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Recent developments of molecular biology have revealed diverse mechanisms of skin diseases, and precision medicine considering these mechanisms requires the frequent objective evaluation of skin phenotypes. Transepidermal water loss (TEWL) is commonly used for evaluating skin barrier function; however, direct measurement of TEWL is time-consuming and is not convenient for daily clinical practice. Here, we propose a new skin barrier assessment method using skin images with topological data analysis (TDA). TDA enabled efficient identification of structural features from a skin image taken by a microscope. These features reflected the regularity of the skin texture. We found a significant correlation between the topological features and TEWL. Moreover, using the features as input, we trained machine-learning models to predict TEWL and obtained good accuracy (R2 = 0.524). Our results suggest that assessment of skin barrier function by topological image analysis is promising.

Panic buying is a consumer behavior caused by negative emotions and social influences after a disaster. This study identifies (1) how panic buying occurs over time and (2) who panic buys. Based on the theoretical background of the behavioral and emotional nature of panic buyers, we conducted empirical segmentation to integrate behavioral and psychological data. The study focused on Japanese consumer packaged goods during the COVID-19 outbreak and found that there were two waves of increased purchases related to the timing of government interventions between February and April 2020. Among them, panic buyers who hoarded due to anxiety were more likely to buy more during the first wave. We identified five segments: strong panic buyers, weak panic buyers, experienced shoppers, rational shoppers, and inactive shoppers. We also confirmed the characteristics of each segment, including demographics, media use behavior, and psychographics such as impulsiveness, price consciousness, conformity, and guilt.

Today's consumer goods markets are rapidly evolving with significant growth in the number of information media as well as the number of competitive products. In this environment, obtaining a quantitative grasp of heterogeneous interactions of firms and customers, which have attracted interest of management scientists and economists, requires the analysis of extremely high-dimensional data. Existing approaches in quantitative research could not handle such data without any reliable prior knowledge nor strong assumptions. Alternatively, we propose a novel method called complex Hilbert principal component analysis (CHPCA) and construct a synchronization network using Hodge decomposition. CHPCA enables us to extract significant comovements with a time lead/delay in the data, and Hodge decomposition is useful for identifying the time-structure of correlations. We apply this method to the Japanese beer market data and reveal comovement of variables related to the consumer choice process across multiple products. Furthermore, we find remarkable customer heterogeneity by calculating the coordinates of each customer in the space derived from the results of CHPCA. Lastly, we discuss the policy and managerial implications, limitations, and further development of the proposed method., Comment: 27 pages with 9 Figures and 7 Tables, including a 2-page Appendix

The hippocampus is generally considered as a brain center for learning and memory. We have recently established an electroporation-mediated gene transfer method to investigate the development of neonatal dentate granule cells in vivo. Using this new technique, we introduced knockdown vectors against Rac1 small GTPase into precursors for dentate granule cells at postnatal day 0. After 21 days, Rac1-deficient cells were frequently mispositioned between the granule cell layer (GCL) and hilus. About 60% of these mislocalized cells expressed a dentate granule cell marker, Prox1. Both the dendritic spine density and the ratio of mature spine were reduced when Rac1 was silenced. Notably, the deficient cells have immature thin processes during migrating in the early neonatal period. Knockdown of another Rac isoform, Rac3, also resulted in mislocalization of neonatally born dentate granule cells. In addition, knockdown of Cdc42, another Rho family protein, also caused mislocalization of the cell, although the effects were moderate compared to Rac1 and 3. Despite the ectopic localization, Rac3- or Cdc42-disrupted mispositioned cells expressed Prox1. These results indicate that Rho signaling pathways differentially regulate the proper localization and differentiation of dentate granule cells.

