gebhart/patrepeval huggingface dataset:
Enhancement of Radiation Sensitivity of Human Squamous Carcinoma Cells by Histone Deacetylase Inhibitors (2004)

Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents with potential for disruption of critical cellular processes in cancer cells. Transcriptional regulation, differentiation, cell cycle arrest, radiation sensitization, and apoptosis have been observed in response to exposure to HDAC inhibitors. In the present study, we observed that several potent HDAC inhibitors, including trichostatin A, suberoylanilide hydroxamic acid, M344 (an analogue of hydroxamic acid), and the cyclic tetrapeptide, depsipeptide (FR90228), modulate cellular responses to ionizing radiation in cells of two human squamous carcinoma lines (SQ-20B and SCC-35), previously characterized as intrinsically resistant to radiation. Also exposure to IC(50) concentrations of these inhibitors, radiation sensitivities were enhanced in both cell lines. Depsipeptide exhibited the greatest effect on SQ-20B cells, decreasing D(0) values from 2.62 Gy to 1.64 Gy. M344 was the most active drug in sensitizing SCC-35 cells, decreasing D(0) values from 1.91 Gy to 1.21 Gy. The mechanisms underlying HDAC inhibitor-induced radiosensitization were further investigated by extending trichostatin A studies to assess cell cycle distributions and levels of apoptosis. Treatment of SQ-20B cells with radiosensitizing concentrations of trichostatin A resulted in cell cycle arrest in G(1) phase (>70%) and inhibition of DNA synthesis. Contrary to previous reports, induction of apoptosis was very low and caspase 3 and 9 were not activated. Taken together, these results implicate G(1) arrest and inhibition of DNA synthesis in the mechanisms underlying radiation sensitization by trichostatin A and support the use of HDAC inhibitors for targeting radioresistant cancers.
Fine particulate matter (PM2.5) inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and skin keratinocytes (2019)

Exposure to fine particulate matter (PM) with diameter <2.5 µm (PM2.5) causes epithelium injury and endothelial dysfunction. Primary cilia are sensory organelles that transmit extracellular signals into intracellular biochemical responses and have roles in physiology. To date, there have been no studies investigating whether PM2.5 affects primary cilia in skin. We addressed this in the present study using normal human epidermal keratinocytes (NHEKs) and retinal pigment epithelium (RPE) cells. We found that formation of primary cilium is increased in differentiated NHEKs. However, treatment with PM2.5 blocked increased ciliogenesis in NHEKs and RPE cells. Furthermore, PM2.5 transcriptionally upregulated small proline rich protein 3 (SPRR3) expression by activating c-Jun, and ectopic expression of SPRR3 inhibits suppressed the ciliogenesis. Accordingly, treatment with c-Jun activator (anisomycin) induced SPRR3 expression, whereas the inhibitor (SP600125) recovered the ciliated cells and cilium length in PM2.5-treated cells. Moreover, c-Jun inhibitor suppressed upregulation of SPRR3 in PM2.5-treated cells. Taken together, our finding suggested that PM2.5 inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and keratinocytes.
Fast and accurate cardinality estimation in cellular-based wireless communications (2015)

Cardinality estimation is of fundamental importance in various wireless communication applications. The performance of any adaptive medium access control in the uplink channel is in fact affected by its accuracy. This paper provides a fresh look at this fundamental problem, and proposes a novel scheme for fast and accurate cardinality estimation. This scheme utilizes the experienced outage probability in detecting IDs of the devices in the uplink. It is observed that for practically relevant values of Signal-to-Interference-plus-Noise Ratio (SINR) threshold, e.g., β ≤ 10 dB, and spreading sequence length, e.g., N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> ≥ 7, the base station is able to estimate the true cardinality with vanishing error in only one shot, even if the network is so populated, e.g., the number of active devices N ≥ 100. Otherwise, one may apply the proposed method in couple of consecutive shots such that in each of which portion of the cardinality is estimated.
ChemInform Abstract: ERGOLINE SYNTHONS: SYNTHESIS OF 3,4‐DIHYDRO‐6‐METHOXYBENZ(CD)INDOL‐5(1H)‐ONE (6‐METHOXY‐UHLE′S KETONE) AND 3,4‐DIHYDROBENZ(CD)INDOL‐5(1H)‐ONE (UHLE′S KETONE) VIA A NOVEL DECARBOXYLATION OF INDOLE‐2‐CARBOXYLATES (1985)

