Miracle-dz/UniFAR-FTUs huggingface dataset:
Corrigendum: Transitivity in Arabidopsis can be primed, requires the redundant action of the antiviral Dicer-like 4 and Dicer-like 2, and is compromised by viral-encoded suppressor proteins.

In plants, worms, and fungi, RNA-dependent RNA polymerases (RDRs) amplify the production of short-interfering RNAs (siRNAs) that mediate RNA silencing. In Arabidopsis, RDR6 is thought to copy endogenous and exogenous RNA templates into double-stranded RNAs (dsRNAs), which are subsequently processed into siRNAs by one or several of the four Dicer-like enzymes (DCL1/4). This reaction produces secondary siRNAs corresponding to sequences outside the primary targeted regions of a transcript, a phenomenon called transitivity. One recognized role of RDR6 is to strengthen the RNA silencing response mounted by plants against viruses. Accordingly, suppressor proteins deployed by viruses inhibit this defense. However, interactions between silencing suppressors and RDR6 have not yet been documented. Additionally, the mechanism underlying transitivity remains poorly understood. Here, we report how several viral silencing suppressors inhibit the RDR6-dependent amplification of virus-induced and transgene-induced gene silencing. Viral suppression of primary siRNA accumulation shows that transitivity can be initiated with minute amounts of DCL4-dependent 21-nucleotide (nt)-long siRNAs, whereas DCL3dependent 24-nt siRNAs appear dispensable for this process. We further show that unidirectional (3/59) transitivity requires the hierarchical and redundant functions of DCL4 and DCL2 acting downstream from RDR6 to produce 21and 22-nt-long siRNAs, respectively. The 3/59 transitive reaction is likely to be processive over >750 nt, with secondary siRNA production progressively decreasing as the reaction proceeds toward the 59-proximal region of target transcripts. Finally, we show that target cleavage by a primary small RNA and 3/59 transitivity can be genetically uncoupled, and we provide in vivo evidence supporting a key role for priming in this specific reaction.
Influenza antivirals and resistance: the next 10 years?

Antivirals against influenza first became available in the 1960s when an adamantane compound, amantadine, was approved for the treatment and prophylaxis of influenza A viruses. Rimantadine, another adamantane drug with fewer side effects than amantadine, was approved for use in the 1990s. In the late 1990s, a new class of rationally designed influenza antivirals known as the neuraminidase (NA) inhibitors (NAIs; namely oseltamivir [TamifluTM, Hoffmann-La Roche] and zanamivir [RelenzaTM, GlaxoSmithKline]) became available. Since this time oseltamivir has become the most widely used influenza antiviral drug around the world, due in part to widespread resistance to the adamantanes and lower patient acceptance of inhaled zanamivir. However, with increasing concerns about oseltamivir resistance in A(H1N1)pdm09 viruses, the case for the development of new influenza antivirals is compelling. Here, the authors highlight some novel anti-influenza compounds that are in late-phase clinical trials, and discuss the likelihood of resistance to these and the current NAI compounds emerging in the next 10 years.
Influence of two bulge loops on the stability of RNA duplexes

Fifty-three RNA duplexes containing two single nucleotide bulge loops were optically melted in 1 M NaCl in order to determine the thermodynamic parameters ΔH°, ΔS°, ΔG°37, and TM for each duplex. Because of the large number of possible combinations and lack of sequence effects observed previously, we limited our initial investigation to adenosine bulges, the most common naturally occurring bulge. For example, the following duplexes were investigated: 5′GGCAXYAGGC/3′CCG YX CCG, 5′GGCAXY GCC/3′CCG YXACGG, and 5′GGC XYAGCC/3′CCGAYX CGG. The identity of XY (where XY are Watson–Crick base pairs) and the total number of base pairs in the terminal and central stems were varied. As observed for duplexes with a single bulge loop, the effect of the two bulge loops on duplex stability is primarily influenced by non-nearest neighbor interactions. In particular, the stability of the stems influences the destabilization of the duplex by the inserted bulge loops. The model proposed to predict the influence of multiple bulge loops on duplex stability suggests that the destabilization of each bulge is related to the stability of the adjacent stems. A database of RNA secondary structures was examined to determine the naturally occurring abundance of duplexes containing multiple bulge loops. Of the 2000 examples found in the database, over 65% of the two bulge loops occur within 3 base pairs of each other. A database of RNA three-dimensional structures was examined to determine the structure of duplexes containing two single nucleotide bulge loops. The structures of the bulge loops are described.
Molecular Mechanisms Underlying Associative Learning

