Miracle-dz/UniFAR-FTUs huggingface dataset:
Podocyte Structural Parameters Do Not Predict Progression to Diabetic Nephropathy in Normoalbuminuric Type 1 Diabetic Patients

Background: Podocyte injury has been implicated in diabetic nephropathy (DN) ranging from normoalbuminuria to proteinuria in both type 1 and type 2 diabetes. Methods: To determine whether podocyte structural parameters predict DN risk in initially normoalbuminuric long-standing type 1 diabetic patients, we performed a nested case-control study in sex and diabetes duration-matched progressors (progression to proteinuria or ESRD, n = 10), non-progressors (normoalbuminuric at follow-up, n = 10), and non-diabetic controls (n = 10). Results: HbA1c and diastolic blood pressure were higher in progressors versus non-progressors. Podocyte number per glomerulus, numerical density of podocyte per glomerulus, and foot process width were not different among groups. The glomerular basement membrane width was greater in progressors versus non-progressors or controls, and in non-progressors versus controls. As expected, the mesangial fractional volume was greater in progressors and non-progressors versus controls, with no differences between progressors and non-progressors. Conclusion: This study does not indicate that podocyte structural changes are preconditions for later DN progression in initially normoalbuminuric type 1 diabetic patients. However, this does not preclude an important role for podocyte injury at a later stage of DN.
Course of pattern-reversed visual evoked cortical potentials in 30 eyes after bony orbital decompression in dysthyroid optic neuropathy

Aim To investigate optic nerve function using the pattern-reversed visual evoked cortical potentials (VECP) before and after bony orbital decompression in dysthyroid optic neuropathy (DON) due to Graves' disease. Methods A total of 30 eyes of 15 patients (n=14 female) were observed over 30±13 months after bony three-wall orbital decompression. We examined visual acuity (VA), VECP P100 amplitudes and latencies, as well as proptosis using Hertel's exophthalmometry. Results Mean logarithm of the minimum angle of resolution (logMAR) VA increased, statistically significantly, by 2.4 lines during 30±13 months (from 0.38±0.25 before surgery to 0.14±0.1 at the end of observation, p=0.0001). All eyes maintained or improved vision by at least one line. Mean postoperative reduction of proptosis was 6.4±3 mm. While VECP P100 amplitudes improved significantly, P100 latencies remained abnormal in 18 eyes (60%) during follow-up of 10±7 months. Nine eyes (30%) with previous latency defects improved in at least one check test, five of which normalised completely. Worsening was evident in seven eyes (23%), and three previously normal eyes developed new pathological latencies. P100 latencies in 14 eyes (47%) remained unchanged. Conclusion After decompression surgery, DON remission was observed in all patients regarding vision and VECP amplitudes. New or persistent P100 latency defects were seen in 60% of eyes after surgery. DON is considered to be caused by compressive ischaemic damage, which further underlines the importance of early decompression surgery.
A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma

The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 overexpression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current treatment strategies. Cyclin-D1 has been postulated as an effective therapeutic target, but the evaluation of this target has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1–driven mouse model in which cyclin-D1 expression can be regulated externally. These mice developed cyclin-D1–expressing lymphomas capable of recapitulating features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo; however, using a combination of in vitro and in vivo assays, we identified a novel prosurvival cyclin-D1 function in MCL cells. Specifically, we found that cyclin-D1, besides increasing cell proliferation through deregulation of the cell cycle at the G1–S transition, sequestrates the proapoptotic protein BAX in the cytoplasm, thereby favoring BCL2’s antiapoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a proapoptotic BH3 mimetic synergistically killed the cyclin-D1–expressing murine lymphomas, human MCL cell lines, and primary lymphoma cells. Our study identifies a role of cyclin-D1 in deregulating apoptosis in MCL cells, and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. This effective combination therapy also might be exploited in other cyclin-D1–expressing tumors.
Vertical-cavity surface-emitting lasers (VCSELs) with high-power and single-spot far-field distributions at 850-nm wavelength by use of petal-shaped light-emitting apertures