Abstract Ergoline Synthons: Synthesis of 3,4‐Dihydro‐6‐methoxybenz[cd]indol‐5(IH)‐one ′ (6‐Methoxy‐Uhle′s Ketone) and 3,4‐Dihydrobenz[cd]indo1‐5(1H)‐one (Uhle′s Ketone) via a Novel Decarboxylation of lndole‐2‐carboxylates.
Towards the Industrialization of New MDO Methodologies and Tools for Aircraft Design (2017)

An overall summary of the Institute of Technology IRT Saint Exupery MDA-MDO project (Multi-Disciplinary Analysis - Multidisciplinary Design Optimization) is presented. The aim of the project is to develop efficient capabilities (methods, tools and a software platform) to enable industrial deployment of MDO methods in industry. At IRT Saint Exupery, industrial and academic partners collaborate in a single place to the development of MDO methodologies; the advantage provided by this mixed organization is to directly benefit from both advanced methods at the cutting edge of research and deep knowledge of industrial needs and constraints. This paper presents the three main goals of the project: the elaboration of innovative MDO methodologies and formulations (also referred to as architectures in the literature 1) adapted to the resolution of industrial aircraft optimization design problems, the development of a MDO platform featuring scalable MDO capabilities for transfer to industry and the achievement of a simulation-based optimization of an aircraft engine pylon with industrial Computational Fluid Dynamics (CFD) and Computational Structural Mechanics (CSM) tools.
Protein-Targeted Gadolinium-Based Magnetic Resonance Imaging (MRI) Contrast Agents: Design and Mechanism of Action (2009)

Magnetic resonance imaging (MRI) is a powerful medical diagnostic technique: it can penetrate deep into tissue, provide excellent soft tissue contrast with sub-millimeter resolution, and does not employ ionizing radiation. Targeted contrast agents provide an additional layer of molecular specificity to the wealth of anatomical and functional information already attainable by MRI. However, the major challenge for molecular MR imaging is sensitivity: micromolar concentrations of Gd(III) are required to cause a detectable signal change, which makes detecting proteins by MRI a challenge. Protein-targeted MRI contrast agents are bifunctional molecules comprising a protein-targeting moiety and typically one or more gadolinium chelates for detection by MRI. The ability of the contrast agent to enhance the MR image is termed relaxivity, and it depends upon many molecular factors, including protein binding itself. As in other imaging modalities, protein binding provides the pharmacokinetic effect of concentrating the agent at the region of interest. Unique to MRI, protein binding provides the pharmacodynamic effect of increasing the relaxivity of the contrast agent, thereby increasing the MR signal. In designing new agents, optimization of both the targeting function and the relaxivity is critical. In this Account, we focus on optimization of the relaxivity of targeted agents. Relaxivity depends upon speciation, chemical structure, and dynamic processes, such as water exchange kinetics and rotational tumbling rates. We describe mechanistic studies that relate these factors to the observed relaxivities and use these findings as the basis of rational design of improved agents. In addition to traditional biochemical methods to characterize ligand-protein interactions, the presence of the metal ion enables more obscure biophysical techniques, such as relaxometry and electron nuclear double resonance, to be used to elucidate the mechanism of relaxivity differences. As a case study, we explore the mechanism of action of the serum-albumin-targeted angiography agent MS-325 and closely related compounds and show how small changes in the metal chelate can impact relaxivity. We found that, while protein binding generally improves relaxivity by slowing the tumbling rate of the complex, in some cases, the protein itself can also negatively affect hydration of the metal complex and/or inner-sphere water exchange. Drawing on these findings, we designed next-generation agents targeting albumin, fibrin, or collagen and incorporating up to four gadolinium chelates. Through judicious molecular design, we show that high-relaxivity complexes with high target affinity can be realized.
Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology (2011)

