Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence-selective recognition of double-stranded RNA and enhanced cellular uptake of cationic nucleobase and backbone-modified peptide nucleic acids

Sequence-selective recognition of complex RNAs in live cells could find broad applications in biology, biomedical research, and biotechnology. However, specific recognition of structured RNA is challenging, and generally applicable and effective methods are lacking. Recently, we found that peptide nucleic acids (PNAs) were unusually well-suited ligands for recognition of double-stranded RNAs. Herein, we report that 2-aminopyridine (M) modified PNAs and their conjugates with lysine and arginine tripeptides form strong (Ka = 9.4 to 17 × 107 M−1) and sequence-selective triple helices with RNA hairpins at physiological pH and salt concentration. The affinity of PNA–peptide conjugates for the matched RNA hairpins was unusually high compared to the much lower affinity for DNA hairpins of the same sequence (Ka = 0.05 to 1.1 × 107 M−1). The binding of double-stranded RNA by M-modified PNA–peptide conjugates was a relatively fast process (kon = 2.9 × 104 M−1 sec−1) compared to the notoriously slow triple helix formation by oligodeoxynucleotides (kon ∼ 103 M−1 sec−1). M-modified PNA–peptide conjugates were not cytotoxic and were efficiently delivered in the cytosol of HEK293 cells at 10 µM. Surprisingly, M-modified PNAs without peptide conjugation were also taken up by HEK293 cells, which, to the best of our knowledge, is the first example of heterocyclic base modification that enhances the cellular uptake of PNA. Our results suggest that M-modified PNA–peptide conjugates are promising probes for sequence-selective recognition of double-stranded RNA in live cells and other biological systems.
Quantitative Analysis of Reduced Arm Swing Frequency in Essential Tremor

Background: Essential tremor (ET) has recently been accepted as a heterogeneous disorder which may be associated with synuclein pathology or a variety of other genetic disorders. Methods: We observed decreased arm swing frequency in 18 of 136 definite ET patients, and recorded the associated arm movements in 18 ET patients and 33 sex- and age-matched healthy controls. Results: The mean frequency of the right arm (p = 0.047), left arm (p = 0.025) and leg (p = 0.030), and the mean arm/leg frequency on the right side (p = 0.048) were significantly lower in ET patients. The mean frequencies for both arms and legs were significantly lower for the more affected side of the body (p = 0.034 and p = 0.036, respectively). Conclusion: We conclude that ET may be associated with decreased arm and leg swing frequencies, especially on the more affected side of the body.
The Chinese physicians' CardiovAscular Risk Evaluation (CARE) survey: an assessment of physicians' own cardiovascular risks

Objective To estimate the 10-year risk of cardiovascular disease (CVD)/coronary heart disease (CHD) in physicians using two models (the Chinese and Framingham models). Methods This was a multicentre, cross-sectional survey, which recruited cardiovascular physicians from 386 medical centres in all 31 provinces and municipalities in China. Cardiovascular risk factors such as body mass index, blood pressure and cholesterol were recorded during enrolment. Control rates (%) of hypertension, hypercholesterolaemia and diabetes were defined according to guidelines. Participants aged ≥35 years completed the Framingham model and participants aged ≤59 years completed the Chinese prediction model. Results A total of 820 (41.5%) women and 1598 (78.7%) men had ≥1 markedly raised CVD risk factors. The Chinese prediction model showed that 22 (1.2%) women and 143 (7.6%) men had a 10-year risk of ischaemic CVD ≥5%, and an above-average level of 10-year ischaemic CVD risk factors was found in 20.6% of women and in 54.6% of men. When the Framingham model was used, 268 (13.6%) women and 724 (35.7%) men had a 10-year absolute risk of CHD ≥5%. Hypertension, diabetes and hypercholesterolaemia were only controlled in 58.2%, 46.6% and 38.5% of participants, respectively. Only 30.3% of physicians with a 10-year risk of CHD ≥10% were using aspirin. Conclusions The results show suboptimal awareness in physicians of their own cardiovascular risks, and low use of prophylactic agents. Improvement of physicians' risk factors in will improve their ability to act as role models in the promotion of primary and secondary prevention initiatives.
Fertilization of rat eggs in vitro.