In this letter, we demonstrate a vertical-cavity surface-emitting laser (VCSEL) with a petal-shaped light-emitting aperture, which is realized by the Zn-diffusion technique, at a wavelength of 850 nm. The demonstrated device behaves like a two-dimensional VCSEL array and each light-emitting unit can have high coherence of in-phase lasing to form a near fundamental supermode emission. The measured far-field distributions of such a device exhibit single-lobe (spot), high-power (>7.5 mW), and narrow divergence angle (~6deg) performance under a wide range of bias current. The ratio of in-phase lasing mode to total lasing modes, which include isolated single mode, in-phase, and out-of-phase modes, has also been analyzed by the measured far-field distributions and the theoretically calculated patterns
Worksite Fitness and Exercise Programs: A Review of Methodology and Health Impact

Purpose. To examine the methodology of worksite fitness and exercise programs and to assess their effect on health-related fitness, cardiac risk factors, life satisfaction and well-being, and illness and injury. Search methods. The 52 studies reviewed cover English-language literature for the period from 1972 to 1994, as identified by a search of the Cumulative Index Medicus, Medline, the Canadian Sport Documentation Centre's “Sport Discus,” computerized bibliography, and my own files. Reports were divided into five controlled experimental studies, 14 quasi-experimental studies with matched controls (one reported in abstract), and 33 other interventions of varied quality. Summary. Methodologic problems include difficulty in allowing for Hawthorne effects, substantial sample attrition, and poor definition of the intervention (exercise or broad-based health promotion). Findings are analyzed by specific fitness and health outcomes. Program participants show small but favorable changes in body mass, skinfolds, aerobic power, muscle strength and flexibility, overall risk-taking behavior, systemic blood pressure, serum cholesterol, and cigarette smoking. Claims of improved mood state are based heavily on uncontrolled studies. Quasi-experimental studies suggest reduced rates of illness and injury among participants, but seasonal and year-to-year differences in health weaken possible conclusions. Conclusions. Participation in worksite fitness programs can enhance health-related fitness and reduce risk-taking behavior, but population effect is limited by low participation rates.
Estimation of the Effect of Slco1B1 Polymorphisms on Lopinavir Plasma Concentration in HIV-Infected Adults

Background The organic anion transporting polypeptides (OATP)/SLCO family represents an important class of hepatic drug uptake transporters that mediate the sodium independent transport of a diverse range of amphipathic organic compounds, including the protease inhibitors. The SLCO1B1 521T>C (rs4149056) single nucleotide polymorphism (SNP) has been consistently associated with reduced transport activity in vivo, and we previously showed an association of this polymorphism with lopinavir plasma concentrations. The aim of this study was to develop a population pharmacokinetic (PK) model to quantify the impact of 521T>C. Methods A population PK analysis was performed with 594 plasma samples from 375 patients receiving lopinavir/ritonavir. Non-linear mixed effects modelling was applied to explore the effects of SLCO1B1 521T>C and patient demographics. Simulations of the lopinavir concentration profile were performed with different dosing regimens considering the different alleles. Results A one-compartment model with first-order absorption best described the data. Population clearance was 5.67 l/h with inter-patient variability of 37%. Body weight was the only demographic factor influencing clearance, which increased 0.5 l/h for every 10 kg increase. Homozygosity for the C allele was associated with a 37% lower clearance, and 14% for heterozygosity, which were statistically significant. Conclusions These data show an association between SLCO1B1 521T>C and lopinavir clearance. The association is likely to be mediated through reduced uptake by hepatocytes leading to higher plasma concentrations of lopinavir. Further studies are now required to confirm the association and to assess the influence of other polymorphisms in the SLCO family on lopinavir PK.
Critical binding and regulatory interactions between Ras and Raf occur through a small, stable N-terminal domain of Raf and specific Ras effector residues

