Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified Nucleoside Triphosphates for In-vitro Selection Techniques

The development of SELEX (Selective Enhancement of Ligands by Exponential Enrichment) provides a powerful tool for the search of functional oligonucleotides with the ability to bind ligands with high affinity and selectivity (aptamers) and for the discovery of nucleic acid sequences with diverse enzymatic activities (ribozymes and DNAzymes). This technique has been extensively applied to the selection of natural DNA or RNA molecules but, in order to improve chemical and structural diversity as well as for particular applications where further chemical or biological stability is necessary, the extension of this strategy to modified oligonucleotides is desirable. Taking into account these needs, this review intends to collect the research carried out during the past years, focusing mainly on the use of modified nucleotides in SELEX and the development of mutant enzymes for broadening nucleoside triphosphates acceptance. In addition, comments regarding the synthesis of modified nucleoside triphosphate will be briefly discussed.
Transgenic Knockdown of Cardiac Sodium/Glucose Cotransporter 1 (SGLT1) Attenuates PRKAG2 Cardiomyopathy, Whereas Transgenic Overexpression of Cardiac SGLT1 Causes Pathologic Hypertrophy and Dysfunction in Mice

Background The expression of a novel cardiac glucose transporter, SGLT1, is increased in glycogen storage cardiomyopathy secondary to mutations in PRKAG2. We sought to determine the role of SGLT1 in the pathogenesis of PRKAG2 cardiomyopathy and its role in cardiac structure and function. Methods and Results Transgenic mice with cardiomyocyte‐specific overexpression of human T400N mutant PRKAG2 cDNA (TGT400N) and transgenic mice with cardiomyocyte‐specific RNA interference knockdown of SGLT1 (TGSGLT1‐DOWN) were crossed to produce double‐transgenic mice (TGT400N/TGSGLT1‐DOWN). Tet‐off transgenic mice conditionally overexpressing cardiac SGLT1 in the absence of doxycycline were also constructed (TGSGLT‐ON). Relative to TGT400N mice, TGT400N/TGSGLT1‐DOWN mice exhibited decreases in cardiac SGLT1 expression (63% decrease, P<0.05), heart/body weight ratio, markers of cardiac hypertrophy, and cardiac glycogen content. TGT400N/TGSGLT1‐DOWN mice had less left ventricular dilation at age 12 weeks compared to TGT400N mice. Relative to wildtype (WT) mice, TGSGLT1‐ON mice exhibited increases in heart/body weight ratio, glycogen content, and markers of cardiac hypertrophy at ages 10 and 20 weeks. TGSGLT1‐ON mice had increased myocyte size and interstitial fibrosis, and progressive left ventricular dysfunction. When SGLT1 was suppressed after 10 weeks of overexpression (TGSGLT1‐ON/OFF), there was a reduction in cardiac hypertrophy and improvement in left ventricular failure. Conclusions Cardiac knockdown of SGLT1 in a murine model of PRKAG2 cardiomyopathy attenuates the disease phenotype, implicating SGLT1 in the pathogenesis. Overexpression of SGLT1 causes pathologic cardiac hypertrophy and left ventricular failure that is reversible. This is the first report of cardiomyocyte‐specific transgenic knockdown of a target gene.
Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA) delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG), a hydrophilic polymer, and trans-activated transcription (TAT) peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEG-maleimide (heterobifunctional PEG) as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a). Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were monodispersed and of <100 nm in size, exhibiting maximum cell transfection ability and very low cytotoxicity. Thus, this research may be of significance in translocating biotherapeutic molecules for intracellular delivery applications.
East African megadroughts between 135 and 75 thousand years ago and bearing on early-modern human origins

The environmental backdrop to the evolution and spread of early Homo sapiens in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change from the continent itself. Our record shows periods of severe aridity between 135 and 75 thousand years (kyr) ago, when the lake's water volume was reduced by at least 95%. Surprisingly, these intervals of pronounced tropical African aridity in the early late-Pleistocene were much more severe than the Last Glacial Maximum (LGM), the period previously recognized as one of the most arid of the Quaternary. From these cores and from records from Lakes Tanganyika (East Africa) and Bosumtwi (West Africa), we document a major rise in water levels and a shift to more humid conditions over much of tropical Africa after ≈70 kyr ago. This transition to wetter, more stable conditions coincides with diminished orbital eccentricity, and a reduction in precession-dominated climatic extremes. The observed climate mode switch to decreased environmental variability is consistent with terrestrial and marine records from in and around tropical Africa, but our records provide evidence for dramatically wetter conditions after 70 kyr ago. Such climate change may have stimulated the expansion and migrations of early modern human populations.
Complexities of emotional responses to social and non-social affective stimuli in schizophrenia