Few effective porcine models of myocardial infarction (MI) related to platelet thrombus formation are available. In this study, we established a novel porcine MI model and examined the effect of dual antiplatelet therapy (DAPT) with aspirin and prasugrel, a P2Y12 antagonist, using this MI model. Thrombotic MI was photochemically induced using rose bengal. Male miniature pigs were divided into 3 treatment groups: Sham, MI, and DAPT. In the DAPT group, aspirin (10 mg/kg, p.o.) and prasugrel (1 mg/kg, p.o.) were administered 4 h before photo-irradiation. Platelet aggregation, MI volume, and cardiac function were evaluated 24 h after photo-irradiation. Inhibition of ADP-induced platelet aggregation in the DAPT group was about 45%, similar to the effects of DAPT in a clinical setting. No MI was observed in the Sham group, and MI volume was 12.9 ± 2.9% in the left ventricle (P = 0.0016) in the MI group. Additionally, an increase in end-systolic volume (P = 0.0006), and a decrease in stroke volume (P = 0.0001) and ejection fraction (P

Although human activity recognition using wearable sensors has become a useful technology, activity recognition using acceleration sensor data is still under development. We obtained ideas from the image field and verified the method of introducing deep metric learning into sensor-based activity recognition. As verification of this method, we confirmed the effect on the estimation accuracy and the effect of the visualization of the feature representation. In addition, we proposed three methods for verification and searched for suitable methods by comparing them. There was a difference in the estimation accuracy and the visualization result with the proposed method. We also confirmed that significant features can be obtained for activity recognition when a suitable method is used.

ARHGEF9, also known as Collybistin, a guanine nucleotide exchange factor for Rho family GTPases, is thought to play an essential role in the mammalian brain. In this study, we prepared a specific polyclonal antibody against ARHGEF9, anti-ARHGEF9, and carried out expression analyses with mouse tissues especially brain. Western blotting analyses demonstrated tissue-dependent expression profiles of ARHGEF9 in the young adult mouse, and strongly suggested a role during brain development. Immunohistochemical analyses revealed developmental stage-dependent expression profiles of ARHGEF9 in cerebral cortex, hippocampus and cerebellum. ARHGEF9 exhibited partial localization at dendritic spines in cultured hippocampal neurons. From the obtained results, anti-ARHGEF9 was found to be a useful tool for biochemical and cell biological analyses of ARHGEF9.

Phactr1 (Phosphatase and actin regulator 1) is abundantly expressed in the central nervous system and considered to regulate various neuronal processes through the regulation of protein phosphorylation and actin cytoskeletal organization. In this study, we prepared a specific antibody against Phactr1, anti-Phactr1, and carried out biochemical and morphological analyses of Phactr1 with mouse brain tissues. Western blotting analyses revealed that Phactr1 was expressed in a tissue-dependent profile in the young adult mouse and in a developmental stage-dependent manner in the mouse brain. In primary cultured hippocampal neurons, while Phactr1 was diffusely distributed in the nucleus and cytoplasm, it was visualized in axon and dendrites with partial colocalization with synapses. Phactr1 was also detected in the synaptosomal and postsynaptic density fractions in biochemical fractionation. Immunohistochemical analyses clarified that Phactr1 was differentially expressed in cortical neurons during corticogenesis; the protein was frequently accumulated in the nucleus at the embryonic stage while it came to diffusely distribute in the cell body at the prepubertal stage. The obtained results suggest that Phactr1 takes part in neuronal functions regulated in a spatiotemporal manner.

MACRO Domain Containing 2 (MacroD2) is a neurodevelopmental disorder-related mono-ADP-ribosylhydrolase. Molecular features of this protein in neural tissues are largely unknown. In this study, we generated a specific antibody against MacroD2, and carried out expression and morphological analyses of the molecule during mouse brain development. In Western blotting, 2 MacroD2 isoforms with molecular masses of ∼70 and ∼75 kDa started to be expressed at embryonic day 16.5, reached the maximal level at postnatal day 8, and then gradually decreased through P30. In contrast, other isoforms with molecular masses of ∼110 and ∼140 kDa gradually increased during embryonic to postnatal development. In immunohistochemical analyses, MacroD2 was strongly detected in cortical neurons in layer II–V at P0 and P7, while the protein expression decreased significantly in the neurons at P30. Immunofluorescence analyses revealed that MacroD2 was mainly distributed in the soma and to a lesser extent in the axon and dendrite of immature primary cultured mouse hippocampal neurons. On the other hand, in the matured hippocampal neurons, while MacroD2 was detected in the soma, it displayed in dendrites a punctate distribution pattern with a partial colocalization with synaptic markers, synaptophysin, and PSD95. The obtained results indicate that MacroD2 is expressed and may have a physiological role in the central nervous system during brain development.

