gebhart/patrepeval huggingface dataset:
Towards understanding transfluthrin efficacy in a pyrethroid-resistant strain of the malaria vector Anopheles funestus with special reference to cytochrome P450-mediated detoxification (2021)

Malaria vector control interventions rely heavily on the application of insecticides against anopheline mosquitoes, in particular the fast-acting pyrethroids that target insect voltage-gated sodium channels (VGSC). Frequent applications of pyrethroids have resulted in resistance development in the major malaria vectors including <i>Anopheles funestus</i>, where resistance is primarily metabolic and driven by the overexpression of microsomal cytochrome P450 monooxygenases (P450s). Here we examined the pattern of cross-resistance of the pyrethroid-resistant <i>An. funestus</i> strain FUMOZ-R towards transfluthrin and multi-halogenated benzyl derivatives, permethrin, cypermethrin and deltamethrin in comparison to the susceptible reference strain FANG. Transfluthrin and two multi-fluorinated derivatives exhibited micromolar potency - comparable to permethrin - to functionally expressed dipteran VGSC in a cell-based cation influx assay. The activity of transfluthrin and its derivatives on VGSC was strongly correlated with their contact efficacy against strain FUMOZ-R, although no such correlation was obtained for the other pyrethroids due to their rapid detoxification by the resistant strain. The low resistance levels for transfluthrin and derivatives in strain FUMOZ-R were only weakly synergized by known P450 inhibitors such as piperonyl butoxide (PBO), triflumizole and 1-aminobenzotriazole (1-ABT). In contrast, deltamethrin toxicity in FUMOZ-R was synergized > 100-fold by all three P450 inhibitors. The biochemical profiling of a range of fluorescent resorufin and coumarin compounds against FANG and FUMOZ-R microsomes identified 7-benzyloxymethoxy-4-trifluoromethylcoumarin (BOMFC) as a highly sensitive probe substrate for P450 activity. BOMFC was used to develop a fluorescence-based high-throughput screening assay to measure the P450 inhibitory action of potential synergists. Azole fungicides prochloraz and triflumizole were identified as extremely potent nanomolar inhibitors of microsomal P450s, strongly synergizing deltamethrin toxicity in <i>An. funestus</i>. Overall, the present study contributed to the understanding of transfluthrin efficacy at the molecular and organismal level and identified azole compounds with potential to synergize pyrethroid efficacy in malaria vectors.
Optical proximity communication using reflective mirrors (2008)

Optical proximity communication (OPxC) with reflecting mirrors is presented. Direct optical links are demonstrated for silicon chips with better than -2.5dB coupling loss, excluding surface losses. OPxC is a true broadband solution with little impairment to the signal integrity for high-speed optical transmission. With wavelength division multiplexing (WDM) enabled OPxC, very high bandwidth density I/O, orders of magnitude higher than the traditional electrical I/O, can be achieved for silicon chips.
Quantification of quantum dots using phage display screening and assay (2009)

A proof-of-concept study showed the quantification of mercaptoacetic acid-coated ZnS-capped CdSe quantum dots (10 nM detection sensitivity and three order linear dynamic range) in biologically-relevant solutions using phage screening and assay.
Phase I bridging study of ch14.18/CHO long-term infusion in recurrent or refractory neuroblastoma patients in Japan. (2016)

