Processing parameters in laser powder bed fusion metal additive manufacturing

JPO acknowledges Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the projects UIDB/00667/2020 and UIDB/50025/2020 .As metallic additive manufacturing grew in sophistication, users have requested greater control over the systems, namely the ability to fully change the process parameters. The goal of this manuscript is to review the effects of major process parameters on build quality (porosity, residual stress, and composition changes) and materials properties (microstructure and microsegregation), and to serve as a guide on how these parameters may be modified to achieve specific design goals for a given part. The focus of this paper is on laser powder bed fusion, but elements can be applied to electron beam powder bed fusion or direct energy deposition techniques.publishersversionpublishe

Bott periodicity and stable quantum classes

We use Bott periodicity to relate previously defined quantum classes to certain "exotic Chern classes" on $BU$. This provides an interesting computational and theoretical framework for some Gromov-Witten invariants connected with cohomological field theories. This framework has applications to study of higher dimensional, Hamiltonian rigidity aspects of Hofer geometry of $\mathbb{CP} ^{n}$, one of which we discuss here.Comment: prepublication versio

Predicting language learners' grades in the L1, L2, L3 and L4: the effect of some psychological and sociocognitive variables

This study of 89 Flemish high-school students' grades for L1 (Dutch), L2 (French), L3 (English) and L4 (German) investigates the effects of three higher-level personality dimensions (psychoticism, extraversion, neuroticism), one lower-level personality dimension (foreign language anxiety) and sociobiographical variables (gender, social class) on the participants' language grades. Analyses of variance revealed no significant effects of the higher-level personality dimensions on grades. Participants with high levels of foreign language anxiety obtained significantly lower grades in the L2 and L3. Gender and social class had no effect. Strong positive correlations between grades in the different languages could point to an underlying sociocognitive dimension. The implications of these findings are discussed

Kick stability in groups and dynamical systems

We consider a general construction of ``kicked systems''. Let G be a group of measure preserving transformations of a probability space. Given its one-parameter/cyclic subgroup (the flow), and any sequence of elements (the kicks) we define the kicked dynamics on the space by alternately flowing with given period, then applying a kick. Our main finding is the following stability phenomenon: the kicked system often inherits recurrence properties of the original flow. We present three main examples. 1) G is the torus. We show that for generic linear flows, and any sequence of kicks, the trajectories of the kicked system are uniformly distributed for almost all periods. 2) G is a discrete subgroup of PSL(2,R) acting on the unit tangent bundle of a Riemann surface. The flow is generated by a single element of G, and we take any bounded sequence of elements of G as our kicks. We prove that the kicked system is mixing for all sufficiently large periods if and only if the generator is of infinite order and is not conjugate to its inverse in G. 3) G is the group of Hamiltonian diffeomorphisms of a closed symplectic manifold. We assume that the flow is rapidly growing in the sense of Hofer's norm, and the kicks are bounded. We prove that for a positive proportion of the periods the kicked system inherits a kind of energy conservation law and is thus superrecurrent. We use tools of geometric group theory and symplectic topology.Comment: Latex, 40 pages, revised versio

Birational cobordism invariance of uniruled symplectic manifolds

A symplectic manifold $(M,\omega)$ is called {\em (symplectically) uniruled} if there is a nonzero genus zero GW invariant involving a point constraint. We prove that symplectic uniruledness is invariant under symplectic blow-up and blow-down. This theorem follows from a general Relative/Absolute correspondence for a symplectic manifold together with a symplectic submanifold. A direct consequence is that symplectic uniruledness is a symplectic birational invariant. Here we use Guillemin and Sternberg's notion of cobordism as the symplectic analogue of the birational equivalence.Comment: To appear in Invent. Mat

Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1

Within study comparisons and risk of bias in international development: Systematic review and critical appraisal