Our results demonstrate that TMPRSS4 has a role in the lung cancer development. The potential use of TMPRSS4 as a biomarker for lung cancer detection or as a predictor of patient's outcome warrants further investigation.
Expression and prognostic significance of survivin inde novoacute myeloid leukaemia (2000)

Survivin is an inhibitor of apoptosis (programmed cell death) overexpressed in various human cancers, but undetectable in normal differentiated tissues. A potential distribution and prognostic significance of survivin in patients with de novo acute myeloid leukaemia (AML) was investigated. By immunofluoresence of bone‐marrow specimens and peripheral blood mononuclear cells, survivin was detected in 75 out of 125 interpretable AML cases (60%), with reactivity in 50–90% of AML cells. Survivin expression correlated with a lower white blood cell count (WBC) ( P = 0·008 by the Mann–Whitney test) and was associated, in the 55 cases of FAB M0/M1/M2, with leukaemic granulocytic maturation (one out of five M/L0, 11 out of 22 M/L1 and 23 out of 28M/L2; P = 0·007 by the Fisher test). In 69 patients treated with the Acute Leukaemia French Association (ALFA) 9000 protocol, survivin expression was significantly associated with a lower WBC ( P = 0·03 by the Mann–Whitney test) and favourable/intermediate cytogenetics ( P = 0·03 by the Fisher test). There was no significant difference in complete remission rate or overall survival between survivin‐positive and survivin‐negative AML patients ( P = 0·15 by the log‐rank test). However, survivin expression became an independent negative prognostic factor for survival when adjusted with the Cox model for established prognostic factors in AML (cytogenetics, age and WBC) or for the ALFA 9000 treatment arm (RR = 2·8 and P = 0·026, by the likelihood‐ratio test). These data suggest that survivin expression may be considered as a new unfavourable prognostic factor of de novo AML and suggest a role for apoptosis inhibition in influencing disease outcome.
Realtime circular object detection based on the statistical compactness estimation (2012)

Gathering statistical and geometrical information by processing the shape contours is the common way of feature extraction on object detection and recognition studies. Compactness is an important shape descriptor which specifies the similarity between a shape and a circle. In this study, we propose a new compactness measure based on examining the distribution of the contour moments with respect to the shape's centroid. First, the contours are extracted with the Edge Drawing algorithm from the image. Then, the contours moments are computed and their distributions are examined. As a result, detection of the circular shapes among the extracted closed contours with a desired circular similarity becomes possible. With its high accuracy and low complexity, the proposed method is a convenient for realtime applications.
Large-scale biophysical parameter estimation in single neurons via constrained linear regression (2005)

Our understanding of the input-output function of single cells has been substantially advanced by biophysically accurate multi-compartmental models. The large number of parameters needing hand tuning in these models has, however, somewhat hampered their applicability and interpretability. Here we propose a simple and well-founded method for automatic estimation of many of these key parameters: 1) the spatial distribution of channel densities on the cell's membrane; 2) the spatiotemporal pattern of synaptic input; 3) the channels' reversal potentials; 4) the intercompartmental conductances; and 5) the noise level in each compartment. We assume experimental access to: a) the spatiotemporal voltage signal in the dendrite (or some contiguous subpart thereof, e.g. via voltage sensitive imaging techniques), b) an approximate kinetic description of the channels and synapses present in each compartment, and c) the morphology of the part of the neuron under investigation. The key observation is that, given data a)-c), all of the parameters 1)-4) may be simultaneously inferred by a version of constrained linear regression; this regression, in turn, is efficiently solved using standard algorithms, without any "local minima" problems despite the large number of parameters and complex dynamics. The noise level 5) may also be estimated by standard techniques. We demonstrate the method's accuracy on several model datasets, and describe techniques for quantifying the uncertainty in our estimates.
Insulator-to-Metal Transition in Nanocrystal Assemblies Driven by in Situ Mild Thermal Annealing (2004)

