trapping limit. Additionally, we show that the overall absorption efficiencies for hexagonal and square lattices of nanowires are very similar.
Effects of Carbamazepine and Novel 10,11‐Dihydro‐5H‐Dibenz[b,f]Azepine‐5‐Carboxamide Derivatives on Synaptic Transmission in Rat Hippocampal Slices (2002)

The effects of carbamazepine on synaptic transmission in rat hippocampal slices were compared with those of two novel analogues (BIA2-093 and BIA2-024) with equivalent anticonvulsant efficacy but with fewer side effects. Carbamazepine (10-1000 microM) inhibited in a concentration-dependent manner the field excitatory postsynaptic potential (fPSP) response, with an EC50 of 263 microM, and also attenuated the presynaptic volley with a similar EC50 value. Carbamazepine was more potent to inhibit the NMDA receptor component of the fPSP (fPSPNMDA), with an EC50 of 160 microM. BIA2-093 and BIA2-024 were nearly equipotent with carbamazepine to inhibit synaptic transmission, and displayed similar potency to inhibit the fPSP (EC50 of 145 microM and 205 microM) and fPSPNMDA responses (EC50 of 198 microM and 206 microM). As with carbamazepine, BIA2-093 and BIA2-024 also attenuated the presynaptic volley with EC50 values ranging from 142 to 322 microM. These results indicate that carbamazepine and its analogues mostly inhibit synaptic transmission through inhibition of conduction, although carbamazepine, but not BIA2-093 and BIA2-024, may also depress NMDA receptor-mediated responses.
Effect of the oxLDL Binding Protein Fc-CD68 on Plaque Extension and Vulnerability in Atherosclerosis (2011)

The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.
Extracellular Signal-regulated Protein Kinase/Jun Kinase Cross-talk Underlies Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation (1998)

Ligand binding to vascular endothelial cell growth factor (VEGF) receptors activates the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK). Possible cross-communication of ERK and JNK effecting endothelial cell (EC) actions of VEGF is poorly understood. Incubation of EC with PD 98059, a specific mitogen-activated protein kinase kinase inhibitor, or transfection with Y185F, a dominant negative ERK2, strongly inhibited VEGF-activated JNK. JNK was also activated by ERK2 expression in the absence of VEGF, inhibited 82% by co-transfection with dominant negative SEK-1, indicating upstream activation of JNK by ERK. VEGF-stimulated JNK activity was also reversed by dominant negative SEK-1. Other EC growth factors exhibited similar cross-activation of JNK through ERK. VEGF stimulated the nuclear incorporation of thymidine, reversed 89% by PD 98059 and 72% by Y185F. Dominant negative SEK-1 or JNK-1 also significantly reduced VEGF-stimulated thymidine incorporation. Expression of wild type Jip-1, which prevents JNK nuclear translocation, inhibited VEGF-induced EC proliferation by 75%. VEGF stimulated both cyclin D1 synthesis and Cdk4 kinase activity, inhibited by PD 98059 and dominant negative JNK-1. Important events for VEGF-induced G1/S progression and cell proliferation are enhanced through a novel ERK to JNK cross-activation and subsequent JNK action.
Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line. (1980)

To isolate a stable tumor cell line capable of producing human interleukin 2 (IL-2; formerly referred to as T cell growth factor), 16 human T and B leukemia cell lines were screened for constitutive and mitogen-stimulated IL-2 production. We found that the T cell leukemia line designated Jurkat-FHCRC produced > 200 U/ml of IL-2 activity after a 24-h stimulation with T cell mitogens. Peak mitogen-induced IL-2 activity was found in supernates harvested from 24-h Jurkat-FHCRC cell cultures stimulated with either 1% phytohemagglutinin or 20 microgram/ml concanavalin A. Addition of the fatty acid derivative phorbol myristate acetate to mitogen-stimulated cultures increased Jurkat-FHCRC IL-2 production to concentrations > 400 U/ml. IL-2 activity observed in such cases represented between 100--300 times that produced in conventional cultures of mitogen- or alloantigen-stimulated normal human peripheral blood or splenic lymphocytes. Jurkat-FHCRC-derived conditioned medium demonstrated equal capacity to promote the sustained in vitro proliferation of either murine or human activated T cell lines confirming the ability of Jurkat-FHCRC cells to produce human IL-2. These studies identify a new source of human IL-2 and establish a valuable reagent for the isolation and further molecular characterization of this immunoregulatory molecule.
Design of a multiphase osteochondral scaffold III: Fabrication of layered scaffolds with continuous interfaces (2009)

