Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits.

PURPOSE To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzyme-linked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS After intravitreal injection in the treated eye, the mean maximum concentrations (C(max)) of bevacizumab in the iris/ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the C(max) was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the C(max) was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.
Utilization of Computers in Clinical Practice - Role of Physician Networks: Preliminary Communication

This study examines the influence of physician networks on the utilization of computers in clinical practice. Data on patient referrals, consultations, professional discussions, and on-call coverage were collected from 24 physicians who comprise a private group practice. Their utilization of a computerized hospital medical information system (HIS) in caring for patients admitted to a 1160-bed private, university affiliated, teaching hospital was determined. A matrix representing the professional relations among these physicians was subjected to smallest space analysis, a form of multidimensional scaling. Also, a number of indices that describe structural and interactional properties of the network and individual physicians were computed. The three-dimensional representation of the network that resulted from the analysis suggests a two-step process of adoption and utilization of medical technology. Physicians who were engaged in outside professional activities and in the training of medical students and house staff were more likely to utilize the system in caring for patients. These physicians, who were more centrally located and dominant in the referral and consultation process, were more likely to influence the practice patterns of their colleagues. The use of network analysis to identify influential physicians whose involvement is essential to the success of efforts aimed at introducing computers into clinical practice is discussed.
Natural history of established low grade cervical intraepithelial (CIN 1) lesions.

UNLABELLED THE AIM of the present study was to ascertain the natural history of cervical intraepithelial lesions 1 (CIN 1) and to develop recommendations to optimize follow-up. PATIENTS AND METHODS Patients referred for colposcopy from January, 1996 to July, 2005 were reviewed. A prospectively maintained database was quarried for demographic, clinical, and pathologic data. RESULTS The cohort included 1,001 patients with CIN 1. At 6 months, 330 patients (49%) regressed to normal, 305 (45%) had persistent low grade, while 45 (7%) progressed to high grade lesions. At 12 months, of those with negative pathology at 6 months, 200 (80%) remained negative, 42 (16%) demonstrated low grade and 9 (4%) progressed to high grade lesions. Of those with low grade lesions at 6 months, 131 (50%) regressed, 121 (46%) had persistent low grade, and 10 (4%) progressed to high grade lesions. CONCLUSION Our data demonstrates a low rate of progression for CIN 1, suggesting it may be reasonable to prolong the screening interval in women with CIN 1.
The early phase of psoriatic arthritis

Evaluation of the preclinical phases of the classic autoimmune diseases including rheumatoid arthritis has been facilitated by the availability of autoantibody and genetic markers that point firmly towards the early dysregulation of the adaptive immune responses. The association of psoriatic disease with the human leucocyte antigen—Cw0602 (HLA-Cw0602) gene has likewise led to the perception that autoimmunity has a pivotal role in early psoriatic arthritis (PsA). However, this HLA-Cw0602 genetic association does not appear to hold for PsA or associated nail, scalp and intergluteal skin involvement. Of note, these three sites of psoriasis are predictive of PsA evolution. For initiation of both skin and nail disease there is a link with Koebnerisation, or site-specific trauma. Nail disease is most common in the dominant hand thumbnail, pointing towards local tissue factors as disease initiators Likewise, for PsA, there is also good evidence for a history of previous joint trauma and histological studies showing microdamage in normal entheses which are typical locations where PsA frequently occurs. Furthermore, subclinical enthesopathy including osteitis is common in subjects with psoriasis but without arthritis. Collectively, these findings indicate that the classic model of adaptive immune dysregulation does not generally hold for the early stages of PsA. The way in which knowledge pertaining to tissue-specific factors in PsA, combined with the emerging data relating to monogenic disorders and animal models, points towards perturbation in the healing response and dysregulation of innate immune responses in early PsA is discussed. The way in which this model explains the clinical disconnect between skin and joint disease and the emerging human data that support it are demonstrated.
Peripheral regulatory T cells and serum transforming growth factor‐&bgr;: Relationship with clinical response to infliximab in Crohn's disease