Rat eggs were recovered from oviducts and inseminated with sperm collected from either the uterus of mated females or the cauda epididymis of males. A mixture of a modified Krebs-Ringer bicarbonate solution and rat serum (4:1) was usually used to incubate the sperm and eggs for 8-12 h. The presence of bovine serum albumin and rat serum in the medium appeared to be very important for the fertilization of rat eggs in vitro. When eggs recovered 1-5 h after ovulation were inseminated with sperm recovered from the uterus of females mated 0.5-1, 4-5, and 10-11 h previously, the proportions of eggs penetrated were 4-7, 85-95, and 32-55%, respectively. Eggs obtained from superovulated mature and immature females were as fertilizable in vitro as were those recovered from the naturally ovulated females. Sperm penetration, however, was not observed when preincubated epididymal sperm were used under the present experimental conditions. This fact and the significantly higher proportions of eggs penetrated by sperm recovered from the uterus at 4-5 and 10-11 h than at 0.5. -i h after mating demonstrated that rat sperm do need capacitation in the female tract before they are capable of penetrating the egg. The time required for capacitation of rat sperm in the female tract appeared to be about 4-5 h. Polyspermy and the presence of supplementary sperm in both the fertilized and unfertilized eggs were very frequently observed.
Recombinant bacterial lipoproteins as vaccine candidates

Recombinant bacterial lipoproteins (RLP) with built-in immuno-stimulating properties for novel subunit vaccine development are reviewed. This platform technology offers the following advantages: easily converts antigens into highly immunogenic RLP using a fusion sequence containing lipobox; the lipid moiety of RLP is recognized as the danger signals in the immune system through the Toll-like receptor 2, so both innate and adaptive immune responses can be induced by RLP; serves as an efficient and cost-effective bioprocess for producing RLP in Escherichia coli and the feasibility and safety of this core platform technology has been successfully demonstrated in animal model studies including meningococcal group B subunit vaccine, dengue subunit vaccine, novel subunit vaccine against Clostridium difficile-associated diseases and HPV-based immunotherapeutic vaccines.
Interleukin-15 Is Critical in the Pathogenesis of Influenza A Virus-Induced Acute Lung Injury

ABSTRACT Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of “cytokine storm” has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44+ CD8+ T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8+ T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in β2-microglobulin by gene targeting and those depleted of CD8+ T cells by in vivo administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8+ T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.
Intrinsic Regional Differences in Androgen Receptors and Dihydrotestosterone Metabolism in Human Preadipocytes

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAs remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.
Tendon‐selective genes identified from rat and human musculoskeletal tissues

Mesenchymal stems cells have a demonstrated ability to differentiate into muscle, bone, and fat. Determining whether these same cells have the ability to differentiate into tendon‐like fibroblasts has been hampered by the lack of specific tendon cell marker genes. In order to identify molecular markers of mature tendon, expression profiling was used to identify genes expressed in adult rat and human tendon tissue compared to other musculoskeletal tissues. Using this technique, approximately 1,600 transcripts appeared to be selectively expressed in rat tendon tissue and approximately 300 transcripts appeared to be selectively expressed in human tendon tissue, with ∼20 genes selectively expressed in both human and rat tendon tissue. Of these common tendon‐selective genes, thrombospon‐din‐4 (THBS4) and tenomodulin (TNMD) were found to have the highest tendon‐selective expression compared to other tissues examined. Interestingly, expression of these tendon‐selective genes, which are present in primary tendon fibroblasts, is lost when these cells are placed in two‐dimensional culture systems. In conclusion, this study has defined a set of tendon‐selective genes present in both adult rat and human tendons. Identification of tendon‐selective genes provides potential molecular tools to facilitate a better understanding of tendon development and tendon repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:289–297, 2010
Are sound dogs mechanically symmetric at trot?

Summary A two-year-old, sound Labrador Retriever was determined to be ’right hind limb dominant’ by comparison of total hind limb moments of support using inverse dynamics. Net joint moments at the hip, tarsal and metatarsophalangeal joints were larger on the right side. Vertical joint reaction forces at the stifle were larger on the right, and horizontal stifle joint reaction forces were smaller on the right. The crus segment was more cranially inclined on the right side through most of stance, but the angle of the resultant stifle joint reaction force vector against the long axis of the crus segment was identical between the right and left sides. The cranially inclined crus segment orientation on one side, coupled with the larger vertical joint reaction force, may result in an internal asymmetry in stifle joint mechanics, although the effects of this on cruciate ligament stresses remain to be determined.
Multi-domain compact modeling for GeSbTe-based memory and selector devices and simulation for large-scale 3-D cross-point memory arrays

