gebhart/patrepeval huggingface dataset:
The growing debate over FDA reform. Food and Drug Administration. (1996)

Advocates for revamping the Food and Drug Administration (FDA) began a major public relations campaign shortly after the 1994 Republican takeover of Congress. FDA-regulated industries released reform proposals and AIDS activists are working with Congress to ensure FDA reform legislation serves patients' true interests. Legislative efforts, however, have been very slow. Senator Kassebaum proposed a reform bill that, among other provisions, speeds up FDA bureaucracy in approving new drugs, and allows promotion of off-label uses of drugs. Off-label promotion is believed by some to potentially harm drug development for treating rare diseases. Among all the reform efforts, the FDA Act is considered important to preserve because its high standards protect the public against dubious or fraudulent drug data.
Realistic Numerical and Analytical Modeling of Light Scattering in Brain Tissue for Optogenetic Applications (2016)

In recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka-Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings. Here, we introduce and study two modified approaches for modeling the distributions of light emanating from a multimode fiber and scattering through tissue, using both realistic numerical Monte Carlo simulations and an analytical approach based on the beam-spread function approach. We demonstrate a good agreement of the new methods' predictions both with recently published data, and with new measurements in mouse brain cortical slices, where our results yield a new cortical scattering length estimate of ∼47 µm at λ = 473 nm, significantly shorter than ordinarily assumed in optogenetic applications.
Light Source Position Measurement Technique Applicable in SOI Technology (2008)

Integrated optical sensors make use of a p-n-junction for light intensity detection, typically. Because of the costs, additional optical components are not available in standard integration processes. Therefore, in higher level optical sensors extra optical components are not part of an integration. In this paper a concept for integration is proposed, which especially allows to measure the angles of a far distance light source relative to the surface of the chip and the coordinate system of the integrated structure. The invention makes use of the stack topology and the light opacity of metal layers in the monolithic integration, the light translucency of , and the electrical light sensitivity of diodes. Because of perfect device isolation the implementation can be done most advantageously in SOI CMOS technology. With minor modifications it is applicable in other integration technologies as well. But leakage currents and device mismatching will limit the obtainable performance additionally.
Dehydrogenative Silane Coupling on Silicon Surfaces via Early Transition Metal Catalysis (2006)

Derivatization of silicon surfaces is an area of intense interest due to the centrality of silicon in the microelectronics industry and because of potential promise for a myriad of other applications. In this paper, we investigate the feasibility of Si-Si bond formation directly on the surface to contrast with the more widely studied Si-C and Si-O bond forming reactions. Functionalization of hydride-terminated silicon surfaces with silanes is carried out via early transition metal mediated dehydrogenative silane coupling reactions. Zirconocene and titanocene catalyst systems were evaluated for heterocoupling of a molecular silane, RSiH3, with a surface Si-H group on Si(s). The zirconocene catalysts proved to be much more reactive than the titanium system, and so the former was examined exclusively. The silanes, aromatic or aliphatic, are bonded to the silicon surface through direct Si-Si bonds, although the level of incorporation of the trihydroarylsilanes was substantially higher than that of the aliphatic silanes. The reaction proceeds on nanocrystalline hydride-terminated porous silicon surfaces, as well as flat Si(100)-H(x) and Si(111)-H interfaces. The reactions were studied by a variety of techniques, including FTIR, SIMS, and XPS.
Poly (ε‐caprolactone) coating delays vancomycin delivery from porous chitosan/β‐tricalcium phosphate composites (2012)

The orthopedic infection, such as osteomyelitis, especially those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains a major complication of open fractures. Local vancomycin delivery is considered to provide better methods when avascular zones prevent the delivery of drugs from conventional routes of administration. Chitosan (CS) delivery system has been developed with the disadvantages, such as mechanically weakness, lacking osteoconductivity, and the initial burst of antibiotics into the environment. The aim of this study was to confirm that the prepared CS/β-tricalcium phosphate (β-TCP) composites coated with poly (ε-caprolactone) (PCL), similar to natural bone in components, had a three-dimensional porous structure and could be used as drug carriers to deliver vancomycin in a sustained and controlled manner effectively for 6 weeks at levels to inhibit MRSA proliferation. We prepared porous CS/β-TCP composites by incorporating β-TCP into the system, and coated the composites with PCL of three different concentrations. The morphological structure of composites, including pore size and porosity, was examined. The result showed that CS/β-TCP coated with 2.5w/v% PCL solution had the best coating effect and it retarded the release of vancomycin in a near zero-order mechanism from 0 to 14 days. The drug delivery was significantly delayed after coated with 2.5w/v% PCL. The quantitative release of vancomycin was extended to 42 days. Therefore PCL coating could be used to retard the release of vancomycin from CS/β-TCP composites in a sustained and controlled manner. Porous CS/β-TCP coated with PCL might be one of the candidate vancomycin carriers for treating MRSA-related osteomyelitis.
Hand Image Segmentation in Video Sequence by GMM: a comparative analysis (2006)