Background: CD4+Foxp3+ regulatory T cells (Treg) inhibit T‐cell proliferation in vitro and are effective in suppressing colitis in mouse models. Tumor necrosis factor (TNF)‐&agr;, which is centrally involved in Crohn's disease (CD) pathogenesis, also impairs Treg function. Here we investigated the influence of anti‐TNF therapy on Treg frequency and function in CD. Methods: Twenty CD patients were treated with infliximab administered at weeks 0, 2, and 6. Blood was collected immediately before the first infusion and after 10 weeks. Treg frequency was quantified by flow cytometry. Treg function was measured using a standard coculture assay. Serum levels of transforming growth factor (TGF)‐&bgr;1 and interleukin (IL)‐10 were measured by enzyme‐linked immunosorbent assay (ELISA). Results: Pretreatment Treg frequency and serum TGF‐&bgr;1 levels were significantly higher in nonresponder than responder patients. Clinical improvement in 12 CD patients was associated with a significant increase of Treg frequency after 10 weeks. Treg were functionally active before and after treatment with infliximab, both in responder and nonresponder CD patients. In responder patients the restoration of Treg pool was accompanied by a parallel significant increase of serum TGF‐&bgr;1 and IL‐10. No significant change in the elevated Treg or serum TGF‐&bgr;1 was seen in nonresponder patients. Conclusions: This study suggests that there may be a relationship between numbers of Treg in the blood, serum TGF‐&bgr;1, and response to infliximab; however, further prospective studies are needed. (Inflamm Bowel Dis 2010)
The Effects of Moderately Raised Classroom Temperatures and Classroom Ventilation Rate on the Performance of Schoolwork by Children (RP-1257)

Two independent field intervention experiments were carried out in school classrooms in late summer (in 2004 and 2005). The air temperature was manipulated by either operating or idling split cooling units installed for the purpose. In one of these experiments, the outdoor air supply rate was also manipulated. The conditions were established for one week at a time in a blind crossover design with repeated measures on two classes of 10- to 12-year-old children. Six to eight exercises exemplifying different aspects of schoolwork (numerical and language-based) were performed as part of normal lessons. Pupils indicated their environmental perceptions and the intensity of any symptoms on visual analogue scales. Their thermal sensation changed from slightly too warm to neutral, and the performance of two numerical and two language-based tests was significantly improved when the temperature was reduced from 25°C to 20°C (77°F to 68°F). When the outdoor air supply rate was increased from 5.2 to 9.6 L/s (11.0 to 20.3 cfm) per person, their performance of four numerical exercises improved significantly, confirming the results of previously reported experiments in the same series. The above improvements were mainly in terms of the speed at which tasks were performed, with negligible effects on error rate. Most school classrooms worldwide experience raised air temperatures during increased thermal loads, e.g., in warm weather; these results show that providing some means of avoiding elevated temperatures would improve educational attainment.
Testing of motor unit synchronization model for localized muscle fatigue

Spectral compression of surface electromyogram (sEMG) is associated with onset of localized muscle fatigue. The spectral compression has been explained based on motor unit synchronization theory. According to this theory, motor units are pseudo randomly excited during muscle contraction, and with the onset of muscle fatigue the recruitment pattern changes such that motor unit firings become more synchronized. While this is widely accepted, there is little experimental proof of this phenomenon. This paper has used source dependence measures developed in research related to independent component analysis (ICA) to test this theory.
ANÁLISE DE CONVERGÊNCIA ESPACIAL NO ESTADO DE MINAS GERAIS: 1975-2003

Este artigo procura identificar possiveis mudancas de disparidade entre os municipios de Minas Gerais entre 1975 e 2003. Para tal, divide a analise em duas etapas. Na primeira utiliza o metodo da Analise Exploratoria de Dados Espaciais (AEDE) por meio da estatistica I de Moran e por meio da analise de identificacao de clusters . A estatistica I de Moran permite, por exemplo, avaliar o grau de correlacao existente entre uma regiao e seus vizinhos considerando uma variavel qualquer de interesse. Ja a analise de clusters permite uma visualizacao simples da formacao de um conglomerado de regioes proximas em um mapa que possuem valores semelhantes, ou seja, permite a visualizacao de clusters caso haja formacao de algum. Na segunda implementa um modelo de convergencia espacial para verificar se, no periodo de analise, as disparidades regionais aumentaram ou diminuiram. Os resultados indicam presenca de autocorrelacao positiva para todos os anos analisados e a formacao de clusters significativos alto-alto e baixo-baixo em todos os anos. No que se refere a convergencia, os resultados mostram que para o periodo 1975 a 2003 nao existe convergencia, ou seja, houve aumento das disparidades regionais no Estado de Minas Gerais. Ja para o periodo de 1996 a 2003 existe convergencia de pib per capta , ou seja, ha uma diminuicao das disparidades regionais.
The RF Front-end of a Blood Flow Sensor for Vascular Graft Applications

This paper presents an RF front-end of a fully integrated inductively powered implantable circuits for blood flow measurement, which are embedded within vascular prosthetic grafts for early detection of graft degradation or failure. The effect of human body on the helix coil design has been carefully characterized. An equivalent circuit model of the coil has been developed. An adaptive link compensation technique was adopted in the backscattering modulator design. A highly efficient rectifier was designed to achieve 65% efficiency.
Students' approach to social network in educational context