Background Many systematic reviews incorporate nonrandomised studies of effects, sometimes called quasi‐experiments or natural experiments. However, the extent to which nonrandomised studies produce unbiased effect estimates is unclear in expectation or in practice. The usual way that systematic reviews quantify bias is through “risk of bias assessment” and indirect comparison of findings across studies using meta‐analysis. A more direct, practical way to quantify the bias in nonrandomised studies is through “internal replication research”, which compares the findings from nonrandomised studies with estimates from a benchmark randomised controlled trial conducted in the same population. Despite the existence of many risks of bias tools, none are conceptualised to assess comprehensively nonrandomised approaches with selection on unobservables, such as regression discontinuity designs (RDDs). The few that are conceptualised with these studies in mind do not draw on the extensive literature on internal replications (within‐study comparisons) of randomised trials. Objectives Our research objectives were as follows: Objective 1: to undertake a systematic review of nonrandomised internal study replications of international development interventions. Objective 2: to develop a risk of bias tool for RDDs, an increasingly common method used in social and economic programme evaluation. Methods We used the following methods to achieve our objectives. Objective 1: we searched systematically for nonrandomised internal study replications of benchmark randomised experiments of social and economic interventions in low‐ and middle‐income countries (L&MICs). We assessed the risk of bias in benchmark randomised experiments and synthesised evidence on the relative bias effect sizes produced by benchmark and nonrandomised comparison arms. Objective 2: We used document review and expert consultation to develop further a risk of bias tool for quasi‐experimental studies of interventions (ROBINS‐I) for RDDs. Results Objective 1: we located 10 nonrandomised internal study replications of randomised trials in L&MICs, six of which are of RDDs and the remaining use a combination of statistical matching and regression techniques. We found that benchmark experiments used in internal replications in international development are in the main well‐conducted but have “some concerns” about threats to validity, usually arising due to the methods of outcomes data collection. Most internal replication studies report on a range of different specifications for both the benchmark estimate and the nonrandomised replication estimate. We extracted and standardised 604 bias coefficient effect sizes from these studies, and present average results narratively. Objective 2: RDDs are characterised by prospective assignment of participants based on a threshold variable. Our review of the literature indicated there are two main types of RDD. The most common type of RDD is designed retrospectively in which the researcher identifies post‐hoc the relationship between outcomes and a threshold variable which determines assignment to intervention at pretest. These designs usually draw on routine data collection such as administrative records or household surveys. The other, less common, type is a prospective design where the researcher is also involved in allocating participants to treatment groups from the outset. We developed a risk of bias tool for RDDs. Conclusions Internal study replications provide the grounds on which bias assessment tools can be evidenced. We conclude that existing risk of bias tools needs to be further developed for use by Campbell collaboration authors, and there is a wide range of risk of bias tools and internal study replications to draw on in better designing these tools. We have suggested the development of a promising approach for RDD. Further work is needed on common methodologies in programme evaluation, for example on statistical matching approaches. We also highlight that broader efforts to identify all existing internal replication studies should consider more specialised systematic search strategies within particular literatures; so as to overcome a lack of systematic indexing of this evidence

The future is now: Model-based clinical trial design for Alzheimer's disease

Failures in trials for Alzheimer's disease (AD) may be attributable to inadequate dosing, population selection, drug inefficacy, or insufficient design optimization. The Coalition Against Major Diseases (CAMD) was formed in 2008 to develop drug development tools (DDT) to expedite drug development for AD and Parkinson's disease.1 CAMD led a process that successfully advanced a clinical trial simulation (CTS) tool for AD through the formal regulatory review process at the US Food and Drug Administration (FDA) and European Medicines Agency (EMA)

Lipocalin-2 Deficiency Impairs Thermogenesis and Potentiates Diet-Induced Insulin Resistance in Mice

Lipocalin (LCN) 2 belongs to the lipocalin subfamily of low-molecular mass-secreted proteins that bind small hydrophobic molecules. LCN2 has been recently characterized as an adipose-derived cytokine, and its expression is upregulated in adipose tissue in genetically obese rodents. The objective of this study was to investigate the role of LCN2 in diet-induced insulin resistance and metabolic homeostasis in vivo. Systemic insulin sensitivity, adaptive thermogenesis, and serum metabolic and lipid profile were assessed in LCN2-deficient mice fed a high-fat diet (HFD) or regular chow diet. The molecular disruption of LCN2 in mice resulted in significantly potentiated diet-induced obesity, dyslipidemia, fatty liver disease, and insulin resistance. LCN2(-/-) mice exhibit impaired adaptive thermogenesis and cold intolerance. Gene expression patterns in white and brown adipose tissue, liver, and muscle indicate that LCN2(-/-) mice have increased hepatic gluconeogenesis, decreased mitochondrial oxidative capacity, impaired lipid metabolism, and increased inflammatory state under the HFD condition. LCN2 has a novel role in adaptive thermoregulation and diet-induced insulin resistanc