Creating temporary doubly curved tensile membrane structures without cutting patterns using high strain fabrics

Tensile surface structures have been used in both permanent and temporary constructions. Using a light, flexible fabric as most important component, these structures have already displayed a great versatility in forms and uses as well as a high material performance and low self weight. Key in using a prestressed fabric is the double curved surface, being it either synclastic or anticlastic. To achieve these shapes using a flat fabric, the complex shapes are approximated by a finite number of flat panels, called cutting patterns. Generating and producing these cutting patterns however requires a lot of expertise, is often very time consuming and requires the need to connect the different panels together, such as welding or stitching. Finding a method that facilitates temporary double curved structures by eliminating the need for a thought out cutting pattern, would greatly simplify the design process and broaden the use of fabrics in architectural applications. During this preliminary research, we tested a very stretchable fabric material (Sioen F5637) to derive its material characteristics. Afterwards we designed a simple double curved structure, which starts from a single flat piece of this material, and modelled the transition from an untensioned, flat piece of fabric to a three dimensional pretensioned curved surface computationally to check the concept’s feasibility. Finally, the results from the computational model were verified with a small-scale prototype. This paper gives an overview of the structure's design process and discusses both the advantages and limitations of using high straining fabrics in real life architectural applications

KLHL12 promotes non-lysine ubiquitination of the dopamine receptors D-4.2 and D-4.4, but not of the ADHD-associated D-4.7 variant

Dopamine D-4 Receptor Polymorphism : The dopamine D-4 receptor has an important polymorphism in its third intracellular loop that is intensively studied and has been associated with several abnormal conditions, among others, attention deficit hyperactivity disorder. KLHL12 Promotes Ubiquitination of the Dopamine D-4 Receptor on Non-Lysine Residues : In previous studies we have shown that KLHL12, a BTB-Kelch protein, specifically interacts with the polymorphic repeats of the dopamine D-4 receptor and enhances its ubiquitination, which, however, has no influence on receptor degradation. In this study we provide evidence that KLHL12 promotes ubiquitination of the dopamine D-4 receptor on non-lysine residues. By using lysine-deficient receptor mutants and chemical approaches we concluded that ubiquitination on cysteine, serine and/or threonine is possible. Differential Ubiquitination of the Dopamine D-4 Receptor Polymorphic Variants : Additionally, we show that the dopamine D-4.7 receptor variant, which is associated with a predisposition to develop attention deficient hyperactivity disorder, is differentially ubiquitinated compared to the other common receptor variants D-4.2 and D-4.4. Together, our study suggests that GPCR ubiquitination is a complex and variable process

The screening score of Mini Nutritional Assessment (MNA) is a useful routine screening tool for malnutrition risk in patients on maintenance dialysis

PURPOSE: Malnutrition is prevalent in patients on dialysis and is associated with morbidity and mortality. Nutritional status can be assessed by a variety of biochemical and physical parameters or nutritional assessment scores. Most of these methods are expensive or cumbersome to use and are not suitable for routine repetitive follow-up in dialysis patients. The Mini Nutritional Assessment (MNA) has a short form screening set (MNA-SF), which would be suitable as a screening tool, but has not been validated yet in dialysis patients. We aimed to assess whether the MNA is an appropriate tool for identifying nutritional problems in dialysis patients. METHOD: MNA, routine biochemistry, physical parameters, comorbidities were assessed in cross-sectional multicentric cohorts of hemodialysis and peritoneal dialysis patients with a longitudinal follow up of 2 years for mortality. RESULTS: In this cohort of 216 patients, mortality was 27.3% at a follow up of 750±350 days. The mean MNA-SF score was 9.9±1.8, with 30.1%, 59.3% and 10.6% of patients categorized as having normal nutritional status, at risk for malnutrition and malnourished, respectively. The screening score was associated with mortality (HR 0.86, 95% CI 0.75-0.98 per point). With normal nutrition as reference, adjusted mortality was 2.50 (95% CI 1.16-5.37) and 3.89 (95% CI 1.48-10.13) for patients at risk for malnutrition and with malnutrition, respectively. After recalibrating the MNA full score for the specificity of some of its domains for dialysis patients, the MNA-SF had a good sensitivity and specificity for not being well nourished (0.95 and 0.63 respectively) in the full score, and a high negative predictive value (0.91). CONCLUSION: The MNA-SF is independently associated with 2 year mortality in dialysis patients. It has a high negative predictive value for excluding being at risk or having malnutrition in the full score. Therefore, it can be advocated as a screening tool for nutritional status in dialysis patients

Associations between the measures of physical function, risk of falls and the quality of life in haemodialysis patients : a cross-sectional study

Background Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients. Methods This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression. Results Of the 113 haemodialysis patients (mean age 67.5 +/- 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R-2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R-2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status. Conclusions More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased

Regulation of G protein-coupled receptors by ubiquitination

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity

Current epigenetic aspects the clinical kidney researcher should embrace

Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu

American Bar Association Criminal Justice Section Report to the House of Delegates

The proposed amendments to the Federal Rules of Evidence, Rules 413-15 regarding the admission of character testimony in cases of sexual abuse and child molestation, have been roundly criticized by the legal community on both substantive and procedural grounds. The ABA has resolved to oppose the substance of these rules, and fear that in addition to the direct concerns regarding the result of the rules, they raise troubling policy issues going forward

On the G-protein-coupled receptor heteromers and their allosteric receptor-receptor interactions in the central nervous system: focus on their role in pain modulation

The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer. This heteromer contributes to morphine-induced tolerance and dependence, since it becomes abundant and develops a reduced G-protein-coupling with reduced signaling mainly operating via beta-arrestin 2 upon chronic morphine treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to the heteromer and the biological actions of morphine. The gender- and ovarian steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR) heterodimers enhances antinociceptive functions and if impaired could contribute to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch. Other mechanism for the antinociceptive actions of acupuncture along meridians may be that it enhances the cross-desensitization of the TRPA1 (chemical nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the nociceptor terminals located along these meridians. Selective ionotropic cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1 heteromeric nociceptor channels by being negative allosteric modulators of these channels leading to antinociception and antihyperalgesia