10568 Background: The primary objective of this study was to assess safety and toxicity of anti-GD2 antibody ch14.18/CHO continuous long term infusion (LTI) used as single agent in Japanese pediatric neuroblastoma patients (pts). The secondary objective was to evaluate pharmacokinetic parameters (PK) to bridge between Japanese and European results. Anti-tumor activity was assessed in patients with evaluable diseases. Methods: Ch14.18/CHO (100 mg/m2/cycle; 3.3mg/kg/cycle below 12 kg body weight) was administered over 10 consecutive days every 5 weeks. If toxicity was acceptable, pts without progression could receive up to five cycles. Blood samples were collected for PK assessment, HACA response, immunophenotype, ADCC, CDC, biochemistry, Fc gamma receptor polymorphisms, and MRD assessment. Results: Ten pts with recurrent/refractory neuroblastoma were enrolled between September 2014 and July 2015. Nine pts (5 boys and 4 girls) were eligible and evaluable for toxicity and response. The median age was 4 (range 2-9) years. Grade 3 or higher toxicities were seen including anemia, leukopenia, neutropenia, elevation of hepatic transaminases, hyponatremia, and urticalia, but all these toxicities were reversible until the next scheduled cycle. No unexpected toxicities were seen. The supportive care guidelines allowed all pts to continue treatment at the same dose level. The PK of ch14.18/CHO in the Japanese pts was not significantly different from that observed in Caucasian pts. Three of nine pts had partial responses evaluated by MIBG scan or tumor marker. One patient progressed with brain metastases after 2 cycles.Eightpatients are alive with stable disease without further chemotherapy (median follow-up period 10 months (range 7-17) from enrollment). Conclusions: Japanese pts receiving ch14.18/CHO LTI for high risk neuroblastoma had similar PK, tolerability and objective response compared to Caucasian patients. These results allow bridging to data of ch14.18/CHO obtained in Caucasian patients for application in front of Asian authorities.
Symbolic debugging of embedded hardware and software (2001)

Symbolic debuggers are system-development tools that can accelerate the validation speed of behavioral specifications by allowing a user to interact with an executing code at the source level. In response to a user query, the debugger must retrieve and display the value of a source variable in a manner consistent with user expectations with respect to the source statement where execution has halted. However, when a behavioral specification has been optimized using transformations, values of variables may either be inaccessible in the runtime state or inconsistent with user expectations. We address the problem that pertains to the retrieval of source values for the globally optimized behavioral specifications. We present a new approach for symbolic debugging. The implementation of the new debugging approach poses several optimization tasks. We formulate the optimization tasks and develop heuristics to solve them. We demonstrate the effectiveness of the proposed approach on a set of designs.
On k-set consensus problems in asynchronous systems (2001)

In this paper, we investigate the k-set consensus problem in asynchronous distributed systems. In this problem, each participating process begins the protocol with an input value and by the end of the protocol must decide on one value so that at most k total values are decided by all correct processes. We extend previous work by exploring several variations of the problem definition and model, including for the first time investigation of Byzantine failures. We show that the precise definition of the validity requirement, which characterizes what decision values are allowed as a function of the input values and whether failures occur, is crucial to the solvability of the problem. For example, we show that allowing default decisions in case of failures makes the problem solvable for most values of k despite a minority of failures, even in face of the most severe type of failures (Byzantine). We introduce six validity conditions for this problem (all considered in various contexts in the literature), and demarcate the line between possible and impossible for each case. In many cases, this line is different from the one of the originally studied k-set consensus problem.
Shared Idiotypes Expressed by Human B-Cell Lymphomas (1989)

Each B-cell lymphoma expresses a surface immunoglobulin that contains unique antigenic determinants (idiotypes). We have produced 199 murine monoclonal antibodies reactive with the idiotypes isolated from 67 patients with follicular small-cleaved-cell lymphoma. These antiidiotype antibodies were analyzed for their ability to react with lymphoma cells from patients other than the one against which each antibody was made. Twenty of the 199 antiidiotype antibodies were reactive with lymphoma cells from more than one patient. Depending on the antibody, the frequency of idiotype sharing ranged from 0.6 to 6.2 percent of B-cell lymphoma tumors evaluated. Tumors could be grouped into distinct families on the basis of their reactivity with these antibodies. In the aggregate, the 20 antibodies reacted with a total of 49 of 150 B-cell lymphomas (33 percent), including 30 of 110 follicular small-cleaved-cell lymphomas (27 percent). Many of these shared idiotypes were expressed by more than one histopathological subtype of lymphoma. We conclude that a panel of antibodies reactive with shared idiotypes can be produced for patients with B-cell lymphoma, obviating the need to produce an antiidiotype antibody for each patient.
Peer Review of Manuscripts Submitted Via the Academy Fellowship Track (2011)

