Miracle-dz/UniFAR-FTUs huggingface dataset:
Empirical Evaluation of Bone Extraction Protocols

The application of high-resolution analytical techniques to characterize ancient bone proteins requires clean, efficient extraction to obtain high quality data. Here, we evaluated many different protocols from the literature on ostrich cortical bone and moa cortical bone to evaluate their yield and relative purity using the identification of antibody-antigen complexes on enzyme-linked immunosorbent assay and gel electrophoresis. Moa bone provided an ancient comparison for the effectiveness of bone extraction protocols tested on ostrich bone. For the immunological part of this study, we focused on collagen I, osteocalcin, and hemoglobin because collagen and osteocalcin are the most abundant proteins in the mineralized extracellular matrix and hemoglobin is common in the vasculature. Most of these procedures demineralize the bone first, and then the remaining organics are chemically extracted. We found that the use of hydrochloric acid, rather than ethylenediaminetetraacetic acid, for demineralization resulted in the cleanest extractions because the acid was easily removed. In contrast, the use of ethylenediaminetetraacetic acid resulted in smearing upon electrophoretic separation, possibly indicating these samples were not as pure. The denaturing agents sodium dodecyl sulfate, urea, and guanidine HCl have been used extensively for the solubilization of proteins in non-biomineralized tissue, but only the latter has been used on bone. We show that all three denaturing agents are effective for extracting bone proteins. One additional method tested uses ammonium bicarbonate as a solubilizing buffer that is more appropriate for post-extraction analyses (e.g., proteomics) by removing the need for desalting. We found that both guanidine HCl and ammonium bicarbonate were effective for extracting many bone proteins, resulting in similar electrophoretic patterns. With the increasing use of proteomics, a new generation of scientists are now interested in the study of proteins from not only extant bone but also from ancient bone.
Site-specific replacement of phosphorothioate with alkyl phosphonate linkages enhances the therapeutic profile of gapmer ASOs by modulating interactions with cellular proteins

Abstract Phosphorothioate-modified antisense oligonucleotides (PS-ASOs) interact with a host of plasma, cell-surface and intracellular proteins which govern their therapeutic properties. Given the importance of PS backbone for interaction with proteins, we systematically replaced anionic PS-linkages in toxic ASOs with charge-neutral alkylphosphonate linkages. Site-specific incorporation of alkyl phosphonates altered the RNaseH1 cleavage patterns but overall rates of cleavage and activity versus the on-target gene in cells and in mice were only minimally affected. However, replacing even one PS-linkage at position 2 or 3 from the 5′-side of the DNA-gap with alkylphosphonates reduced or eliminated toxicity of several hepatotoxic gapmer ASOs. The reduction in toxicity was accompanied by the absence of nucleolar mislocalization of paraspeckle protein P54nrb, ablation of P21 mRNA elevation and caspase activation in cells, and hepatotoxicity in mice. The generality of these observations was further demonstrated for several ASOs versus multiple gene targets. Our results add to the types of structural modifications that can be used in the gap-region to enhance ASO safety and provide insights into understanding the biochemistry of PS ASO protein interactions.
Comparison of the Sex-Specific Associations Between Systolic Blood Pressure and the Risk of Cardiovascular Disease: A Systematic Review and Meta-analysis of 124 Cohort Studies, Including 1.2 Million Individuals

Background and Purpose— Conflicting results have been reported on whether the association between increments in systolic blood pressure (SBP) and cardiovascular disease differs between men and women. We performed a systematic review with meta-analysis to compare reliably sex-specific associations between SBP and cardiovascular risk. Methods— PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between January 1, 1966, and March 31, 2012. Studies were selected if they presented sex-specific estimates, with associated variability, of the relative risk for either ischemic heart disease or stroke according to SBP. The data were pooled using random effects models with inverse variance weighting, and estimates of the ratio of the relative risks per 10 mm Hg increment in SBP, comparing women with men, were derived. Results— Data from 124 prospective cohort studies, including information on 1197 472 individuals (44% women) and 26 176 stroke and 24 434 ischemic heart disease events, were included. Overall, there was no evidence to suggest a sex difference in the relationship between SBP and either the risk of stroke (pooled ratio of relative risks, 0.98 [95% confidence interval, 0.96; 1.01]; P=0.13) or ischemic heart disease (pooled ratio of relative risks, 1.00 [95% confidence interval, 0.97; 1.04]; P=0.85). Conclusions— Elevated levels of SBP are a major risk factor for stroke and ischemic heart diseases in both women and men. This study unequivocally demonstrates the broadly similar impact of SBP increments on cardiovascular outcomes in both sexes.
Integrin α3β1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt

This study demonstrates that integrin α3β1 interactions with both α3- and α5-containing laminins regulate ureteric bud (UB) development by functionally modulating the Akt signaling pathway. In addition, the work done shows that K63-linked polyubiquitination plays a previously unrecognized role in integrin α3β1–dependent cell signaling required for UB development and that this may be a novel general mechanism whereby integrins regulate signaling pathways.
Development of an experimental diet for determining bioavailable choline concentration and its application in studies with soybean lecithin.