Dusp22 (dual-specificity phosphatase 22) is considered to regulate various cellular processes through the regulation of protein dephosphorylation. In this study, we prepared a specific antibody against Dusp22, anti-Dusp22, and carried out expression analyses with mouse tissues and cultured cell lines. Western blotting analyses demonstrated a tissue-dependent expression profile of Dusp22 in the adult mouse, and strongly suggested the presence of isoforms with larger molecular masses. In fibroblast NIH3T3 cells, while both endogenous and Myc-tagged Dusp22 was diffusely distributed in the cytoplasm, Myc-Dusp22 was partially colocalized with actin cytoskeleton. From the obtained results, anti-Dusp22 was found to be a useful tool for biochemical and cell biological analyses of Dusp22.

Erythropoietic protoporphyria is a genetic disease characterized by sensitivity to sunlight caused by the accumulation of protoporphyrin IX. Photoprotection against ultraviolet A and visible light is necessary for erythropoietic porphyria patients because the absorption spectrum of protoporphyrin IX lies in both ultraviolet A and visible light region. We developed a novel index, in vitro porphyrin protection factor, based on the protoporphyrin IX absorbance spectrum. We also selected appropriate photoprotective products designed according to protoporphyrin IX absorbance. The porphyrin protection factors of a combination of make‐up base with a powder as well as with a liquid foundation were significantly higher than those of a conventional sunscreen product, even at a small application dose. An in‐use test carried out for 6 months showed that the efficacy of these products was 78.3%, and no adverse reactions were observed. Male subjects preferred liquid foundation, whereas all female subjects used powder foundation. The preference of the subjects could lead to the long‐term use of the tested products. In conclusion, this study provided a new approach to improve photoprotection in erythropoietic protoporphyria patients.

Service research has emphasized triad relationships between a firm, employees and customers. To coordinate these stakeholders effectively, it is highly important to understand what service activities are beneficial to all or some of these stakeholders. Yet, the recent increase in C2C interaction may make the problem more complex. This study proposes a methodology combining statistical techniques and agent-based modeling, which makes it possible to assess the joint impact of each service value and C2C interaction on the payoffs.

Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

It is well known that the trigger for actinic keratosis (AK) mainly depends on UV exposure. We evaluated the effects of long-term use of sunscreen on the histopathological and dermoscopic changes of AK in aged patients. Eighteen months use of sunscreen produced no change in the number of actinic keratoses or the advancement of histological grade. Although a significant decrease was not observed in the number of positive cells of p53, Ki-67 and COX-2 of the subjects who used sunscreen for 18 months, the downward tendencies of these proteins were observed. The continued use of sunscreen decreased the number of CD31-positive vessels significantly using the Chalkley method, and a significant improvement in scaling and vessel dots was found by dermoscopic study. Moreover, a relationship was found in the amount of sunscreen use and the number of actinic keratoses. Considering these results, it was thought that application of sunscreen reduces the risk of advancement of AK to higher grade AK and squamous cell carcinoma.

The present study examined the effects of prasugrel in a mouse model of thrombosis-induced neointimal hyperplasia. Following carotid artery injury by application of ferric chloride solution, thrombus formation was assessed on Day 1 and neointimal thickening was assessed on Day 21. Single administrations of prasugrel at 0.3-3mg/kg (p.o.) resulted in a dose-related and sustained inhibition of ADP-induced platelet aggregation through 24h. Single and multiple (1 and 3 weeks) administration of prasugrel (3mg/kg loading and 1mg/kg/day maintenance doses) resulted in a marked inhibition of neointimal thickening in the injured artery. In the dose-response study, a single administration of prasugrel at 0.3-3mg/kg (p.o.) dose-relatedly inhibited thrombus formation and neointimal thickening on Days 1 and 21, respectively. The degree of neointimal hyperplasia in the injured artery correlated significantly with the thrombus indices, time to occlusion and patency rate. To explore possible mechanisms of inhibition of neointimal hyperplasia by prasugrel, mRNA expression levels of inflammatory and fibrosis markers were determined in injured arteries. Prasugrel treatment resulted in reduced MCP-1, ICAM-1 and TGF-β mRNA levels on Day 2 (24h after the injury) and Day 8 (1 week after the injury) in the target arteries. In conclusion, we found that a single oral loading dose of prasugrel markedly prevented neointimal hyperplasia by inhibiting platelet activation and thrombus formation and was associated with inhibition of the expression of inflammatory and fibrosis markers, including MCP-1, ICAM-1 and TGF-β, in the injured arteries.