When the American Society for Microbiology set out to create a topflight entry into the new world of online, open-access journals, it had a number of assets in its favor. Endorsement by the American Academy of Microbiology (AAM), ASM’s honorific branch, was one of the critical assets. The AAM is home to more than 2,000 Academy Fellows, each of whom has been identified by a highly selective election process as an outstanding, internationally respected scientist. When mBio was launched, AAM Fellows were given the opportunity to submit their research findings on a privileged track (see http://mbio.asm.org/site/misc/fellows.xhtml for complete details), similar to that provided to members of the National Academy of Sciences for publication in that organization’s Proceedings. This track can lead to very rapid decisions when the editors accept the reviews provided by the submitting author.
Topological supramolecular network enabled highly conductive and stretchable organic bioelectronics (2022)

Abstract Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular level feature sizes. This longstanding material limitation in organic bioelectronics has impeded the full exploitation of its unique benefits. Here, we introduce a new molecular engineering strategy based on rationally designed topological supramolecular networks, which allows effective decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We achieve two orders of magnitude improvement in the conductivity under 100% strain in physiological environment, along with the capability for direct photopatterning down to 2 μm. These unprecedented capabilities allow us to realize previously inaccessible bioelectronic applications including high-resolution monitoring of ‘soft and malleable’ creatures, e.g., octopus, and localized neuromodulation down to single nucleus precision for controlling organ-specific activities through delicate tissues, e.g., brainstem.
Cardiovascular and Metabolic Regulation by the Adiponectin/C1q/Tumor Necrosis Factor–Related Protein Family of Proteins (2012)

C ardiovascular disease, including ischemic heart disease, is the major cause of morbidity and mortality in developed countries. Obese states are closely linked to the development of metabolic dysfunction and cardiovascular disorders. 4] onversely, a few adipokines are downregulated by obesity, and these factors typically exert beneficial actions on obesitylinked disorders.
3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent (2018)

IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, we focused attention on potency, ligand efficiency (LE), and physicochemical properties and have identified compounds <b>24</b> and (<i>R</i>)-<b>28</b> as having robust in vivo activity.
Scalable Process for the Production of a Highly Energetic Bromoacetylene Building Block (2018)

3-(Bromoethynyl)azetidine is a highly energetic building block (decomposition energy up to −1800 J g–1) that was required in multikilogram quantities for the production of an API. The development of a four-step, fully telescoped, scalable sequence for its synthesis is described, along with a detailed safety study of the corresponding hydrochloride salt in order to determine the potential explosive properties and transport classification. A screen of counterions identified the (+)-camphorsulfonic acid salt as the most suitable form for mitigation of the energetic properties, as judged by differential scanning calorimetry (onset 182 °C, energy −876 J g–1). This case study demonstrates how a daunting chemical structure can be “tamed” by chemical process development, tuning of molecular properties, and thorough safety investigations.
Effect of the surface coating on the magnetic nanoparticle smectic-A liquid crystal interaction (2006)

The behavior of smectic-A liquid crystals with magnetic particles has not been very well characterized. The authors have studied the interaction of a smectic-A liquid crystal with magnetic nanoparticles. They concentrate on the effect of the particles’ surface coating or functionalization compound. The surface coating in a nanoparticle is used to avoid phase separation and in biological applications to identify a particular cell or protein. Thus it is important to see how the surface coating interacts with the liquid crystal in conjunction with the magnetic nanoparticles. They have found out that depending on the surface coating the interaction of the nanoparticles with the liquid crystal varies. This variation is related to how the surface coating aligns the liquid crystal, how it contributes to the relative concentration of the nanoparticles in the liquid crystal-nanoparticle mixture, and how it affects the magnetic energy of the system.
Isolation enhancement between two closely spaced circular patches using dgs (2017)