Genetic and biochemical evidence suggests that the Ras protooncogene product regulates the activation of the Raf kinase pathway, leading to the proposal that Raf is a direct mitogenic effector of activated Ras. Here we report the use of a novel competition assay to measure in vitro the relative affinity of the c-Raf-1 regulatory region for Ras-GTP, Ras-GDP, and 10 oncogenic and effector mutant Ras proteins. c-Raf-1 associates with normal Ras and the oncogenic V12 and L61 forms of Ras with equal affinity. The moderately transforming mutant Ras[E30K31] also bound to the c-Raf-1 regulatory region with normal affinity. Transformation-defective Ras effector mutants Ras[N33], Ras[S35], and Ras[N38] bound poorly. In contrast, the transformation defective Ras[G26I27] and Ras[E45] mutants bound to the c-Raf-1 regulatory region with nearly wild-type affinity. A stable, high-affinity Ras-binding region of c-Raf-1 was mapped to a 99-amino-acid subfragment of the first 257 residues. The smallest Ras-binding region identified consisted of N-terminal residues 51 to 131, although stable expression of the domain and high-affinity binding were improved by the presence of residues 132 to 149. Deletion of the Raf zinc finger region did not reduce Ras-binding affinity, while removal of the first 50 amino acids greatly increased affinity. Phosphorylation of Raf[1-149] by protein kinase A on serine 43 resulted in significant inhibiton of Ras binding. demonstrating that the mechanism of cyclic AMP downregulation results through structural changes occurring exclusively in this small Ras-binding domain.
Upregulation of myosin Va by Snail is involved in cancer cell migration and metastasis

Cell migration, which involves acto‐myosin dynamics, cell adhesion, membrane trafficking and signal transduction, is a prerequisite for cancer cell metastasis. Here, we report that an actin‐dependent molecular motor, unconventional myosin Va, is involved in this process and implicated in cancer metastasis. The mRNA expression of myosin Va is increased in a number of highly metastatic cancer cell lines and metastatic colorectal cancer tissues. Suppressing the expression of myosin Va by lentivirus‐based RNA interference in highly metastatic cancer cells impeded their migration and metastasis capabilities both in vitro and in vivo. In addition, the levels of myosin Va in cancer cell lines are positively correlated with the expression of Snail, a transcriptional repressor that triggers epithelial–mesenchymal transition. Repression or overexpression of Snail in cancer cells caused reduced or elevated levels of myosin Va, respectively. Furthermore, Snail can bind to an E‐box of the myosin Va promoter and induce its activity, which indicates that Snail might act as a transcriptional activator. These data demonstrate an essential role of myosin Va in cancer cell migration and metastasis, and suggest a novel target for Snail in its regulation of cancer progression.
Measurement of Hysteresis Loop on Soft Magnetic Materials Using Lock-In Amplifier

A new method is proposed to measure the magnetic hysteresis as a function of temperature. It is based on the spectral decomposition of magnetization and measurement of different harmonics using the harmonic-detection function of a lock-in amplifier. Applying this method, a measuring system of the BH loop was designed and fabricated. This system gives spectra of magnetic flux density B driven by an ac-magnetic field h. The BH loops are reconstructed from the spectra of the B. The spectra and BH loops were measured for a NiZn ferrite toroid at various temperatures. When the temperature increases from the room temperature, the higher harmonics of the spectra increase. Approaching the Curie temperature TC from below, magnetic loss and nonlinearity of the BH loops increase, and the loop shows the saturation just below TC.
Smoking cessation attempts among adolescent smokers: a systematic review of prevalence studies