Nanoimprint lithography manufacturing equipment utilizes a patterning technology that involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Additionally, as this technology does not require an array of widediameter lenses and the expensive light sources necessary for advanced photolithography equipment, NIL equipment achieves a simpler, more compact design, allowing for multiple units to be clustered together for increased productivity. In this paper, we review the progress and status of the FPA-1200NZ2C wafer imprint system and FPA-1100NR2 mask replication system. To address high volume manufacturing concerns, an FPA-1200NZ2C four-station cluster tool is used in order to meet throughput and cost of ownership requirements (CoO). Throughputs of up to 90 wafers per hour were achieved by applying a multi-field dispense method. Mask life of up to 125 lots, using a contact hole test mask were demonstrated. A mix and match overlay of 3.4 nm has also been achieved and a single machine overlay across the wafer of 2.1nm in X, 1.9nm in Y was also demonstrated. In addition, data is also presented on mask replication. Critical elements of a replication platform include image placement (IP) accuracy and critical dimension uniformity (CDU). Data is presented on both of these subjects. With respect to image placement, an IP accuracy (after removing correctables) of 0.8nm in X, 1.0nm in Y has been demonstrated.

Vasodilator-stimulated phosphoprotein (VASP) is a member of actin regulatory proteins implicated in platelet adhesion. In addition, phosphorylation of VASP is utilised for the assessment of platelet reactivity in patients treated with P2Y12 receptor antagonists, a class of antiplatelet agents. However, the role of VASP in platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of P2Y12 receptor antagonists remains unclear. We investigated these effects using heterozygous and homozygous VASP knockout rats generated with a CRISPR/Cas9 system. Baseline characteristics, such as haematology and other biochemical parameters, were comparable among the genotypes. In vitro platelet aggregation stimulated by adenosine diphosphate (ADP) or collagen, P-selectin expression of rat platelets treated with ADP, and in vivo thrombocytopenia induced by collagen were also comparable among the genotypes. In addition, in vivo thrombogenesis in a ferric chloride-induced arterial thrombosis model and bleeding time were also comparable among the genotypes. Furthermore, the in vitro antiplatelet effect of prasugrel, a third-generation P2Y12 receptor antagonist, was unaffected by VASP knockout. Although phosphorylated VASP is still an important surrogate marker specific for P2Y12 antagonists, our findings demonstrate that VASP is not a major mediator of platelet aggregation, thrombogenesis, haemostasis, and the antiplatelet effect of prasugrel in rats.

Nanoimprint lithography manufacturing equipment utilizes a patterning technology that involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. The technology faithfully reproduces patterns with a higher resolution and greater uniformity compared to those produced by photolithography equipment. Additionally, as this technology does not require an array of widediameter lenses and the expensive light sources necessary for advanced photolithography equipment, NIL equipment achieves a simpler, more compact design, allowing for multiple units to be clustered together for increased productivity. In this paper, we review the progress and status of the FPA-1100NR2 mask replication system and also discuss the methods used on wafer imprint systems to extend the life of a replica mask. Criteria that are crucial to the success of a replication platform include image placement (IP) accuracy and critical dimension uniformity (CDU). Data is presented on both of these subjects. With respect to image placement, an IP accuracy (after removing correctables) of 0.8nm in X, 1.0nm in Y has been demonstrated. Particle adders were studied by cycling the tool for more than 16000 times and measuring particle adders. Additionally, new methods, including on-tool wafer inspection and in-situ mask cleaning are being studied to further extend the replica mask life.