This paper presents a new Defected Ground Structure (DGS) to enhance the isolation between two closely spaced circular patches for wireless applications. The antennas are placed on a Roger substrate with a relative permittivity of 3 and thickness of 1.52 mm. Four arcs are slotted on the ground underneath the substrate to eliminated the mutual current interacting between the elements. An enhancement of 26 dB has been achieved with a separation of 0.05 λo at 4.8 GHz. The total realized gain at the resonance frequency after the isolation is 5.2 dB. The array is suitable for applications where compact circular patches array is suitable.
Abstract #1492: Role of microRNA-101 in regulating histone methyltransferase EZH2 in cancer (2009)

Background: Prostate and breast cancer are major causes of cancer-related deaths. Prostate and breast cancer are genetic diseases that develop as a result of dysregulated gene function and environmental factors. Like other cancers, many complex molecular events initiate breast cancer development. Currently, there is no clear understanding of the genetic events that govern the ability of breast cancer cells to migrate and colonize at distant sites. Importantly, however, understanding the molecular mechanisms leading to cancer metastasis may lead to the identification of novel targets for individualized therapeutic intervention. Recent studies indicate that selected miRNAs may play a role in human cancer pathogenesis. MicroRNAs are endogenous non-coding RNAs that regulate gene expression through translational repression by binding to a target mRNA. Our previous studies showed that EZH2 has properties consistent with those of an oncogene, as overexpression promotes cell proliferation, colony formation, and increased invasion of benign cells in vitro and in vivo. Methods and Results: We transfected miR-101 precursor in prostate and breast carcinoma cells and found histone methyltransferase EZH2 was decreased at both transcript and protein levels by qPCR and immunoblots. miR-101 overexpression could also inhibit EZH2-mediated cell proliferation, invasion, and anchorage-independent growth. Re-introduction of EZH2 can rescue its function repressed by miR-101. At the epigenome, introduction of microRNA-101 resulted in reduced histone H3-lysine 27 trimethylation and reactivation of EZH2 repressed tumor suppressors such as ADRB2 and E-cadherin. Furthermore, we have demonstrated that microRNA-101 expression is anti-correlated with EZH2 expression in tumor tissues. Importantly, the genomic loci of microRNA-101 are lost in prostate and breast cancer as well as other aggressive tumors overexpressing EZH2. Conclusion: Our study suggests a mechanism by which genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways resulting in cancer progression and metastasis. Approaches to re-introduce microRNA-101 into tumors may have therapeutic benefit by reverting the epigenetic program of tumor cells to a more normal state. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1492.
Correlation between infrared phonon modes and dielectric relaxation in Bi2O3–ZnO–Nb2O5 cubic pyrochlore (2002)

Analysis of the dielectric relaxation phenomena in Bi2O3–ZnO–Nb2O5 cubic pyrochlore utilizing the Arrhenius equation is revisited to include recent high-frequency measurements. The fitting parameters obtained are further analyzed by comparison with theoretical and experimental activation energies of better understood relaxation systems such as dipolar glasses and relaxor ferroelectrics. The attempt jump frequency obtained from the Arrhenius fit (ν0∼4.385 THz) is found in correspondence with the resonant frequencies of the polar phonon modes previously identified by infrared spectroscopy. This correlation, and in particular the role of the O–A–O and O′–A–O′ bending phonon modes in driving the relaxation, is discussed.
Controlling the familywise error rate in widefield optical neuroimaging of functional connectivity in mice (2023)

RFT can lead to highly inflated FWERs. Although <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>t</mml:mi></mml:mrow> </mml:math> -distribution RFT can be accurate, it is sensitive to statistical assumptions. Permutation inference is robust to statistical errors and accurately controls the FWER.
Formalizing the movement of microparticles in a continuous flow microfluidic device for field flow fractionation (2015)