This paper describes different approaches of realtime GMM (Gaussian mixture method) background subtraction algorithm using video sequences for hand image segmentation. In each captured image, the segmentation takes place where pixels belonging to the hands are separated from the background based on background extraction and skin-color segmentation. A time-adaptive mixture of Gaussians is used to model the distribution of each pixel color value. For an input image, every new pixel value is checked, deciding if it matches with one of the existing Gaussians based on the distance from the mean in terms of the standard deviation. The best matching distribution parameters are updated and its weight is increased. It is assumed that the values of the background pixels have low variance and large weight. These matched pixels, considered as foreground, are compared based on skin color thresholds. The hands position and other attributes are tracked by frame. That enables us to distinguish the hand movement from the background and other objects in movement, as well as to extract the information from the movement for dynamic hand gesture recognition
Land use and management influences on surface soil organic carbon in Tasmania (2013)

The effects of environmental parameters, land-use history, and management practices on soil organic carbon (SOC) concentrations, nitrogen, and bulk density were determined in agricultural soils of four soil types in Tasmania. The sites sampled were Dermosols, Vertosols, Ferrosols, and a group of texture-contrast soils (Chromosol and Sodosol) each with a 10-year management history ranging from permanent perennial pasture to continuous cropping. Rainfall, Soil Order, and land use were all strong explanatory variables for differences in SOC, soil carbon stock, total nitrogen, and bulk density. Cropping sites had 29–35% less SOC in surface soils (0–0.1 m) than pasture sites as well as greater bulk densities. Clay-rich soils contained the greatest carbon stocks to 0.3 m depth under pasture, with Ferrosols containing a mean of 158 Mg C ha–1, Vertosols 112 Mg C ha–1, and Dermosols 107 Mg C ha–1. Texture-contrast soils with sandier textured topsoils under pasture had a mean of 69 Mg C ha–1. The range of values in soil carbon stocks indicates considerable uncertainty in baseline values for use in soil carbon accounting. Farmers can influence SOC more by their choice of land use than their day-to-day soil management. Although the influence of management is not as great as other inherent site variables, farmers can still select practices for their ability to retain more SOC.
An Apple a Day: Which Bacteria Do We Eat With Organic and Conventional Apples? (2019)

Apples are among the most consumed fruits world-wide. They represent a source of direct human exposure to bacterial communities, which is less studied. We analyzed the apple microbiome to detect differences between tissues and the impact of organic and conventional management by a combined approach of 16S rRNA gene amplicon analysis and qPCR, and visualization using fluorescence <i>in situ</i> hybridization and confocal laser scanning microscopy (FISH-CLSM). Each apple fruit harbors different tissues (stem, peel, fruit pulp, seeds, and calyx), which were colonized by distinct bacterial communities. Interestingly, fruit pulp and seeds were bacterial hot spots, while the peel was less colonized. In all, approximately 10<sup>8</sup> 16S rRNA bacterial gene copy numbers were determined in each g apple. Abundances were not influenced by the management practice but we found a strong reduction in bacterial diversity and evenness in conventionally managed apples. In addition, despite the similar structure in general dominated by <i>Proteobacteria</i> (80%), <i>Bacteroidetes</i> (9%), <i>Actinobacteria</i> (5%), and <i>Firmicutes</i> (3%), significant shifts of almost 40% of bacterial genera and orders were monitored. Among them, especially bacterial signatures known for health-affecting potential were found to be enhanced in conventionally managed apples. Our results suggest that we consume about 100 million bacterial cells with one apple. Although this amount was the same, the bacterial composition was significantly different in conventionally and organically produced apples.
Open-loop band excitation Kelvin probe force microscopy (2012)

A multidimensional scanning probe microscopy approach for quantitative, cross-talk free mapping of surface electrostatic properties is demonstrated. Open-loop band excitation Kelvin probe force microscopy (OL BE KPFM) probes the full response-frequency-potential surface at each pixel at standard imaging rates. The subsequent analysis reconstructs work function, tip-surface capacitance gradient and resonant frequency maps, obviating feedback-related artifacts. OL BE KPFM imaging is demonstrated for several materials systems with topographic, potential and combined contrast. This approach combines the features of both frequency and amplitude KPFM and allows complete decoupling of topographic and voltage contributions to the KPFM signal.
Design and Thermal Characteristics of a Synthetic Jet Ejector Heat Sink (2004)

