Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies.

Complications of guided surgery and immediate loading in oral implantology: a report of 12 cases

Objectives: The growing interest in minimally invasive surgery, together with the possibility of fitting prostheses with immediate function, have led to the development of software capable of planning and manufacturing a surgical guide and prosthesis that can be placed upon conclusion of the implant surgery step. The present study evaluates the surgical and prosthetic complications of implant treatment with the guided surgery technique, together with patient comfort during and after treatment. Patients and methods: A retrospective observational study was made of 19 patients with partially or totally edentulous upper and/or lower maxillae, involving the placement of a total of 122 implants. All cases were planned and operated upon with the guided surgery technique. Results: A total of 122 implants were placed in 14 males and 5 females. The intraoperative surgical complications comprised a lack of primary stability, while the postoperative complications consisted of infections and a lack of implant osteointegration. Ten implants failed. The prosthetic complications in turn comprised loosening of the provisional prosthesis screws, prosthesis tooth fracture, and a lack of passive fit of the immediate prosthesis. The degree of patient satisfaction was evaluated using a verbal scale. Conclusions: Implant restoration with the guided surgery technique and immediate functional loading is a predictable procedure, provided patient selection and the surgical technique are adequate, affording lesser postoperative morbidity and increased patient satisfaction thanks to the immediate restoration of esthetics and function

Independent and combined associations of risky single-occasion drinking and drinking volume with alcohol use disorder: Evidence from a sample of young Swiss men.

BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially harmful alcohol use pattern associated with increased alcohol use disorder (AUD). However, RSOD is commonly associated with a higher level of alcohol intake, and most studies have not controlled for drinking volume (DV). Thus, it is unclear whether the findings provide information about RSOD or DV. This study sought to investigate the independent and combined effects of RSOD and DV on AUD. METHODS: Data were collected in the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) among 5598 young Swiss male alcohol users in their early twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized linear models for binomial distributions provided evidence regarding associations of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were significantly related to the number of AUD criteria. The slope of the interaction was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears to be a harmful pattern of drinking, associated with increased AUD and it moderated the relationship between DV and AUD. This study highlighted the importance of taking drinking patterns into account, for both research and public health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

Combined application of continuous wavelet transform-zero crossing technique in the simultaneous spectrophotometric determination of perindopril and indapamid in tablets

Signal processing methods based on the combined use of the continuous wavelet transform (CWT) and zero-crossing technique were applied to the simultaneous spectrophotometric determination of perindopril (PER) and indapamide (IND) in tablets. These signal processing methods do not require any priory separation step. Initially, various wavelet families were tested to identify the optimum signal processing giving the best recovery results. From this procedure, the Haar and Biorthogonal1.5 continuous wavelet transform (HAAR-CWT and BIOR1.5-CWT, respectively) were found suitable for the analysis of the related compounds. After transformation of the absorbance vectors by using HAAR-CWT and BIOR1.5-CWT, the CWT-coefficients were drawn as a graph versus wavelength and then the HAAR-CWT and BIOR1.5-CWT spectra were obtained. Calibration graphs for PER and IND were obtained by measuring the CWT amplitudes at 231.1 and 291.0 nm in the HAAR-CWT spectra and at 228.5 and 246.8 nm in BIOR1.5-CWT spectra, respectively. In order to compare the performance of HAAR-CWT and BIOR1.5-CWT approaches, derivative spectrophotometric (DS) method and HPLC as comparison methods, were applied to the PER-IND samples. In this DS method, first derivative absorbance values at 221.6 for PER and 282.7 nm for IND were used to obtain the calibration graphs. The validation of the CWT and DS signal processing methods was carried out by using the recovery study and standard addition technique. In the following step, these methods were successfully applied to the commercial tablets containing PER and IND compounds and good accuracy and precision were reported for the experimental results obtained by all proposed signal processing methods.

Fatigue analysis of brackets with and without scallop for bridge and other deck structure using effective notch stress.

