gebhart/patrepeval huggingface dataset:
Development of an on-chip detection of Zika virus and antibodies simultaneously using array of nanowells (2018)

ABSTRACT Zika virus (ZIKV) infections are an emerging health pandemic of significant medical importance. ZIKV appeared recently in the Americas from Africa via the South Pacific. The current outbreak has garnered attention by exhibiting unique characteristics of devastating neurodevelopmental defects in newborns of infected pregnant women. Current guidelines for ZIKV diagnostics developed by the Center of Diseases Control and Prevention (CDC) consist of nucleic acid testing, plaque reduction neutralization test (PRNT), and a serologic test for IgM detection. To better accommodate and comply with these guidelines, we developed a simultaneous on-chip detection of ZIKV and anti-ZIKV antibodies using an array of nanowells. Using on-chip microengraving, we were able to detect anti-ZIKV antibodies and their immunoglobulin isotypes. In parallel, applying on-chip real-time PCR with epifluorescence microscopy, we were able to quantify ZIKV viral load as low as one copy. To test clinical samples of patients at the postconvalescent stage, we analyzed samples from 8 patients. The on-chip nanowells could effectively identify antibodies that reacted against ZIKV envelope protein and their isotypes with high sensitivity and specificity. The small sample requirement with high specificity and sensitivity and combined molecular and serological tests could potentially be very advantageous and beneficial in accurate detection of Zika infection for better disease monitoring and management.
Assessment of protein inclusions in cultured cells using automated image analysis (2022)

Proteinaceous inclusions are associated with neurodegenerative diseases and cell models are often used to determine genetic and chemical modifiers of their formation. This protocol involves the usage of automated microscopy and machine learning-based image analysis to accurately quantify the levels of protein inclusion formation in cultured cells from fluorescence microscopy images. This protocol is highly scalable and can be applied to a few images or large datasets. For complete details on the use and execution of this protocol, please refer to McAlary et al. (2022).
Advancements in the Time-Frequency Approach to Multichannel Blind Source Separation (2012)

The ability of the human cognitive system to distinguish between multiple, simultaneously active sources of sound is a remarkable quality that is often taken for granted. This capability has been studied extensively within the speech processing community andmany an endeavor at imitation has beenmade. However, automatic speech processing systems are yet to perform at a level akin to human proficiency (Lippmann, 1997) and are thus frequently faced with the quintessential cocktail party problem: the inadequacy in the processing of the target speaker/s when there are multiple speakers in the scene (Cherry, 1953). The implementation of a source separation algorithm can improve the performance of such systems. Source separation is the recovery of the original sources from a set of observations; if no a priori information of the original sources and/or mixing process is available, it is termed blind source separation (BSS). Rather than rely on the availability of a priori information of the acoustic scene, BSS methods often employ an assumption on the constituent source signals, and/or an exploitation of the spatial diversity obtained through a microphone array. BSS has many important applications in both the audio and biosignal disciplines, including medical imaging and communication systems.
Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator (2011)

We have investigated a novel series of acid-derived γ-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent γ-secretase modulator, which lowered Aβ42, increased Aβ38, but had little to no effect on Aβ40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain Aβ42 levels in CF-1 mice and Fischer rats, as well as plasma Aβ42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.
Assessing the Value of Source-Over-Streamer Acquisition in the Barents Sea (2020)

Summary We will present an innovative new-generation TopSeis acquisition with dense near-offset illumination and long offsets for FWI applied in a 5000 km2 area over the Greater Castberg area in the Barents Sea. We will highlight how accurate deblending was a key processing step to uncover the potential of these blended data. We will also examine decimation tests so as to compare with conventional and short-offset conventional acquisition approaches. We will also show several examples of the first fast-track volume and compare with vintage data from the area.
Effect of secreted phospholipase A2 group IID, IIE, and IIF-deficiency on allergen-driven asthma phenotype (2013)