Background: Adaptive emotional responses are important in interpersonal relationships. We investigated self-reported emotional experience, physiological reactivity, and micro-facial expressivity in relation to the social nature of stimuli in individuals with schizophrenia (SZ). Method: Galvanic skin response (GSR) and facial electromyography (fEMG) were recorded in medicated outpatients with SZ and demographically matched healthy controls (CO) while they viewed social and non-social images from the International Affective Pictures System. Participants rated the valence and arousal, and selected a label for experienced emotions. Symptom severity in the SZ and psychometric schizotypy in CO were assessed. Results: The two groups did not differ in their labeling of the emotions evoked by the stimuli, but individuals with SZ were more positive in their valence ratings. Although self-reported arousal was similar in both groups, mean GSR was greater in SZ, suggesting differential awareness, or calibration of internal states. Both groups reported social images to be more arousing than non-social images but their physiological responses to non-social vs. social images were different. Self-reported arousal to neutral social images was correlated with positive symptoms in SZ. Negative symptoms in SZ and disorganized schizotypy in CO were associated with reduced mean fEMG. Greater corrugator mean fEMG activity for positive images in SZ indicates valence-incongruent facial expressions. Conclusion: The patterns of emotional responses differed between the two groups. While both groups were in broad agreement in self-reported arousal and emotion labels, their mean GSR, and fEMG correlates of emotion diverged in relation to the social nature of the stimuli and clinical measures. Importantly, these results suggest disrupted self awareness of internal states in SZ and underscore the complexities of emotion processing in health and disease.
Do Babies Learn From Baby Media?

In recent years, parents in the United States and worldwide have purchased enormous numbers of videos and DVDs designed and marketed for infants, many assuming that their children would benefit from watching them. We examined how many new words 12- to 18-month-old children learned from viewing a popular DVD several times a week for 4 weeks at home. The most important result was that children who viewed the DVD did not learn any more words from their monthlong exposure to it than did a control group. The highest level of learning occurred in a no-video condition in which parents tried to teach their children the same target words during everyday activities. Another important result was that parents who liked the DVD tended to overestimate how much their children had learned from it. We conclude that infants learn relatively little from infant media and that their parents sometimes overestimate what they do learn.
Failure Analysis of Two-Dimensional Carbon-Epoxy Composite Plate Pinned Joint

The aim of this study is to investigate failure strength and failure mode of a mechanically fastened carbon-epoxy composite plate of arbitrary orientation. The failure load and the failure mode are analyzed numerically and experimentally. The numerical method includes two steps. First, the stress distribution in the plate is calculated by the use of finite-element method. Second, the failure load and the failure mode are predicted by means of Tsai-Hill and fiber tensile-compressive failure criteria. A computer program was developed which can be used to calculate the failure load, the failure mode, and the propagation of failure. The distance-to-diameter, E/D , and width-to-diameter, W/D , ratios in the plate are changed from 1 to 5 and 2 to 5, respectively. It is found that full bearing strength is developed when E/D and W/D ratios are equal to or greater than 4.
Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure

Aims To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms. Design Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control (n = 6484) and a Mendelian randomization analysis (n = 1020), using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy. Setting A longitudinal birth cohort in South West England. Participants Participants of the Avon Longitudinal Study of Parents and Children (ALSPAC). Measurements Smoking status during pregnancy was self-reported by mother and partner in questionnaires administered at pregnancy. Latent classes of offspring smoking initiation (non-smokers, experimenters, late-onset regular smokers and early-onset regular smokers) were previously developed from questionnaires administered at 14–16 years. A genetic variant, rs1051730, was genotyped in the mothers. Findings Both mother and partner smoking were similarly positively associated with offspring smoking initiation classes, even after adjustment for confounders. Odds ratios (OR) [95% confidence interval (CI)] for class membership compared with non-smokers were: experimenters: mother OR = 1.33 (95% CI = 1.06, 1.67), partner OR = 1.28 (95% CI = 1.06, 1.55), late-onset regular smokers: mother OR = 1.80 (95% CI = 1.43, 2.26), partner OR = 1.86 (95% CI = 1.52, 2.28) and early-onset regular smokers: mother OR = 2.89 (95% CI = 2.12, 3.94), partner OR = 2.50 (95% CI = 1.85, 3.37). There was no clear evidence for a dose–response effect of either mother or partner smoking heaviness on class membership. Maternal rs1051730 genotype was not clearly associated with offspring smoking initiation class in pre-pregnancy smokers (P = 0.35). Conclusion The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms.
Years of Optimum Health Lost Due to Complications After Acute Ischemic Stroke: Disability-Adjusted Life-Years Analysis