Objective: To synthesise estimates of the prevalence of cessation attempts among adolescent smokers generally, and according to age and level of cigarette consumption. Data sources: PubMed, ERIC, and PsychInfo databases and Internet searches of central data collection agencies. Study selection: National population-based studies published in English between 1990 and 2005 reporting the prevalence, frequency and/or duration of cessation attempts among smokers aged ⩾10 to <20 years. Data extraction: Five reviewers determined inclusion criteria for full-text reports. One reviewer extracted data on the design, population characteristics and results from the reports. Data synthesis: In total, 52 studies conformed to the inclusion criteria. The marked heterogeneity that characterised the study populations and survey questions precluded a meta-analysis. Among adolescent current smokers, the median 6-month, 12-month and lifetime cessation attempt prevalence was 58% (range: 22–73%), 68% (range 43–92%) and 71% (range 28–84%), respectively. More than half had made multiple attempts. Among smokers who had attempted cessation, the median prevalence of relapse was 34, 56, 89 and 92% within 1 week, 1 month, 6 months, and 1 year, respectively, following the longest attempt. Younger (age<16 years) and non-daily smokers experienced a similar or higher prevalence of cessation attempts compared with older (age ⩾16 years) or daily smokers. Moreover, the prevalence of relapse by 6 months following the longest cessation attempt was similar across age and smoking frequency. Conclusions: The high prevalence of cessation attempts and relapse among adolescent smokers extends to young adolescents and non-daily smokers. Cessation surveillance, research and program development should be more inclusive of these subgroups.
Cultured human fibroblasts contain a large pool of precursor beta 1-integrin but lack an intracellular pool of mature subunit.

Previous work has shown the presence of an important intracellular pool of beta 1-integrin subunit in human skin fibroblasts as detected with monoclonal antibody DH12 [De Strooper, B. , Van der Schueren, B. , Jaspers, M. , Saison, M. , Spaepen, M. , Van Leuven, F. , Van den Berghe, H. & Cassiman, J. J. (1989) J. Histochem. Cytochem. 37,299-307]. To analyze this more quantitatively, a radioimmunoassay with radioiodinated monoclonal antibody was developed. The total amount of specific binding sites for monoclonal antibody DH12 on skin fibroblasts was between 0.8-1.5 x 10(6)/cell. After permeabilizing the cells with digitonin, a threefold increase in specific binding was observed, which suggested that about 60% of the total amount of beta 1-subunit was localized intracellularly. From pulse/chase experiments, it was deduced that an important pool of precursor subunit, as defined by its sensitivity to endoglycosidase treatment, existed in fibroblasts. Since in steady-state-labeling conditions, at least three to four times more precursor than mature subunit was immunoprecipitated with monoclonal antibody DH12, we suggested that the intracellular pool of beta 1-integrin subunit is mainly precursor pool. This precursor pool contains a degradation compartment and a maturation compartment. Other investigators have found evidence for a recirculating pool of mature integrin in Chinese hamster ovary cells. Therefore, the presence of a recirculating pool of integrin in human fibroblasts was also considered. The data obtained with mAb DH12 showed that less than 10% of the surface pool of integrin was internalized by endocytosis. Since, however, cross linking of beta 1-integrins with polyclonal antibodies leads to rapid endocytosis of most of the integrin, it remains possible that the quantitatively small effect was actually an artefact induced by the divalent mAb. We conclude that the intracellular pool of beta 1-integrins observed in our previous studies consists of precursor and that in skin fibroblasts no mature beta 1-integrin is available intracellularly for rapid quantitative modulations at the cell surface.
The effects of socio sponsorships in different levels of reputation: the role of communication channel

Profile: Strategy and Management (STR) Department of Strategy and Management // Advisor: Siv Skard This thesis was written as a part of the Master of Science in Economics and Business Administration at NHH. Neither the institution, the advisor or the sensors are through the approval of this thesis responsible for neither the theories and methods used, nor results and conclusions drawn in this work.
Cord-Blood 25-Hydroxyvitamin D Levels and Risk of Respiratory Infection, Wheezing, and Asthma

OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated with a lower risk of wheezing in offspring. The relationship between cord-blood levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We hypothesized that cord-blood levels would be inversely associated with risk of respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a history of respiratory infection at 3 months of age or a history of wheezing at 15 months of age and then annually thereafter. Incident asthma was defined as doctor-diagnosed asthma by the time the child was 5 years old and reported inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood level of 25(OH)D was 44 nmol/L (interquartile range: 29–78). Follow-up was 89% at the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse association with risk of respiratory infection by 3 months of age (odds ratio: 1.00 [reference] for ≥75 nmol/L, 1.39 for 25–74 nmol/L, and 2.16 [95% confidence interval: 1.35–3.46] for <25 nmol/L). Likewise, cord-blood 25(OH)D levels were inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of age (all P < .05). Additional adjustment for more than 12 potential confounders did not materially change these results. In contrast, we found no association between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS: Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma.
Use of sunscreen, sunburning rates, and tanning bed use among more than 10 000 US children and adolescents.

OBJECTIVES To describe the association of sunscreen use, sunburning, and tanning bed use by age, sex, residence, and psychosocial variables associated with tan-seeking behaviors, and to compare these findings with sun protection recommendations from federal agencies and cancer organizations. METHODS A cross-sectional study, from all 50 states, of 10 079 boys and girls 12 to 18 years of age in 1999. Data were collected from self-report questionnaires with the children of the participants from the Nurses Health Study (Growing Up Today Study). RESULTS The prevalence of sunscreen use was 34.4% with girls more likely to use sunscreen than boys (40.0 vs 26.4, odds ratio: 1.86; 95% confidence interval: 1.70-2.03). Eighty-three percent of respondents had at least 1 sunburn during the previous summer, and 36% had 3 or more sunburns. Nearly 10% of respondents used a tanning bed during the previous year. Girls were far more likely than boys to report tanning bed use (14.4 vs 2.4), and older girls (ages 15-18) were far more likely than younger girls (ages 12-14) to report tanning bed use (24.6% vs 4.7). Tanning bed use increased from 7% among 14-year-old girls to 16% by age 15, and more than doubled again by age 17 (35%; N = 244). Multivariate analysis demonstrated that attitudes associated with tanning, such as the preference for tanned skin, having many friends who were tanned, and belief in the worth of burning to get a tan, were generally associated with sporadic sunscreen use, more frequent sunburns, and increased use of tanning beds. CONCLUSIONS Our findings suggest that many children are at subsequent risk of skin cancer because of suboptimal sunscreen use, high rates of sunburning, and tanning bed use. Recommendations in the United States for improved sun protection and avoidance of tanning beds and sunburning, which began in the early 1990s, have been primarily unheeded. Nationally coordinated campaigns with strong policy components must be developed and sustained to prevent skin cancer in a new generation of children and adolescents.
Quadriceps Moment Arm and Quadriceps Forces After Total Knee Arthroplasty

Knee prosthetic designs that increase quadriceps moment arm can reduce quadriceps tension and patellofemoral compressive forces. Six knees from cadavers were tested on the Oxford knee rig, which simulates closed chain knee extension under load. Three conditions were tested sequentially for each knee: Normal, Control (implanted with the Osteonics 7000 knee design), and Scorpio (implanted with the Osteonics Scorpio design). The center of flexion-extension of the Scorpio design was 10 mm posterior to that of Control that served to lengthen the quadriceps moment arm. An electromagnetic tracking system measured dynamic knee kinematics, and a uniaxial load cell measured quadriceps tension. The Scorpio design reduced quadriceps tension when compared with the Normal or Control knee ranging from 5% to 20%. This was statistically significant at flexion angles greater than 50°. In three knees, the patellar component was instrumented with a triaxial load cell that measured patellofemoral forces. Patellofemoral forces were lower with the Scorpio design compared with the Control. Increasing quadriceps lever arm reduces quadriceps forces and can facilitate activities of daily living and enhance patient rehabilitation. Reduced quadriceps forces may result in reduced patellofemoral forces that can have a beneficial effect on anterior knee pain, patellar component wear, and loosening.