Attempts to determine choline bioavailability have encountered criticism of experimental diets and protocol. Our objectives were to develop a choline-deficient soy isolate diet to quantify bioavailable choline concentration of soybean lecithin and to compare results to those obtained with a purified diet. In Assay 1, weight gain of chicks fed a choline-free crystalline amino acid diet responded linearly (P < .01) to graded doses of choline chloride, fluid lecithin (FL), or deoiled lecithin (DL). Multiple linear regression analysis indicated a bioavailable choline content of 2.3 and 3.7% for FL and DL, respectively. In Assay 2, a choline-deficient soy isolate diet was supplemented with 2-amino-2-methyl-1-propanol (AMP) to inhibit choline biosynthesis. Weight gain, feed intake, and feed efficiency increased (P < .05) markedly with the addition of choline chloride, but supplemental methionine or betaine had no effect (P > .10). Addition of 10% soybean meal to the diet severely deficient in choline per se produced a growth response (P < .05), whereas the same addition to the diet made adequate in choline did not elicit a growth response. In Assay 3, addition of graded levels of choline chloride, FL, or DL to the choline-deficient soy isolate diet containing AMP resulted in a linear (P < .01) increase in weight gain and feed intake. Multiple linear regression analysis indicated a bioavailable choline content of 2.0 and 3.5% for FL and DL, respectively. The AMP-containing soy isolate diet seems well suited for determination of bioavailable choline content in products containing secondary nutrients. Bioavailable choline content of FL and DL was similar to estimates of total choline content, suggesting that the choline in these products was fully available.
Early Literacy Achievements, Population Density and the Transition to Modern Growth

The transition from economic stagnation to sustained growth is often modeled thanks to "population-induced" productivity improvements, which are assumed rather than derived from primary assumptions. In this paper the effect of population on productivity is derived from optimal behavior. More precisely, both the number and location of education facilities are chosen optimally by municipalities. Individuals determine their education investment depending on the distance to the nearest school, and also on technical progress and longevity. In this setting, higher population density enables the set-up costs of additional schools to be covered, opening the possibility to reach higher educational levels. Using counterfactual experiments we find that one-third of the rise in literacy can be directly attributed to the effect of density, and one-sixth is linked to higher longevity. Moreover, the effect of population density in the model is consistent with the available evidence for England, where it is shown that schools were established at a high rate over the period 1540-1620. (JEL: O41, I21, R12, J11) (c) 2007 by the European Economic Association.
Complete Genome Sequence of Porcine Reproductive and Respiratory Syndrome Virus Strain QY2010 Reveals a Novel Subgroup Emerging in China

ABSTRACT QY2010 is a highly pathogenic North American-type porcine reproductive and respiratory syndrome virus (PRRSV). The complete genome sequence shows that QY2010 shares low sequence identity (60 to 88.7%) to all known PRRSV isolates. Phylogenetic analyses further reveal that QY2010 constitutes a novel subgroup within the North American genotype of PRRSV.
International Journal of Nanomedicine Dovepress Convection-enhanced Delivery of Methotrexate-loaded Maghemite Nanoparticles Enav Corem-salkmon

Convection-enhanced delivery (CED) is a novel approach for delivering drugs directly into brain tumors by intracranial infusion, enabling the distribution of high drug concentrations over large tissue volumes. This study was designed to present a method for binding methotrexate (MTX) to unique crystalline, highly ordered and superparamagnetic maghemite nanoparticles via human serum albumin (HSA) coating, optimized for CED treatments of gliomas. Naked nanoparticles and HSA-or polyethylene glycol (PEG)-coated nanoparticles with/without MTX were studied. In vitro results showed no toxicity and a similar cell-kill efficacy of the MTX-loaded particles via HSA coating to that of free MTX, while MTX-loaded particles via PEG coating showed low efficacy. In vivo, the PEG-coated nanoparticles provided the largest distributions in normal rat brain and long clearance times, but due to their low efficacy in vitro, were not considered optimal. The naked nanoparticles provided the smallest distributions and shortest clearance times. The HSA-coated nanoparticles (with/without MTX) provided good distributions and long clearance times (nearly 50% of the distribution volume remained in the brain 3 weeks post treatment). No MTX-related toxicity was noted. These results suggest that the formulation in which HSA was bound to our nanoparticles via a unique precipitation method, and MTX was bound covalently to the HSA, could enable efficient and stable drug loading with no apparent toxicity. The cell-kill efficacy of the bound MTX remained similar to that of free MTX, and the nanoparticles presented efficient distribution volumes and slow clearance times in vivo, suggesting that these particles are optimal for CED.
Adaptive Event-Triggered Control Based on Heuristic Dynamic Programming for Nonlinear Discrete-Time Systems