textabstractThis thesis primarily attempts to solve some long standing issues regarding classical eyelid conditioning. More speciﬁcally, what is the speciﬁc role of cerebellar LTD in classical eyeblink conditioning, and how does the answer change the view on cerebellar functioning on associative motor learning. The approach used in this thesis is a combination of the above mentioned genetic approach with classical conditioning experiments. The genetic techniques are by far best possible in mice because of their fast breeding and the availability of genetically well characterized inbred strains. Often gene function is tested by creating transgenic or knockout mice. In transgenic mice, artiﬁcial DNA is introduced in the genome of a mouse, which will lead to expression of the transgene in the adult animal. In knockout mice a targeted gene is completely deleted from the genome. The protein that was coded by this gene will no longer be expressed. To be able to study the effect of genetic lesions on classical conditioning we needed a system that could reliably measure the performance of a mouse on such a learning task. Some studies using mice in eyeblink conditioning tasks already existed. All these studies used electromyographic (EMG) recordings of the MOO muscle to assess responsiveness on the training paradigm. Attempts to repeat this procedure led to the realization that to obtain reliable EMG recordings of the MOO muscle in a mouse over a number of consecutive days is close to impossible, simply because of the small size of a mouse eyelid. We therefore developed a new system that could reliably measure eyelid position over time in mice. Since it makes use of magnetism we called it the magnetic distance measurement technique (MDMT).
Etiology, diagnosis and management of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a common health care problem, yet many aspects of this diagnosis remain poorly understood. Its etiology is often debated and remains a significant area of research. The diagnosis of CRS is based on subjective symptoms, duration of symptoms and objective evidence of inflammation. Each of these criteria must be met to make a diagnosis of CRS. Management of CRS often involves a combination of systemic and topical therapies with surgery reserved for patients who fail medical therapy. This review provides a comprehensive view of the etiology, diagnosis and management of CRS.
HUBUNGAN KEBIASAAN BEROLAHRAGA DENGAN TINGKAT STRES PADA MAHASISWA FAKULTAS KEDOKTERAN UNIVERSITAS RIAU TAHUN PERTAMA

ABSTRACT Prevalence of stress occasion on medical students is pretty high, especially first grade medical students. Problems of adaptation to new environment are the most common cause of stress occuring on first grade medical students. Stress can become negative effect for individual. Various strategies of stress management were done to reduce stress, one of them was exercise. Routine exercise can reduce incidence and severity of mood disorders related to stress. This study was aimed to understand the correlation between exercise habits and stress levels on first grade medical students of Faculty of Medicine, University of Riau. This study used analytic design with cross-sectional approach. Study samples were 166 samples using total sampling technique. Data were accumulated using Medical Student Stressor Questionnaire (MSSQ) that had been modified for stress levels and exercise habits questionnaire. The obtained data were analyzed using Chi Square test and obtained a value of p=0,045 (p<0,05) that showed that there was a significant correlation between exercise habits and stress levels. Keyword: stress levels, exercise habits, first grade medical students, MSSQ
Bacteriophages as anti-infective agents: recent developments and regulatory challenges

