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Understanding the connections between galaxy stellar mass, star formation rate, and dark matter halo mass represents a key goal of the theory of galaxy formation. Cosmological simulations that include hydrodynamics, physical treatments of star formation, feedback from supernovae, and the radiative transfer of ionizing photons can capture the processes relevant for establishing these connections. The complexity of these physics can prove difficult to disentangle and obfuscate how mass-dependent trends in the galaxy population originate. Here, we train a machine-learning method called Explainable Boosting Machines (EBMs) to infer how the stellar mass and star formation rate of nearly 6 million galaxies simulated by the Cosmic Reionization on Computers project depend on the physical properties of halo mass, the peak circular velocity of the galaxy during its formation history v peak, cosmic environment, and redshift. The resulting EBM models reveal the relative importance of these properties in setting galaxy stellar mass and star formation rate, with v peak providing the most dominant contribution. Environmental properties provide substantial improvements for modeling the stellar mass and star formation rate in only ≲10% of the simulated galaxies. We also provide alternative formulations of EBM models that enable low-resolution simulations, which cannot track the interior structure of dark matter halos, to predict the stellar mass and star formation rate of galaxies computed by high-resolution simulations with detailed baryonic physics.

Infertility is a widespread issue which is estimated to affect up to 17.5% of the global population. Evidence suggests that the most common causes of female infertility are ovulation disorders (e.g., polycystic ovary syndrome). That said, lifestyle factors such as dietary patterns, stress, alcohol consumption, smoking, and obesity are key determinants which have been shown to impact female physiology and significantly decrease the chances of conception. Obesity has been widely recognized as a significant factor that negatively impacts ovarian stimulation in women and is associated with several reproductive disorders, including anovulation, subfertility, and infertility. Despite improvements in fertility treatments, obesity remains a challenge particularly for fertility clinics because of the poorer pregnancy outcomes observed within the population. In this article, we will explore the effects of weight loss on female fertility and review the various strategies that have been shown to be effective in reducing obesity and improving reproductive outcomes.

Thrombosis of the lung microvasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis that is endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting Spike-induced TMEM16 activation. As TMEM16F plays an important role in stimulating the procoagulant activity of platelets, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Here we show that Spike, present either on the virion envelope or on the cell plasma membrane, promotes platelet activation, adhesion and spreading. Spike was active as a sole agonist or, even more effectively, by enhancing the function of known platelet activators. In particular, Spike-induced a marked procoagulant phenotype in platelets, by enhancing Ca2+ flux, phosphatidylserine externalization on the platelet outer cell membrane, and thrombin generation. Eventually, this increased thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine blocked this Spike-induced procoagulant response. These findings provide a pathogenic mechanism to explain lung thrombosis-associated with severe COVID-19 infection. We propose that Spike, present in SARS-CoV-2 virions or exposed on the surface of infected cells in the lungs, enhances the effects of inflammation and leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing Niclosamide for COVID-19 therapy.

Menschliche Zähne sind täglich chemischen Erosionsprozessen ausgesetzt, die zu einer Verschlechterung der Zahnsubstanz führen können. Verantwortlich hierfür sind in erster Line das Konsumieren von Säurehaltigen Getränken und Speisen. Niedriger pH, sowie Komplexierende Stoffe führen zu einer Demineralisierung des Zahn Hydroxylapatits {Ca5(PO4)3OH}2) (HAP). Es wird geschätzt dass weltweit 30-50% der Milchzähne und 20-45% der permanenten Zähne von Zahnerosion betroffen sind. Folgen von Zahnerosion können ein erhöhtes Kariesrisiko, Zahnsensibilität, Zahnverfärbung und im schlimmsten Fall Zahnverlust sein. Eine potentielle Maßnahme um Zahnerosion entgegenzuwirken stellt die Förderung der Remineralisierung dar, indem die Calcium und Phosphat-Konzentration im Speichel erhöht wird, z.B. durch die Gabe von Casein, einem Milchprotein. Die im Casein enthaltenen Ca9(PO4)6 Nanocluster können in die erodierte Zahnsubstanz eingebaut werden und die Schäden rückgängig machen. Unter Verwendung der Weißlichtinterferometrie zur Rauheitsanalyse zeigen wir die Dynamik der DEM/REM Prozesse in-Vitro und zeigen in Fallstudien die Anwendung von Ca Kaseinat als wenig intrusive Behandlungsmethode mit REM Potential in-Vivo.

Menschliche Zähne sind täglich chemischen Erosionsprozessen ausgesetzt, die zu einer Verschlechterung der Zahnsubstanz führen können. Verantwortlich hierfür sind in erster Line das Konsumieren von Säurehaltigen Getränken und Speisen. Niedriger pH, sowie Komplexierende Stoffe führen zu einer Demineralisierung des Zahn Hydroxylapatits {Ca5(PO4)3OH}2) (HAP). Es wird geschätzt dass weltweit 30-50% der Milchzähne und 20-45% der permanenten Zähne von Zahnerosion betroffen sind. Folgen von Zahnerosion können ein erhöhtes Kariesrisiko, Zahnsensibilität, Zahnverfärbung und im schlimmsten Fall Zahnverlust sein. Eine potentielle Maßnahme um Zahnerosion entgegenzuwirken stellt die Förderung der Remineralisierung dar, indem die Calcium und Phosphat-Konzentration im Speichel erhöht wird, z.B. durch die Gabe von Casein, einem Milchprotein. Die im Casein enthaltenen Ca9(PO4)6 Nanocluster können in die erodierte Zahnsubstanz eingebaut werden und die Schäden rückgängig machen. Unter Verwendung der Weißlichtinterferometrie zur Rauheitsanalyse zeigen wir die Dynamik der DEM/REM Prozesse in-Vitro und zeigen in Fallstudien die Anwendung von Ca Kaseinat als wenig intrusive Behandlungsmethode mit REM Potential in-Vivo.

Human teeth are subject to chemical erosion processes that can lead to a loss of tooth hard substance. Low pH and complexing agents in food and drink can demineralize the dental hydroxyapatite. It is estimated that 20-45 % of permant teeth worldwide are affected by tooth errosion. This can lead to increased caries risk, tooth sensitivity, tooth colouration and in the worst case tooth loss. One potential treatment of tooth errosion is the promotion of naturally ocurring remineralisation processes, e.g. by application of caseine milk protein. The Ca9(PO4)6 nanoclusters have the potential to cure damaged tooth material. Using vertical scanning interferometry we show the dynamics of de- and remineralisation tooth samples by analysis of the surface roughness development.

Background Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. Methods Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. Results We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH2-TH17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. Conclusion High consumption of digestible carbohydrates is associated with increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

‘Rotatinuous’ stocking is a grazing management strategy based on animal behavioural responses to sward structure which is designed to maximize herbage intake per unit of grazing time. It is an alternative to traditional grazing management practices focusing on pasture use efficiency and maximizing herbage accumulation and harvesting. To investigate this approach, Italian ryegrass (Lolium multiflorum) pastures grazed by sheep were evaluated in 2014 and 2015 under two contrasting grazing management strategies. Paddocks were distributed under a complete randomized block design with four replicates. Grazing management strategies were: traditional rotational stocking (RT), with pre- and post-grazing sward heights of 25 and 5 cm, respectively, and ‘Rotatinuous’ stocking (RN), with pre- and post-grazing sward heights of 18 and 11 cm, respectively. Thirty-two castrated Texel × Polwarth crossbred lambs were randomly allocated to treatments. As a consequence of grazing strategies, the stocking cycles were 12 and 4, with resting periods of 13 and 35 days, respectively, for RN and RT treatments. Herbage production, total herbage harvested, and feed conversion efficiency were 28%, 20%, and 40%, respectively, greater for RN than for RT treatment. Although the stocking rate was lower, the average daily gain per animal and live weigh gain per hectare were 153% and 43%, respectively, greater for the RN treatment. Despite the RN treatment being orientated to maximize herbage intake per unit of grazing time, it results in greater total herbage production and harvesting. We conclude that the ‘Rotatinuous’ stocking strategy is not necessarily reversed by low herbage harvesting efficiency. This innovation in grazing management conciliates high herbage and animal production at the same time.

type:Journal Article, IR-drop induced by launch switching activity (LSA) in capture mode during at-speed scan testing increases delay along not only logic paths (LPs) but also clock paths (Cps). Excessive extra delay along LPs compromises test yields due to false capture failures, while excessive extra delay along CPs compromises test quality due to test clock stretch. This paper is the first to mitigate the impact of LSA on both LPs and CPs with a novel LCPA (Logic/Clock Path-Aware) at-speed scan test generation scheme, featuring (1) a new metric for assessing the risk of false capture failures based on the amount of LSA around both LPs and CPs, (2) a procedure for avoiding false capture failures by reducing LSA around LPs or masking uncertain test responses, and (3) a procedure for reducing test clock stretch by reducing LSA around CPs. Experimental results demonstrate the effectiveness of the LCPA scheme in improving test yields and test quality., 2015 IEEE 24th Asian Test Symposium (ATS), 22-25 November 2015, Mumbai, India, source:DOI: 10.1109/ATS.2015.25

The chapter provides an overview of the developments in synchronic and diachronic corpus-linguistic research into World Englishes (WE), detailing methodological concerns such as sampling frames, representativeness, corpus size, and statistical modelling on the one hand and the broadening scope of corpus-based research from ENL to ESL and EFL varieties on the other hand. It also surveys areas in which corpus-evidence has been applied in the study of WE (e.g. as a testing bed for models of WEs, for the study of language contact, typology and change or as a source of evidence for sociolinguistic and pragmatic variation), providing ample illustration from seminal research papers and recent studies in the field.

The chapter provides an overview of the developments in synchronic and diachronic corpus-linguistic research into World Englishes (WE), detailing methodological concerns such as sampling frames, representativeness, corpus size, and statistical modelling on the one hand and the broadening scope of corpus-based research from ENL to ESL and EFL varieties on the other hand. It also surveys areas in which corpus-evidence has been applied in the study of WE (e.g. as a testing bed for models of WEs, for the study of language contact, typology and change or as a source of evidence for sociolinguistic and pragmatic variation), providing ample illustration from seminal research papers and recent studies in the field.

This chapter investigates the persistence and development of so-called dialect roots, that is, features of local forms of British English that are transplanted to overseas territories. It discusses dialect input and the survival of features, independent developments within overseas communities, including realignments of features in the dialect inputs, as well as contact phenomena when English speakers interact with those of other dialects and languages. The diagnostic value of these roots is exemplified with selected cases from around the world (Newfoundland English, Liberian English, Caribbean Englishes), which are assessed with reference to the archaic/dynamic character of individual features in new-dialect formation and language-contact scenarios.

After a brief overview of the main developments in the field of World Englishes (WEs) research, particularly with respect to different typologies and models of WEs, as well as advances in methodology, this introductory chapter provides short chapter summaries.

After a brief overview of the main developments in the field of World Englishes (WEs) research, particularly with respect to different typologies and models of WEs, as well as advances in methodology, this introductory chapter provides short chapter summaries.

This chapter investigates the persistence and development of so-called dialect roots, that is, features of local forms of British English that are transplanted to overseas territories. It discusses dialect input and the survival of features, independent developments within overseas communities, including realignments of features in the dialect inputs, as well as contact phenomena when English speakers interact with those of other dialects and languages. The diagnostic value of these roots is exemplified with selected cases from around the world (Newfoundland English, Liberian English, Caribbean Englishes), which are assessed with reference to the archaic/dynamic character of individual features in new-dialect formation and language-contact scenarios.

Glioblastoma IV (GBM) is one of the deadliest malignant diseases in adults and is characterized by a high mutation rate and multiple traits to suppress inborn and acquired immunity. We here approached autophagy-related cell death in newly established GBM cell lines derived from individual tumor isolates. Treatment with a small molecule, termed Vacquinol-1 (Vac) exhibited 100% GBM cell death, which was related to mitochondrial dysfunction, calcium-induced endoplasmic reticulum (ER)-stress, and autophagy. The toxicity of Vac was significantly increased by the inhibition of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). TRPM7 is overexpressed in GBM as well as in many other tumors and thus may be a potential target by the natural compound carvacrol. Of note, at higher concentrations, Vac also induced growth inhibition and cell death in non-transformed cell types. However, in the presence of the TRPM7 inhibitor carvacrol, the tumor-selective effect of Vac was very much increased. Results given in the present study are based on long-term video microscopy using IncuCyteZOOM®, calcium measurements, and 3D ultrastructural analysis using the cryofixed material.

Glioblastoma IV (GBM) is one of the deadliest malignant diseases in adults and is characterized by a high mutation rate and multiple traits to suppress inborn and acquired immunity. We here approached autophagy-related cell death in newly established GBM cell lines derived from individual tumor isolates. Treatment with a small molecule, termed Vacquinol-1 (Vac) exhibited 100% GBM cell death, which was related to mitochondrial dysfunction, calcium-induced endoplasmic reticulum (ER)-stress, and autophagy. The toxicity of Vac was significantly increased by the inhibition of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). TRPM7 is overexpressed in GBM as well as in many other tumors and thus may be a potential target by the natural compound carvacrol. Of note, at higher concentrations, Vac also induced growth inhibition and cell death in non-transformed cell types. However, in the presence of the TRPM7 inhibitor carvacrol, the tumor-selective effect of Vac was very much increased. Results given in the present study are based on long-term video microscopy using IncuCyteZOOM®, calcium measurements, and 3D ultrastructural analysis using the cryofixed material.

This chapter discusses the relevance of language contact in smaller-scale migration and linguistic diaspora situations for the study of World Englishes (WEs). It provides definitions of the terms diaspora and diasporic language variety and establishes a practice-oriented view of language use that acknowledges the speakers’ linguistic agency in constructing social meaning. It explores intersections of WEs with sociolinguistic identity construction (1) by attempting to bridge the gap between language mixing and WEs research; (2) by problematizing the role of the immigrant generation in the use of ethnolinguistic features; (3) by teasing apart factors on language contact in multiple migration scenarios; and (4) by highlighting the relevance of urban multi-ethnolects for WEs. Contextualizing WEs studies with these different theoretical perspectives pushes the boundaries of the discipline toward foregoing essentialist categories (such as “varieties” or “ethnolects”) in favor of more fluid concepts (such as “processes,” “practices,” or “repertoires”). The chapter thus uses concepts from migration and diaspora studies to show their benefit for future research of WEs.

Linguistic typology is concerned with classifying human languages and with identifying structural similarities and differences between these languages. Dialectology is the study of typically vernacular and regionally restricted and/or distinctive forms of language. Dialect typology focuses on the intersection between typology and dialectology. In this chapter, we (1) review the set of language-external factors (variety type, world region, exposure to contact) that has been used to categorize World Englishes, (2) summarize the literature about (vernacular) universals, angloversals, and related notions in World Englishes, and (3) discuss work on parameters of structural diversity in World Englishes (analyticity versus syntheticity, complexity versus simplicity).

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. RESULTS: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS: Among children with later-onset SMA, those who received

Tissue perfusion and mass transport in the vicinity of implant surfaces prior to integration or bonding may play a crucial role in modulating cellular activities associated with bone remodeling, in particular, at early stages of the integration process. Furthermore, fluid displacements have been postulated to transduct mechanical stress signals to bone cells via loading-dependent flow of interstitial fluid through the lacunocanalicular network of bone. Thus, an understanding and new possibilities for influencing these processes may be of great importance for implant success. An ex vivo model was developed and validated for investigation of fluid displacements in bone after endoprosthesis implantation. This model serves to explicate the effects of surgical intervention as well as mechanical loading of the implant-bone construct on load-induced fluid flow in the vicinity of the implant. Using this model, we intend to quantify perfusion and extravascular flow dynamics in the vicinity of implants and define optimal conditions for enhancing molecular transport of osteotropic agents from the implant surface to apposing bone as well as from the blood supply to the implant surface. Furthermore, the elucidation of main transport pathways may help in understanding the distribution of wear particles in bone surrounding implant, a process which has been postulated to cause osteolysis and implant loosening

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. RESULTS: In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS: Among children with later-onset SMA, those who re

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BACKGROUND: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODS: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTS: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disea

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Contains fulltext : 173237.pdf (Author’s version preprint ) (Open Access) Contains fulltext : 173237.pdf (Publisher’s version ) (Open Access)

Dieses Buch gibt einen Überblick zur Biodiversität von Flussauen in Deutschland. Es basiert auf der Zusammenstellung umfangreicher Daten, die im Rahmen verschiedenster Publikationen und Gutachten erhoben wurden. Bei aller Heterogenität zeigen die Ergebnisse deutlich, dass Flussauen nach wie vor Hotspots der Biodiversität sind – und dass Revitalisierungen der Auen sehr erfolgreich sein können. Obwohl Flussauen zu den artenreichsten Lebensräumen in Mitteleuropa gehören, besonders unter Belastungen und  Veränderungen gelitten haben und vielfach renaturiert werden, fehlt bislang eine Zusammenfassung des Kenntnisstandes zu ihrer Biodiversität. Dieses Buch soll diese Lücke füllen.

Dieses Buch gibt einen Überblick zur Biodiversität von Flussauen in Deutschland. Es basiert auf der Zusammenstellung umfangreicher Daten, die im Rahmen verschiedenster Publikationen und Gutachten erhoben wurden. Bei aller Heterogenität zeigen die Ergebnisse deutlich, dass Flussauen nach wie vor Hotspots der Biodiversität sind – und dass Revitalisierungen der Auen sehr erfolgreich sein können. Obwohl Flussauen zu den artenreichsten Lebensräumen in Mitteleuropa gehören, besonders unter Belastungen und  Veränderungen gelitten haben und vielfach renaturiert werden, fehlt bislang eine Zusammenfassung des Kenntnisstandes zu ihrer Biodiversität. Dieses Buch soll diese Lücke füllen.