We report on exploration of internanocrystal coupling in assemblies of CoPt3 nanocrystals (i.e., artificial atom solids) probed by variable temperature charge transport measurements. Nanocrystal devices can be tuned in situ from Mott insulating to metallic behavior using mild thermal annealing. Thermal analysis suggests that the observed insulator-to-metal transition is due to melting and reorganization of the nanocrystal ligand shells causing a reduction in mean internanocrystal distance and is not due to nanocrystal ligand desorption or nanocrystal sintering.
Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action (2015)

In this article, we identify a new inhibitor of hepatitis C virus (HCV) infection, delphinidin, that prevents HCV entry. This natural compound, a plant pigment responsible for the blue-purple color of flowers and berries, belongs to the flavonoid family, like the catechin EGCG, the major component present in green tea extract, which is also an inhibitor of HCV entry. We studied the mode of action of these two compounds against HCV and demonstrated that they both act directly on the virus, inducing a bulging of the viral envelope. This deformation might be responsible for the observed inhibition of virus attachment to the cell surface. The discovery of such HCV inhibitors with an unusual mode of action is important to better characterize the mechanism of HCV entry into hepatocytes and to help develop a new class of HCV entry inhibitors.
ANALYSIS OF PIN FINS INCLUDING RADIATION AND TRANSIENTS (2020)

The design of fins for heat transfer enhancement remains a topic of great interest in a number of engineering areas and applications, despite extensive literature on the subject. One can apply detailed computational methods for simultaneous convection, conduction, and radiation heat transfer, but such approaches are not suitable for rapid, routine design studies. So, there is still a place for approximate analytical and low-cost numerical methods, and that is the subject of the first part of this paper. Developed here is an enhanced low-order model (LOM) that extends traditional pin fin analysis to include a more realistic radiation treatment and that further allows temperature-dependent thermal conductivity, variable heat transfer coefficients over the tip and sides of the fin with variable area distribution, and transient response. The LOM solution procedure was packaged in a MATLAB code intended for routine use by designers and analysts. Next, a novel reduced-order modeling (ROM) technique was developed and illustrated, which couples heat transfer coefficient information from a computational fluid dynamics/conjugate heat transfer (CFD/CHT) simulation with the new LOM, boasting significantly reduced run times with comparable accuracy to the original full-scale simulations.
Multicenter clinical trial of ultrasonic circular cyclo coagulation in patients with open-angle glaucoma: One year results (2014)

International audience
Artificial Intelligence in Drug Design—The Storm Before the Calm? (2018)

Artificial intelligence in drug design in experiencing a wave of excitement not seen since the emergence of computational chemistry in the late 1980s and early 1990s. Apparently failing to learn the lessons of recent history, we are promised imminent and pervasive solutions to the ills of drug design and significant increases in productivity as we seek to deliver innovative new therapeutics. However, do significant issues remain to be answered before AI enters the day-to-day toolbox of the practicing medicinal chemist?
Application of a Fluorescent Histone Acetyltransferase Assay to Probe the Substrate Specificity of the Human p300/CBP-Associated Factor (2000)

Histone N-acetyltransferases (HATs) are a group of enzymes which acetylate specific lysine residues in the N-terminal tails of nucleosomal histones to promote transcriptional activation. Recent structural and enzymatic work on the GCN5/PCAF HAT family has elucidated the structure of their catalytic domain and mechanism of histone acetylation. However, the substrate specificity of these enzymes has not been quantitatively investigated. Utilizing a novel microplate fluorescent HAT assay which detects the enzymatic production of coenzyme A (CoA), we have compared the activities of the HAT domains of human PCAF and its GCN5 homologue from yeast and Tetrahymena and found that they have similar kinetic parameters. PCAF was further assayed with a series of different length histone H3 peptide substrates, which revealed that the determinants for substrate recognition lie within a 19-residue sequence. Finally, we evaluated the acetylation of three putative PCAF substrates, histones H3 and H4 and the transcription factor p53, and have determined that histone H3 is significantly preferred over the histone H4 and p53 substrates. Taken together, the fluorescent acetyltransferase assay presented here should be widely applicable to other HAT enzymes, and the results obtained with PCAF demonstrate a strong substrate preference for the N-terminal residues of histone H3.
Experimental investigation of multipath richness for multi-element transmit and receive antenna arrays (2002)