The biennial meeting on ‘Exploiting Bacteriophages for Bioscience, Biotechnology and Medicine’, held in London, UK, on 20 January 2012, and chaired by George Salmond (University of Cambridge, UK) hosted over 50 participants representing 13 countries. The highly multidisciplinary meeting covered a diverse range of topics, reflecting the current expansion of interest in this field, including the use of bacteriophages as the source of biochemical reagents for molecular biology, bacteriophages for the treatment of human and animal diseases, bacteriophage-based diagnostics and therapeutic delivery technologies and necessity for, and regulatory challenges associated with, robust clinical trials of phage-based therapeutics. This report focuses on a number of presentations from the meeting relating to cutting-edge research on bacteriophages as anti-infective agents.
Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease

In chronic kidney disease (CKD), the decline in the glomerular filtration rate is associated with increased morbidity and mortality and thus poses a major challenge for healthcare systems. While the contribution of tissue-derived miRNAs and mRNAs to CKD progression has been extensively studied, little is known about the role of urinary exosomes and their association with CKD. Exosomes are small, membrane-derived endocytic vesicles that contribute to cell-to-cell communication and are present in various body fluids, such as blood or urine. Next-generation sequencing approaches have revealed that exosomes are enriched in noncoding RNAs and thus exhibit great potential for sensitive nucleic acid biomarkers in various human diseases. Therefore, in this study we aimed to identify urinary exosomal ncRNAs as novel biomarkers for diagnosis of CKD. Since up to now most approaches have focused on the class of miRNAs, we extended our analysis to several other noncoding RNA classes, such as tRNAs, tRNA fragments (tRFs), mitochondrial tRNAs, or lincRNAs. For their computational identification from RNA-seq data, we developed a novel computational pipeline, designated as ncRNASeqScan. By these analyses, in CKD patients we identified 30 differentially expressed ncRNAs, derived from urinary exosomes, as suitable biomarkers for early diagnosis. Thereby, miRNA-181a appeared as the most robust and stable potential biomarker, being significantly decreased by about 200-fold in exosomes of CKD patients compared to healthy controls. Using a cell culture system for CKD indicated that urinary exosomes might indeed originate from renal proximal tubular epithelial cells.
The epidemiology of pneumococcal carriage and infections in Malaysia

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.
Reducing Diagnostic Errors in Musculoskeletal Trauma by Reviewing Non-Admission Orthopaedic Referrals in the Next-Day Trauma Meeting

INTRODUCTIONDiagnostic errors in orthopaedics are usually caused by missing a fracture or misreading radiographs. The aim of this study was to document the pick-up rate of the wrong diagnoses by reviewing X-rays and casualty notes in the next-day trauma meeting. PATIENTS AND METHODSThe casualty notes and radiographs of 503 patients were prospectively reviewed in the daily trauma meeting between August 2002 and December 2002 in a district general hospital. The relevant data were collected and analysed by a single assessor. RESULTSThe false positive rate for making an orthopaedic diagnosis was 12.6% (i.e.) diagnosing a fracture, when none existed). The false negative (missing) rate was 4%, while 2.4% incidental findings were missed, or at least not documented, after reading the X-rays. There were 7.8% wrong diagnoses made. The majority of the patients were seen by the senior house officers. CONCLUSIONSThe medicolegal significance of false negative diagnosis is obviously greater. In a busy emergency departme.
Health Benefits of Nut Consumption

Nuts (tree nuts and peanuts) are nutrient dense foods with complex matrices rich in unsaturated fatty and other bioactive compounds: high-quality vegetable protein, fiber, minerals, tocopherols, phytosterols, and phenolic compounds. By virtue of their unique composition, nuts are likely to beneficially impact health outcomes. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease and gallstones in both genders and diabetes in women. Limited evidence also suggests beneficial effects on hypertension, cancer, and inflammation. Interventional studies consistently show that nut intake has a cholesterol-lowering effect, even in the context of healthy diets, and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Thus it is clear that nuts have a beneficial impact on many cardiovascular risk factors. Contrary to expectations, epidemiologic studies and clinical trials suggest that regular nut consumption is unlikely to contribute to obesity and may even help in weight loss. Safety concerns are limited to the infrequent occurrence of nut allergy in children. In conclusion, nuts are nutrient rich foods with wide-ranging cardiovascular and metabolic benefits, which can be readily incorporated into healthy diets.
Auto- and cross-regulation of the hnRNPs D and DL

