Fractal nature in fat crystal networks

The determination of the mechanical and rheological characteristics of several plastic fats requires a detailed understanding of the microstructure of the fat crystal network aggregates. The fractal approach is useful for the characterization of this microstructure. This review begins with information on fractality and statistical self-similar structure. Estimations for fractal dimension by means of equations relating the volume fraction of solid fat to shear elastic modulus G’ in linear region are described. The influence of interesterification on fractal dimension decrease (from 2,46 to 2,15) for butterfat-canola oil blends is notable. This influence is not significant for fat blends without butterfat. The need for an increase in research concerning the relationship between fractality and rheology in plastic fats is emphasized.La determinación de las características mecánicas y reológicas de ciertas grasas plásticas requiere conocimientos detallados sobre las microestructuras de los agregados que forman la red de cristales grasos. El estudio de la naturaleza fractal de estas microestructuras resulta útil para su carac­terización. Este artículo de información se inicia con descripciones de la dimensión fractal y de la "autosimilitud estadística". A continuación se describe el cálculo de la dimensión fractal mediante ecuaciones que relacionan la fracción en volumen de grasa sólida con el módulo de recuperación (G') dentro de un comportamiento viscoelástico lineal. Se destaca la influencia que la interesterificación ejerce sobre la dimensión fractal de una mezcla de grasa láctea y aceite de canola (que pasa de 2,64 a 2,15). Esta influencia no se presenta en mezclas sin grasa láctea. Se insiste sobre la necesidad de incrementar las investi­gaciones sobre la relación entre reología y estructura fractal en grasas plásticas.Peer reviewe

PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90-180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs -1664 [1190], respectively; difference, 5172; 95% CI 2929-7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH

Миграция и эмиграция поволжских немцев

This article presents an overview of current simulation methods describing the interaction of grinding process and grinding machine structure, e.g., vibrations, deflections, or thermal deformations. Innovative process models which describe the effects of the grinding wheel–workpiece interaction inside the contact zone are shown in detail. Furthermore, simulation models representing the static and dynamic behaviour of a grinding machine and its components are discussed. Machine tool components with a high influence on the process results are modelled more detailed than those with low influence. The key issue of the paper is the coupling of process and machine tool models for predicting the interactions of process and machine. Several coupling methods are introduced and the improvements of the simulation results are documented. On the basis of the presented simulation approaches, grinding processes and machines can be designed more effectively resulting in higher workpiece quality and process stability

Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function. Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218). Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3–12.0); NPHP1, 13.5 years (interquartile range 10.5–16.5); NPHP4, 16.0 years (interquartile range 11.0–25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7–28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline. Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling

Hypertension in children with chronic kidney disease: pathophysiology and management

Arterial hypertension is very common in children with all stages of chronic kidney disease (CKD). While fluid overload and activation of the renin–angiotensin system have long been recognized as crucial pathophysiological pathways, sympathetic hyperactivation, endothelial dysfunction and chronic hyperparathyroidism have more recently been identified as important factors contributing to CKD-associated hypertension. Moreover, several drugs commonly administered in CKD, such as erythropoietin, glucocorticoids and cyclosporine A, independently raise blood pressure in a dose-dependent fashion. Because of the deleterious consequences of hypertension on the progression of renal disease and cardiovascular outcomes, an active screening approach should be adapted in patients with all stages of CKD. Before one starts antihypertensive treatment, non-pharmacological options should be explored. In hemodialysis patients a low salt diet, low dialysate sodium and stricter dialysis towards dry weight can often achieve adequate blood pressure control. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are first-line therapy for patients with proteinuria, due to their additional anti-proteinuric properties. Diuretics are a useful alternative for non-proteinuric patients or as an add-on to renin–angiotensin system blockade. Multiple drug therapy is often needed to maintain blood pressure below the 90th percentile target, but adequate blood pressure control is essential for better renal and cardiovascular long-term outcomes

Tool wear in dry helical milling for hole-making in AISI H13 hardened steel

Helical milling is a hole-making process which can be applied to achieve high-quality finished boreholes in hardened steels. Due to the drilling process limitations, which are intensified when applied in hardened steels, the helical milling process can be applied on hole-making tasks in moulds and dies industry, since milling have been widely applied in moulds and dies machining to replace high-cost operations like grinding and electrical discharge machining. However, to succeed in achieving high-quality boreholes in hardened parts, which presents high added value due to previous operations, tool wear in the helical milling of hardened steels should be more investigated. In the present study, dry helical milling tool life tests were conducted in AISI H13 hardened steel parts, varying the cutting velocity. The flank wear on frontal cutting edges was progressively measured through optical microscopy, and SEM/EDS was performed in frontal and peripheral worn cutting edges. The wear occurred progressively in the flank of the frontal cutting edges with adhesion and oxidation as main wear mechanisms. In the peripheral edges, coating loss, and adhesion of workpiece material in the tool clearance surface were observed, besides fracture in the tool nose flank with the highest cutting velocity. A nested ANOVA was performed to evaluate the burr height in the borehole exit. The tool life stage was statistically significant in the burr height.publishe

Estudo experimental do uso de rebolos convencionais na usinagem do aço VP-50 utilizado na retificação cilíndrica, por meio de diferentes métodos de lubrirrefrigeração

A retificação é um processo de usinagem preciso, sendo uma das etapas mais caras na fabricação dos moldes para injeção de termoplásticos. Na retificação o rebolo é a ferramenta abrasiva responsável pela retirada do material. O número de tipos de abrasivos e granulometrias disponíveis são bastante grandes e junto com a quantidade de ligas possíveis, estruturas e durezas, além dos formatos, fazem com que se chegue a um número enorme de produtos. O conhecimento das suas características técnicas, vantagens, defeitos e condições de trabalho são fundamentais para os engenheiros de produto, de processos e, naturalmente, para os gerentes de área industrial, identificarem qual o rebolo mais indicado para realização do processo de retificação. Dentre os aços utilizados na fabricação de moldes para injeção de termoplásticos destaca-se o aço VP-50, o qual foi o aço usado neste experimento, sendo usinado pelo processo de retificação cilíndrica. No processo de retificação, também foi adotado para fins de experimento dois métodos de lubrirrefrigeração, sendo eles o método convencional com lubrirrefrigeração abundante e o MQL que é a técnica com mínima quantidade de lubrirrefrigeração. O objetivo deste trabalho foi analisar de forma comparativa o desempenho de corte executado com três tipos de rebolos convencionais: rebolo de óxido de alumínio branco, rebolo de carbureto de silício verde e rebolo de carbureto de silício preto com óxido de alumínio branco. Os resultados foram analisados e comparados pelas variáveis de saída dos três tipos de rebolos, tipo de refrigeração e espessura equivalente de corte

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Background Nephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised.Methods In 120 patients with severe NPHP-AC phenotypes, five pools of genomic DNA with 24 patients each were prepared which were used as templates in order to PCR amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on an Illumina Genome-Analyser and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease based heteroduplex screening and confirmed by Sanger sequencing.Results For proof of principle, DNA from patients with known mutations was used and detection of 22 out of 24 different alleles (92% sensitivity) was demonstrated. MPR led to the molecular diagnosis in 30/120 patients (25%) and 54 pathogenic mutations (27 novel) were identified in seven different NPHP-AC genes. Additionally, in 24 patients only single heterozygous variants of unknown significance were found.Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single gene disorders. The lack of mutations in 75% of patients in this cohort indicates further extensive heterogeneity in NPHP-AC