Miracle-dz/UniFAR-FTUs huggingface dataset:
An acetylcholinesterase-mediated density shift technique demonstrates that coated vesicles from chick myotubes may contain both newly synthesized acetylcholinesterase and acetylcholine receptors

Coated vesicles isolated from 17 d chick embryo skeletal muscle contain acetylcholine receptors (AChRs) as shown by the presence of specific, latent binding sites for 125I-alpha bungarotoxin (125I-alpha-BTX). Since these coated vesicles also contain AChE (Benson et al., 1985), we hypothesized that a coated vesicle could carry both molecules: one an integral membrane protein, the other a secreted protein. An AChE- mediated density shift technique was used to obtain data that indicate that most isolated coated vesicles contain AChE and that some contain AChRs as well. Similar results were obtained with coated vesicles isolated from cultured chick embryo myotubes treated briefly with diisopropylfluorophosphate (DFP) to inactivate all preexisting AChE and allowed to synthesize AChE for 2 1/2 hr. These data are compatible with the hypothesis that both an integral plasma membrane protein, AChR, and a secretory protein, AChE, traverse the identical pathway after synthesis, as proposed by Rotundo and Fambrough (1980a). We suggest that coated vesicles are important intermediates in the exocytotic pathway, and that the large percentage of coated vesicles utilized for exocytotic transport can explain the rapid net increase in surface area achieved during myotube development. We also discuss the potential utility of the AChE-mediated density shift in studying the exocytotic and endocytotic pathways in other cell types, and possible pitfalls associated with its use.
High-Sensitivity C-Reactive Protein and Cognitive Function in Older Women

Background: Inflammatory processes may be involved in the development of dementia, although findings from epidemiologic studies directly examining inflammatory markers and dementia or its precursor, impaired cognitive function, are inconsistent. Methods: We measured plasma levels of the inflammatory marker, C-reactive protein, using a high-sensitivity assay (hs-CRP) in 4231 older participants of the Women's Health Study, who provided blood samples between 1992 and 1996 when they were age 60 to 90 years. From 1998 to 2000, we administered a battery of 5 cognitive tests measuring general cognition, verbal memory, and category fluency. Using multiple linear regression, we compared mean cognitive test scores across quintiles of hs-CRP, adjusting for potential confounding factors. Results: There was a wide distribution of hs-CRP levels among these women, and a large proportion had levels considered to reflect a high risk of cardiovascular disease. We observed no suggestion, however, that higher hs-CRP levels were associated with poorer cognitive performance. For example, on a global score combining results of all the cognitive tests, mean scores among women in the highest quintile of hs-CRP did not differ from those in the lowest quintile (multivariable-adjusted mean difference = 0.04; 95% confidence interval [CI]: −0.02 to 0.11, P for trend across quintiles = 0.38). Conclusion: Overall, in these women, we found no evidence of a link between hs-CRP, a marker of inflammation, and decrements in cognitive function.
Security analysis of the joint encryption and compressed sensing

This paper addresses the perfect secrecy analysis of the scenario for encryption via compressed sensing. In this system the measurement matrix is generated based on a secret seed and is considered as a shared secret key between sender and receiver. The knowledge of signal sparsity and shared secret key enables receiver to recover the original submitted signal. It was shown that the Shannon-sense perfect secrecy is not achievable in general in such an algorithm. Although, in this paper it is proven that a weaker sense perfect secrecy may be achieved under some assumptions. The mutual information between source and encrypted message sets is estimated to analyze the perfect secrecy problem in general for unknown statistical distribution over source message set. The numerical evidence is given to support theoretical results.
Comparative biochemistry of CO2 fixation and the evolution of autotrophy.

Carbon dioxide fixation is a polyphyletic trait that has evolved in widely separated prokaryotic branches. The three principal CO2-assimilation pathways are (i) the reductive pentose-phosphate cycle, i.e. the Calvin-Benson cycle; (ii) the reductive citric acid (or Arnon) cycle; and (iii) the net synthesis of acetyl-CoA from CO/CO2, or Wood pathway. Sequence analysis and the comparative biochemistry of these routes suggest that all of them were shaped to a considerable extent by the evolutionary recruitment of enzymes. Molecular phylogenetic trees show that the Calvin-Benson cycle was a relatively late development in the (eu)bacterial branch, suggesting that some form(s) of carbon assimilation may have been operative before chlorophyll-based photosynthesis. On the other hand, the ample phylogenetic distribution of both the Arnon and the Wood pathways does not allow us to infer which one of them is older. However, different lines of evidence, including experimental reports on the NiS/FeS-mediated C-C bond formation from CO and CH3SH are used here to argue that the first CO2-fixation route may have been a semi-enzymatic Wood-like pathway.
Embryonic development of goldfish (Carassius auratus): A model for the study of evolutionary change in developmental mechanisms by artificial selection