HnRNP D, better known as AUF1, is an extensively studied protein that controls a variety of cellular pathways. Consequently, its expression has to be tightly regulated to prevent the onset of pathologies. In contrast, the cellular functions and regulation of its ubiquitously expressed paralog hnRNP DL are barely explored. Here, we present an intricate crosstalk between these two proteins. Both hnRNP D and DL are able to control their own expression by alternative splicing of cassette exons in their 3′UTRs. Exon inclusion produces mRNAs degraded by nonsense-mediated decay. Moreover, hnRNP D and DL control the expression of one another by the same mechanism. Thus, we identified two novel ways of how hnRNP D expression is controlled. The tight interconnection of expression control directly links hnRNP DL to hnRNP D-related diseases and emphasizes the importance of a systematic analysis of its cellular functions.
From fiber to fabric: interactive clothing for virtual humans

The virtual world is currently limited in the graphic representation and visualization of material designs. The limitation is in part due to the limited range and the relative simplicity of spectral properties of the materials simulated in a virtual environment. Our work starts with a fast classification and retrieval for handling the large numbers of multi-scale texture samples of complex deformable materials, such as, woven and knitted fabrics. We have developed a general system that can also serve as a unified platform for other material analysis and classification and a 3D panel design system for 3D clothing modeling and draping. Multi-scale color theme indexing for image acquisition and retrieval can be more intuitively supported by a multi-touch gesture interface that is now the preferred mode of interacting with tablets, screens, and other visual communication devices. These also add to the collaborative modes of input and retrieval in fabric and fashion design for virtual agents. In this paper we describe the process of texture analysis of real fabric materials and preliminary models for the 3D texture generation for virtual clothing, color theme design, and ultimately 3D draping based on robust collision detection methods.
Advances and perspectives from genetic research: development of biological markers in Alzheimer’s disease

Despite important recent advances, a full understanding of the (genetic) etiology of Alzheimer’s disease (AD) is still a long way off. Large collaborative efforts are ongoing, as well as the exploration of various sources of genetic variation. Evidence supports the view that Mendelian early-onset familial forms of AD are caused by rare and usually highly penetrant mutations in three genes (APP, PSEN1 and PSEN2). Considering sporadic late-onset AD (LOAD), the APOE ε4 allele is by far the best-established risk gene. Recently published large-scale genome-wide analyses point to additionally relevant genetically associated loci, particularly CLU, PICALM and CR1. These susceptibility loci support existing hypotheses about the amyloid, lipid, chaperone and chronic inflammatory mechanisms in AD pathogenesis, and are therefore likely to provide the basis for the development of hypothesis-driven novel biomarker candidates. Additional genes, listed online in AlzGene (e.g., GAB2 or SORL1) have repeatedly shown risk effects in LOAD, and may be true risk genes, but this is much less certain. New epigenetic research provided some evidence that DNA modifications maybe involved in LOAD (e.g., post-mortem studies described both hypo- and hyper-methylation in AD-related susceptibility genes). With respect to biomarkers, elderly nondemented APOE ε4 carriers demonstrated distinct cerebrospinal fluid biomarker signatures and alterations of brain glucose metabolism similar to those observed in AD. Future research should evaluate the usefulness of newly detected AD risk genes and epigenetic changes as potential biomarkers towards genetic profiling of AD or for correlation with endophenotypes and therapeutic outcome.
Object creation based on free virtual grid with ARGlass

Object creation is popular in AR applications. People always load a model instead of creating models by themselves because loading a model is a simple replacement of creating people's own models if they lack the drawing skill or capability to use sophisticated modeling software proficiently. Our work provides people with an intuitive and convenient modeling method to create their own models.
Suicide contagion among psychiatric inpatients

