Miracle-dz/UniFAR-FTUs huggingface dataset:
Recommendations for Planning Pilot Studies in Clinical and Translational Research

Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337
Plant polyphenols regulate chemokine expression and tissue repair in human keratinocytes through interaction with cytoplasmic and nuclear components of epidermal growth factor receptor system.

AIMS To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin [Pd], quercetin [Qr], and rutin). RESULTS Epidermal growth factor receptor (EGFR)-controlled chemokines CXCL8/interleukin 8 (IL-8), CCL2/monocyte chemotactic protein-1 (MCP-1), and CXCL10/interferon gamma-produced protein of 10 kDa (IP-10) were modulated by transforming growth factor alpha (TGF-α) and by the tumor necrosis factor alpha/interferon gamma combination (T/I). EGFR phosphorylation, nuclear translocation, and downstream cytoplasmic signaling pathways (extracellular regulation kinase [ERK]1/2, p38, STAT3, and PI-3K) were studied. All PPs did not affect TGF-α-induced STAT3 phosphorylation, whereas they suppressed T/I-activated NFkappaB and constitutive and T/I-induced but not TGF-α-induced ERK1/2 phosphorylation. Vb and Qr suppressed total EGFR phosphorylation, but they synergized with TGF-α to enhance nuclear accumulation of phosphorylated EGFR. Vb strongly inhibited TGF-α-induced p38 phosphorylation and T/I-induced NFkappaB and activator protein-1 (AP-1) binding to DNA. Vb was an effective inhibitor of T/I-stimulated chemokine synthesis, and it accelerated scratch wound healing in vitro. Anti-inflammatory and wound healing activities of Vb were confirmed in vivo in the full-thickness excision wound. Although Pd and Rv did not affect EGFR activation/translocation, they and Qr synergized with TGF-α and T/I in the induction of IL-8 transcription/synthesis while opposing enhanced MCP-1 and IP-10 transcription/synthesis connected with pharmacologically impaired EGFR functioning. INNOVATION PPs perturb the EGFR system in human keratinocytes, and this effect may be implicated in the regulation of inflammatory and repair-related processes in the skin. CONCLUSION Anti-inflammatory and wound healing effects of PPs depend on their interaction with EGFR-controlled cytoplasmic and nuclear pathways rather than on their direct redox properties.
Binding of basement‐membrane laminin by Escherichia coli

An invasive Escherichia coli (EIEC) isolate was found to bind basement‐membrane laminin in a saturable and time‐dependent manner. Excess of unlabelled laminin inhibited the binding of the radioactively labelled protein. Non‐invasive E. coli K‐12 exhibited only low‐level laminin binding but introduction of the virulence‐associated plasmid from the EIEC isolate led to high‐level binding. Expression of a receptor for laminin on the bacteria was therefore associated with the presence of the virulence plasmid. Scatchard plot analysis Indicated approximately 1000 receptors per bacterial cell, and a Kd of high‐affinity binding of 0.5 pM. A laminin‐binding protein which correlated with the presence of the plasmid was isolated and characterized. Its sequence of the eight amino‐terminal amino acids was identical to that of the LamB protein of E. coli, although the molecular mass of the two in sodium dodecyl sulphate/polyacrylamide gel (SDS‐PAGE) appeared to be slightly different. Both proteins reacted in immunoblot assays with polyclonal antisera raised against either protein, and both proteins bound laminin. Southern‐blot hybridization analysis established that both the EIEC strain and the K‐12 strains with or without the virulence plasmid contained one lamB gene only, and no laminin‐binding protein appeared when the virulence plasmid was introduced into bacteria deleted for the lamB gene. On the basis of these results we suggest that native LamB protein of E. coli or a modified variant of it serves as a major receptor for laminin binding and is present at an increased level in invasive E. coli containing the virulence plasmid.
Next-Generation Sequencing-Aided Rapid Molecular Diagnosis of Occult Macular Dystrophy in a Chinese Family

Purpose: To show early, rapid and accurate molecular diagnosis of occult macular dystrophy (OMD) in a four-generation Chinese family with inherited macular dystrophy. Methods: In the current study, we comprehensively screened 130 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the proband of a four-generation Chinese family that has suffered from maculopathy without a definitive diagnosis for over 10 years. Variants were filtered and analyzed to identify possible disease-causing variants before validation by Sanger sequencing. Results: Two heterozygous mutations—RP1L1 c.133 C > T (p.Arg45Trp), which is a hot spot for OMD, and ABCA4 c.6119 G > A (p.Arg2040Gln), which was identified in Stargardt’s disease were found in three patients, but neither of the mutations was found in the unaffected individuals in the same family, who are phenotypically normal or in the normal control volunteers. Conclusion: These results cannot only confirm the diagnosis of OMD in the proband, but also provide presymptomatic diagnosis of the proband’s children before the onset of visual acuity impairment and guidance regarding the prognosis and management of these patients. Heterozygous mutations of RP1L1 c.133 C > T (p.Arg45Trp) and ABCA4 c.6119 G > A (p.Arg2040Gln) are likely responsible for OMD. Our results further extend our current understanding of the genetic basis of OMD, and emphasize the importance of molecular diagnosis and genetic counseling for OMD.
A distributed primal-dual algorithm for computation of generalized Nash equilibria via operator splitting methods

