Miracle-dz/UniFAR-FTUs huggingface dataset:
A simple model for the function of proteoglycans and collagen in the response to compression of the intervertebral disc

The nucleus pulposus of the intervertebral disc exerts a pressure which enables it to support axial compression when contained by the annulus fibrosus. The disc was modelled as a thick-walled cylindrical pressure vessel in which the nucleus was contained radially by the annulus. As a result, the stress in the annulus had radial (compressive) as well as tangential (tensile) components. The radial stress at a given point in the annulus was considered to be balanced by the internal pressure which is expected to arise from the attraction of water by proteoglycans. There was a reasonable agreement between the calculated radial stress distribution and published results on the distribution of water within the annulus. As the internal pressure is expected to be isotropic, the annulus was expected to contribute to the axial resistance to compression of the disc; this contribution would be equal, in magnitude, to the radial stress. Predictions of the pressure distribution within the annulus were similar to published experimental measurements made in the radial and axial directions. The tangential stress within the annulus was considered to arise from the restoring stress in its strained collagen fibrils.
Spanwise Inclination and Meandering of Large-Scale Structures in a High-Reynolds-Number Turbulent Boundary Layer

Surveys of the skin-friction velocity under a high-Reynoldsnumber turbulent boundary layer were conducted to obtain the imprint generated by large-scale structures in the logarithmic region. Two spanwise arrays of hot-films, separated in the streamwise direction, were employed to investigate the evolution of the large-scale footprint with the emphasis on usage for future real-time control. An estimate of the downstream footprint, based on the upstream input, is compared directly to the measurement from the second array. Firstly, Fourier decomposition and proper orthogonal decomposition reveal the spanwise homogeneity and periodicity. Then, by using Taylors hypothesis as a first-principal estimate, the anticipated on/off-control for targeting high-speed structures is 68.3 % accurate in terms of timing. When only considering the spanwise modes that remain coherent, and their individual convective speeds, the accuracy is improved to 72.7 %. In the final part, we elucidate on the spanwise inclination and meandering of large-scale structures. It is shown how inclined structures do not drift in the spanwise direction in the conditionally averaged results.
Dose Pattern and Effectiveness of Paliperidone Extended-Release Tablets in Patients With Schizophrenia

Objectives:The objectives of this 12-week multicenter, open-label, noncomparative study were to evaluate the overall effectiveness of paliperidone extended release (ER), the feasibility of maintaining patients on the initial dose of 6 mg, and the relationship between dose pattern and treatment response in schizophrenic patients with inadequate responses to initial treatment in a natural setting. Methods:All patients received 6 mg of paliperidone ER during the first 2 weeks, and subsequently, the dose was adjusted at each visit based on the patient response. We examined the response rate and the effectiveness of different dose patterns of paliperidone ER such as "early increase (dose increased to 9 mg at week 2)," "late increase (dose increased to 9 mg at week 4)," and "maintenance group. " Results:The response rate based on the Clinical Global Impression of Improvement or Severity response criteria was 33.6% or 61.7%, respectively. The proportion of patients who stayed with the initial dose of 6 mg was 44.5% and the response rate of these patients was 79.8%. When the treatment response to the initial dose of 6 mg is inadequate (Clinical Global Impression of Improvement ≥4 at week 2), an early increase in the dose seems to be more effective than maintenance or late increase of the initial dose. Conclusions:This study suggests that paliperidone ER may be an effective and well-tolerated antipsychotics in the treatment of patients with schizophrenia.
The FVII Activating Protease Cleaves Single-Chain Plasminogen Activators

A serine protease isolated from plasma sharing structural characteristics with a hepatocyte growth factor activator-like protease has been demonstrated recently to activate FVII. Accordingly, it was named ‘FVII activator’. Until now an impact of this protease on the fibrinolytic system has not been reported. We islolated the protease from cryo-poor plasma by subsequent ion exchange chromatography and adsorption to immobilized heparin and/or aprotinin. Incubation of single-chain plasminogen activators (sc-PAs) with the FVII activator revealed significant activation of urokinase sc-PA (scu-PA) and tissue sc-PA (sct-PA) in vitro. It was enhanced in the presence of calcium and heparin. Compared to kallikrein, a more efficient activation of scu-PA was observed, whereas sct-PA appeared to be a poorer substrate for the FVI activator. At low protease concentrations and in the presence of heparin the scu-PA activation was comparable to plasmin. Employing recalcified whole blood thrombelastography, the lysis of initially formed fibrin was observed after addition of a combination of scu-PA and the FVII activator, whereas the scu-PA alone had a negligible effect at the concentration used. The study results as presented demonstrate that the FVII activator is a potent activator of sc-PAs in vitro. Whether it plays a physiological role in fibrinolysis deserves further investigation. Its comparatively high affinity to heparin assumes a function in cell surface or matrix events.
Analysis of association of clinical correlates and 5‐HTTLPR polymorphism with suicidal behavior among Chinese methamphetamine abusers