Background and Purpose— Complications after stroke increase disability or death. The disability-adjusted life-year (DALY) metric, developed by the World Health Organization to measure the global burden of disease, integrates both mortality and disability. Widely used in population-level data analyses, it has not been applied to individual patient-level data captured in outcome registries. Methods— We analyzed patient-level data from the outcome registry of 1254 consecutive patients with acute ischemic stroke enrolled between September 1, 2004, and August 31, 2005, in South Korea. For each subject, we calculated DALY lost due to the qualifying stroke and then analyzed additional DALY lost due to complications after stroke. Results— For 1233 patients with available 3-month outcomes, the average DALY lost due to the index stroke was 3.82 (95% CI, 3.68 to 3.96). Any complications, neurological complications, and medical complications occurred in 34.0%, 20.8%, and 24.0%, respectively. The additional DALYs lost associated with any, neurological, and medical complications were 2.11 (95% CI, 1.78 to 2.44), 2.15 (95% CI, 1.72 to 2.59), and 1.99 (95% CI, 1.59 to 2.40), respectively. Patients with 1 complication had 1.52 (95% CI, 1.15 to 1.89) additional DALY lost, and those with ≥2 complications had 2.69 (95% CI, 2.18 to 3.20) additional DALY lost. Conclusion— Early poststroke complications deprive patients of approximately 2 years of optimum health. Greater numbers of complications are associated with greater loss of healthy life-years. DALY analysis quantifies the burden of poststroke complications with a uniform metric potentially useful for health system planners.
Extracting projective structure from single perspective views of 3D point sets

A number of recent papers have argued that invariants do not exist for three-dimensional point sets in general position, which has often been misinterpreted to mean that invariants cannot be computed for any three-dimensional structure. It is proved by example that although the general statement is true, invariants do exist for structured three-dimensional point sets. Projective invariants are derived for two object classes: the first is for points that lie on the vertices of polyhedra, and the second for objects that are projectively equivalent to ones possessing a bilateral symmetry. The motivations for computing such invariants are twofold: they can be used for recognition, and they can be used to compute projective structure. Examples of invariants computed from real images are given. <<ETX>>
An Empirical Model of Multiword Expression Decomposability

This paper presents a construction-inspecific model of multiword expression decomposability based on latent semantic analysis. We use latent semantic analysis to determine the similarity between a multiword expression and its constituent words, and claim that higher similarities indicate greater decomposability. We test the model over English noun-noun compounds and verb-particles, and evaluate its correlation with similarities and hyponymy values in WordNet. Based on mean hyponymy over partitions of data ranked on similarity, we furnish evidence for the calculated similarities being correlated with the semantic relational content of WordNet.
Informational, but not Intrinsically Motivating Gamification': Preliminary Findings

Motivational psychology suggests that informationally designed gamification can increase intrinsic motivation. However, there has been little empirical research to test this assumption. In a first experiment we compared whether a gamified and a non-gamified application differed in terms of usability, intrinsic motivation and need satisfaction. No significant differences emerged, yet descriptive data and participants' open-ended answers indicated that there were differences in how informational game elements such as scoreboards were perceived. We conclude with a discussion of implications and opportunities for future research.
The Natural History of Primary Biliary Cirrhosis

From the time that Hanot described the clinical entity of hypertrophic cirrhosis [25a] until the larger series of Ahrens et al. [I], Sherlock [66], and Hoffbauer [27] were published between 1950 and 1960, only scattered cases or small clusters of patients with primary biliary cirrhosis (PBC) had been reported. Indeed the extensive review of the literature conducted by the group at the Rockefeller Institute and published in 1950 yielded only 25 certain cases [ I ] . Elaboration of the natural history of the disease was subsequently facilitated by better definition of the pathology, the development of the mitochondria1 antibody test and the application of automated biochemical screening of sera so that sufficient cases could be detected and observed. Thus, in the last 20 years, in which several groups including our own have accumulated as many as 200 cases each, many of the clinical features of PBC have been clarified. This review of the natural history of PBC considers those features necessary to make the diagnosis. The epidemiology, diagnosis, course, associated diseases and causes of death are discussed with no consideration of pathogenesis and therapy as these are described elsewhere in this issue. It is inevitable that not all of the large number of potentially relevant papers written about aspects of PBC in the past two decades could be quoted; those selected are representative of the topics discussed, and we apologize in advance for the necessary omissions. Where appropriate, comparisons are made with our personal observations.
A Successful, Long-Term Exercise Program for Women With Fibromyalgia Syndrome and Chronic Fatigue and Immune Dysfunction Syndrome