The design and thermal performance of a synthetic-air-jet-based heat sink for high-power dissipation electronics is discussed. Each fin of a plate-fin heat sink is straddled by a pair of two-dimensional synthetic jets, thereby creating a jet ejector system that entrains cool ambient air upstream of the heat sink and discharges it into the channels between the fins. The jets are created by periodic pressure variations induced in a plenum by electromagnetic actuators. The performance of the heat sink is assessed using a thermal test die encased in a heat spreader that is instrumented with a thermocouple. The case-to-ambient thermal resistance under natural convection with the heat sink is 3.15°C∕W. Forced convection with the synthetic jets enables a power dissipation of 59.2W at a case temperature of 70°C, resulting in a case-to-ambient thermal resistance of 0.76°C∕W. The synthetic-jet heat sink dissipates ∼40% more heat compared to steady flow from a ducted fan blowing air through the heat sink. The synthetic jets generate a flow rate of 4.48 CFM through the heat sink, resulting in 27.8 W/CFM and thermal effectiveness of 0.62. The effect of fin length on the thermal resistance of the heat sink is discussed. Detailed measurements on an instrumented heat sink estimate that the average heat transfer coefficients in the channel flow between the fins is 2.5 times that of a steady flow in the ducts at the same Reynolds Number.
More “mapping” in brain mapping: Statistical comparison of effects (2003)

The term "mapping" in the context of brain imaging conveys to most the concept of localization; that is, a brain map is meant to reveal a relationship between some condition or parameter and specific sites within the brain. However, in reality, conventional voxel-based maps of brain function, or for that matter of brain structure, are generally constructed using analyses that yield no basis for inferences regarding the spatial nonuniformity of the effects. In the normal analysis path for functional images, for example, there is nowhere a statistical comparison of the observed effect in any voxel relative to that in any other voxel. Under these circumstances, strictly speaking, the presence of significant activation serves as a legitimate basis only for inferences about the brain as a unit. In their discussion of results, investigators rarely are content to confirm the brain's role, and instead generally prefer to interpret the spatial patterns they have observed. Since "pattern" implies nonuniform effects over the map, this is equivalent to interpreting results without bothering to test their significance, a practice most of the experimentally-trained would eschew in other contexts. In this review, we appeal to investigators to adopt a new standard of data presentation that facilitates comparison of effects across the map. Evidence for sufficient effect size difference between the effects in structures of interest should be a prerequisite to the interpretation of spatial patterns of activation.
Homomorphic encryption and secure comparison (2008)

We propose a protocol for secure comparison of integers based on homomorphic encryption.We also propose a homomorphic encryption scheme that can be used in our protocol, makes it more efficient than previous solutions, and can also be used as the basis of efficient and general secure Multiparty Computation (MPC). We show how our comparison protocol can be used to improve security of online auctions, and demonstrate that it is efficient enough to be used in practice. For comparison of 16 bits numbers with security based on 1024 bits RSA (executed by two parties), our implementation takes 0.28 sec including all computation and communication. Using precomputation, one can save a factor of roughly 10.
The mitochondrial DNA transfer RNA<sup>Lys</sup>A→G<sup>[8344]</sup> mutation and the syndrome of myoclonic epilepsy with ragged red fibres [MERRF] (1993)

The mitochondrial DNA (mtDNA) transfer RNA (tRNA)Lys A-->G(8344) mutation was identified in seven patients. These patients and their relatives were assessed clinically; in one family the mutation was deduced to be present in four generations. The phenotype in index cases was consistent with the syndrome of myoclonic epilepsy with ragged red fibres, with the core clinical features of myoclonus, ataxia and seizures. Amongst other features, progressive external ophthalmoplegia, Leigh's syndrome and stroke-like episodes were observed, well recognized in mitochondrial myopathies but novel manifestations of this genotype. Samples of blood and muscle were analysed for the proportion of mutant mtDNA using an oligonucleotide hybridization technique. The proportion of mutant mtDNA in blood was significantly greater in symptomatic than asymptomatic cases. Furthermore, the proportion of mutant mtDNA in blood correlated with age of onset of disease and clinical severity assessed by a simple scale. Study of disease associated with the tRNA(Lys) A-->G(8344) mutation provides further insight into the pathogenesis and transmission of mitochondrial diseases. Quantification of the proportion of mtDNA in tissues demonstrates that this is a major factor determining the course of disease, but other, as yet unidentified factors are also likely to play a role.
Abstract 5566: CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth. (2013)