A novel compact model is developed by coupling comprehensive physical equations from electrical, thermal and phase-transition domains in order to capture their correlations that exist in GeSeTe (GST) device physics. Several non-ideal effects during GST-based memory cell operations have been studied with particular focus on cell Read/Write margins and reliability issues. Finally, large-scale 3-D cross-point memory array circuits have been simulated with developed physics-based models to further explore the design constraints.
Graduate school recommender system: Assisting admission seekers to apply for graduate studies in appropriate graduate schools

In this paper, we present an applied research on designing and developing a recommender system for graduate admission seekers which can help them to choose graduate school matching their entire academic profile. Here we have developed a technique to transform relational database for students' all types of relevant information into a universal database format using academic data of successful students who have already got opportunity to study abroad. After that we have developed an algorithm for grad school recommender system which can calculate similarity between training and test data set based on weighted scores using mean squared deviation similarity metrics. We have used K-nearest Neighbor algorithm for calculating top N similar users for the test users and recommend Top K universities to users from N similar users. Finally our proposed recommender system will recommend list of universities to apply for graduate admission to pursue higher study abroad with funding.
The Effect of Parameter Estimation on Upper‐sided Bernoulli Cumulative Sum Charts

The Bernoulli cumulative sum (CUSUM) chart has been shown to be effective for monitoring the rate of nonconforming items in high‐quality processes where the in‐control proportion of nonconforming items (p0) is low. The implementation of the Bernoulli CUSUM chart is often based on the assumption that the in‐control value p0 is known; therefore, when p0 is unknown, accurate estimation is necessary. We recommend using a Bayes estimator to estimate the value of p0 to incorporate practitioner knowledge and to avoid estimation issues when no nonconforming items are observed in phase I. We also investigate the effects of parameter estimation in phase I on the upper‐sided Bernoulli CUSUM chart by using the expected value of the average number of observations to signal (ANOS) and the standard deviation of the ANOS. It is found that the effects of parameter estimation on the Bernoulli CUSUM chart are more significant than those on the Shewhart‐type geometric chart. The low p0 values inherent to high‐quality processes imply that a very large, and often unrealistic, sample size may be needed to accurately estimate p0. A methodology to identify a continuous variable to monitor is highly recommended when the value of p0 is low and the required phase I sample size is impractically large. Copyright © 2012 John Wiley & Sons, Ltd.
unspot cycles recorded in Mesoproterozoic carbonate biolaminites

Well-preserved carbonate biolaminites from the early Mesoproterozoic Wumishan Formation (ca. 1.5–1.45 Ga) of North China show submillimeter-scale yearly couplets that consist of alternating dark and light laminae, and are texturally similar to those reported from Holocene tufas. Power spectrum and wavelet transform analyses of laminar couplet thickness variations and geochemical series (Ca, Fe, Co/Ti, Cr/Ti, and Br) reveal a prominent periodicity at 9.0–11.7 and a less prominent periodicity at 19.7–21.4 couplets. These coherent periodic modes match well with the 11-yr Schwabe sunspot cycle and 22-yr
Problems with animal models of chronic liver disease: Suggestions for improvement in standardization

The availability of appropriate animal models is crucial in studying various disorders, including those of the liver. However, although a large assortment of animals with genetic, acquired and experimentally induced hepatic disorders are available ( l ) , there still remains a lack of a satisfactory animal model of chronic liver disease with hepatic encephalopathy (HE) and abnormalities in nitrogen metabolism, as seen in man. This point is illustrated by the study of Snodgrass (2) reported in this issue of Hepatology, in which he found no change in the activities of the urea cycle enzymes in the liver of rats with carbon tetrachloride (CC14)-induced cirrhosis. He concludes that this animal model is inadequate. The lack of an ideal animal model has greatly hindered progress in defining the primary pathophysiologic mechanism responsible for the mediation of abnormalities of nitrogen metabolism and HE. Furthermore, in HE research the general dissatisfaction with animal models has led to investigators developing their own, possibly unique models, which makes comparison between studies virtually impossible. As a consequence, this field is highly controversial and little consensus on any issue has been achieved. The theme of this editorial is that adoption of a limited number of well-characterized animal models which are reproducible and can be made available in any investigator’s laboratory would help to rectify the situation. Clearly, before attempting to foster this approach, we have to examine the animal models of chronic liver disease presently available and their suitability as models of human disease. Because of their potential for reproducibility, two rat models in particular will be examined: CC1, cirrhosis and end-to-side portacaval shunt. Recent improvements in the methods of administration of CC1, have produced an apparently easily generated cirrhosis model in the rat (3-5). Prior to this standardization, our colleagues interested in collagen had used this type of model extensively despite its notorious unpredictability (6). Abnormalities in collagen metabolism, portal hypertension and ascites have been observed in this model (6). Recently, it has been used to study other features of chronic liver disease. The stimulating paper of Snodgrass (2) reports that the activities of urea cycle enzymes are not depressed in
Interobserver Variability in the Measurement of Lower Leg Compartment Pressures