Due to functional requirement of a structural detail brackets with and without scallop are frequently used in bridges, decks, ships and offshore structure. Scallops are designed to serve as passage way for fluids, to reduce weld length and plate distortions. Moreover, scallops are used to avoid intersection of two or more welds for the fact that there is the presence of inventible inherent initial crack except for full penetrated weld and the formation of multi-axial stress state at the weld intersection. Welding all around the scallop corner increase the possibility of brittle fracture even for the case the bracket is not loaded by primary load. Avoiding of scallop will establish an initial crack in the corner if bracket is welded by fillet welds. If the two weld run pass had crossed, this would have given a 3D residual stress situation. Therefore the presences and absence of scallop necessitates the 3D FEA fatigue resistance of both types of brackets using effective notch stress approach ( ). FEMAP 10.1 with NX NASTRAN was used for the 3D FEA. The first and main objective of this research was to investigate and compare the fatigue resistance of brackets with and without scallop. The secondary goal was the fatigue design of scallops in case they cannot be avoided for some reason. The fatigue resistance for both types of brackets was determined based on approach using 1 mm fictitiously rounded radius based on IIW recommendation. Identical geometrical, boundary and loading conditions were used for the determination and comparison of fatigue resistance of both types of brackets using linear 3D FEA. Moreover the size effect of bracket length was also studied using 2D SHELL element FEA. In the case of brackets with scallop the flange plate weld toe at the corner of the scallop was found to exhibit the highest and made the flange plate weld toe critical for fatigue failure. Whereas weld root and weld toe at the weld intersections were the highly stressed location for brackets without scallop. Thus weld toe for brackets with scallop, and weld root and weld toe for brackets without scallop were found to be the critical area for fatigue failure. Employing identical parameters on both types of brackets, brackets without scallop had the highest except for full penetrated weld. Furthermore the fatigue resistance of brackets without scallop was highly affected by the lack of weld penetration length and it was found out that decreased as the weld penetration was increased. Despite the fact that the very presence of scallop reduces the stiffness and also same time induce stress concentration, based on the 3D FEA it is worth concluding that using scallop provided better fatigue resistance when both types of brackets were fillet welded. However brackets without scallop had the highest fatigue resistance when full penetration weld was used. This thesis also showed that weld toe for brackets with scallop was the only highly stressed area unlike brackets without scallop in which both weld toe and weld root were the critical locations for fatigue failure when different types of boundary conditions were used. Weld throat thickness, plate thickness, scallop radius, lack of weld penetration length, boundary condition and weld quality affected the fatigue resistance of both types of brackets. And as a result, bracket design procedure, especially welding quality and post weld treatment techniques significantly affect the fatigue resistance of both type of brackets.

Repair of segmental bone defects with fiber-reinforced composite: a study of material development and an animal model on rabbits