Background: Highly divergent morphology among the different goldfish strains (Carassius auratus) may make it a suitable model for investigating how artificial selection has altered developmental mechanisms. Here we describe the embryological development of the common goldfish (the single fin Wakin), which retains the ancestral morphology of this species. Results: We divided goldfish embryonic development into seven periods consisting of 34 stages, using previously reported developmental indices of zebrafish and goldfish. Although several differences were identified in terms of their yolk size, epiboly process, pigmentation patterns, and development rate, our results indicate that the embryonic features of these two teleost species are highly similar in their overall morphology from the zygote to hatching stage. Conclusions: These results provide an opportunity for further study of the evolutionary relationship between domestication and development, through applying well‐established zebrafish molecular biological resources to goldfish embryos. Developmental Dynamics 242:1262–1283, 2013. © 2013 Wiley Periodicals, Inc.
Reference compensation for localized surface-plasmon resonance sensors

OF DISSERTATION REFERENCE COMPENSATION FOR LOCALIZED SURFACE-PLASMON RESONANCE SENSORS Noble metal nanoparticles supporting localized surface plasmon resonances (LSPR) have been extensively investigated for label free detection of various biological and chemical interactions. When compared to other optical sensing techniques, LSPR sensors offer label-free detection of biomolecular interactions in localized sensing volume solutions. However, these sensors also suffer from a major disadvantage – LSPR sensors remain highly susceptible to interference because they respond to both solution refractive index change and non-specific binding as well as specific binding of the target analyte. These interactions can severely compromise the measurement of the target analyte in a complex unknown media and hence limit the applicability and impact of the sensor. In spite of the extensive amount of work done in this field, there has been a clear absence of efforts to make LSPR sensors immune to interfering effects. The work presented in this document investigates, both experimentally and numerically, dualand tri-mode LSPR sensors that utilize the multiple surface plasmon modes of gold nanostructures to distinguish target analyte from interfering bulk and non-specific binding effects. Finally, a series of biosensing experiments are performed to examine various regeneration assays for LSPR sensors built on indium tin oxide coated glass substrate.
Training-Based SWIPT: Optimal Power Splitting at the Receiver

We consider a point-to-point system with simultaneous wireless information and power transfer (SWIPT) over a block-fading channel. Each transmission block consists of a training phase and a data transmission phase. Pilot symbols are transmitted during the training phase for channel estimation at the receiver. To enable SWIPT, the receiver adopts a power-splitting design, such that a portion of the received signal is used for channel estimation or data detection, while the rest is used for energy harvesting. We optimally design the power-splitting ratios for both training and data phases to achieve the best ergodic capacity performance while maintaining a required energy harvesting rate. Our result shows how a power-splitting receiver can make the best use of the received pilot and data signals to obtain optimal SWIPT performance.
A Simplified Approach for Predicting Pulsed-Laser-Induced Carrier Generation in Semiconductor

Simplified analytic expressions are presented for calculating pulsed-laser induced charge generation in devices with collection volumes of any size. The expressions for charge generation by single-photon absorption for various limiting cases are applied to charge-collection measurements for a bulk Si photodiode, and single-event upsets in a 90-nm CMOS, silicon on insulator (SOI), static random-access memory (SRAM). Strong quantitative agreement between the simplified expressions, the full numerical calculations, and the experimental data serves to validate the analytical expressions. Furthermore, despite the complexity of determining charge deposited via two-photon absorption, the analytic expressions exhibit excellent agreement with full charge-generation simulations utilizing nonlinear-optical beam propagation software. These expressions therefore, represent a convenient and accurate method for estimating pulsed-laser induced charge generation in specified volumes, and are particularly relevant for two-photon absorption, which previously has required the use of complex numerical approaches.
Adaptive Evolution and Functional Redesign of Core Metabolic Proteins in Snakes