Objectives: To determine whether interobserver technical variations and errors in the measurement of compartment pressures may affect measurement accuracy. Methods: Four above-knee cadaveric specimens were used to create a consistent model of lower leg compartment syndrome. Thirty-eight physicians examined the limbs and measured 4 compartment pressures using the Intra-Compartmental Pressure Monitor (Stryker Orthopaedics). They were observed for correct assembly and use of the monitor. Measurements obtained were compared with known pressures. Results: Of the total number of compartment measurements, 31% were made using the correct technique, 39% were made with lesser errors in technique, and 30% were made with catastrophic errors. Only 60% of measurements made with the correct technique were within 5 mm Hg of the standard pressure. Accuracy dropped to 42% for measurements taken with small errors in technique and 22% when a catastrophic error was committed. Conclusions: Variations in use of a commercially available pressure monitor exist, and errors are common. Proper use improved accuracy, but even with proper technique, 40% of the measurements were >5 mm Hg from the actual pressure. Based on our data, measurement accuracy with this device should be questioned and viewed within a range. Regular review and education of technique is strongly recommended.
Parasitism and food web dynamics of juvenile Pacific salmon

There is an increasing realization of the diverse mechanisms by which parasites and pathogens influence the dynamics of host populations and communities. In multi-host systems, parasites may mediate food web dynamics with unexpected outcomes for host populations. Models have been used to explore the potential consequences of interactions between hosts, parasites and predators, but connections between theory and data are rare. Here, we consider sea louse parasites (Lepeophtheirus salmonis), which directly increase mortality of juvenile salmon hosts (Oncorhynchus spp.). We use mathematical models and field-based experiments to investigate how the indirect effects of parasitism via predation influence mortality of sympatric juvenile chum salmon (O. keta) and pink salmon (O. gorbuscha). Our experiments show that coho salmon predators (O. kisutch) selectively prey on pink salmon and on parasitized prey. Preference for pink salmon increased slightly when prey were parasitized by sea lice, although there was considerable uncertainty regarding this result. Despite this uncertainty, we show that even the small increase in preference that we observed may be biologically significant. We calculate a critical threshold of pink salmon abundance above which chum salmon may experience a parasite-mediated release from predation as predation shifts towards preferred prey species. This work highlights the importance of considering community interactions, such as predation, when assessing the risk that emerging parasites and pathogens pose to wildlife populations.
Human acquired naevi are clonal

Naevi are nearly universal in humans, yet their cellular origin remains obscure. Understanding the cellular and molecular mechanisms involved in naevus development may be important in understanding the pathogenesis of malignant melanoma. This study aimed to discover whether human acquired naevi are premalignant by examining whether they are clonal. To determine clonality naevi were removed and separated into epithelial and naevus cell fractions and the DNA prepared and digested by a methylase-sensitive restriction enzyme. The highly polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by a polymerase chain reaction and examined by gel electrophoresis and autoradiography. In polyclonal cell populations both alleles are usually seen as two distinct bands, whilst clonal populations yield a single band. Using these techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from 40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal, while all of the epithelial cell controls were polyclonal. These data are novel and have great importance for understanding the development of human acquired naevi and cutaneous malignant melanoma. Because mono-clonality is a marker of neoplasia, or preneoplasia, our data support the hypothesis that common acquired naevi should be considered to be premalignant lesions, similar to colonic polyps. Such lesions may have undergone the first molecular step(s) in the development of cutaneous malignant melanoma. Understanding the events involved may lead to new methods of prevention and treatment. 1998 Lippincott Williams & Wilkins