Abstract Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. Methamphetamine (MAP) abusers are commonly noted as having psychosis, depression and suicidal behavior. The goals of the present study were (i) to investigate relations of clinical correlates, such as gender, drug use behavior, psychiatric comorbidity and psychiatry family history, with suicidal behavior among Chinese MAP abusers; and (ii) to investigate whether there is an association between a polymorphism in the promotor region of the serotonin transporter gene (5‐HTTLPR) and suicidal behavior among Chinese MAP abusers. A total of 439 MAP abusers from a hospital and detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. The 5‐HTTLPR polymorphism was compared between 94 MAP abusers with suicide attempts and 294 MAP abusers without suicide attempts, for whom DNA data were available. The results of the present study indicate that among MAP abusers in Taiwan, suicide attempts were significantly related to female gender, history of MAP‐induced psychotic disorder, history of MAP‐induced depressive disorder, and family history of psychotic disorders. Among suicide attempters, the attempters with moderate to severe lethality used higher MAP doses than those with minimal to mild lethality. In the present sample the triallelic 5‐HTTLPR polymorphism (S, LG, LA) was not associated with MAP‐induced depressive disorder, MAP‐induced psychotic disorder or suicidal behavior, but studies with larger sample sizes are warranted before excluding the role of the 5‐HTTLPR polymorphisms in suicidal behavior among MAP abusers.
Cognitive-Behavioral Treatment of Irritable Bowel Syndrome

ABSTRACT There is increasing evidence that supports the view that irritable bowel disorder (IBS) is a disorder of brain-gut function. Cognitive-behavioral therapy (CBT) has received increased attention in light of this recent shift in the conceptualization of IBS. This review has two main aims. The first is to provide a critical review of controlled trials on CBT for IBS. The second is to discuss ways of further developing CBT interventions that are more clinically relevant and meaningful to health care providers and individuals with a diagnosis of IBS. A theme from a CBT intervention will be presented to illustrate how CBT interventions can be incorporated within a larger social context. A review of CBT for IBS lends some limited support for improvement in some IBS symptoms and associated psychosocial distress. This conclusion needs to be expressed with some caution, however, in light of many methodological shortcomings including small sample sizes, inadequate control conditions and failure to identify primary versus secondary outcome measures. In addition, future studies will need to further develop more relevant CBT protocols that more fully integrate the patient's perspective and challenge social cognitions about this stigmatized disorder.
Child vocalization composition as discriminant information for automatic autism detection

Early identification is crucial for young children with autism to access early intervention. The existing screens require either a parent-report questionnaire and/or direct observation by a trained practitioner. Although an automatic tool would benefit parents, clinicians and children, there is no automatic screening tool in clinical use. This study reports a fully automatic mechanism for autism detection/screening for young children. This is a direct extension of the LENATM (Language ENvironment Analysis) system, which utilizes speech signal processing technology to analyze and monitor a child's natural language environment and the vocalizations/speech of the child. It is discovered that child vocalization composition contains rich discriminant information for autism detection. By applying pattern recognition and machine learning approaches to child vocalization composition data, accuracy rates of 85% to 90% in cross-validation tests for autism detection have been achieved at the equal-error-rate (EER) point on a data set with 34 children with autism, 30 language delayed children and 76 typically developing children. Due to its easy and automatic procedure, it is believed that this new tool can serve a significant role in childhood autism screening, especially in regards to population-based or universal screening.
Evaluation of Third‐Generation Screening and Confirmatory Assays for HCV Antibodies

A third‐generation (gen.) screening and immunoblot assay (Ortho EIA‐3.0; Chiron RIBA‐3 prototype), using antigens derived from the capsid and different nonstructural regions (NS3, NS4 and NS5) of the hepatitis C virus viral genome, were evaluated in comparison with the corresponding second‐gen. assays (Ortho EIA‐2.0; revised Ortho EIA‐2.5; Chiron RIBA‐2). In 203 depository sera of blood donors, positive in EIA‐2.0, specificity of the screening assays was improved as shown by an increase in positive predictive value for viral carrier state from 0.23 (EIA‐2.0) to 0.37 (EIA‐2.5) and 0.52 (EIA‐3.0). Comparing the confirmation patterns on RIBA‐2 and RIBA‐3, this amelioration was mainly due to the specific elimination of false‐positive c22‐3 and c100‐3 reactions. Antibody response to the newly added NS5 antigen was not as prevalent as to the other antigens and had only a minor influence in sample allocation. In contrast, screening of 1,560 volunteer blood donors and 47 hemodialysis patients revealed 3 additional positive sera, only reacting with the NS5 antigen. However none of these isolated NS5 reactions could be confirmed on synthetic peptides [INNO‐LIA: NS5(p)] and none was PCR positive. A documented seroconversion, detected earlier with EIA‐3.0, was related to a better immunological response to the NS3 antigen and not to the additional NS5. From this pilot study third‐gen. assays appeared extremely useful in the reevaluation of HCV‐seropositive depository sera. However the additional value of the NS5 antigen in blood donor screening is still hypothetical and remains to be established in larger screening studies.
Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans

• In low‐oxygen environments, such as high‐altitude, control of blood sugar is disrupted. Further, the activity of the sympathetic nervous system is known to increase when the availability of oxygen is decreased. • We have investigated the possibility that the increase in sympathetic activity is partially responsible for the disruption in blood sugar control. • Using gasbags filled with low‐oxygen gas, together with a commonly used blood pressure medication (clonidine) that inhibits the sympathetic nervous system, we have shown that breathing low oxygen disrupts blood sugar control, and that this disruption is prevented when the nervous system is inhibited. • This finding has important implications for people travelling to high altitudes, and for people who suffer from conditions characterized by low oxygen, such as sleep apnoea and lung diseases.
Prenatal and lactation nicotine exposure affects morphology and function of brown adipose tissue in male rat offspring

ABSTRACT The aim of this study was to investigate the effects of prenatal and lactation nicotine exposure on the morphology and function of brown adipose tissue (BAT) in male rat offspring. We conducted a morphological assay and gene expression study of interscapular BAT (iBAT) in male rat offspring. The male offspring from nicotine-exposed dams exhibited higher body weight and iBAT weight. Hematoxylin and eosin staining and transmission electron microscopy showed that iBAT from nicotine-exposed male offspring presented a “whitening” phenotype characterized by lipid droplet accumulation and impaired mitochondria with a randomly oriented and fractured cristae. The expression of the iBAT structure and function-related genes all decreased in nicotine-exposed male offspring. These data indicate that prenatal and lactation nicotine exposure affects morphology and function of iBAT in male rat offspring.
Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140

ABSTRACT CCR5 serves as a requisite fusion coreceptor for clinically relevant strains of human immunodeficiency virus type 1 (HIV-1) and provides a promising target for antiviral therapy. However, no study to date has examined whether monoclonal antibodies, small molecules, or other nonchemokine agents possess broad-spectrum activity against the major genetic subtypes of HIV-1. PRO 140 (PA14) is an anti-CCR5 monoclonal antibody that potently inhibits HIV-1 entry at concentrations that do not affect CCR5's chemokine receptor activity. In this study, PRO 140 was tested against a panel of primary HIV-1 isolates selected for their genotypic and geographic diversity. In quantitative assays of viral infectivity, PRO 140 was compared with RANTES, a natural CCR5 ligand that can inhibit HIV-1 entry by receptor downregulation as well as receptor blockade. Despite their divergent mechanisms of action and binding epitopes on CCR5, low nanomolar concentrations of both PRO 140 and RANTES inhibited infection of primary peripheral blood mononuclear cells (PBMC) by all CCR5-using (R5) viruses tested. This is consistent with there being a highly restricted pattern of CCR5 usage by R5 viruses. In addition, a panel of 25 subtype C South African R5 viruses were broadly inhibited by PRO 140, RANTES, and TAK-779, although ∼30-fold-higher concentrations of the last compound were required. Interestingly, significant inhibition of a dualtropic subtype C virus was also observed. Whereas PRO 140 potently inhibited HIV-1 replication in both PBMC and primary macrophages, RANTES exhibited limited antiviral activity in macrophage cultures. Thus CCR5-targeting agents such as PRO 140 can demonstrate potent and genetic-subtype-independent anti-HIV-1 activity.
Reduced Paraoxonase1 Activity Is a Risk for Atherosclerosis in Patients with Systemic Lupus Erythematosus

Abstract: Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonase1 (PON1) and arylesterase activities, and lipid‐profile in 37 SLE patients and 30 age‐/sex‐matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti‐oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 ± 13.9 year, follow‐up time 6.7 ± 6.2 year, SLEDAI 2 (0–15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured anti‐oxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 ± 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 ± 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL‐C, HDL‐C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti‐PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL‐subfractions or enzyme abnormalities in HDL remodeling.
Interictal psychopathology in patients with ictal fear

We assessed the hypothesis that psychopathology is overrepresented in patients with temporal lobe epilepsy (TLE) who experience ictal fear. Eleven such patients were matched with two control groups: patients who had TLE without ictal fear and patients who had generalized epilepsy. On several MMPI scales, the TLE-ictal fear group scored significantly higher than the two control groups, which did not differ ssignificantly from each other. Furthermore, the TLE-ictal fear group had more MMPI clinical scales that were pathologically elevated, had significantly more patients with histories of admission to psychiatric hospitals, and had more MMPI profiles that were psychotic than either of the control groups.
Optimization of an antenna for wireless energy transfer

Inductive links is the most popular solution to wirelessly send power and data from an external transmitter to implantable biomedical device. This paper proposes the optimized design of a wireless energy transfer devices, by means of an evolutionary optimization method. This procedure is developed in order to increase the transfer efficiency and the robustness of the coupling, with the aim of minimizing the average power loss.
Cost-effectiveness in goal-directed therapy: are the dollars spent worth the value?