This paper presents the design of a novel adaptive event-triggered control method based on the heuristic dynamic programming (HDP) technique for nonlinear discrete-time systems with unknown system dynamics. In the proposed method, the control law is only updated when the event-triggered condition is violated. Compared with the periodic updates in the traditional adaptive dynamic programming (ADP) control, the proposed method can reduce the computation and transmission cost. An actor–critic framework is used to learn the optimal event-triggered control law and the value function. Furthermore, a model network is designed to estimate the system state vector. The main contribution of this paper is to design a new trigger threshold for discrete-time systems. A detailed Lyapunov stability analysis shows that our proposed event-triggered controller can asymptotically stabilize the discrete-time systems. Finally, we test our method on two different discrete-time systems, and the simulation results are included.
Infectivity phenotypes of H3N2 influenza A viruses in primary swine respiratory epithelial cells are controlled by sialic acid binding

Please cite this paper as: Bateman et al. (2012) Infectivity phenotypes of H3N2 influenza A viruses in primary swine respiratory epithelial cells are controlled by sialic acid binding. Influenza and Other Respiratory Viruses 6(6), 424–433.
Extending static analysis by mining project-specific rules

Commercial static program analysis tools can be used to detect many defects that are common across applications. However, such tools currently have limited ability to reveal defects that are specific to individual projects, unless specialized checkers are devised and implemented by tool users. Developers do not typically exploit this capability. By contrast, defect mining tools developed by researchers can discover project-specific defects, but they require specialized expertise to employ and they may not be robust enough for general use. We present a hybrid approach in which a sophisticated dependence-based rule mining tool is used to discover project-specific programming rules, which are then transformed automatically into checkers that a commercial static analysis tool can run against a code base to reveal defects. We also present the results of an empirical study in which this approach was applied successfully to two large industrial code bases. Finally, we analyze the potential implications of this approach for software development practice.
Income inequality, social capital and self-inflicted injury and violence-related mortality

Background: The objective of the study was to investigate the relation of income inequality and indicators of social capital to self-inflicted injury mortality (suicide) and violence-related mortality, and to the share of total mortality that is due to these two causes of death in 35 developed countries. Methods: An ecological study including 30 European countries, including former communist countries, and five developed countries from other parts of the world was carried out. Countries were included if there was information available about mortality and income inequality, and if they had been included in the European/World Values Surveys of 2000. The main outcome measures were self-inflicted injury and violence-related mortality and the percentage of total mortality that was due to these two causes of death. Results: There were important variations between former communist Europe and other developed countries. In other developed countries income inequality was significantly, but negatively, correlated with self-inflicted deaths, but not with violence-related deaths. In former communist countries, it was found that income inequality was correlated with violence-related deaths, but not self-inflicted deaths. Only in former communist countries did adjusting for the level of preparedness to help others reduce the associations. Conclusions: The expectation that income inequality would have a relatively strong association with the two causes of death indicating mortality due to self-infliction and violence was only partly confirmed, that is, only for former communist countries and only for violence-related mortality. The expectation that adjusting indicators of social capital would lower associations was also only partly confirmed.
Solo, together, apart: evaluating modes of CSCL for learning a problem solving task

This paper describes an experiment that examines how computer supported collaboration influences how children learn to solve a simple puzzle. We found that collaboration resulted in relatively poor performance during a 'training' period, but that it appeared to aid puzzle comprehension during a later 'testing' period. Results also showed that girls found it harder than boys to solve the puzzle when collaborating.
Sequence Learning in a Single Trial

While recurrent neural networks can store pattern sequences through incremental learning, there could be a trade-off between network capacity and the speed of learning. The brain may solve this problem by using a two-stage system: a compact, low-capacity subsystem for rapid temporary storage of a few sequences, and a larger, high-capacity, slow learning subsystem for long-term storage of all sequences. In this study, we evaluate the ability of sparsely connected networks to learn pattern sequences in a single exposure using very high learning rates. The key factor is the amount of recurrent inhibition in the system. Our results indicate that post-synaptic gating in the learning rule enhances the rapid learning ability of networks. We also suggest how such rapid learning networks could transfer their memories to long-term storage.
A Cascaded Coupled Inductor-Reverse High Step-Up Converter Integrating Three-Winding Coupled Inductor and Diode–Capacitor Technique

