Miracle-dz/UniFAR-FTUs huggingface dataset:
Virus-specific interaction between the human cytomegalovirus major capsid protein and the C terminus of the assembly protein precursor

We previously identified a minimal 12-amino-acid domain in the C terminus of the herpes simplex virus type 1 (HSV-1) scaffolding protein which is required for interaction with the HSV-1 major capsid protein. An alpha-helical structure which maximizes the hydropathicity of the minimal domain is required for the interaction. To address whether cytomegalovirus (CMV) utilizes the same strategy for capsid assembly, several glutathione S-transferase fusion proteins to the C terminus of the CMV assembly protein precursor were produced and purified from bacterial cells. The study showed that the glutathione S-transferase fusion containing 16 amino acids near the C-terminal end was sufficient to interact with the major capsid protein. Interestingly, no cross-interaction between HSV-1 and CMV could be detected. Mutation analysis revealed that a three-amino-acid region at the N-terminal side of the central Phe residue of the CMV interaction domain played a role in determining the viral specificity of the interaction. When this region was converted so as to correspond to that of HSV-1, the CMV assembly protein domain lost its ability to interact with the CMV major capsid protein but gained full interaction with the HSV-1 major capsid protein. To address whether the minimal interaction domain of the CMV assembly protein forms an alpha-helical structure similar to that in HSV-1, peptide competition experiments were carried out. The results showed that a cyclic peptide derived from the interaction domain with a constrained (alpha-helical structure competed for interaction with the major capsid protein much more efficiently than the unconstrained linear peptide. In contrast, a cyclic peptide containing an Ala substitution for the critical Phe residue did not compete for the interaction at all. The results of this study suggest that (i) CMV may have developed a strategy similar to that of HSV-1 for capsid assembly; (ii) the minimal interaction motif in the CMV assembly protein requires an alpha-helix for efficient interaction with the major capsid protein; and (iii) the Phe residue in the CMV minimal interaction domain is critical for interaction with the major capsid protein.
Development of Inner Ear (Cochlear and Vestibular) Function in the Fetus-Neonate

The development of function in the various receptors in the inner ear was studied in the neonatal rat, which is altricious with respect to hearing, using short latency evoked potentials, both auditory (ABR) and vestibular (VsEP). It was found that VsEPs could be recorded from all the vestibular end-organs by post natal day (PND) 8, whilst ABR could only be recorded from all animals on PND 14, showing the earlier onset of vestibular function in the inner ear. These results are discussed with relation to onset of inner ear function in the human fetus.
Analysis of Clinical Trials Involving Non-cavitated Caries Lesions

Treatments to halt or reverse the progression of noncavitated caries lesions are of increasing interest. Diagnostic technologies under development offer potential for the assessment of gradual progression and regression of such lesions. Many therapies directed at correcting demineralization-remineralization imbalance should, in principle, protect enamel similarly across lesion severities from initiation to near cavitation. If this is so, and if acceptable reproducibility and predictive validity can be demonstrated for a diagnostic of acceptable cost, then clinical trials of agents to prevent cavitation can become more efficient by the use of outcome indices that reflect, in addition to cavitation, the expansion and regression of non-cavitated lesions. However, to achieve such a benefit will require data analyses that fully exploit ordinal or continuous-scale outcome measures. We consider comparison of such measures of lesion status between treatment groups, with most attention to ordinal categorical data. Interim data from a clinical trial in Lithuanian children are used for illustration.
SHORT COMMUNICATION Changes in Australian brushtail possum (Trichosurus vulpecula) den site use following density reduction

The den use of possums (Trichosurus vulpecula) may be density dependent, meaning that individuals change their denning behaviour in response to changes in population density. Increases in den use due to changes in density may result in increases in bovine tuberculosis (Mycobacterium bovis; bTB) transmission among possums, as infection has previously been correlated with den use. In this study, the den use of a possum population was monitored in 2011 before and after a density reduction event. Females increased their den use following density reduction, but males did not. However, den use was more dependent on the sex of the individual than density reduction, with males having greater den use than females. A second site of different habitat where density reduction was not carried out was also monitored for den use, in 2012. In contrast to the manipulated site, den use did not differ between monitoring events or possum sex at this site. Possums at this site also had greater den use than possums at the manipulated site. This research suggests that bTB transmission risk may not be uniform among habitats. In addition, to prevent potential increases in transmission risk from bTB-infected possums surviving control, pest control operations should aim to remove the majority of possums in a population.
Cardiovascular disease following pre-eclampsia: understanding the mechanisms.