In this paper, we propose a distributed algorithm for computation of a generalized Nash equilibrium (GNE) in noncooperative games over networks. We consider games in which the feasible decision sets of all players are coupled together by a globally shared affine constraint. Adopting the variational GNE as a refined solution, we reformulate the problem as that of finding the zeros of a sum of monotone operators through a primal-dual analysis and an augmentation of variables. Then we introduce a distributed algorithm based on forward-backward operator splitting methods. Each player only needs to know its local objective function, local feasible set, and a local block of the affine constraint, and share information with its neighbours. We show convergence of the proposed algorithm for fixed step-sizes. Numerical simulations are given for networked Cournot competition with bounded market capacities.
Dependence of the achilles tendon reflex on the excitability of spinal reflex pathways

Muscle afferent activity from the triceps surae was recorded during experimentally induced alterations in amplitude of the Achilles tendon jerk. No changes in the neural afferent response to tendon percussion or in the background level of neural activity occurred when the reflex response was altered by discomfort, distraction, changes in attention, or changes in the rate of tendon percussion. Reinforcement of the Achilles tendon jerk by forceful contraction of the forearm muscles did not alter the relationship between intensity of the tendon tap and amplitude of the evoked neural afferent volley. Nevertheless, such maneuvers lowered the reflex threshold and raised reflex sensitivity so that a smaller afferent volley was required to produce a tendon jerk, and an increase in the afferent volley produced a disproportionately greater increase in reflex electromyographic activity than would have occurred at rest. Reinforcement maneuvers potentiated the H‐reflex but did not alter the electrically induced afferent volley or the background level of neural activity. It is concluded that these changes in reflex responsiveness occurred through intrinsic spinal mechanisms independent of the fusimotor system.
Tres novelas para la misma historia: el encuentro entre Cortés y Xicoténcatl

En la primera mitad del siglo XIX una situacion similar en Europa y America pudo facilitar la insurgencia de la novela historica, en el momento de gran tension productiva y afirmativa de la Modernidad en cuanto epoca de la dominante historico-cultural burguesa, fundada en la fe en el progreso cientifico y tecnologico, en el proyecto historico-politico de la emancipacion humana y en la certeza acerca de la superioridad absoluta del modelo cultural de Occidente; ademas la Revolucion francesa, las guerras napoleonicas y antinapoleonicas en Europa y las guerras de Independencia americanas favorecen el sentido de participacion del pueblo en la idea de nacion y abren el camino a la definitiva afirmacion de la clase burguesa como clase dominante no solo en lo economico y cultural sino tambien en lo politico.
Improved live-wire algorithm for kidney image segmentation

Live-Wire segmentation algorithm is an interactive tool for efficient, accurate and reproducible boundary extraction which requires minimal user input. But the traditional Live-Wire algorithm is sensitive to noise and inefficient to distinguish between strong and weak edges in the image. To overcome the two drawbacks, this paper proposes an improved Live-Wire algorithm, its cost function is redefined: (1) change the Laplace operator into Canny and Sobel operators to construct the multiple cost terms, differences between Canny and Sobel operators allow them to contribute to the total cost calculation without redundant information; (2) redefine the gradient magnitude function of the cost function as nonlinear weighting edge gradient, the nonlinear weighting procedure can solve the undistinguished edge problem very well. Experiments are conducted on simulation and real image of the kidney. The experimental results prove that the proposed algorithm is really of good performance in the two drawbacks.
Test—Retest Reliability of the Geriatric Institutional Assessment Profile

The Geriatric Institutional Assessment Profile (GIAP) is a self-administered survey of hospital nurses designed to assess a hospital's readiness to implement geriatric programs. The GIAP measures nurses' knowledge and attitudes toward older adults as well as the organizational attributes that support or constrain geriatric best practices. Test—retest reliability estimates of the GIAP were conducted with a sample of 166 direct care nurses in three urban, university-affiliated hospitals over a 3-week time period. Intraclass correlation coefficients of GIAP scales and subscales ranged between . 82 and . 92, demonstrating good to very good reliability. The GIAP is a reliable measure of organizational attributes of the hospital relevant to geriatric care.
Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation.