The movement of microparticles in a continuous flow microfluidic device employing dielectrophoresis for purposes of field-flow fractionation is a challenging problem since there are several forces incorporated. For instance, forces due to inertia, gravity, buoyancy, dielectrophoresis and virtual mass are accounted for in this system. The governing equations for particle movement are solved conventionally using finite difference method. This device is designed to be used in biomedical engineering for separation of cancer cells from blood. As per the model, the levitation height is independent of the radius, volumetric flow rate and microchannel height, under steady state conditions, of the microparticles when subjected to dielectrophoresis. On the other hand, it is dependent on the applied voltage and electrode/gap length. While the levitation height, under transient conditions, is dependent on all these parameters. This shows that understanding the particle movement at high level of abstraction is necessary in order to avoid fundamental errors in the design of systems that can make use of this behavior. In this paper we use Event-B formal methods in order to formalize and validate the movement of microparticles under DEP. This is achieved by modeling the dynamic behavior that can predict the trajectory of microparticles as a transition state based system. The proposed model can provide early understanding of the behavior of the system at high level of abstraction, and therefore, can help validating several aspects of the design which is beneficial to designers of DEP-FFF microdevice at early stages of the design process.
Toxins of Pseudomonas aeruginosa: New Perspectives (1983)

Toxin A is a protein with a molecular mass of approximately 66,000 daltons whose production is regulated by iron. The toxicity of toxin A is due to its ability to inhibit protein synthesis. A role for toxin A in infections due to Pseudomonas aeruginosa is supported by its extreme toxicity, its production by most clinical isolates, the decreased virulence of nontoxic mutants, and the results of immunologic studies of animals and humans.
Ultra wide band MIR MEMS FTIR spectrometer (2019)

Infrared portable spectral sensors are greatly required for rapid and simultaneous analysis of material composition; triggering new applications in the domain of on-site spectroscopy. At the same time, miniaturization of Fourier transform infrared (FTIR) spectrometers based on the silicon technology has been proven to be one of the most promising approaches for wide spectral range applications. In this work, we present a fiber-free MEMS FTIR spectrometer working in the wavelength range of 1.8 &mu;m to 6.8 &mu;m (5500-1470 cm<sup>-1</sup>). The spectrometer is based on the use of a monolithically integrated scanning Michelson interferometer, assembled with external reflecting micro-optical part, which is responsible for light coupling to and from the MEMS chip. The measured signal-to-noise ratio of the spectrometer is larger than 5000:1 with a spectral resolution of 66 cm<sup>-1</sup>. The experimental results of measuring the transmission of a polystyrene reference calibration film show four absorption peaks in the Mid Infra-Red (MIR) range at 3.27, 3.5, 5.15, 6.24 &mu;m in close agreement with theoretical predictions.
Using a 3D needle–tissue force distribution basis to optimise the design of an instrumented needle (2013)

International audience
Solid State Reactions - Theoretical and Experimental Aspects (1984)

(1984). Solid State Reactions - Theoretical and Experimental Aspects. Drug Development and Industrial Pharmacy: Vol. 10, No. 8-9, pp. 1175-1276.
Identification of Molecular Mechanisms by which NASH-derived Inflammation alters Hepatic Lipid Metabolism (2019)

Obesity and the metabolic syndrome, caused by high caloric intake combined with a sedentary lifestyle, are currently reaching pandemic dimensions worldwide. The hepatic consequence is an imbalance in fatty acid homeostasis, which results in hepatic lipid accumulation, a critical characteristic of non-alcoholic fatty liver disease (NAFLD). NAFLD can progress towards non-alcoholic steatohepatitis (NASH) which can ultimately lead to NASH-driven hepatocellular carcinoma (HCC). Chronic inflammation and inflammatory cytokines, derived from activated immune cells, strongly affect hepatic fatty acid metabolism and are implicated in NASH and NASH-derived HCC. However, underlying molecular mechanisms and signalling pathways are not known in detail yet.