Rationale : Exaggerated inflammation and remodeling in the airways of patients with asthma occurs through complex Th2 cytokine, chemokine, growth factor, and eicosanoid interactions. The mammalian genome encodes 10 secreted phospholipase A 2 (sPLA 2 )s. The role of these sPLA 2 s in eicosanoid biosynthesis has been unclear. We have found that mice that lack groups X and V (respectively Henderson, W.R., Jr. et al. J Exp Med 2007; 204:865-77 and Henderson, W.R., Jr. et al. PLOS ONE 2013; DOI:10.1371/journal.pone.0056172) sPLA 2 s show reduction in Th2 cytokine-driven airway hyperresponsiveness (AHR) and inflammation. Data are lacking regarding the effect on asthma phenotype of the group IID, IIE, and IIF sPLA 2 enzymes that share a common three-dimensional structure with group V and X sPLA 2 s. Study Aim : Determine the role of group IID, IIE, and IIF sPLA 2 s in the mediation of airway inflammation and AHR in an ovalbumin (OVA)-induced mouse asthma model. Results : Airway infiltration by eosinophils (by morphometric analysis) and lung IL-5 release (by qPCR) were decreased in OVA-treated sPLA 2 -IID and IIE knockout (KO) mice compared to wildtype (WT) controls. These parameters of the asthma phenotype were unaffected by sPLA 2 -IIF deficiency. OVA-induced airway mucus metaplasia (by alcian blue histopathology) and AHR (by invasive plethysmography to inhaled methacholine) were not different between WT and sPLA 2 -IID, IIE, and IIF KOs. Conclusions : These results direct attention to the potential role of group IID and IIE sPLA 2 s in IL-5-mediated trafficking of eosinophils to the airways in allergen-driven asthma. Research Funding Source : National Institutes of Health grant HL36235.
Surrogate post-coital testing for contraceptive efficacy against human sperm activity in the ovine vaginal model† (2020)

High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm. Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen. No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM). Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.
Abstract IA8: A new class of drugs active in T-ALL is revealed in a zebrafish screen (2014)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer frequently associated with activating NOTCH1 mutations and dysregulation of MYC. We performed two complementary screens to identify novel agents with activity against T-ALL: i) a zebrafish screen for small molecules toxic to MYC-overexpressing thymocytes, and ii) a human T-ALL cell line screen for small molecules that synergize with Notch inhibitors. “Hits” common to both screens included perphenazine, a phenothiazine antipsychotic that induced apoptosis of fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled to mass spectrometry, we identified protein phosphatase 2A (PP2A) as the critical perphenazine target. In line with this finding, T-ALL cell lines treated with perphenazine underwent apoptosis associated with rapid dephosphorylation of multiple PP2A substrates, indicating that perphenazine binds and activates the PP2A tumor supressor. Moreover, shRNA knockdown of the scaffolding or catalytic subunits of PP2A attenuated the activity of perphenazine, indicating that PP2A is required for its antileukemic activity. Finally, treatment of primary human T-ALLs with pherphenazine suppressed cell growth and caused dephosphorylated of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurrent “rediscovery” of phenothiazines as a class of drugs with anti-cancer effects and highlight the therapeutic potential of pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates. Citation Format: Alejandro Gutierrez, Li Pan, Richard Groen, Frederic Baleydier, Alex Kentsis, Jason Marineau, Ruta Grebliunaite, Elena Kozakewich, Casie Reed, Francoise Pflumio, Sandrine Poglio, Benjamin Uzan, Paul Clemons, Lynn Verplank, Frank An, Jason Burbank, Stephanie Norton, Nicola Tolliday, Hanno Steen, Andrew P. Weng, Huipin Yuan, James E. Bradner, Constantine Mitsiades, A. Thomas Look, Jon C. Aster. A new class of drugs active in T-ALL is revealed in a zebrafish screen. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA8.
Identification of Thermus thermophilus HB8 tRNA (Gm18) methyltransferase gene (2000)

For the purpose of identification of the gene for Thermus thermophilus tRNA (Gm18) methyltransferase [tRNA (guanosine-2'-)-methyltransferase, EC 2.1.1.34], the purified enzyme from native source was analyzed by the peptide-mass mapping. The target gene encoded the amino acid sequences of the obtained peptides was searched in data from Thermus thermophilus HB8 genome-sequencing project. We found the target gene AB05130, which was expected to encode a protein composed of 194 amino acid residues and the molecular mass of this protein was calculated as 22083. The recombinant protein was expressed in E. coli as an active form. The Gm18 formation activity of the purified recombinant protein was confirmed by in vitro methylation followed by two-dimensional thin layer chromatography and Liquid Chromatography/Mass Spectrum analysis of substrate tRNA.
ChemInform Abstract: INVERSION OF CONFIGURATION IN THE BROMINATION OF VINYLIC MERCURIALS (1973)

Abstract Aus den definierten Vinylbromiden (I) entstehen über die Lithio‐Verbindungen ′ (II) mit Hg(II)‐bromid (III) die Organomercuri‐Derivate (IV), die in Schwefelkohlenstoff unter nahezu ausschließlicher Inversion zu (V) bromiert werden.
INTENSIVE CHEMOTHERAPY and G-CSF for HIV-ASSOCIATED NON-HODGKIN'S LYMPHOMA(LNHIV-91 regimen) (1997)

