A Toolkit for Exploring Augmented Reality Through Construction with Children

International audienceAugmented Reality begins to be widely mainstream among children, due to some interactive successes in video games and social networks. Based on this interest, we present CartonEd, an open and complete toolkit suitable for children dedicated to the construction of an augmented reality headset device. The toolkit let the children play and explore augmented reality with and beyond handheld devices. Inspired by the Do-It-Yourself movement, the toolkit includes different components such as blueprints, tutorials, videos, mobile apps, a software development kit and an official website. Among the mobile applications, one is implemented to guide the children through the construction process while experiencing augmented reality. To validate our solution (in particular the construction process and the guiding app) and understand its effect on children in regard to their relation to the augmented reality, we conducted four construction sessions. Our study examines the usability of the guiding app and the construction process. We report in this paper the main components of the CartonEd toolkit and the results of an evaluation among 57 children and teenagers (ages 8-16), showing a positive outcome about their own constructed device (all functional), their feelings and wishes regarding the augmented reality

Earthquakes in California in 1898

The following paper is a continuation of similar records furnished by officers of the Lick Observatory, and completes the list up to the end of 1898. It records all the shocks observed or felt on Mount Hamilton, and all those reported to the Lick Observatory by letter, as well as newspaper reports of such earthquakes as occurred in the State during the year. It also includes a number of shocks in various localities on the Pacific coast which it was thought might not have \u27been recorded in other reports. No systematic examination of newspapers has been made, however, and some reports of earthquakes may have escaped notice

Earthquakes in California in 1896 and 1897

The following paper is a continuation of similar records furnished by officers of the Lick Observatory, and completes the list up to the end of 1897. It records all the shocks observed or felt on Mount Hamilton and all those reported to the Lick Observatory by letter, as well as newspaper reports of such earthquakes as occurred in the State during the year. It also includes a number of shocks in various localities on the Pacific coast which it was thought might not have been recorded in other reports. No systematic examination of newspapers has been made, however, and some reports of earthquakes may have escaped notice

Earthquakes in California in 1894

The following report is a continuation of similar records, and brings the list up to the end of the year 1894. It contains accounts of all the shocks observed or felt on Mount Hamilton and all those reported to the Lick Observatory by letter, as well as newspaper reports of earthquakes occurring in the State during that year. Many newspapers have been examined, and this bulletin is largely made up from their reports. Some may have escaped notice. It has been the object especially to record earthquakes occurring in California, but a number of shocks are here recorded which do not properly belong in a record of California earthquakes, which have been included for fear they may have escaped other compilers. The records of the United States Weather Bureau and of the United States Light-House Board, together with the present list, will afford a fairly complete account of the California earthquakes of 1894

Earthquakes in California in 1893

The following paper is a continuation of similar records furnished by officers of the Lick Observatory, and completes the list up to the .end of 1893. It records all the shocks observed or felt on Mount Hamilton, and all those reported to the Lick Observatory by letter, as .well as newspaper reports of such earthquakes as occurred in the State during that year. It also includes a number of shocks in various localities on the Pacific coast, which it was thought might not have been recorded in other reports. No systematic examination of newspapers has been made, however, and some reports of earthquakes may have escaped notice

Haploinsufficiency of Dmxl2, Encoding a Synaptic Protein, Causes Infertility Associated with a Loss of GnRH Neurons in Mouse

International audienceCharacterization of the genetic defects causing gonadotropic deficiency has made a major contribution to elucidation of the fundamental role of Kisspeptins and Neurokinin B in puberty onset and reproduction. The absence of puberty may also reveal neurodevelopmental disorders caused by molecular defects in various cellular pathways. Investigations of these neurodevelopmental disorders may provide information about the neuronal processes controlling puberty onset and reproductive capacity. We describe here a new syndrome observed in three brothers, which involves gonadotropic axis deficiency, central hypothyroidism, peripheral demyelinating sensorimotor polyneuropathy, mental retardation, and profound hypoglycemia, progressing to nonautoimmune insulin-dependent diabetes mellitus. High-throughput sequencing revealed a homozygous in-frame deletion of 15 nucleotides in DMXL2 in all three affected patients. This homozygous deletion was associated with lower DMXL2 mRNA levels in the blood lymphocytes of the patients. DMXL2 encodes the synaptic protein rabconnectin-3a, which has been identified as a putative scaffold protein for Rab3-GAP and Rab3-GEP, two regulators of the GTPase Rab3a. We found that rabconnectin-3a was expressed in exocytosis vesicles in gonadotropin-releasing hormone (GnRH) axonal extremities in the median eminence of the hypothalamus. It was also specifically expressed in cells expressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) within the pituitary. The conditional heterozygous deletion of Dmxl2 from mouse neurons delayed puberty and resulted in very low fertility. This reproductive phenotype was associated with a lower number of GnRH neurons in the hypothalamus of adult mice. Finally, Dmxl2 knockdown in an insulin-secreting cell line showed that rabconnectin-3a controlled the constitutive and glucose-induced secretion of insulin. In conclusion, this study shows that low levels of DMXL2 expression cause a complex neurological phenotype, with abnormal glucose metabolism and gonadotropic axis deficiency due to a loss of GnRH neurons. Our findings identify rabconectin-3a as a key controller of neuronal and endocrine homeostatic processes

Evidence of pseudoprogression in patients treated with PD1/ PDL1 antibodies across tumor types

Background: PD(L)1 antibodies (anti-PD(L)-1) have been a major breakthrough in several types of cancer. Novel patterns of response and progression have been described with anti-PD(L)-1. We aimed at characterizing pseudoprogression (PSPD) among patients with various solid tumor types treated by anti-PD(L)-1. Methods: All consecutive patients (pts) enrolled in phase 1 trials with advanced solid tumors and lymphomas treated in phase I clinical trials evaluating monotherapy by anti-PD(L)-1 at Gustave Roussy were analyzed. We aimed to assess prevalence and outcome of PSPD across tumor types. We also intended to describe potential clinical and pathological factors associated with PSPD. Results: A total of 169 patients treated with anti-PD(L)-1 were included in the study. Most frequent tumor types included melanoma (n = 57) and non-small cell lung cancer (n = 19). At first tumor evaluation 77 patients (46%) presented with immune unconfirmed progressive disease. Six patients (8%) experienced PSPD: 2 patients with partial response; 4 patients with stable disease. Increase in target lesions in the first CT-scan was more frequently associated to PSPD (67% vs 33%; P = .04). Patients with a PSPD had a superior survival when compared to patients progressing (median OS: 10.7 months vs 8.7 months; P = .07). Conclusions: A small subset of PSPD patients may experience response after an initial progression. Assessment of the current strategy for immune-related response evaluations may require further attention

E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis.

The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis

Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2

Objective: To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. Methods: In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). Results: 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). Conclusions: Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing