Parallel Progress Research Articles

A hybrid conjugated method for assembly sequence generation and explode view generation

PurposeThe purpose of this paper is to develop an efficient hybrid method that can collectively address assembly sequence generation (ASG) and exploded view generation (EVG) problem effectively. ASG is an act of finding feasible collision free movement of components of a mechanical product in accordance with the assembly design. Although the execution of ASG is complex and time-consuming in calculation, it is highly essential for efficient manufacturing process. Because of numerous limitations of the ASG algorithms, a definite method is still unavailable in the computer-aided design (CAD) software, and therefore the explosion of the product is not found to be in accordance with any feasible disassembly sequence (disassembly sequence is reverse progression of assembly sequence). The existing EVG algorithms in the CAD software result in visualization of the entire constituent parts of the product over single screen without taking into consideration the feasible order of assembly operations; thus, it becomes necessary to formulate an algorithm which effectively solves ASG and EVG problem in conjugation. This requirement has also been documented as standard in the “General Information Concerning Patents: 1.84 Standards for drawings” in the United States Patent and Trademark office (2005) which states that the exploded view created for any product should show the relationship or order of assembly of various parts that are permissible.Design/methodology/approachIn this paper, a unique ASG method has been proposed and is further extended for EVG. The ASG follows a deterministic approach to avoid redundant data collection and calculation. The proposed method is effectively applied on products which require such feasible paths of disassembly other than canonical directions.FindingsThe method is capable of organizing the assembly operations as linear or parallel progression of assembly such that the assembly task is completed in minimum number of stages. This result is further taken for EVG and is found to be proven effective.Originality/valueAssembly sequence planning (ASP) is performed most of the times considering the geometric feasibility along canonical axes without considering parallel possibility of assembly operations. In this paper, the proposed method is robust to address this issue. Exploded view generation considering feasible ASP is also one of the novel approaches illustrated in this paper.

Molecular pathogenesis of acquired aplastic anemia.

The application of next-generation sequencing (NGS) has enhanced our understanding of the genetic landscape in acquired aplastic anemia (AA). Parallel progress has been in addressing aspects underlying immune dysregulation in disease pathogenesis. Novel insights into the molecular and biologic mechanisms have led to a shift in the paradigm of AA, from a solely autoimmune pathogenic concept toward its recognition as a multifaceted pathophysiology characterized by cytogenetic abnormalities, recurrent somatic mutations, telomere attrition, and immune dysregulation. The detection of recurrent driver mutations disrupting myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)-associated genes has suggested a pathophysiologic link between clonal hematopoiesis in AA and the later development of these clonal disorders. Further, certain AA-related somatic genetic alterations may have clinical implications on treatment response, disease progression, and survival following immunosuppressive therapy. Going forward, wider validation of these genetic abnormalities will allow for their incorporation into a more informative risk stratification system that does not rely solely on clinical factors.

THE ROLE AND POSITION OF A WOMAN IN THE REPUBLICAN AND OTTOMAN PERIOD

Ever since the beginning of Turkish civilisation, women have played a very important role in Turkish societies, just as equally in social life or family life. As the family is highly regarded and valued as the basis of a country, so was the role of a woman regarded as highly relevant and of great importance and value. In various sources the role of a woman was confirmed to be meaningful even in the politic life of the Turks and in the legal composition. Women who had the choice of legal rights in societal life of old Turks have lost a great portion of the same and have never regained them until late. The role of women in society was greatly limited. Clothes were being changed and new norms such as - wearing cloaks were enforced. Emancipation of Turkish women the first steps towards rights acquirement in various areas, the downfallen and destructive approach and the Turkish nationalism has shown a parallel progress along with the process. With the proclamation of the constitution, the movements of women have started to untwist in society and women have gained intensity in discussion.

THE ROLE AND POSITION OF A WOMAN IN THE REPUBLICAN AND OTTOMAN PERIOD

Ever since the beginning of Turkish civilisation, women have played a very important role in Turkish societies, just as equally in social life or family life. As the family is highly regarded and valued as the basis of a country, so was the role of a woman regarded as highly relevant and of great importance and value. In various sources the role of a woman was confirmed to be meaningful even in the politic life of the Turks and in the legal composition. Women who had the choice of legal rights in societal life of old Turks have lost a great portion of the same and have never regained them until late. The role of women in society was greatly limited. Clothes were being changed and new norms such as - wearing cloaks were enforced. Emancipation of Turkish women the first steps towards rights acquirement in various areas, the downfallen and destructive approach and the Turkish nationalism has shown a parallel progress along with the process. With the proclamation of the constitution, the movements of women have started to untwist in society and women have gained intensity in discussion.

Silicon Contact Defects Get Fired

The large majority of installed photovoltaics today are based on silicon. Improvements in their performance and reductions in their manufacturing cost can have a direct global impact on the photovoltaic market, provided this can be realized with minimal disruption to existing manufacturing lines. Recently in Nature Energy, Ballif and colleagues demonstrate an easily integrated method based on a single firing thermal anneal to passivate rear contacts in silicon solar cells.

Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy.

Accumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells (CTCs), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTCs die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells (DTCs) in the bone marrow is the result of interaction of DTCs with bone marrow microenvironment. DTCs in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTCs, DTCs in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTCs in the bone marrow is always related to minimal residual diseases (MRDs). This review outlines the difference between CTCs and DTCs in the bone marrow and describes how this difference affects the clinical values of CTCs and DTCs, such as metastasis and recurrence. We suggest that DTCs remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTCs to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.

Effect of SiO2 on loss of catalysis of inherent metallic species in CO2 gasification of coke from lignite

Inherent metallic species retained by coal char or coke, such as Na and Ca, behave as catalysts in gasification. The char/coke normally contains inherent SiO2, which can react with the inherent catalysts to form silicates, resulting in catalyst deactivation over the range of pyrolysis, carbonization and gasification, and thereby reducing the char/coke reactivity. The present authors simulated the inherent catalyst deactivation experimentally by blending a Victorian lignite with SiO2, briquetting the SiO2/lignite blend, carbonizing the briquette, and then gasifying the coke with CO2. The kinetic analysis of the gasification employed a comprehensive model, which assumed progress in parallel of non-catalytic and catalytic gasification. The model quantitatively described the measured kinetics of the coke gasification with different SiO2 contents over a range of coke conversion up to 99.9%. The kinetic analysis revealed that the SiO2 deactivated substantial and entire portions of the most active catalyst and its precursor, respectively, before the gasification (i.e., during the carbonization). The catalyst deactivation also occurred during the gasification, but mainly following a self-deactivation mechanism that involved no silicates formation.

On the qualitative dynamics of rotating disks: Thermal shocks and structural integrity

Within engineering circles, overriding breakthroughs have allowed rotating mechanisms to be safely embedded under severe operational circumstances as well as harsh loads. Meanwhile, a literature survey reflects that the implementation of functionally graded materials (FGMs) has revolutionized the characteristics of rotating disks in industrial segments. One of the most challenging situations for FG rotating disks is exposure to multi-dimensional thermal shocks during heating (ascendant) and cooling (descendant), when even materials with high fracture resistance may become deficient. In this paper, a general picture is drawn of a transient thermoelastic design of FG rotating disks to mitigate failure issues stemming from ascendant/descendant thermal gradients and body forces. Contrary to the majority of reports, thermal and displacement fields of the rotating system are affected in both radial and circumferential paths in the polar system, indicating the need for two-dimensional analysis of transient heat transfer. Material properties of the geometry can be judiciously chosen in the r and θ directions, underpinning a practical recipe in the load-bearing capacity of the model for in-situ applications. Transient numerical simulations of deflections, stresses, and thermal fields of a circular annular disk are graphically elaborated using the Fourier and polynomial differential quadrature approaches. On the basis of awareness of the nature of the applied loads, it is found that an appropriate selection criterion of the variation of the material properties from among all available candidates noticeably ameliorates the impact of temperature shocks on the centrifugal force of the rotary system. With regard to the yielding criteria of the structures, the outcomes of the proposed study extend the boundaries of current traditional designs, demonstrating parallel progress in theories and viable materials.

Genome Editing in Human Neural Stem and Progenitor Cells.

Experimental tools for precise manipulation of mammalian genomes enable reverse genetic approaches to explore biology and disease. Powerful genome editing technologies built upon designer nucleases, such as CRISPR/Cas9, have recently emerged. Parallel progress has been made in methodologies for the expansion and differentiation of human pluripotent and tissue stem cells. Together these innovations provide a remarkable new toolbox for human cellular genetics and are opening up vast opportunities for discoveries and applications across the breadth of life sciences research. In this chapter, we review the emergence of genome editing technologies and how these are being deployed in studies of human neurobiology, neurological disease, and neuro-oncology. We focus our discussion on CRISPR/Cas9 and its application in studies of human neural stem and progenitor cells.