Until now only some individual suicide epidemics in psychiatric hospitals have been reported, and the quantitative effect of suicide contagion on inpatient suicide rates seems to be very limited. On the other hand, an increase in inpatient suicide rates has been reported in many countries, and suicide contagion may thus have growing importance in the future. The author reviews first briefly the literature on suicide contagion among psychiatric inpatients. The factors predisposing to suidice contagion relating to the hospital, staff, and patients are discussed. Finally, some practical measures for the prevention of suicide contagion in psychiatric wards are suggested.
Evaluation of a Mobile Health Intervention to Improve Anti-Retroviral Treatment Retention in South Africa

Evaluation of a Mobile Health Intervention to Improve Anti-Retroviral Treatment Retention in South Africa by Ambereen Jaffer MPH, Boston University, 1998 BSc, University of California Los Angeles, 1996 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health Walden University August 2015
Sequential pulse therapy with itraconazole and terbinafine to treat onychomycosis of the fingernails

OBJECTIVE: To determine the effectiveness and safety of sequential pulse therapy with itraconazole and terbinafine for treating onychomycosis of the fingernails. DESIGN/METHODS: Open, prospective, multicenter, non-industry-sponsored study lasting up to 48 weeks, which recruited patients from outpatient dermatology clinics in North America. A total of 20 patients with onychomycosis of the fingernails were treated with sequential pulse therapy consisting of one pulse of itraconazole (200 mg twice daily for 1 week) followed 3 weeks later by a pulse of terbinafine (250 mg twice daily for 1 week). Patients were evaluated 4 months from the start of treatment, and if there was mycological evidence of onychomycosis, a supplemental or 'booster' pulse of itraconazole was offered to the patient. The final follow-up observation was carried out 39-48 weeks from the start of therapy. The outcomes evaluated were mycological cure (negative light microscopy and culture), clinical cure (nail appears completely or totally normal) and complete cure (clinical and mycological cure). RESULTS: There were 14 patients with fingernail onychomycosis owing to Trichophyton rubrum and six with Candida onychomycosis. At week 26 from the start of therapy there was mycological cure in 19 of 20 patients. One of the patients with Candida onychomycosis was still clinically affected with mycological evidence of disease and was therefore offered an extra pulse of itraconazole, which resulted in a subsequent cure. At weeks 39-48 from the start of therapy there was mycological cure, clinical cure and complete cure in all 20 patients. Gastrointestinal side effects and headache were reported by three patients and one patient, respectively. These were transient and all patients completed therapy with no dropouts. CONCLUSION: Sequential itraconazole-terbinafine pulse therapy was effective, safe and associated with a high compliance. ( J Dermatol Treat (2000) 11: 151-154)
Effects of prenatally exposed diclofenac sodium on rat heart tissue:a stereological and histological study

Background/aim: Diclofenac sodium (DS) can cross the placental barrier and affect the fetus, and its consumption during pregnancy may cause developmental malformation of embryos. This study investigates the effect of prenatally applied DS on the quantitative morphology of the adult rat heart. Materials and methods: Pregnant rats were divided into three groups (control, sham, and test). The rats in the test group were injected with DS; the control group received physiological saline (1 mL; 1 mg/kg, i.m.) from the 5th to the 20th day of pregnancy; and the rats in the sham group were not injected at all. At the 20th postnatal week, all the offspring were euthanized under deep anesthesia and tissue samples were obtained by perfusion fixation. After routine histological procedures, the paraffin sections were stained with hematoxylin and eosin and examined stereologically and histologically. Results: The volume of the cardiac ventricle wall of each offspring rat was estimated using Cavalieri's principle. The volume of the ventricle walls of the test group was found to be significantly less than that of the controls. Conclusion: Further studies are required to determine how DS has this effect, by reducing the number of myocytes and decreasing the size of these cells affecting the connective tissue.