Abstract Medulloblastomas (MBs) are an aggressive class of intracranial pediatric tumors. Current multimodality treatments for MBs include surgery, ionizing radiation, and chemotherapy. Toxic side effects of therapies coupled with high incidence of recurrence and the metastatic spread warrants development of more effective, less toxic therapies for this disease. CARP-1/CCAR1 is a peri-nuclear phospho-protein that is a co-activator of the cell cycle regulatory anaphase promoting complex/cyclosome (APC/C) E3 ligase. CARP-1 functional mimetics (CFMs) are a novel class of small molecule compounds that interfere with CARP-1 binding with APC/C subunit APC-2, and suppress growth of a variety of cancer cells in part by promoting apoptosis. Here we investigated MB growth inhibitory potential of the CFM-1, 4, and 5, and found that CFMs inhibit growth of MB cells. CFM suppression of MB cell growth involved elevated CARP-1 expression, activation of pro-apoptotic stress-activated protein kinase (SAPK) p38, and apoptosis. Gene-array-based analysis of the CFM-4-treated Daoy MB cells indicated down-regulation of a number of key cell growth and metastasis-promoting genes including cell motility regulating small GTP binding protein p21Rac1, and extracellular matrix metallopeptidase (MMP)-10. Moreover, CFM-4 treatment stimulated expression of a number of growth inhibitory and apoptosis-inducing molecules such as neurotropin (NTF)3, while knock-down of NTF3 interfered with MB growth inhibitory effects of CFM-4. CFMs also attenuated biological properties of the MB cells by blocking their abilities to migrate, form colonies in suspension, and invade through the matrix-coated membranes. Together our data support anti-MB properties of CFM-4, and provide a proof-of-concept basis for further development of CFMs as potential anti-cancer agents for MBs. Citation Format: Abdelkader E. Ashour, Shazia Jamal, Vino Cheryan, Ahmed M. Alafeefy, Edi Levi, Adi L. Tarca, Lisa A. Polin, Arun K. Rishi. CARP-1 functional mimetics (CFMs): a novel class of small molecule inhibitors (SMIs) of medulloblastoma cell growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2013-5566
Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel (2020)

ABSTRACT Background The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Methods We tested plasma for COVID (SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Results ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. However, ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.
Homoleptic Rare‐Earth Metal(III) Tetramethylaluminates: Structural Chemistry, Reactivity, and Performance in Isoprene Polymerization (2007)

The complexes [Ln(AlMe4)3] (Ln=Y, La, Ce, Pr, Nd, Sm, Ho, Lu) have been synthesized by an amide elimination route and the structures of [Lu{(micro-Me)2AlMe2}3], [Sm{(micro-Me)2AlMe2}3], [Pr{(micro-Me)2AlMe2}3], and [La{(micro-Me)2AlMe2}2{(micro-Me)3AlMe}] determined by X-ray crystallography. These structures reveal a distinct Ln3+ cation size-dependency. A comprehensive insight into the intrinsic properties and solution coordination phenomena of [Ln(AlMe4)3] complexes has been gained from extended dynamic 1H and 13C NMR spectroscopic studies, as well as 1D 89Y, 2D 1H/89Y, and 27Al NMR spectroscopic investigations. [Ce(AlMe4)3] and [Pr(AlMe4)3] have been used as alkyl precursors for the synthesis of heterobimetallic alkylated rare-earth metal complexes. Both carboxylate and siloxide ligands can be introduced by methane elimination reactions that give the heterobimetallic complexes [Ln{(O2CAriPr)2(micro-AlMe2)}2(AlMe4)(C6H14)n] and [Ln{OSi(OtBu)3}(AlMe3)(AlMe4)2], respectively. [Pr{OSi(OtBu)3}(AlMe3)(AlMe4)2] has been characterized by X-ray structure analysis. All of the cerium and praseodymium complexes are used as precatalysts in the stereospecific polymerization of isoprene (1-3 equivalents of Et2AlCl as co-catalyst) and compared to the corresponding neodymium-based initiators reported previously. The superior catalytic performance of the homoleptic complexes leads to quantitative yields of high-cis-1,4-polyisoprene (>98%) in almost all of the polymerization experiments. In the case of the binary catalyst mixtures derived from carboxylate or siloxide precatalysts quantitative formation of polyisoprene is only observed for nLn:nCl=1:2. The influence of the metal size is illustrated for the heterobimetallic lanthanum, cerium, praseodymium, neodymium, and gadolinium carboxylate complexes, and the highest activities are observed for praseodymium as a metal center in the presence of one equivalent of Et2AlCl.