The Repair of segmental defects in load-bearing long bones is a challenging task because of the diversity of the load affecting the area; axial, bending, shearing and torsional forces all come together to test the stability/integrity of the bone. The natural biomechanical requirements for bone restorative materials include strength to withstand heavy loads, and adaptivity to conform into a biological environment without disturbing or damaging it. Fiber-reinforced composite (FRC) materials have shown promise, as metals and ceramics have been too rigid, and polymers alone are lacking in strength which is needed for restoration. The versatility of the fiber-reinforced composites also allows tailoring of the composite to meet the multitude of bone properties in the skeleton. The attachment and incorporation of a bone substitute to bone has been advanced by different surface modification methods. Most often this is achieved by the creation of surface texture, which allows bone growth, onto the substitute, creating a mechanical interlocking. Another method is to alter the chemical properties of the surface to create bonding with the bone – for example with a hydroxyapatite (HA) or a bioactive glass (BG) coating. A novel fiber-reinforced composite implant material with a porous surface was developed for bone substitution purposes in load-bearing applications. The material’s biomechanical properties were tailored with unidirectional fiber reinforcement to match the strength of cortical bone. To advance bone growth onto the material, an optimal surface porosity was created by a dissolution process, and an addition of bioactive glass to the material was explored. The effects of dissolution and orientation of the fiber reinforcement were also evaluated for bone-bonding purposes. The Biological response to the implant material was evaluated in a cell culture study to assure the safety of the materials combined. To test the material’s properties in a clinical setting, an animal model was used. A critical-size bone defect in a rabbit’s tibia was used to test the material in a load-bearing application, with short- and long-term follow-up, and a histological evaluation of the incorporation to the host bone. The biomechanical results of the study showed that the material is durable and the tailoring of the properties can be reproduced reliably. The Biological response - ex vivo - to the created surface structure favours the attachment and growth of bone cells, with the additional benefit of bioactive glass appearing on the surface. No toxic reactions to possible agents leaching from the material could be detected in the cell culture study when compared to a nontoxic control material. The mechanical interlocking was enhanced - as expected - with the porosity, whereas the reinforcing fibers protruding from the surface of the implant gave additional strength when tested in a bone-bonding model. Animal experiments verified that the material is capable of withstanding load-bearing conditions in prolonged use without breaking of the material or creating stress shielding effects to the host bone. A Histological examination verified the enhanced incorporation to host bone with an abundance of bone growth onto and over the material. This was achieved with minimal tissue reactions to a foreign body. An FRC implant with surface porosity displays potential in the field of reconstructive surgery, especially regarding large bone defects with high demands on strength and shape retention in load-bearing areas or flat bones such as facial / cranial bones. The benefits of modifying the strength of the material and adjusting the surface properties with fiber reinforcement and bone-bonding additives to meet the requirements of different bone qualities are still to be fully discovered.

Design of an amplifier and an instrumentation setup for a harsh environment heat flux measurement application – case axial flux electric machine

Measurement is a tool for researching. Therefore, it is important that the measuring process is carried out correctly, without distorting the signal or the measured event. Researches of thermoelectric phenomena have been focused more on transverse thermoelectric phenomena during recent decades. Transverse Seebeck effect enables to produce thinner and faster heat flux sensor than before. Studies about transverse Seebeck effect have so far focused on materials, so in this Master’s Thesis instrumentation of transverse Seebeck effect based heat flux sensor is studied, This Master’s Thesis examines an equivalent circuit of transverse Seebeck effect heat flux sensors, their connectivity to electronics and choosing and design a right type amplifier. The research is carried out with a case study which is Gradient Heat Flux Sensors and an electrical motor. In this work, a general equivalent circuit was presented for the transverse Seebeck effect-based heat flux sensor. An amplifier was designed for the sensor of the case study, and the solution was produced for the measurement of the local heat flux of the electric motor to improve the electromagnetic compatibility.

Experimental analysis of pressure drop and flow redistribution in axial flows in rod bundles

Fuel elements of PWR type nuclear reactors consist of rod bundles, arranged in a square array, and held by spacer grids. The coolant flows, mainly, axially along the rods. Although such elements are laterally open, experiments are performed in closed type test sections, originating the appearance of subchannels with different geometries. In the present work, utilizing a test section of two bundles of 4x4 pins each, experiments were performed to determine the friction and the grid drag coefficients for the different subchannels and to observe the effect of the grids in the crossflow, in cases of inlet flow maldistribution.

Combined effects of diethylpropion and alcohol on locomotor activity of mice: participation of the dopaminergic and opioid systems