Fimbriae belong to a class of extracellular filamentous proteins which are involved in the attachment of bacteria to host tissues. Bordetella pertussis, the etiological agent of whooping cough, produces two serologically distinct fimbriae. We show that, like a number of other B. pertussis virulence genes, transcription of the fimbrial subunit genes (fim) is positively controlled by trans‐acting polypeptides encoded by the bvg locus. In addition to this coordinate control, transcription of the fim genes is regulated at an individual level by phase variation. This process is characterized by a switching between a high and low level of expression of a particular fim gene. We have identified a conserved DNA region, located close to the start of the fim genes, which is likely to be involved in both positive regulation by the bvg locus, and phase variation. This promoter region contains a stretch of approximately 15 C residues and it appears that phase transitions occur by small insertions or deletions in this C‐rich region. We propose that these mutations affect transcription of the fim genes by varying the distance between the binding site for an activator and the −10 box. The fim promoter shows homology with the pertussis toxin promoter, which is also positively regulated by the bvg locus.
Whitepaper of NEWS 2010 Shared Task on Transliteration Generation

Transliteration is defined as phonetic translation of names across languages. Transliteration of Named Entities (NEs) is necessary in many applications, such as machine translation, corpus alignment, cross-language IR, information extraction and automatic lexicon acquisition. All such systems call for high-performance transliteration, which is the focus of shared task in the NEWS 2010 workshop. The objective of the shared task is to promote machine transliteration research by providing a common benchmarking platform for the community to evaluate the state-of-the-art technologies.
The Quest for an English-Speaking Nāgārjuna

Over the past century Nāgārjuna’s Mūlamadhyamakakārikā ( MMK ) has been translated, in part and in its entirety, into an array of languages. Although a number of English translations have appeared, a philologically reliable yet readable English rendering of the MMK has remained a desideratum. A new translation by Mark Siderits and Shōryū Katsura now supersedes Jay Garfield’s previously popular MMK translation, which, made in reliance on only the Tibetan version of the MMK , is often problematic ( The Fundamental Wisdom of the Middle Way , Oxford, 1995). Siderits’ and Katsura’s attempt to improve upon previous translations of the MMK was recently acknowledged by the Khyentse Foundation, which at the 17th Congress of the International Association of Buddhist Studies awarded them its 2014 “Prize for Outstanding Translation. ”
Theoretical and Experimental Investigation of Switching Ripple in the DC-Link Voltage of Single-Phase H-Bridge PWM Inverters

Direct current (DC)-link voltage ripple analysis is essential for determining harmonic noise and for DC-link capacitor design and selection in single-phase pulse-width modulation (PWM) inverters. This paper provides an extensive theoretical analysis of DC-link voltage ripple for full-bridge (H-bridge) inverters, with simulation and experimental verifications, considering a DC source impedance (non-ideal DC voltage source). The DC voltage ripple amplitude is theoretically estimated as a function of the output current, both amplitude and phase angle, and the modulation index. It consists of a switching frequency component and a double-fundamental frequency component (i.e., 100 Hz), thereby both components are considered in the analysis. In particular, the peak-to-peak distribution, maximum amplitude, and root mean square (RMS) values of the voltage switching ripple over the fundamental period are obtained. Based on the DC voltage requirements, simple and effective guidelines for designing DC-link capacitors are obtained.
Machine control using radial basis value functions and inverse state projection

Typical real world machine control tasks have some characteristics which makes them difficult to solve: Their state spaces are high-dimensional and continuous, and it may be impossible to reach a satisfying target state by exploration or human control. To overcome these problems, in this paper, we propose (1) to use radial basis functions for value function approximation in continuous space reinforcement learning and (2) the use of learned inverse projection functions for state space exploration. We apply our approach to path planning in dynamic environments and to an aircraft autolanding simulation, and evaluate its performance.
Buddhism and the Postmodern Novel: Severo Sarduy’s Cobra

This essay considers the postmodern engagement with Buddhism as a philosophy and a practice through the lens of Severo Sarduy’s Cobra (1972). It argues that a closer alignment of contemporary Buddhist studies with literary criticism can help us to better understand both contemporary writing in general and particular works of fiction. Sarduy’s Cobra and the criticism around it manifest the potential benefits of such a cross-disciplinary engagement. Although most critics have taken the novel to embody “Buddhist” themes, few have critically engaged the literature on Buddhism to see what this might actually mean. By placing Cobra alongside some contemporary work in Buddhist studies, I argue that the novel both understands and laments its own Orientalism. Cobra thus closes with a call for a future philosophy of global engagement—a call, I argue, that is still relevant for literary criticism today.
Millimeter-Wave High Radiation Efficiency Planar Waveguide Series-Fed Dielectric Resonator Antenna (DRA) Array: Analysis, Design, and Measurements