CO2 Gasification of Sugar Cane Bagasse: Quantitative Understanding of Kinetics and Catalytic Roles of Inherent Metallic Species

A total of 18 chars from the pyrolysis of six trios of sugar cane bagasses (SCBs; original, water-washed, and acid-washed) were gasified with CO2 at 900 °C, aiming at a quantitative description of the rate of gasification catalyzed by inherent metallic species and a correlation of the catalytic activity and its change during the gasification with the metallic species composition. The measured kinetics was described quantitatively over a range of char conversion, 0–0.999, by a model that assumed progress in parallel of the catalytic gasification and non-catalytic gasification, together with the presence of a catalytic precursor and three to four types of catalysts having different activities and deactivation characteristics. A series of regression analyses was scrutinized and reached expression of initial catalytic activity as a linear function of Na, K, Ca, Fe, and Si concentrations in the char with a correlation factor (r2) of >0.98. The catalyst precursor contributed fully by water-soluble Na, K, and Ca...

Emerging trends in metal oxide electrocatalysis: Bifunctional oxygen catalysis, synergies and new insights from in situ studies

Metal oxide electrocatalysts with minimal or no reliance on precious metals can display outstanding activity in oxygen catalysis and thus hold promise as materials for sustainable energy storage/conversion technologies. We review recent progress in the preparation of oxides for bifunctional oxygen reduction/evolution applications (ORR/OER) and include a summary of benchmark performances achieved over the past 3 years. Parallel and complementary progress on development of activity descriptors for the OER in oxides is also covered; special attention is dedicated to synergistic effects and the importance of support choice and oxide/support interactions to maximize activity and ensure stability. Finally, exciting mechanistic insights on OER and bifunctional ORR/OER oxide catalysis gained from recent in situ and operando X-ray experiments from the recent literature are discussed.

Students’ Energy Understanding Across Biology, Chemistry, and Physics Contexts

Energy is considered both as a disciplinary core idea and as a concept cutting across science disciplines. Most previous approaches studied progressing energy understanding in specific disciplinary contexts, while disregarding the relation of understanding across them. Hence, this study provides a systematic analysis of cross-disciplinary energy learning. On the basis of a cross-sectional study with n = 742 students from grades 6, 8, and 10, we analyze students’ progression in understanding energy across biology, chemistry, and physics contexts. The study is guided by three hypothetical scenarios that describe how the connection between energy understanding in the three disciplinary contexts changes across grade levels. These scenarios are compared using confirmatory factor analysis (CFA). The results suggest that, from grade 6 to grade 10, energy understanding in the three disciplinary contexts is highly interrelated, thus indicating a parallel progression of energy understanding in the three disciplinary contexts. In our study, students from grade 6 onwards appeared to have few problems to apply one energy understanding across the three disciplinary contexts. These findings were unexpected, as previous research concluded that students likely face difficulties in connecting energy learning across disciplinary boundaries. Potential reasons for these results and the characteristics of the observed cross-disciplinary energy understanding are discussed in the light of earlier findings and implications for future research, and the teaching of energy as a core idea and a crosscutting concept are addressed.

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003-13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10-10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10-8DHFR p=8·37 × 10-7 MTRNR2L2 p=2·15 × 10-9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10-4DHFR p=8·45 × 10-4MTRNR2L2 p=1·20 × 10-3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10-8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16-0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06-0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes.

In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality. We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes. Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER. Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.

Genomic Analyses of Breast Cancer Progression Reveal Distinct Routes of Metastasis Emergence

A main controversy in cancer research is whether metastatic abilities are present in the most advanced clone of the primary tumor or result from independently acquired aberrations in early disseminated cancer cells as suggested by the linear and the parallel progression models, respectively. The genetic concordance between different steps of malignant progression is mostly unexplored as very few studies have included cancer samples separated by both space and time. We applied whole exome sequencing and targeted deep sequencing to 26 successive samples from six patients with metastatic estrogen receptor (ER)-positive breast cancer. Our data provide support for both linear and parallel progression towards metastasis. We report for the first time evidence of metastasis-to-metastasis seeding in breast cancer. Our results point to three distinct routes of metastasis emergence. This may have profound clinical implications and provides substantial novel molecular insights into the timing and mutational evolution of breast cancer metastasis.

Abstract P6-01-04: Evolutionary analyses of matched primary and metastatic breast cancer reveal both linear and parallel progression with lack of axillary lymph node involvement

Abstract This abstract was withdrawn by the authors.

倍数含量筛法与恒等式((a/b)×(b/a)=1 )的妙用

本文挖掘出倍数含量及等差项同数列的概念，根据倍数含量重叠规律及等差项同数列的性质，对自然数列中倍数出现规律作了深入的探讨。作为应用，我们证明了偶数哥德巴赫猜想与孪生素数猜想。 We introduce the notions of multiple content and parallel arithmetic series. Based on the overlap law of multiple contents and properties of parallel arithmetic progressions, we discuss the appearance rule of multiples in the series of natural numbers. As applications, we prove the even number Goldbach’s conjecture and the twin prime conjecture.