The multi-element antenna arrays concept with M elements at the mobile station (MS) in combination with N elements at the base station (BS) is experimentally investigated. Forschini (1996) has shown very promising results to improve the spectral efficiency in a rich scattering environment. The performance of the M/spl times/N concept is evaluated in terms of the number of independent parallel channels, diversity gain and total capacity in an outdoor to indoor microcellular environment. It is shown that the eigenanalysis provides a tool to describe the effective number of parallel channels in a multi-element array configuration. Practical results on spectral efficiency are presented for different antenna setups applied to different propagation scenarios. Also it is shown that polarization diversity is an attractive solution to achieve decorrelated antenna elements and subsequently provide a more robust system in terms of spectral efficiency within the microcell. Results show that a total capacity of 27.9 b/s/Hz can be achieved for an uncorrelated propagation environment and 17 b/s/Hz for a correlated one with a mean signal to noise ratio (SNR) of 30 dB in the case of a 4/spl times/4 antenna set-up.
Hypersensitivity Pneumonitis Caused by Fungi (2010)

Hypersensitivity pneumonitis (HP) is a complex syndrome caused by an exaggerated immune response to the inhalation of a large variety of organic particles. The most frequent antigens that cause HP worldwide are bird proteins (pigeon breeders' disease) and bacteria (Saccharopolyspora rectivirgula). However, fungi are also implicated in many cases, including occupational and nonoccupational outbreaks. The clinical course of the disease is highly variable and its diagnosis clinically challenging since no specific test or biomarker allows a consistent diagnosis. Therefore, a combination of symptoms, bronchoalveolar lavage findings, chest imaging, lab tests, and often biopsies are needed for an accurate diagnosis. Regardless of the cause or the responsible environment, the histopathology is similar and usually consists of a granulomatous interstitial bronchiolocentric pneumonitis characterized by the presence of poorly formed granulomas and a prominent interstitial infiltrate composed of lymphocytes, plasma cells, and macrophages. However, some patients may show a "nonspecific interstitial pneumonia" pattern, or even a usual interstitial pneumonia-like pattern. Importantly, patients with chronic HP may evolve to interstitial fibrosis or develop emphysematous changes, although the reason(s) for these different pathological responses are presently unclear. This review provides a general overview of HP, emphasizing its fungal etiologies, and also examines the currently used clinical criteria for diagnosis and proposes an alternative classification. Challenges for future research include identification of biomarkers that may predict outcome and progression (primarily of chronic HP), and the need for a better understanding of the underlying molecular and genetic mechanisms of the disease.
Quantifying the Energetic Cost Tradeoffs of Photovoltaic Pumping Systems for Sub-Saharan African Smallholder Farms (2022)

Abstract As solar technologies have matured, irrigation using photovoltaic pumping systems (PVPSs) has gained popularity in developing markets as an effective means to alleviate poverty and increase food security. Yet there remains a barrier to adoption; the upfront cost of PVPS poses a financial burden for many low-income farmers. In a PVPS, the capital cost of the solar array contributes a large portion of upfront system costs. The solar pump is the largest energy consumer in the system, thus its efficiency directly impacts the size and cost of the solar array. There is limited quantitative understanding about how solar pump efficiency affects the capital cost of the solar array. This study presents a technoeconomic framework to directly quantify the impact of solar pump efficiency on the cost of the solar array in a PVPS for a range of hydraulic operating conditions. New empirical efficiency scaling laws were created by characterizing the efficiencies of 4-inch multistage centrifugal borehole pumps and induction motors. The utility of the technoeconomic framework is demonstrated through a case study comparing solar pump architectures with motors of different efficiencies. Results indicate that, despite increased motor cost, the use of high efficiency motors in solar pumps may lead to an overall cost reduction in a PVPS. Counter to the conventional capital cost-driven process, this work demonstrates that an efficiency-driven design process could improve low-cost, solar-powered system design. Engineers and system designers can leverage the presented framework during the design process to make informed decisions to achieve more cost-effective PVPS.