A low cost general architecture for a substrate integrated waveguide (SIW) series-fed dielectric resonator antenna (DRA) array, formed by two different slot polarizations, is proposed. In addition, a novel, simple, and generic transmission line (T.L.) circuit model, along with a fast and generic formulation for the new linear array antenna, is developed. The model can be used for reflection coefficient and radiation pattern (gain) calculations. The experimental data from two linear array modules, operating at the millimeter-wave band, are used to verify the simulated results of HFSS and the proposed model results. The measured radiation pattern for a 4 &times; 1 SIW-DRA array demonstrates a broadside beam with a radiated gain of 11.70 dB over an operating impedance bandwidth of 4.70%. Moreover, the simulated radiation efficiency is more than 90%.
Anthranilate Synthase and Chorismate Mutase Activities in Stem Rust-Inoculated and Elicitor-Treated Resistant, Moderately Resistant, and Susceptible Near-Isogenic Wheat Lines

Abstract Anthranilate synthase and chorismate mutase activities which control the flow of substrate from chorismate into the tryptophan pathway and into the phenylalanine/tyrosine pathway, respectively, were examined in three near isogenic wheat lines of Triticum aestivum L. (cv. Prelude Sr 5, highly resistant to stem rust infection; cv. Prelude Sr 24, moderately resistant; cv. Prelude srx, susceptible). The activities of both enzymes were found to increase in response to inoculation with the stem rust fungus Puccinia graminis f. sp. tritici or treatment with Pgt elicitor. Thus, both the tryptophan branch and the phenylalanine branch appear to contribute to the resistance response in wheat leaves. Only the cytosolic but not the plastidic fraction of the enzyme activities appears to be affected by fungal infection or elicitor treatment. Some differences with respect to degree and time dependency of enzyme activation were noticed between the three wheat lines following inoculation but not after treatment with the Pgt elicitor.
Bitter stimuli modulate the feeding decision of a blood-sucking insect via two sensory inputs

The gustatory system of animals is involved in food quality assessment and controls the feeding decision of an individual confronted with a potential alimentary source. Triatomines are haematophagous insects that feed on vertebrate blood. Once they reach a potential host, they walk over the host skin searching for an adequate site to pierce. Then, they insert their stylets and take a first sampling gorge to decide whether food is acceptable. Our work reveals that the presence of bitter compounds inhibits the feeding behavior of these bugs. Firstly, triatomines decreased their feeding behavior if substrates spread with quinine or caffeine were detected by external receptors localized exclusively in the antennae. Morphological inspections along with electrophysiological recordings revealed the existence of four gustatory sensilla located in the tip of the antenna that respond to both bitter tastants. The absence of these bitter detectors by antennal ablation reversed the observed feeding inhibition evoked by bitter compounds. Secondly, once triatomines pumped the first volume of food with bitter compounds (quinine, caffeine, berberine, salicin), a decrease in their feeding behavior was observed. Morphological inspections revealed the existence of eight gustatory sensilla located in the pharynx that might be responsible for the internal bitter detection. Finally, we found that a brief pre-exposure to bitter compounds negatively modulates the motivation of bugs to feed on an appetitive solution. Results presented here highlight the relevance of bitter taste perception in the modulation of the feeding behavior of a blood-sucking insect.
Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study

Background Emphysema on CT is a risk factor for all-cause mortality in persons with and without airflow obstruction; however, causes of death associated with emphysema remain uncertain, particularly in the general population. Aims To test associations between quantitatively assessed emphysema on CT and cause of death in persons with and without a substantial smoking history. Methods The Multi-Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45–84 years and without clinical cardiovascular disease, in 2000–2002. Per cent emphysema was defined on cardiac CT as per cent of lung voxels less than −950 Hounsfield units; emphysema on CT was defined as per cent emphysema above the upper limit of normal. Cause of death was classified by administrative codes. Proportional-hazards models were adjusted for age, race/ethnicity, gender, body mass index, smoking status, pack-years, coronary artery calcium, site and education. Additional adjustment for lung function was made in a subset with spirometry from 2004 to 2006. Results There were 1091 deaths over 12 years median follow-up. Emphysema on CT was strongly associated with increased mortality due to respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular disease. Associations persisted among participants with fewer than 10 pack-years and those without physician-diagnosed respiratory disease, and were similar after adjustment for airflow measures and in persons without airflow limitation. Conclusions Quantitatively assessed emphysema on CT is associated with greater respiratory disease and lung cancer mortality, even among persons without traditional risk factors.