Objective: To evaluate the efficacy, safety and virological impact of intensive chemotherapy associated with G-CSF in HIV-associated NHL. Patients: 52 consecutive HIV+ patients with agressive NHL and CD4+ cells≥100 /mm3 were included in the study from Dec 1, 91 to Dec 1, 96. Male: 44, female: 8, Mean age: 36,8 (±8.8). CDC group A: 37, group B: 15. Mean CD4 cell count: 318 /mm3 (± 159) (range, 100-910). Mean CD8 cell count: 1125 /mm3 (± 586) (range, 190-2430). Burkitt: 19, large cell: 23, immunoblastic: 7, anaplastic: 3. Bulky disease: 15; stage IV: 25; bone marrow+: 7; CNS+: 9; B symptoms: 21; LDH > N: 33. Therapy: Induction with ACVBP (week 1,3,5): doxorubicine 75 mg/m2 day1, cyclophosphamide 1,2 g/m2 day1, vindesine 2 mg/m2 day1 and 5, bleomycine 10 mg day1 and 5, prednisolone 60 mg/m2 day1to5. Consolidation with CVM(week 8,10,12): cyclophosphamide 1 g/m2 day1, etoposide 200 mg/m2 day 1&2, methotrexate 3 g/m2 day2 + folinic acid. Intrathecal chemotherapy with MTX 12mg ± Ara-C 30 mg was given at day 2 of each ACVBP cycle. G-CSF 5µg/kg day 6 to 13 of each cycle: 300 µg if weight < 70 kg, 480 µg if > 70 kg. Patients with bulky disease at entry received a fourth cycle of ACVBP at induction. Clinical results: Median follow-up: 42 months (Dec 10, 96). Complete remission: 37 (71%). Relapse: 7. Alive in CR: 18; deaths: 31(18 with NHL). The median survival is 16,6 months. The 3-year survival probability is projected to be 36,6%. Virology: Mean acid-dissociated p24Ag was evaluated in the first 33 patients. Its level dropped by day6 (−48%, p<.001), remained stable with G-CSF and reached baseline value at end of therapy. Conclusions: The LNHIV-91 regimen is highly effective in HIV+ patients with agressive NHL and CD4+ cells ≥100 /mm3. Long term disease free survival is projected to be above 35% at 3 years.
Ethanol, not detectably metabolized in brain, significantly reduces brain metabolism, probably via action at specificGABA(A) receptors and has measureable metabolic effects at very low concentrations (2013)

Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we measured the effect of alcohol on metabolism of [3-¹³C]pyruvate in the adult Guinea pig brain cortical tissue slice and compared the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-¹³C]ethanol. Analyses of metabolic profile clusters suggest that the significant reductions in metabolism induced by ethanol (10, 30 and 60 mM) are via action at neurotransmitter receptors, particularly α4β3δ receptors, whereas very low concentrations of ethanol may produce metabolic responses owing to release of GABA via GABA transporter 1 (GAT1) and the subsequent interaction of this GABA with local α5- or α1-containing GABA(A)R. There was no measureable metabolism of [1,2-¹³C]ethanol with no significant incorporation of ¹³C from [1,2-¹³C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabelled ethanol.
A Meso-Scale Rolling-Contact Gripping Mechanism for Robotic Surgery (2015)

A new, compact 2 degree-of-freedom mechanism 4.1 mm in diameter suitable for robotically controlled surgical operations is presented. Current commercially available robotically controlled instruments achieve high dexterity defined by three degrees of freedom and relatively confined swept volume at just under 1 cm in diameter. Current smaller diameter instruments result in high part count and large swept volumes (less dexterity). A meso-scale rolling contact gripping mechanism is proposed as an alternative. The manufacturing of the parts is made feasible by Metal Laser Sintering, which can produce parts that are difficult to replicate with traditional manufacturing methods. The resulting instrument has only 6 parts and a small swept volume. Instrument actuation and control by a surgical robotic system is demonstrated.
Deep intelligent network for device-free people tracking (2019)