The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol (EtOH) and diethylpropion (DEP) we examined the locomotion-activating effects of these drugs given alone or in combination in mice. We also determined whether this response was affected by dopamine (DA) or opioid receptor antagonists. A total of 160 male Swiss mice weighing approximately 30 g were divided into groups of 8 animals per group. The animals were treated daily for 7 consecutive days with combined EtOH + DEP (1.2 g/kg and 5.0 mg/kg, ip), EtOH (1.2 g/kg, ip), DEP (5.0 mg/kg, ip) or the control solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/kg, ip), the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip), or vehicle. On days 1, 7 and 10 after the injections, mice were assessed in activity cages at different times (15, 30, 45 and 60 min) for 5 min. The acute combination of EtOH plus DEP induced a significantly higher increase in locomotor activity (day 1: 369.5 ± 34.41) when compared to either drug alone (day 1: EtOH = 232.5 ± 23.79 and DEP = 276.0 ± 12.85) and to control solution (day 1: 153.12 ± 7.64). However, the repeated administration of EtOH (day 7: 314.63 ± 26.79 and day 10: 257.62 ± 29.91) or DEP (day 7: 309.5 ± 31.65 and day 10: 321.12 ± 39.24) alone or in combination (day 7: 459.75 ± 41.28 and day 10: 427.87 ± 33.0) failed to induce a progressive increase in the locomotor response. These data demonstrate greater locomotion-activating effects of the EtOH + DEP combination, probably involving DA and/or opioid receptor stimulation, since the daily pretreatment with HAL (day 1: EtOH + DEP = 395.62 ± 11.92 and EtOH + DEP + HAL = 371.5 ± 6.76; day 7: EtOH + DEP = 502.5 ± 42.27 and EtOH + DEP + HAL = 281.12 ± 16.08; day 10: EtOH + DEP = 445.75 ± 16.64 and EtOH + DEP + HAL = 376.75 ± 16.4) and NAL (day 1: EtOH + DEP = 553.62 ± 38.15 and EtOH + DEP + NAL = 445.12 ± 55.67; day 7: EtOH + DEP = 617.5 ± 38.89 and EtOH + DEP + NAL = 418.25 ± 61.18; day 10: EtOH + DEP = 541.37 ± 32.86 and EtOH + DEP + NAL = 427.12 ± 51.6) reduced the locomotor response induced by combined administration of EtOH + DEP. These findings also suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by the combination.

Assessment of the diagnostic value of diffusion tensor imaging in patients with spinal cord compression: a meta-analysis

We investigated the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging (DTI) in patients with spinal cord compression (SCC) using a meta-analysis framework. Multiple scientific literature databases were exhaustively searched to identify articles relevant to this study. Mean values and standardized mean differences (SMDs) were calculated for the ADC and FA in normal and diseased tissues. The STATA version 12.0 software was used for statistical analysis. Of the 41 articles initially retrieved through database searches, 11 case-control studies were eligible for the meta-analysis and contained a combined total of 645 human subjects (394 patients with SCC and 251 healthy controls). All 11 studies reported data on FA, and 9 contained data related to the ADC. The combined SMDs of the ADC and FA showed that the ADC was significantly higher and the FA was lower in patients with SCC than in healthy controls. Subgroup analysis based on the b value showed higher ADCs in patients with SCC than in healthy controls at b values of both ≤500 and >500 s/mm2. In summary, the main findings of this meta-analysis revealed an increased ADC and decreased FA in patients with SCC, indicating that DTI is an important diagnostic imaging tool to assess patients suspected to have SCC.

Prevention of enzymatic browning of yacon flour by the combined use of anti-browning agents and the study of its chemical composition

Yacon roots present functional properties because of the high levels of fructooligosaccharides (FOS), which are considered as prebiotic fibers. In addition, yacon roots are rich in phenolic compounds. During the processing of yacon, the freshly cut surface undergoes rapid enzymatic browning. Control of enzymatic browning during processing is very important to preserve the appearance of yacon flour. In this study, it was evaluated the combined effect of anti-browning agents (ascorbic acid, citric acid and L-cysteine) on the inhibition of enzymatic browning of yacon, using Response Surface Methodology. The yacon pre-treated with anti-browning agents in concentrations of 15.0 mM for ascorbic acid, 7.5 mM for citric acid and 10.0 mM for L-cysteine was used for the processing of flour. Yacon flour presented an attractive color and good sensory properties, without residual aroma. The contents of FOS and phenolic compounds obtained in yacon flour were 28.60 g.100 g- 1 and 1.35 g.100 g- 1. Yacon flour can be considered as a potential functional food, especially due to high levels of FOS, which allows for its use in formulation of various foods.

The effect of nonlinear frequency compression and linear frequency transposition on speech perception in school-aged children

The primary objective of this study is to determine whether nonlinear frequency compression and linear transposition algorithms provide speech perception benefit in school-aged children.