There is a need to improve current treatments for articular cartilage injuries. This article is the third in a series describing the design and development of an osteochondral scaffold based on collagen-glycosaminoglycan and calcium phosphate technologies for regenerative repair of articular cartilage defects. The previous articles in this series described methods for producing porous, three-dimensional mineralized collagen-GAG (CGCaP) scaffolds whose composition can be reproducibly varied to mimic the composition of subchondral bone, and pore microstructure and mineral phase can be modified. This article describes a method, "liquid-phase cosynthesis," that enables the production of porous, layered scaffolds that mimic the composition and structure of articular cartilage on one side, subchondral bone on the other side, and the continuous, gradual or "soft" interface between these tissues: the tidemark of articular joints. This design enables the layered scaffolds to be inserted into the subchondral bone at an osteochondral defect site without the need for sutures, glue, or screws, with a highly interconnected porous network throughout the entire osteochondral defect. Moreover, the differential moduli of the osseous and cartilaginous compartments enable these layered scaffolds to exhibit compressive deformation behavior that mimics the behavior observed in natural articular joints.
Doomsday: predicting which node will fail when on supercomputers (2018)

Predicting which node will fail and how soon remains a challenge for HPC resilience, yet may pave the way to exploiting proactive remedies before jobs fail. Not only for increasing scalability up to exascale systems but even for contemporary supercomputer architectures does it require substantial efforts to distill anomalous events from noisy raw logs. To this end, we propose a novel phrase extraction mechanism called TBP (time-based phrases) to pin-point node failures, which is unprecedented. Our study, based on real system data and statistical machine learning, demonstrates the feasibility to predict which specific node will fail in Cray systems. TBP achieves no less than 83% recall rates with lead times as high as 2 minutes. This opens up the door for enhancing prediction lead times for supercomputing systems in general, thereby facilitating efficient usage of both computing capacity and power in large scale production systems.
SRY (sex determining region Y)-box2 (Sox2)/poly ADP-ribose polymerase 1 (Parp1) complexes regulate pluripotency (2012)

To gain insight into mechanisms controlling SRY (sex determining region Y)-box 2 (Sox2) protein activity in mouse embryonic stem cells (ESCs), the endogenous Sox2 gene was tagged with FLAG/Hemagglutinin (HA) sequences by homologous recombination. Sox2 protein complexes were purified from Sox2/FLAG/HA knockin ESCs, and interacting proteins were defined by mass spectrometry. One protein in the complex was poly ADP-ribose polymerase I (Parp1). The results presented below demonstrate that Parp1 regulates Sox2 protein activity. In response to fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling, Parp1 auto-poly ADP-ribosylation enhances Sox2-Parp1 interactions, and this complex inhibits Sox2 binding to octamer-binding transcription factor 4 (Oct4)/Sox2 enhancers. Based on these results, we propose a unique mechanism in which FGF signaling fine-tunes Sox2 activity through posttranslational modification of a critical interacting protein, Parp1, and balances the maintenance of ESC pluripotency and differentiation. In addition, we demonstrate that regulation of Sox2 activity by Parp1 is critical for efficient generation of induced pluripotent stem cells.
Ex Vivo Discrimination between Normal and Pathological Tissues in Human Breast Surgical Biopsies Using Bioimpedance Spectroscopy (1999)