Background Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts. Methodology/Principal Findings We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins experienced unprecedented levels of positive selection, coevolution, convergence, and reversion at functionally critical residues. We examined Cytochrome C oxidase subunit I (COI) in detail, and show that it experienced extensive modification of normally conserved residues involved in proton transport and delivery of electrons and oxygen. Thus, adaptive changes likely altered the flow of protons and other aspects of function in CO, thereby influencing fundamental characteristics of aerobic metabolism. We refer to these processes as “evolutionary redesign” because of the magnitude of the episodic bursts and the degree to which they affected core functional residues. Conclusions/Significance The evolutionary redesign of snake COI coincided with adaptive bursts in other mitochondrial proteins and substantial changes in mitochondrial genome structure. It also generally coincided with or preceded major shifts in ecological niche and the evolution of extensive physiological adaptations related to lung reduction, large prey consumption, and venom evolution. The parallel timing of these major evolutionary events suggests that evolutionary redesign of metabolic and mitochondrial function may be related to, or underlie, the extreme changes in physiological and metabolic efficiency, flexibility, and innovation observed in snake evolution.
Differentiation of IncL and IncM Plasmids Associated with the Spread of Clinically Relevant Antimicrobial Resistance

Introduction bla OXA-48, bla NDM-1 and bla CTX-M-3 are clinically relevant resistance genes, frequently associated with the broad-host range plasmids of the IncL/M group. The L and M plasmids belong to two compatible groups, which were incorrectly classified together by molecular methods. In order to understand their evolution, we fully sequenced four IncL/M plasmids, including the reference plasmids R471 and R69, the recently described bla OXA-48-carrying plasmid pKPN-El.Nr7 from a Klebsiella pneumoniae isolated in Bern (Switzerland), and the bla SHV-5 carrying plasmid p202c from a Salmonella enterica from Tirana (Albania). Methods Sequencing was performed using 454 Junior Genome Sequencer (Roche). Annotation was performed using Sequin and Artemis software. Plasmid sequences were compared with 13 fully sequenced plasmids belonging to the IncL/M group available in GenBank. Results Comparative analysis of plasmid genomes revealed two distinct genetic lineages, each containing one of the R471 (IncL) and R69 (IncM) reference plasmids. Conjugation experiments demonstrated that plasmids representative of the IncL and IncM groups were compatible with each other. The IncL group is constituted by the bla OXA-48-carrying plasmids and R471. The IncM group contains two sub-types of plasmids named IncM1 and IncM2 that are each incompatible. Conclusion This work re-defines the structure of the IncL and IncM families and ascribes a definitive designation to the fully sequenced IncL/M plasmids available in GenBank.
Temporal dimensions of organizational learning : a review and directions for future research

This paper examines temporal dimensions of organizational learning. Organizational learning is a process phenomenon that unfolds over time. However, only scant attention has been paid to the role of time in theories of organizational learning and reviews of the field. The objective of this paper is to conceptualize the temporal dimensions of organizational learning, to review existing work that has implicitly or explicitly addressed time, and to identify directions for future research. Three sets of prior findings are discerned, concerning time as a resource for organizational learning; the timing and temporal structuring of organizational learning; and the role of the past, present, and future in organizational learning. Each of these perspectives offers unique insights, but is far from saturated; moreover, future research may be enriched by integrating approaches.
Gap Junction Blockers Decrease Defibrillation Thresholds Without Changes in Ventricular Refractoriness in Isolated Rabbit Hearts

Background—The maintenance and termination of reentry arrhythmias are determined by tissue properties such as refractoriness and conduction velocity. Although the effects of Na+ and K+ channel block on electrophysiological properties and defibrillation threshold (DFT) have been studied, little is known about the effect of gap junction blockers on defibrillation and tissue electrophysiological properties. Methods and Results—Triplicate DFTs (volts) were obtained before and 15 minutes after 4 &mgr;mol/L 16-doxyl-stearic acid (16-DSA, n=8), 1 mmol/L 1-heptanol (n=12) (both gap junction blockers), 3 &mgr;g/mL lidocaine (a sodium channel blocker) (n=8), and respective controls (n=27) in isolated perfused rabbit hearts. DFT decreased after 16-DSA (23±14%, P <0.01) and 1-heptanol (21±16%, P <0.01) but increased after lidocaine (26±28%, P <0.05). Ventricular fibrillation cycle length (VFCL) and QRS duration increased after all 3 agents, by 36±19% and 44±16% (16-DSA), 87±42% and 49±15% (heptanol), and 57±20% and 43±26% (lidocaine), respectively (all P <0.01). Spatially averaged temporal VFCL dispersion decreased significantly after all 3 agents, by 47±42% (16-DSA, P <0.05), 74±19% (1-heptanol, P <0.01), and 82±13% (lidocaine, P <0.01), respectively. Ventricular effective refractory period and monophasic action potential duration at 90% repolarization were unchanged after 16-DSA and 1-heptanol (P =NS) but increased after lidocaine (16±13%, P <0.01, and 6±5%, P =NS, respectively). There were no significant changes in DFT or any other electrophysiological variable in control hearts. Conclusions—Electrical uncoupling by 16-DSA and 1-heptanol significantly lowers DFT and dispersion of VFCL without altering refractoriness; lidocaine, at doses resulting in similar slowing of conduction, increases DFT.
Syndicated Loans in Emerging Markets