This article describes an ongoing, long-term clinical exercise program for women with fibromyalgia syndrome (FMS), some of whom also have chronic fatigue and immune dysfunction syndrome (CFIDS). The recorded outcomes from the most recent year of the program also are reported. Participants engaged in sessions lasting 50-70 minutes, 5 days per week; each session involved aerobic activity, resistance training, and other dynamic exercise. One group was in the program for 3 years and another group was in the program for 2 years. Program outcomes for the year (comparing beginning and end-of-year results) are presented for both groups on physical fitness, psychosocial, and FMS/CFIDS symptoms. The outcomes support that all of the women appear to have benefited from the program in numerous ways, suggesting that the program works. Also, those outcomes are in agreement with past research reported in this journal. Implications for clinical nurse specialists working with FMS/CFIDS patients are discussed.
Using Group Support Systems for Software Inspections

Software engineering sometimes appears to be years behind other disciplines in terms of predictability and quality. But we like to argue that the software industry is facing problems now that other industries have yet to face. Constructing a high-quality, million-line program is daunting. Fortunately, progress is occurring and merging two important areas: software process improvement and technological support. The authors describe their experience implementing a group support system (GSS) for software inspections in an industrial environment. The results confirm their belief that such support can improve the efficiency and effectiveness of inspections, provided the inspections are properly conducted.
Comparative Analysis of Intrusion-Tolerant System Architectures

Today, institutions want to build open systems and provide services to the public via the Internet. Such systems would potentially expose security vulnerabilities, and become susceptible to attacks. Therefore, security is critical in order to ensure confidentiality, integrity, and availability for system data and services. With increasing sophistication of security attacks the protection of open system is more challenging. Intrusion tolerance should be part of the overall defense in-depth security solution. In this paper, we will study and compare different approaches to intrusion-tolerant system architectures, focusing on three different lines of approach. The case study of an Open Archival Information System will be used to illustrate the security features of those architectures in the face of malicious attacks. We also include a qualitative and comparative analysis with respect to confidentiality, integrity, availability, and data exfiltration.
Does Working from Home Work? Evidence from a Chinese Experiment

About 10% of US employees now regularly work from home (WFH), but there are concerns this can lead to “shirking from home. ” We report the results of a WFH experiment at CTrip, a 16,000-employee, NASDAQ-listed Chinese travel agency. Call center employees who volunteered to WFH were randomly assigned to work from home or in the office for 9 months. Home working led to a 13% performance increase, of which about 9% was from working more minutes per shift (fewer breaks and sick-days) and 4% from more calls per minute (attributed to a quieter working environment). Home workers also reported improved work satisfaction and experienced less turnover, but their promotion rate conditional on performance fell. Due to the success of the experiment, CTrip rolled-out the option to WFH to the whole firm and allowed the experimental employees to re-select between the home or office. Interestingly, over half of them switched, which led to the gains from WFH almost doubling to 22%. This highlights the benefits of learning and selection effects when adopting modern management practices like WFH.
Evolution of blood pressure management in acute intracerebral hemorrhage

Intracerebral hemorrhage (ICH) remains a prevalent and severe cause of death and disability worldwide. Control of the hypertensive response in acute ICH has been a mainstay of ICH management, yet the optimal approaches and the yield of recommended strategies have been difficult to establish despite a large body of literature. Over the years, theoretical and observed risks and benefits of intensive blood pressure reduction in ICH have been studied in the form of animal models, radiographic studies, and two recent large, randomized patient trials. In this article, we review the historical and developing data and discuss remaining questions surrounding blood pressure management in acute ICH.
A Real Options Approach to Economic Exposure Management

Exchange rate volatility is not only a source of concern for firms but also of profit opportunities. If adjustment costs and lags are low, managers can adjust their input or output decisions to raise the firm’s expected profits. Notwithstanding the resulting higher profit variability, the actual risk perceived by the managers may fall as they are probably more averse to downsiderisk—such as financial distress—than to risk in general. Hence, this paper argues that optimal economic exposure management consists of exploiting the upward profit potential of real exchange rate volatility, while keeping downside risk under control. It is shown that option theory provides useful new principles for economic exposure management by bringing out the crucial role of adjustment costs.