Ex vivo bioimpedance data measured on normal and cancerous female breast tissues are reported. They clearly show that the electrical properties of normal tissues, surrounding tissues, and carcinoma are different. These differences lie in the conductivity, in the characteristic frequency (frequency of the maximum of the imaginary part of the bioimpedance), and also in the shape of the Bode plots. Modeling using an R-S-Zcpe model is reported as well as indexes extracted from the real and imaginary parts of the bioimpedance. Even if a classification of the different types of tissues remains a difficult task and leads to much less precise diagnosis than microscopic examination, the electrical behavior of mammary tissue could be used to develop a noninvasive technique for early breast cancer detection.
The role of cerebral amyloid β accumulation in common forms of Alzheimer disease (2005)

For approximately 80 years following Alzheimer's description of the disease that bears his name, a gulf divided researchers who believed that extracellular deposits of the amyloid beta (Abeta) peptide were pathogenic from those who believed that the deposits were secondary detritus. Since 1990, the discoveries of missense mutations in the Abeta peptide precursor (APP) and the APP-cleaving enzyme presenilin 1 (PS1) have enabled much progress in understanding the molecular, cellular, and tissue pathology of the aggregates that accumulate in the interstices of the brains of patients with autosomal dominant familial Alzheimer disease (AD). Clarification of the molecular basis of common forms of AD has been more elusive. The central questions in common AD focus on whether cerebral and cerebrovascular Abeta accumulation is (a) a final neurotoxic pathway, common to all forms of AD; (b) a toxic by-product of an independent primary metabolic lesion that, by itself, is also neurotoxic; or (c) an inert by-product of an independent primary neurotoxic reaction. Antiamyloid medications are entering clinical trials so that researchers can evaluate whether abolition of cerebral amyloidosis can mitigate, treat, or prevent the dementia associated with common forms of AD. Successful development of antiamyloid medications is critical for elucidating the role of Abeta in common AD.
MOLECULAR INSIGHTS INTO PROSTATE CANCER PROGRESSION: THE MISSING LINK OF TUMOR MICROENVIRONMENT (2005)

Cancer is not a single cell disease. Aberrant cancer cells and their interactive microenvironment are needed for prostate cancer to progress to androgen independence and distant metastasis. It is highly plausible that newly evolved prostate cancer cell clones dominate cancer metastasis after cell-cell and cell-matrix interaction with the host microenvironment, rather than the selection or expansion of a preexisting prostate cancer cell clone(s). Based on this premise potential molecular targets in the microenvironment are especially emphasized. Further elucidation of the molecular mechanisms underlying tumor-stromal interaction may yield improved medical treatments for prostate cancer growth and metastasis.
Expression of estrogen receptor alpha with a Tet-off adenoviral system induces G0/G1 cell cycle arrest in SKBr3 breast cancer cells (2009)

Endocrine therapies targeting estrogen action are pivotal for the prevention and treatment of ER-positive breast cancers. Previous studies sought to recreate hormone responsiveness by the stable expression of ERα in the ER-negative MDA-MB-231 breast cancer cells. Paradoxically, estrogen inhibits breast cancer cell growth when an exogenous ERα is expressed. In this study, we have built on previous studies by developing a Tet-off adenoviral system to express ERα in the ER-negative SKBr3 breast cancer cells that over-express both EGFR and HER2. This system efficiently delivers ERα and the expression level of ERα is controlled by doxycycline in a concentration-dependent manner. The growth of SKBr3 was inhibited by ERα expression and further inhibited in the presence of 1 nM 17β-estradiol. SKBr3 cells were arrested at G0/G1 cell cycle upon ERα expression, which corresponded to an increase of p21Cip1/Waf1, hypo-phosphorylation of pRb and decrease of E2F1. Estrogen also reduced EGFR and HER2 expression in SKBr3 cells after ERα was expressed. Given that estrogen-induced increase of p21Cip1/Waf1 and decrease of E2F1 was also observed in MDA-MB-231 cells stably transfected with ERα, our results suggest that a common pathway might be shared by different breast cancer cell lines whose growth is suppressed by ectopic ERα and estrogen.