Thermally engineered flip-chip (FC) InGaN/GaN well-ordered nanocolumn array light-emitting diodes (LEDs) are demonstrated for the first time. A directional photoluminescence beam profile was observed from the n-side bottom of the GaN nanocolumns, which maintained an optically damage-free periodic arrangement of nanocolumns through the FC process involving Si substrate removal by wet etching. The developed LED achieved single-peak emission at $\sim 570$ nm in the middle of the visible range. The thermal resistance of the nanocolumn LED was significantly reduced using the FC configuration.

The present study was designed to characterize the pharmacological profile of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist. In the radioligand-binding assay, CS-3150 inhibited (3)H-aldosterone binding to mineralocorticoid receptor with an IC50 value of 9.4nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 36 and 713nM, respectively. CS-3150 also showed at least 1000-fold higher selectivity for mineralocorticoid receptor over other steroid hormone receptors, glucocorticoid receptor, androgen receptor and progesterone receptor. In the reporter gene assay, CS-3150 inhibited aldosterone-induced transcriptional activation of human mineralocorticoid receptor with an IC50 value of 3.7nM, and its potency was superior to that of spironolactone and eplerenone, whose IC50s were 66 and 970nM, respectively. CS-3150 had no agonistic effect on mineralocorticoid receptor and did not show any antagonistic or agonistic effect on glucocorticoid receptor, androgen receptor and progesterone receptor even at the high concentration of 5μM. In adrenalectomized rats, single oral administration of CS-3150 suppressed aldosterone-induced decrease in urinary Na(+)/K(+) ratio, an index of in vivo mineralocorticoid receptor activation, and this suppressive effect was more potent and longer-lasting than that of spironolactone and eplerenone. Chronic treatment with CS-3150 inhibited blood pressure elevation induced by deoxycorticosterone acetate (DOCA)/salt-loading to rats, and this antihypertensive effect was more potent than that of spironolactone and eplerenone. These findings indicate that CS-3150 is a selective and highly potent mineralocorticoid receptor antagonist with long-lasting oral activity. This agent could be useful for the treatment of hypertension, cardiovascular and renal disorders.

Neuregulin-1 (NRG1) is a well-recognized risk gene for schizophrenia and is often implicated in the neurodevelopmental hypothesis of this illness. Alternative splicing and proteolytic processing of the NRG1 gene produce more than 30 structural variants; however, the neuropathological roles of individual variants remain to be characterized. On the basis of the neurodevelopmental hypothesis of schizophrenia, we administered eNRG1 (0.1~1.0 µg/g), a core epidermal growth factor-like (EGF) domain common for all splicing NRG1 variants, to neonatal mice and compared their behavioral performance with mice challenged with a full mature form of type 1 NRG1 variant. During the neonatal stage, recombinant eNRG1 protein administrated from the periphery passed the blood-brain barrier and activated its receptor (ErbB4) in the brain. In adults, the mice receiving the highest dose exhibited lower locomotor activity and deficits in prepulse inhibition and tonedependent fear learning, although the hearing reduction of the eNRG1-treated mice may explain these behavioral deficits. Neonatal eNRG1 treatment also significantly potentiated MK-801-driven locomotor activity in an eNRG1 dose-dependent manner. In parallel eNRG1 treatment enhanced MK-801-driven c-Fos induction and decreased immunoreactivity for NMDA receptor subunits in adult brain. In contrast, mice that had been treated with the same molar dose of a full mature form of type 1 NRG1 as neonates did not exhibit hypersensitivity to MK-801. However, both animal models exhibited similar hypersensitivity to methamphetamine. Collectively, our findings suggest that aberrant peripheral NRG1 signals during neurodevelopment alter later behavioral traits and auditory functions in the NRG1 subtype-dependent manner.

Nanoimprint Lithography (NIL) has been shown to be an effective technique for replication of nano-scale features. Jet and Flash Imprint Lithography* (J-FIL*) involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is crosslinked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. There are many criteria that determine whether a particular technology is ready for high volume semiconductor manufacturing. Included on the list are overlay, throughput and defectivity. Imprint lithography, like any lithographic approach requires that defect mechanisms be identified and eliminated in order to consistently yield a device. NIL has defect mechanisms unique to the technology, and they include liquid phase defects, solid phase defects and particle related defects. Especially more troublesome are hard particles on either the mask or wafer surface. Hard particles run the chance of creating a permanent defect in the mask, which cannot be corrected through a mask cleaning process. If Cost of Ownership (CoO) requirements are to be met, it is critical to minimize particle formation and extend mask life. To meet the CoO requirements, mask life must meet or exceed 1000 wafers. If, we make the conservative assumption that every particles causes damage to the mask pattern, the number of particle adders must be less than 0.001 pieces per wafer pass in the NIL tool. Therefore, aggressive strategies are needed to reduce particles in the tool. In this paper, we will report on the techniques required to meet this condition and will describe how the particle reduction techniques can be extended to our FPA-1200NZ2C system.