Recent radio frequency (RF) sensing techniques use a network of RF sensors to detect and locate people that do not carry any devices and can operate in non line-of-sight environments. Model-based device-free RF sensing systems use statistical models to quantify human presence and motion based on the received RF signal measurements. However, such methods often require the fine tuning of multiple model-dependent parameters in order to achieve sub meter accuracy. In this work, we propose to use deep neural networks together with visual tracking systems to effectively generate training data so as to learn a general model. Our method can automatically produce human motion and occupancy images from RF sensor network measurements without the need for manual RF model parameter tuning.
Unconditional Security of Time-Energy Entanglement Quantum Key Distribution Using Dual-Basis Interferometry (2014)

High-dimensional quantum key distribution (HDQKD) offers the possibility of high secure-key rate with high photon-information efficiency. We consider HDQKD based on the time-energy entanglement produced by spontaneous parametric down-conversion and show that it is secure against collective attacks. Its security rests upon visibility data-obtained from Franson and conjugate-Franson interferometers-that probe photon-pair frequency correlations and arrival-time correlations. From these measurements, an upper bound can be established on the eavesdropper's Holevo information by translating the Gaussian-state security analysis for continuous-variable quantum key distribution so that it applies to our protocol. We show that visibility data from just the Franson interferometer provides a weaker, but nonetheless useful, secure-key rate lower bound. To handle multiple-pair emissions, we incorporate the decoy-state approach into our protocol. Our results show that over a 200-km transmission distance in optical fiber, time-energy entanglement HDQKD could permit a 700-bit/sec secure-key rate and a photon information efficiency of 2 secure-key bits per photon coincidence in the key-generation phase using receivers with a 15% system efficiency.
Robust and flexible estimation of data-dependent stochastic mediation effects: a proposed method and example in a randomized trial setting (2017)

Causal mediation analysis can improve understanding of the mechanisms underlying epidemiologic associations. However, the utility of natural direct and indirect effect estimation has been limited by the assumption of no confounder of the mediator-outcome relationship that is affected by prior exposure---an assumption frequently violated in practice. We build on recent work that identified alternative estimands that do not require this assumption and propose a flexible and double robust semiparametric targeted minimum loss-based estimator for data-dependent stochastic direct and indirect effects. The proposed method treats the intermediate confounder affected by prior exposure as a time-varying confounder and intervenes stochastically on the mediator using a distribution which conditions on baseline covariates and marginalizes over the intermediate confounder. In addition, we assume the stochastic intervention is given, conditional on observed data, which results in a simpler estimator and weaker identification assumptions. We demonstrate the estimator's finite sample and robustness properties in a simple simulation study. We apply the method to an example from the Moving to Opportunity experiment. In this application, randomization to receive a housing voucher is the treatment/instrument that influenced moving to a low-poverty neighborhood, which is the intermediate confounder. We estimate the data-dependent stochastic direct effect of randomization to the voucher group on adolescent marijuana use not mediated by change in school district and the stochastic indirect effect mediated by change in school district. We find no evidence of mediation. Our estimator is easy to implement in standard statistical software, and we provide annotated R code to further lower implementation barriers.
Reuse Distance Based Circuit Replacement in Silicon Photonic Interconnection Networks for HPC (2014)

Optical interconnects, which support the transport of large bandwidths over warehouse-scale distance, can help to further scale data-movement capabilities in high performance computing (HPC) platforms. However, due to the circuit switching nature of optical systems and additional peculiarities, such as sensitivity to temperature and the need for wavelength channel locking, optical links generally show longer link initialization delays. These delays are a major obstacle in exploiting the high bandwidth of optics for application speedups, especially when low-latency remote direct memory access (RDMA) is required or small messages are used. These limitations can be overcome by maintaining a set of frequently used optical circuits based on the temporal locality of the application and by maximizing the number of reuses to amortize initialization overheads. However, since circuits cannot be simultaneously maintained between all source-destination pairs, the set of selected circuits must be carefully managed. This paper applies techniques inspired by cache optimizations to intelligently manage circuit resources with the goal of maximizing the circuit successful 'hit' rate. We propose the concept of "circuit reuse distance" and design circuit replacement policies based on this metric. We profile the reuse distance based on a group of representative HPC applications with different communications patterns and show the potential to amortize circuit setup delay over multiple circuit requests. We then develop a Markov transition matrix based reuse distance predictor and two circuit replacement policies. The proposed predictor provides significantly higher accuracy than traditional maximum likelihood prediction and the two replacement policies are shown to effectively increase the hit rate compared to the Least Recently Used policy. We further investigate the tradeoffs between the realized hit rate and energy consumption. Finally, the feasibility of the proposed concept is experimentally demonstrated using silicon photonic devices in an FPGA-controlled network test bed.