The properties of Web 2.0 have caused discussion in the educational context. The awareness of the students regarding the potential of Web 2.0 also made up a portion of this discussion. Therefore, the aim of this study is to respond to the question of how elementary school students use Web 2.0 and depending on the usage of Web 2.0 it is aimed to discuss Web 2.0 in general and social network in specific for education. This research, case study, is carried out in depth to determine; elementary school students’ Web 2.0 usages. The 25 participants are students chosen with the ‘maximum diversity sampling’ technique. The data are gathered by interview and focus group discussions. Content analysis was used. As a result, it is determined that students grouped under five categories which were identified as: viewers, communicators, collaborators, information seekers and producers. It is also determined that students do not fully use the cooperation and sharing properties of Web 2.0 and usually play a passive role in.
Mutations That Abrogate Human Immunodeficiency Virus Type 1 Reverse Transcriptase Dimerization Affect Maturation of the Reverse Transcriptase Heterodimer

ABSTRACT The specific impact of mutations that abrogate human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) dimerization on virus replication is not known, as mutations shown previously to inhibit RT dimerization also impact Gag-Pol stability, resulting in pleiotropic effects on HIV-1 replication. We have previously characterized mutations at codon 401 in the HIV-1 RT tryptophan repeat motif that abrogate RT dimerization in vitro, leading to a loss in polymerase activity. The introduction of the RT dimerization-inhibiting mutations W401L and W401A into HIV-1 resulted in the formation of noninfectious viruses with reduced levels of both virion-associated and intracellular RT activity compared to the wild-type virus and the W401F mutant, which does not inhibit RT dimerization in vitro. Steady-state levels of the p66 and p51 RT subunits in viral lysates of the W401L and W401A mutants were reduced, but no significant decrease in Gag-Pol was observed compared to the wild type. In contrast, there was a decrease in processing of p66 to p51 in cell lysates for the dimerization-defective mutants compared to the wild type. The treatment of transfected cells with indinavir suggested that the HIV-1 protease contributed to the degradation of virion-associated RT subunits. These data demonstrate that mutations near the RT dimer interface that abrogate RT dimerization in vitro result in the production of replication-impaired viruses without detectable effects on Gag-Pol stability or virion incorporation. The inhibition of RT activity is most likely due to a defect in RT maturation, suggesting that RT dimerization represents a valid drug target for chemotherapeutic intervention.
Investigation of a Z α-like Peptide Motif in Koi Herpesvirus

Koi herpesvirus (KHV) is responsible for high mortality in the common carp, a global food staple of which over 1.5 million metric tons is harvested annually. The objective of this study is to investigate B-DNA interactions with a hypothesized Zα, or Z-DNA binding, domain in the KHV open reading frame 112 (ORF112) peptide motif. Mutations analogous to the Y84A and N62D mutations have been shown to be critical for Z-DNA binding in proteins with Zα domains. Therefore, circular dichroism (CD) spectra were collected of the wild type (WT), Y84A mutant, and N62D mutant ORF112 proteins titrated into poly(dGdC) and calf thymus B-DNA. The WT and Y84A mutant proteins bound to two distinct DNA conformations that did not indicate a Bto Z-DNA transition, and the N62D mutation prevented any conformational change. The results indicate that B-DNA interacts with the Zα-like peptide motif in a non-sequence specific manner to form a unique structure that requires the Asn 62 residue and is affected structurally by the Tyr 84 residue.
Extraction de connaissances à partir de l'usage des outils professionnels de communication et de collaboration

La multiplication des outils de communication et de collaboration (media sociaux, e-mail, conference a distance, etc.) a entraine ces dernieres annees une explosion du volume de donnees non-structurees. Or, ces donnees (contenus et usages des outils) recelent une connaissance explicite et tacite de valeur, souvent inexploitee. Cette connaissance apporte un contexte essentiel pour comprendre les documents de reference existants – plus structures – qui ont ete produits de maniere collaborative, permettant a tout employe de donner un sens a leur contenu et favoriser ainsi la collaboration. Apres avoir decrit differentes classifications de connaissances, les outils de communication et de collaboration sont categorises sur la base de travaux precedents dans le domaine du travail collaboratif, puis au travers de theories sur les medias. Une approche bottom-up est proposee pour extraire la connaissance en utilisant des methodes quantitatives et des methodes qualitatives (i.e. des entretiens, questionnaires, pop-ups, fichiers de traces, etc.). Cette connaissance sera utilisee dans le but de developper un modele qui servira de base pour des collaborations plus efficaces et plus efficientes.
Transient Little’s Law for the First and Second Moments of G/M/1/N Queue Measures