Patients with acute coronary syndrome with diabetes mellitus (DM) exhibit an impaired platelet inhibitory response to clopidogrel which is only partially understood. DM was induced by the administration of streptozotocin (STZ) to 9-week-old mice. The antithrombotic effects of clopidogrel (10 mg/kg/d, orally × 5 days) were determined using a FeCl3-induced thrombosis model employing wild-type (WT), apolipoprotein E (apoE)-deficient, and diabetic apoE-deficient mice at 21 weeks. Antiplatelet effects were determined using flow cytometry. The antithrombotic effects of clopidogrel were similar in WT and apoE-deficient mice but were attenuated in diabetic apoE-deficient mice with the percent inhibition of thrombus area (µm2) by clopidogrel being 85.5% (WT mice), 75.0% (apoE-deficient mice), and 1.9% (diabetic apoE-deficient mice). The time to first occlusion and lumen stenosis also reflected a significant loss of the antithrombotic effects of clopidogrel in diabetic apoE-deficient mice. Ex vivo platelet activation, which was assessed using ADP-induced expression of activated glycoprotein IIb/IIIa, was completely inhibited by clopidogrel in these three groups of mice. In contrast, the effect of clopidogrel on the ex vivo expression of platelet P-selectin induced by protease-activated receptor 4–activating peptide was diminished in diabetic apoE-deficient mice compared with that in WT and apoE-deficient mice. These data suggest that diabetic apoE-deficient mice may serve as a useful model to better understand the impaired responses to clopidogrel in patients with DM, which may partially reflect a reduction of the effect of clopidogrel on thrombin-induced platelet activation.

Imprint lithography has been shown to be an effective technique for replication of nano-scale features. Jet and Flash* Imprint Lithography (J-FIL*) involves the field-by-field deposition and exposure of a low viscosity resist deposited by jetting technology onto the substrate. The patterned mask is lowered into the fluid which then quickly flows into the relief patterns in the mask by capillary action. Following this filling step, the resist is cross-linked under UV radiation, and then the mask is removed, leaving a patterned resist on the substrate. Criteria specific to any lithographic process for the semiconductor industry include overlay, throughput and defectivity. The purpose of this paper is to describe the technology advancements made in the reduction of particle adders in an imprint tool. Hard particles on a wafer or mask create the possibility of creating a permanent defect on the mask that can impact device yield and mask life. By using material methods to reduce particle shedding and by introducing an air curtain system, test stand results demonstrate the potential for extending mask life to better than 1000 wafers.

In our previous study, we screened autism spectrum disorder (ASD) patients with and without sleep disorders for mutations in the coding regions of circadian-relevant genes, and detected mutations in several clock genes including NR1D1. Here, we further screened ASD patients for NR1D1 mutations and identified three novel mutations including a de novo heterozygous one c.1499 G > A (p.R500H). We then analyzed the role of Nr1d1 in the development of the cerebral cortex in mice. Acute knockdown of mouse Nr1d1 with in utero electroporation caused abnormal positioning of cortical neurons during corticogenesis. This aberrant phenotype was rescued by wild type Nr1d1, but not by the c.1499 G > A mutant. Time-lapse imaging revealed characteristic abnormal migration phenotypes in Nr1d1-deficient cortical neurons. When Nr1d1 was knocked down, axon extension and dendritic arbor formation of cortical neurons were also suppressed while proliferation of neuronal progenitors and stem cells at the ventricular zone was not affected. Taken together, Nr1d1 was found to play a pivotal role in corticogenesis via regulation of excitatory neuron migration and synaptic network formation. These results suggest that functional defects in NR1D1 may be related to ASD etiology and pathophysiology.