EALTHCARE FINANCING has become a fixed agenda of international discussions on health policy. An aging population coupled with an insatiable demand for new and costly medical technology pose an unpredictable challenge for future healthcare funding. 1–3 Under such economic pressure, policymakers are expected to deliver cost-containment solutions for efficient and sustainable healthcare provision. On first sight, this idea seems to conflict with the clinicians’ main concern of delivering comprehensive care to the patients, who then often dismiss the positive effect of careful resource allocation on longterm care provision and, consequently, on the overall good to society. 4 Cost-effectiveness analysis combines both principles by pooling clinical and economic benefit before suggesting sustainable strategies of effective resource allocation. 5–7 In this paper, the authors review the available literature on cost-effectiveness analysis and goal-directed therapy (GDT).
Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders

Significance Alterations in the efficacy of neuronal inhibition mediated by GABAA receptors (GABAARs) containing β3 subunits are continually implicated in autism spectrum disorders (ASDs). In vitro, the plasma membrane stability of GABAARs is potentiated via phosphorylation of serine residues 408 and 409 (S408/9) in the β3 subunit, an effect that is mimicked by their mutation to alanines. Here, we created a mouse in which S408/9 have been mutated to alanines (S408/9A). S408/9A mice exhibited altered dendritic spine structure, increased repetitive behavior, decreased social interaction, and an epileptic phenotype. Thus, mutation of S408/9 reproduces the core deficits seen in humans with ASDs. Collectively, our results suggest that alterations in phosphorylation and/or activity of β3-containing GABAARs may directly contribute to the pathophysiology of ASDs. Alterations in the efficacy of neuronal inhibition mediated by GABAA receptors (GABAARs) containing β3 subunits are continually implicated in autism spectrum disorders (ASDs). In vitro, the plasma membrane stability of GABAARs is potentiated via phosphorylation of serine residues 408 and 409 (S408/9) in the β3 subunit, an effect that is mimicked by their mutation to alanines. To assess if modifications in β3 subunit expression contribute to ASDs, we have created a mouse in which S408/9 have been mutated to alanines (S408/9A). S408/9A homozygotes exhibited increased phasic, but decreased tonic, inhibition, events that correlated with alterations in the membrane stability and synaptic accumulation of the receptor subtypes that mediate these distinct forms of inhibition. S408/9A mice exhibited alterations in dendritic spine structure, increased repetitive behavior, and decreased social interaction, hallmarks of ASDs. ASDs are frequently comorbid with epilepsy, and consistent with this comorbidity, S408/9A mice exhibited a marked increase in sensitivity to seizures induced by the convulsant kainic acid. To assess the relevance of our studies using S408/9A mice for the pathophysiology of ASDs, we measured S408/9 phosphorylation in Fmr1 KO mice, a model of fragile X syndrome, the most common monogenetic cause of ASDs. Phosphorylation of S408/9 was selectively and significantly enhanced in Fmr1 KO mice. Collectively, our results suggest that alterations in phosphorylation and/or activity of β3-containing GABAARs may directly contribute to the pathophysiology of ASDs.
Shedding and survival of herpes simplex virus from 'fever blisters'.

Shedding of herpesvirus by adults with herpes labialis and survival of the virus in the environment were examined. In nine adults with virus-positive herpes labialis, herpesvirus was detected in the anterior oral pool of seven (78%) and on the hands of six (67%). Herpesviruses isolated from patients with oral lesions were found to survive for as long as two hours on skin, three hours on cloth, and four hours on plastic. These findings support earlier recommendations for the protection of neonates from adults with "fever blisters. " In addition, environmental surfaces may be a source of transmission of herpesvirus to the neonate.
The myelinated axon is dependent on the myelinating cell for support and maintenance: Molecules involved

The myelin‐forming cells, oligodendrocytes and Schwann cells, extend processes that spirally wrap axons and provide the insulation that allows rapid saltatory conduction. Recent data suggest a further role for the myelin‐forming cells in axonal support and maintenance. This Mini‐Review summarises some of the data that support this view and highlights the molecules involved. © 2004 Wiley‐Liss, Inc.