A customer in a service system and an outside observer (manager or designer of the system) estimate the system performance differently. Unlike the outside observer, the customer can never find himself in an empty system. Therefore, the sets of scenarios, relevant for the two at a given time, differ. So differ the meanings and values of the performance measures of the queue: expected queue length and expected remaining waiting time (workload). The difference between the two viewpoints can be even more significant when steady-state values of the queue measures are reached slowly, or even are never reached. In this paper, we obtain the relations between the means and variances of the measures in transient time and in steady state for a capacitated FCFS queue with exponentially distributed service time. In particular, a formula similar to Little’s law is derived for the means of the queue measures. Several examples support the validity and significance of the results.
Diagnostic value of the lymphocyte proliferation test in nickel contact allergy and provocation in occupational coin dermatitis

The lymphocyte proliferation test (LPT) was compared with the patch test in the diagnosis of nickel contact sensitivity Of the 21 subjects with nickel contact allergy, the patch test detected 28 (95%) The subject remaining negative in the patch test was positive in the intradennat test. 18/21 subjects with nickel contact sensitivity were positive in the LPT. Where as in the control group 2/23 was false positive These results were obtained at nickel sulfate concentrations of less than. 10 μg/ml higher concentrations led to nonspecific lymphocyte stimulation. 3 nickel‐sensitive cashiers with suspected coin contact‐induced deterioration of their hand eczema were challenged by having them count nickel‐containing coins daily for 15 min. 2 of them developed vesicular eczema on their palms and fingers in 2 to 3 days. The present results show that the LPT is a reliable additional test in the diagnosis of nickel contact sensitivity. Furthermore, provocation is a valuable procedure when assessing the relevance of nickel contact in occupational hand eczema in certain occupations.
Hexagonal minimum Steiner tree construction for Y architecture: A case of non-Manhattan routing

Construction of cost-effective global routing trees is one of the primary keys in today's interconnect centric VLSI layout design under DSM (deep sub-micron) regime. In order to reduce the interconnect delay, traditional Manhattan (M-) routing architectures are currently being replaced by the diagonal X architectures. A recent routing architecture is based on Y interconnects, involving the pervasive use of 0°, 60°, and 120° oriented global and semi-global wirings. Unlike the X-routing, Y-routing is observed to support regular routing grid, which is important for simplifying manufacturing processes as well as for routing and design rule checking algorithms. In this paper, we propose a novel Y-routing algorithm that can solve reasonably sized problems in nominal time. Moreover, it can be easily extended for routing with any uniform orientation. Experimental results are quite encouraging and far better than the previously existing solution.
Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis

ObjectiveIcariin prevents bone loss by stimulating new bone formation and by inhibiting bone resorption. However, less is known about how icariin affects marrow adiposity. This lack of information is a vital problem, as the degree of marrow adipogenesis may be an alternative indicator of the severity of osteoporosis in relation to the degree of osteogenesis and osteoblastogenesis. To explore this question, we tested the effects of icariin on bone mineral density (BMD) and marrow fat content in a rat model of postmenopausal osteoporosis. MethodsThirty-six 3-month-old female Sprague-Dawley rats were randomly assigned to one of the following treatment groups: sham operation, ovariectomized controls, and ovariectomized rats treated orally with either 17&bgr;-estradiol or icariin for 12 weeks. BMD and marrow fat fraction were dynamically measured on weeks 0, 6, and 12. After 12 weeks of treatment, serum 17&bgr;-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. ResultsOvariectomized controls experienced a marked increase in fat fraction over time, with increases of 40% between weeks 0 and 6 and 69.4% between weeks 6 and 12 (P < 0.001). Marrow adiposity in ovariectomized controls was dramatically higher than that in sham rats on week 6; however, a reduction in BMD was detected in ovariectomized rats on week 12 (P < 0.001). Ovariectomized rats had levels of serum alkaline phosphatase and serum C-terminal telopeptide of type I collagen that were 49.4% and 67.2% higher, respectively, than those of sham rats (P < 0.001). The density, size, and volume of marrow adipocytes in ovariectomized controls were 57.3%, 29.5%, and 163% higher, respectively, than those in sham rats. Early icariin treatment decreased bone biomarker levels, inhibited bone degeneration, and restored marrow fat infiltration and adipocyte parameters to the levels observed in sham rats. Overall, the osteoprotective effect of icariin was comparable with that of 17&bgr;-estradiol; however, icariin did not produce uterine estrogenicity. ConclusionsEarly icariin treatment restores marrow adiposity in the estrogen-deficient rat model.