Pre-eclampsia is a disease unique to human pregnancy, affecting approximately 5% of pregnant women. It is defined by the maternal syndrome of de novo hypertension (occurring after 20 weeks of gestation) and proteinuria. It is cured by delivery of the placenta, typically with complete clinical resolution by the third postpartum month [1]. Despite major advances in understanding its pathophysiology, its cause remains unknown.
The overloaded right heart and ventricular interdependence

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored.
ECONOMIC EVALUATION A BAYESIAN APPROACH TO ECONOMIC ANALYSES OF CLINICAL TRIALS : THE CASE OF STENTING VERSUS BALLOON ANGIOPLASTY

New results about the costs and effects of a new therapy may be weighted with prior information. As such, classical confidence intervals surrounding the costs and effects of a therapy may not reflect the real uncertainties. Bayesian techniques may improve this by formalizing the way that prior information is taken into account in assessing the new evidence. Costs and effects can be analysed separately, but also, when considering the balance between costs and effects, they can be analysed simultaneously. Here, an example is given using data from two trials that compared costs and effectiveness of stent implantation with balloon angioplasty. The Bayesian results make it clear that different prior distributions may lead to different decisions, and it is concluded that even Bayesian analysis may not always reflect the process of capturing the remaining uncertainties. Copyright © 2000 John Wiley & Sons, Ltd.
Obsessive and compulsive symptoms in prediagnosed Huntington's disease.

OBJECTIVE Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease. METHOD The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non-gene-expanded controls from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as "near-to-onset" (< 9 estimated years to onset), "mid-to-onset" (9-15 years to onset), and "far-to-onset" (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender. RESULTS All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying. CONCLUSION Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status.
Aetiology of coronary heart disease

Papers p 1273 It is a common tendency in science to argue that in order for my pet hypothesis to be correct yours has to be wrong. Indeed, it is somewhat unsatisfying for both yours and mine to be right at the same time. Barker's work on the fetal and infant origins of coronary heart disease has stimulated such reactions.1 The two positions are that coronary heart disease is determined by factors associated with growth in utero or in the first year of life or that it is caused by social conditions and lifestyle acting later in life. Among the arguments for the former is the body of work that Barker and colleagues have produced over 15 years.2 Arguing for the importance of contemporaneous influences is that coronary heart disease rates can be reduced within five years by reducing cholesterol levels,3 giving up smoking,4 or reducing blood pressure levels.5 Rates of coronary heart disease are strongly related to social class6 and changed rapidly …
Are history and physical examination a good screening test for sleep apnea?

OBJECTIVE To determine whether presenting clinical history, pharyngeal examination, and the overall subjective impression of the clinician could serve as a sensitive screening test for sleep apnea. DESIGN Blinded comparison of history and physical examination with results of nocturnal polysomnography. SETTING Sleep clinic of a tertiary referral center. PATIENTS A total of 410 patients referred for suspected sleep apnea syndrome. Most patients reported snoring. MEASUREMENTS All patients were asked standard questions and given an examination relevant to the diagnosis of the sleep apnea syndrome, and all had full nocturnal polysomnography. Patients with more than ten episodes of apnea or hypopnea per hour of sleep were classified as having sleep apnea. Stepwise linear logistic regression was used to develop two predictive models of sleep apnea: one based on the presence of characteristic clinical features, age, sex, and body mass index; and one based on subjective clinical impression. RESULTS The prevalence of sleep apnea in our patients was 46%. Only age, body mass index, male sex, and snoring were found to be predictors of sleep apnea. The logistic rule discriminated between patients with and without sleep apnea (receiver operating characteristic [ROC] area, 0.77 [95% Cl, 0.73 to 0.82]). For patients with a predicted probability of apnea of less than 20%, the clinical model had 94% sensitivity and 28% specificity. Subjective impression alone identified correctly only 52% of patients with sleep apnea and had a specificity of 70%. CONCLUSIONS In patients with a high predicted probability of the sleep apnea syndrome, subjective impression alone or any combination of clinical features cannot serve as a reliable screening test. However, in patients with a low predicted probability of sleep apnea, the model based on clinical data was sufficiently sensitive to permit about a 30% reduction in the number of unnecessary sleep studies.
The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes

Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative. Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes. Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA. Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
P2Y receptor-mediated stimulation of Müller glial DNA synthesis.

PURPOSE To determine whether activation of P2Y receptors may increase the DNA synthesis rate of cultured Müller cells and to investigate whether adenosine 5'-triphosphate (ATP)-induced Müller cell proliferation is mediated by an intracellular calcium increase. METHODS Primary cultures of Müller cells of the guinea pig were treated with test substances for 16 hours. The DNA synthesis rate was assessed by a bromodeoxyuridine immunoassay, and ATP-induced elevations of the intracellular calcium concentration were recorded by fura-2 imaging. RESULTS ATP or uridine triphosphate (UTP) increased the DNA synthesis rate whereas alpha,beta-methylene-ATP, 2-methyl-thio-ATP, and adenosine were ineffective, indicating that the action of ATP was through P2Y receptors. The effect of ATP was dose dependent, with an EC(50) of 5.9 microM. The mitogenic effect of ATP required an elevation of the intracellular calcium and a calcium influx into Müller cells. Blockers of calcium-permeable channels (nickel ions) or of calcium-dependent potassium (BK) channels (iberiotoxin, charybdotoxin) inhibited the ATP-stimulated DNA synthesis. In calcium-imaging experiments, ATP-evoked intracellular calcium transients were significantly shortened in the presence of extracellular nickel ions or of iberiotoxin. A correlation was found between the duration of the ATP-evoked calcium transients and the basal proliferation rate of the cultures. CONCLUSIONS The results indicate that the ATP-induced elevation of Müller glial DNA synthesis is dependent on an influx of calcium ions from the extracellular space and that the inhibiting effect of BK channel blockers on ATP-evoked DNA synthesis is caused by an inhibition of this influx. The amount of the calcium influx seems to be directly correlated to the strength of the ATP-evoked proliferation.
Differentiation and migration of endoderm in the rat and mouse at implantation

The initial differentiation of endoderm at the time of onset of implantation, and the subsequent rapid differentiation of visceral and parietal endoderm were studied in the rat and mouse. Transmission electron microscopy illustrates the reorientation and loosening of embryonic cell mass cells during implantation, as well as cytological evidence that endoderm cells have differentiated. Using scanning electron microscopy, parietal endoderm consists of individual stellate cells with numerous peripheral branching filopodia. As these cells migrate abembryonically, the rest of the embryonic cell mass becomes recom‐pacted. The visceral endoderm proliferates and forms a columnar epithelium which has the cytological characteristic of an absorptive epithelium and is able to ingest exogenous proteins. Thus, by 24 hours after implantation, the two endo‐dermal derivatives have assumed widely diverse shapes and different types of associations and rates of replication, and are probably performing different functions.
A dimension-depending multiplicity result for the Schrödinger equation

We consider the Schrödinger equation { −∆u+ V (x)u = λK(x)f(u) in R ; u ∈ H(R ), (Pλ) where N ≥ 2, λ ≥ 0 is a parameter, V,K : R → R are radially symmetric functions, and f : R → R is a continuous function with sublinear growth at infinity. We first prove that for λ small enough no non-zero solution exists for (Pλ), while for λ large enough at least two distinct non-zero radially symmetric solutions do exist. By exploiting a Ricceri-type three-critical points theorem, the principle of symmetric criticality and a group-theoretical approach, the existence of at least N − 3 (N mod 2) distinct pairs of non-zero solutions is guaranteed for (Pλ) whenever λ is large enough, N 6= 3, and f is odd.
Complexity limitations on quantum computation