TAVR vs SAVR: Rising Expectations and Changing Indications for Surgery in Response to PARTNER II

Despite the criticisms and concerns raised on the data published in the PARTNER II trial and related analyses, we are undeniably witnessing a revolution in the management of aortic valve disease, in which conventional full sternotomy surgical aortic valve replacement (SAVR), with all related complications and clinical burden, will soon become a nonviable option. Several of the findings described in the PARTNER II trial, although considerable as points of incongruence and study biases in comparison with SAVR, could be taken as lessons to found a new course in SAVR and redesign the respective roles of surgery and interventional procedures in aortic disease. In particular, the results of these trials can actually be considered as a stimulus to invest more effort to improve the current surgical practice that should embrace alternative solutions and least invasive approaches to provide a competitive advantage over percutaneous procedures. An analysis of these points in light of the more recent findings on transcatheter valve durability, thrombosis, and postprocedural complications is provided. Considerations on the parallel progress of SAVR and on the need for a behavioral change in the surgical community are discussed.

Low-density lipoprotein receptor deficiency impaired mice osteoblastogenesis in vitro.

Postmenopausal osteoporosis affected most elderly women with co-existence of lipid and bone metabolism disorders. However, the cellular and molecular mechanisms underlying the parallel progression and cross-talk of these systems remained unclear. In the present study, low-density lipoprotein receptor knockout (LDLR-/-) mice were chosen to elucidate the effect of LDLR in regulating the differentiation of osteoblasts, which were responsible for bone formation and modulation of osteoclastogenesis. Primary osteoblasts were isolated from the calvarium of newborn LDLR-/- or wild-type mice followed by osteoblastic differentiation culture in vitro. Alkaline phosphatase activity was significantly decreased in LDLR-/- osteoblasts compared to wild-type controls, combined with calcium deposit formation delay, implying impaired osteoblastogenesis in vitro. Consistent with these findings, the expression of runt-related transcription factor 2 (Runx2) was decreased 3 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls. Moreover, the expression of Osterix was decreased 7 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls, later than Runx2.However, the osteoclastogenesis modulation role of osteoblasts was unaffected by the LDLR deficiency, evidenced by the same level of osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) axis between LDLR-/- and wild-type control osteoblasts. Our results provide a novel insight into the role of LDLR during osteoblastic differentiation and improve understanding of cross-talk between bone and lipid metabolisms.

VASCULAR CALCIFICATION, ATHEROSCLEROSIS AND BONE LOSS (OSTEOPOROSIS): NEW PATHOPHYSIOLOGICAL MECHANISMS AND FUTURE PERSPECTIVES FOR PHARMACOLOGICAL THERAPY

Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover and development of the osteoporosis. The latest data support the correlation of osteoporosis and atherosclerosis, indicating the parallel progression of two tissue destruction processes with increased fatal and nonfatal coronary events, as well as a higher fracture risk. Patients with osteoporosis, have a higher risk of cardiovascular diseases than subjects with normal bone. Many proteins responsible for bone formation and resorption have been identified in the arterial wall. Vascular calcification includes mostly osteogenic and, to a lesser extent chondrogenic differentiation of osteoblasts and osteoclast-like cells. It has been shown that many of the regulators of bone formation and resorption some bone structural proteins, such as osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) are also expressed in the atherosclerotic plaque. When RANKL binds to RANK, osteoclasts are activated and bone resorption occurs and processes of vascular calcification become also activated. OPG, protein homologue to receptor activator of nuclear factor-κB (RANK), can bind to RANKL, blocking the binding of RANKL to RANK, that results in inhibition of differentiation of preosteoclasts to mature osteoclasts, lower osteoclast capacity for resorption of bone mineral matrix, and development vascular calcification. The latest data supports that cathepsin K, a cysteine protease, can efficiently degrade type I and II collagen, both of which are major matrix components of the bone and atherosclerotic plaque. These findings further underscore the potential of cathepsin K as a target for novel molecules to treat osteoporosis and atherosclerosis. Thus, the discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in the process of bone remodeling, vascular calcification and atherosclerosis has made progress in understanding the mechanisms of disease development and possibly to develop new dual therapies. New therapies for osteoporosis and atherosclerosis that may potentially improve or augment existing treatments include the recently approved anti-receptor activator of NF-κB-ligand monoclonal antibody fms (denosumab) and the cathepsin K inhibitor odanacatib, presently in the late stage of clinical development.