There has been a considerable expansion of the volume of syndicated loans in emerging markets in the recent years. We provide the first analysis of the determinants of the decision of banks to syndicate a loan on a sample of loan facilities from 50 emerging countries. We show the significant role of loan characteristics and of financial development, banking regulation, and legal institutions, on the decision to syndicate a loan. We support the efforts of authorities to increase banking competition and efficiency, and to implement binding banking regulation on capital requirement to promote the expansion of syndicated loans.
“I remember thinking …”: Neural activity associated with subsequent memory for stimulus-evoked internal mentations

Conscious thought involves an interpretive inner monologue pertaining to our waking experiences. Previous studies focused on the mechanisms that allow us to remember externally presented stimuli, but the neurobiological basis of the ability to remember one’s internal mentations remains unknown. In order to investigate this question, we presented participants with sentences and scanned their neural activity using functional magnetic resonance imaging (fMRI) as they incidentally produced spontaneous internal mentations. After the scan, we presented the sentences again and asked participants to describe the specific thoughts they had during the initial presentation of each sentence. We categorized experimental trials for each participant according to whether they resulted in subsequently reported internal mentations or not. The results show that activation within classic language processing areas was associated with participants’ ability to recollect their thoughts. Activation within mostly right lateralized and medial “default-mode network” regions was associated with not reporting such thoughts.
Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA

Objectives Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. Methods Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. Results The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10−4, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10−7, OR 0.71; case-only pmeta=1.9×10−4, OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. Conclusions These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.
Integrating biomarkers to predict renal and cardiovascular drug efficacy

The prevalence of chronic kidney disease is increasing worldwide, and forecasts for 2030 indicate that the number of patients requiring renal replacement therapies will more than double. The increase in requirement of renal replacement therapies and the availability of only few proven effective therapies highlight the need to develop new drugs and intervention strategies. In the current drug development and registration process a single renal risk marker is selected and a drug is targeted towards that risk marker. However, there are multiple causes of renal disease that may not all be captured by a single risk marker alone, and drugs have multiple effects beyond the target risk marker (so-called off-target effects). There have been several examples of medications that show a beneficial effect on a risk marker (e.g. blood pressure), but did not improve clinically meaningful outcomes (e.g. myocardial infarction, stroke). Better prediction of drug effects on clinical outcomes may be achieved by risk scores that integrate the effect on multiple risk markers, instead of using single markers alone. In this thesis we determined whether an approach that integrates medication response in multiple risk markers (the so-called PRE score) can be implemented in drug development. We show that the PRE score does a consistently better job at predicting long-term drug effects, compared to using single risk markers alone. The PRE score could be used to provide an early assessment of a medicine’s clinical efficacy and therefore has promising implications for implementation in practice, such as in clinical drug development or regulatory decision-making.
Validity of Power Settings of the Wahoo KICKR Power Trainer.

PURPOSE To assess the validity of power output settings of the Wahoo KICKR Power Trainer (KICKR) using a dynamic calibration rig (CALRIG) over a range of power outputs and cadences. METHODS Using the KICKR to set power outputs, powers of 100-999 W were assessed at cadences (controlled by the CALRIG) of 80, 90, 100, 110, and 120 rpm. RESULTS The KICKR displayed accurate measurements of power of 250-700 W at cadences of 80-120 rpm with a bias of -1.1% (95% limits of agreement [LoA] -3.6% to 1.4%). A larger mean bias in power was observed across the full range of power tested, 100-999 W (4.2%, 95% LoA -20.1% to 28.6%), due to larger biases of 100-200 and 750-999 W (4.5%, 95% LoA -2.3% to 11.3%, and 13.0%, 95% LoA -24.4% to 50.3%), respectively. CONCLUSIONS Compared with a CALRIG, the KICKR has acceptable accuracy reporting a small mean bias and narrow LoA in the measurement of power output of 250-700 W at cadences of 80-120 rpm. Caution should be applied by coaches and sports scientists when using the KICKR at power outputs of <200 W and >750 W due to the greater variability in recorded power.