This paper introduces a cascaded high step-up converter realized with a tightly coupled three-winding coupled inductor. Compared with existing high step-up converters, the proposed converter features that the smaller the turns ratio, the larger the conversion gain. So, the name coupled inductor-reverse is given to represent reverse-coupled inductor principle of operation. In addition, diode–capacitor circuit is introduced to not only recycle leakage energy to output, but also further lift voltage conversion gain. This paper illustrates operation principle of the proposed converter, discusses effect of leakage inductance on voltage gain, and deduces voltage and current stresses of components. Finally, a prototype rated at 400 W has been established, and experimental results verify correctness of the above theoretical analysis.
A Proactive Indoor Positioning System in Randomly Deployed Dense WiFi Networks

A new approach for indoor positioning is presented, aimed at designing a WiFi positioning system that is feasible and convenient for both service providers and end users. In the proposed approach, only access points (APs) need to collect the received signal strengthes (RSS) of mobile devices, and use these RSS samples to jointly estimate the devices' locations. To enhance the accuracy of positioning, the relationship between the RSS samples and their geometrical locations is explored, leading to a sparse Bayesian model for the radio power map of the RSS observations of each AP. With more than 20 training anchors, the accuracy of the proposed model-based positioning method can be lower than 3.4 meters in an indoor space with only 4 randomly deployed APs, which outperforms the fingerprinting method by 0.4 meter. Extensive experimental results also verify that the proposed positioning service can offer considerable accuracy with only limited efforts in training, suggesting that the prototype is realistic for randomly deployed dense WiFi networks.
Wechsler Adult Intelligence Scale

A wood preservative composition having deep penetration capability, leaving a clean surface and imparting high retention of active preservative within the wood, which consists primarily of (a) an organic wood preservative agent, (b) a hydrophobic agent, and (c) small amounts of an amorphous vinylic-type polymer, in a penetrating organic solvent. The preservative may be pentachlorophenol, an oxathiin compound or other preservative preferably of low mammalian toxicity. The hydrophobic agent may be fatty acids and their esters, fatty alcohols and paraffin waxes. The amorphous polymer may be a polystyrene, a polymethylmethacrylate, a polyvinylformal, an atactic polypropylene or other such amorphous polymer. The penetrating solvent may be most suitably chloroform, methylene chloride, trichloroethylene or liquefied petroleum gas, although others may be used. Solutions suitable for deep penetration pressure treatment are preferred. The active preservative penetrates and becomes immobilized within the penetrated wood microstructure.
Achieving Consensus in Self-Organizing Wireless Sensor Networks: The Impact of Network Topology on Energy Consumption

Achieving consensus on common global parameters through totally decentralized algorithms is a topic that has attracted considerable attention in the last few years. Several algorithms have been developed, among which the most popular is the average consensus method. The main advantage of these approaches is that they do not require a fusion center. But, on the other hand, they are typically based on iterative algorithms, whose energy consumption is proportional to the time necessary to achieve consensus. This time depends on the network topology, as well as on the transmit power of each node. In this paper, we show that there exists an optimal transmit power that minimizes the overall energy consumption necessary to achieve the global estimate within a given accuracy and that this power depends on the network topology.
Segmental and global longitudinal strain and strain rate based on echocardiography of 1266 healthy individuals: the HUNT study in Norway.

AIMS To study the distribution of longitudinal systolic strain and strain rate (SR) as indicators of myocardial deformation according to age and sex in a healthy population. METHODS AND RESULTS Longitudinal strain and SR were determined in 1266 healthy individuals from three standard apical views, using a combination of speckle tracking (ST) and tissue Doppler imaging (TDI) to track regions of interest (ROIs). To test applicability of the reference values, we used a subset of the population to compare four methods of assessing myocardial deformation: (1) a combination of TDI and ST; (2) TDI with fixed ROIs; (3) TDI with tracking of ROIs; and (4) ST. Mean (SD) overall global longitudinal strain and SR were -17.4% (2.3) and -1.05 s(-1) (0.13) in women, and -15.9% (2.3) and -1.01 s(-1) (0.13) in men. Deformation indices decreased with increasing age. The combined and ST methods showed identical SR, but values were significantly lower than those obtained by TDI. Strain was overestimated by the ST method (18.4%) compared with the combined method (17.4%). CONCLUSION The reference values for global and segmental longitudinal strain and SR obtained from this population study are applicable for use in a wide clinical setting.
Benchmarks Based on Anti-Parallel Patterns for the Evaluation of GPUs

We put forward “anti-parallel patterns” to guide the parall el performance analysis process. Anti-parallel patterns or APPs are commo n parts of parallel programs that cause these programs to have less than ideal perfo rmance, where the ideal speedup equals the number of processors. We present be nchmarks to model the behavior of APPs on parallel platforms. Each benchmark c ontains only one APP and is configurable to mimic all its instances. We show how ben chmarks can be used to qualitatively and quantitatively understand and co mpare parallel hardware. Experiments with NVIDIA and AMD GPUs reveal their differenc es.