We use the powerful tools of counting complexity and generic oracles to help understand the limitations of the complexity of quantum computation. We show several results for the probabilistic quantum class BQP. BQP is low for PP, i.e., PP/sup BQP/=PP. There exists a relativized world where P=BQP and the polynomial-time hierarchy is infinite. There exists a relativized world where BQP does not have complete sets. There exists a relativized world where P=BQP but P/spl ne/UP/spl cap/coUP and one-way functions exist. This gives a relativized answer to an open question of Simon.
Effect of mitomycin-C on contraction and migration of human nasal mucosa fibroblasts: implications in dacryocystorhinostomy

Aim To determine the effect of mitomycin-C (MMC) on the contraction and migration of human nasal mucosal fibroblasts (HNMFs) in vitro in order to identify the least concentration of MMC required to prevent cicatrix development following dacryocystorhinostomy (DCR). Methods Primary cultures of HNMFs were established from nasal mucosal tissues of patients undergoing DCR. Myofibroblast transformation of HNMFs was induced using transforming growth factor-β (TGF-β1) and confirmed by immunostaining for α-smooth muscle actin (α-SMA). Collagen gel contraction assay was employed to study contraction in the presence or absence of TGF-β1 (5 and 10 ng/mL) and MMC (0.2 and 0.4 mg/mL). Scratch wound assay was employed to determine the influence of MMC treatment on cell migration. Quantification of gel contraction and wound closure was done using Image J software. Results α-SMA expression increased with TGF-β1 treatment in a time- and dose-dependent manner indicating myofibroblast transformation of HNMFs. MMC inhibited TGF-β1- induced collagen gel contraction in a dose-dependent manner (0.4 mg/mL>0.2 mg/mL). Further, there was a decrease in the migration of MMC-treated HNMFs, resulting in delayed wound closure that corroborated with the loss of actin stress fibres. Conclusions MMC successfully inhibited TGF-β1-induced myofibroblast transformation, collagen gel contraction and significantly reduced the migration of HNMFs to cover the wound even at a low concentration of 0.2 mg/mL. This study provides evidence that low concentration and short duration of MMC treatment is efficient in reducing increased contraction and migration of HMNFs in response to injury.
Nanoscale post-breakdown conduction of HfO/sub 2//SiO/sub 2/ MOS gate stacks studied by enhanced-CAFM

An enhanced conductive atomic force microscope has enabled a measurement of the conduction through a HfO/sub 2//SiO/sub 2/ gate stack until breakdown (BD) in a single measurement, with nanometer resolution. Before the stack BD, the current-voltage characteristic shows several conduction modes. After BD, switchings between different conduction states were observed, showing that BD is a reversible phenomenon.
Age- and sex-related risk factors for adolescent suicide.

OBJECTIVE To examine the impact of age and sex on adolescent suicide risk. METHOD A standard psychological autopsy protocol was used to compare 140 suicide victims with 131 community controls. The risk factors for older (> or = 16 years) and younger, and for male and female suicide were compared. RESULTS Mood disorders, parental psychopathology, lifetime history of abuse, availability of a gun, and past suicide attempt conveyed significant risk for suicide across all 4 demographic groups. Psychopathology, particularly substance abuse (alone and comorbid with mood disorder), was more common and conveyed a much higher risk for suicide in the older versus younger adolescents. Younger suicide victims showed lower suicidal intent. Males chose more irreversible methods, and conduct disorder was both more prevalent and a more significant risk factor in males. CONCLUSIONS The increased rate of suicide in older versus younger adolescents is due in part to greater prevalence of psychopathology, namely substance abuse, and greater suicidal intent in the older population. The increased rate in males is less easily explained, but it may stem from method choice and the greater prevalence of and risk conveyed by conduct disorder in males.