Aberrant lysosomal carbohydrate storage accompanies endocytic defects and neurodegeneration in Drosophila benchwarmer

Lysosomal storage is the most common cause of neurodegenerative brain disease in preadulthood. However, the underlying cellular mechanisms that lead to neuronal dysfunction are unknown. Here, we report that loss of Drosophila benchwarmer (bnch), a predicted lysosomal sugar carrier, leads to carbohydrate storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions. At the bnch larval neuromuscular junction, we observe similar inclusions and find defects in synaptic vesicle recycling at the level of endocytosis. In addition, loss of bnch slows endosome-to-lysosome trafficking in larval garland cells. In adult bnch flies, we observe age-dependent synaptic dysfunction and neuronal degeneration. Finally, we find that loss of bnch strongly enhances tau neurotoxicity in a dose-dependent manner. We hypothesize that, in bnch, defective lysosomal carbohydrate efflux leads to endocytic defects with functional consequences in synaptic strength, neuronal viability, and tau neurotoxicity

Family members dealing with childhood cancer : a study on the role of family functioning and cancer appraisal

Objectives: Childhood cancer is a life-threatening disease that poses significant challenges to the life of the diagnosed child and his/her family members. Based on the ABCX-model, the aim of the current study was to explore the association between family functioning, cancer appraisal and the individual adjustment of patients, parents and siblings. Methods: Participants were 60 children with leukemia or non-Hodgkin lymphoma, 172 parents and 78 siblings (115 families). Time since diagnosis varied from zero to 33 months. Patients, parents and siblings completed the Family Environment Scale (FES), Perceived Stress Scale, Situation-Specific Emotional Reactions Questionnaire and Pediatric Quality of Life Inventory/Maudsley Marital Questionnaire. Results: Family functioning and the appraisal of the cancer diagnosis proved to be related to patients', parents' and siblings' cancer-related emotions and quality of life post-diagnosis. In addition, family members differed in their perception of some family functioning domains, the appraisal of the cancer diagnosis, positive feelings and quality of life. Discussion: Our findings led to the conclusion that family functioning and the appraisal of the cancer diagnosis are important for the individual adjustment of patients, parents and siblings when facing a diagnosis of cancer in the child. Differences across members within one family and differences between families speak to the need of screening all family members and intervening at the level of individual as well as the family unit

Couples dealing with pediatric blood cancer : a study on the role of dyadic coping

Objective: Pediatric cancer is a life-threatening disease that poses significant challenges to the ill child and his/her parents. Among the studies investigating risk and protective factors for the individual and relationship adjustment of parents being confronted with pediatric cancer, couple factors - such as dyadic coping - gained little research attention. Therefore, the aim of the current study was to explore the association between dyadic coping and individual/relationship outcomes of parents in the context of pediatric cancer. Methods: Participants were 59 couples of children diagnosed with leukemia or Non-Hodgkin lymphoma. Time since diagnosis varied from diagnosis to 20 months. Both parents completed the DCI-short, DASS21, PIP, and MMQ. Results: Positive dyadic coping (i.e., supportive and common dyadic coping) and negative dyadic coping proved to be related to individual and relational outcomes of parents facing cancer in their child. In addition, while men and women reported to be equally satisfied with their partner and their sexual relationship, women reported higher levels of individual maladjustment. Conclusion: Our findings led to the conclusion that dyadic coping is important for both individual as well as relationship outcomes of parents when facing a diagnosis of cancer in their child. When meeting with families, both partners should be invited as a unit in order to best capture couple level experiences. Also, clinicians should be sensitive to relational and sexual issues besides individual issues, taking into account evidence-based standards for psychosocial care in pediatric oncology

Wisata Air Hemaq BeniungDi Kabupaten Kutai Barat

Wisata Air Hemaq Beniung yang berlokasi di Juaq Asa, Kabupaten Kutai Barat merupakan Salah satu destinasi unggulan saat ini yang ada di Kabupaten Kutai Barat wisata ini merupakan sebuah danau buatan cukup sering dikunjungi oleh wisatawan lokal dan non lokal namun, infrastruktur, fasilitas, dan daya dukung ruang rekreasi objek wisata yang masih belum memadai aktivitas wisata serta belum optimal dalam merespon konteks dan potensi site, berpengaruh pada tingkat kepuasan pengunjung yang merasa kurang nyaman dan mudah jenuh, tujuan dari adanya fasilitas-fasilitas pendukung seperti wahana, edukasi, pameran dan pusat umkm dapat menarik lebih banyak pengunjung baik lokal, non lokal, bahkan mancanegara, sehingga perekonomian masyarakat di Kutai Barat meningkat. Pendekatan desain arsitektur yang digunakan dalam Wisata Air Hemaq Beniung Di Kabupaten Kutai Barat ini adalah wawancara, observasi, dokumentasi, & studi literatur melalui buku dan jurnal, Proses wawancara dilakukan guna memperoleh pendapat dari para pengunjung, observasi secara langsung guna memperoleh pengalaman dan pengamatan melalui diri sendiri, Dokumentasi foto sebagai kelengkapan dokumentasi sebagai sarana informasi, Studi literatur guna mencari dan mempertajam ide-ide, informasi baru, serta pemecahan masalah sehingga didapati bahwa kondisi sebuah kawasan objek wisata yang didominasi oleh ruang terbuka hijau dengan suasana khas hutan hujan tropis dan keragaman hayatinya serta potensi sosial�budaya yang masih lestari, menjawab bahwa lingkungan dan alam memiliki peran penting dalam mendukung dan mengoptimalkan daya tarik dan keberlanjutan pada Kawasan objek wisata. Dengan demikian diharapkan perancangan fasilitas wisata yang terintegrasi dengan lingkungan alam dapat mewadahi aktivitas wisatawan serta memberikan ruang interaksi antara alam dan manusia melalui pendekatan Arsitektur Ekologis. Yang mana dengan memanfaatkan potensi alam semaksimal mungkin guna mendukung efektivitas fasilitas Wisata Air Hemaq Beniung agar terciptanya keselarasan antara alam dan manusia

The chemistry of La on the Si(001) surface

This paper reports state-of-the-art electronic structure calculations of La adsorption on the Si(001) surface. We predict La chains in the low coverage limit, which condense in a stable phase at a coverage of 1/5 monolayer. At 1/3 monolayer we predict a chemically rather inert, stable phase. La changes its oxidation state from La(3+) at lower coverages to La(2+) at coverages beyond 1/3 monolayer. In the latter oxidation state, one electron resides in a state with a considerable contribution from La-d and f states.Comment: 10 pages, 13 figures, 3 table

Numb “Adapting” Notch for Endocytosis

AbstractDuring sensory organ precursor divisions in Drosophila, the numb gene product segregates asymmetrically into one of the two daughter cells, to which it confers a specific fate by inhibiting Notch signaling. In this issue of Developmental Cell, Berdnik et al. show that Numb recruits α-Adaptin and that this physical interaction plays a role in downregulating Notch, presumably by stimulating endocytosis of Notch

Family adjustment when facing pediatric cancer : the role of parental psychological flexibility, dyadic coping, and network support

Objectives Pediatric cancer is a life-threatening disease that poses significant challenges to the life of all family members (diagnosed child, parents, and siblings) and the family as a whole. To date, limited research has investigated family adjustment when facing pediatric cancer. The aim of the current study was to explore the role of protective factors at the individual (parental psychological flexibility), intrafamilial (dyadic coping) and contextual level (network support) in explaining family adjustment as perceived by parents of children with leukemia or non-Hodgkin lymphoma. In addition, we were interested to see whether these protective factors could be predictive for family adjustment at a later time point. Method Participants were 70 mothers and 53 fathers (80 families) of children with leukemia or non-Hodgkin lymphoma. Mean time since diagnosis was 5.26 (T1) and 18.86 (T2) months post-diagnosis. Parents completed the Acceptance and Action Questionnaire II (to assess psychological flexibility), Dyadic Coping Inventory, a network support questionnaire, Impact on Family Scale and the Family Adjustment Scale. Both concurrent and prospective association models were tested. Results Psychological flexibility, dyadic coping and network support proved to be cross-sectionally and positively related to parents' perception of family adjustment post-diagnosis; psychological flexibility and dyadic coping proved to predict better family adjustment over time. Conclusion Our findings led to the conclusion that protective factors at all three levels (individual, intrafamilial and contextual) are important for explaining family adjustment as perceived by parents facing a diagnosis of cancer in their child. Interventions targeting the individual, couple, as well as family level are warranted to enhance family adjustment

Mask Conversions for d+1 shares in Hardware, with Application to Lattice-based PQC

The conversion between arithmetic and Boolean mask representations (A2B & B2A) is a crucial component for side-channel resistant implementations of lattice-based cryptography. In this paper, we present a first- and high-order masked, unified hardware implementation which can perform both A2B & B2A conversions. We optimize the operation on several layers of abstraction, applicable to any protection order. First, we propose novel higher-order algorithms for the secure addition and B2A operation. This is achieved through, among others, an improved method for repeated masked modular reduction and through the X2B operation, which can be viewed as a conversion from any type of additive masking to its Boolean representation. This allows for the removal of a full secure addition during B2A post-processing. Compared to prior work, our $B2A_q$ requires 51/46/45 % less fresh randomness at first through third protection order when implemented in software or hardware. Secondly, on the circuit level, we successfully introduce half-cycle data paths and demonstrate how careful, manual masking is a superior approach for masking highly non-linear operations and providing first- and high-order security. Our techniques significantly reduce the high latency and fresh randomness overhead, typically introduced by glitch-resistant masking schemes and universally composable gadgets, including HPC3 by Knichel et al. presented at CCS 2022. Compared to state-of-the-art algorithms and masking techniques, our unified and high-throughput hardware implementation requires up to 89/84/86 % fewer clock cycles and 78/71/55 % fewer fresh random bits. We show detailed performance results for first-, second- and third-order protected implementations on FPGA. Our proposed algorithms are proven secure in the glitch extended probing model and their implementations are validated via practical lab analysis using the TVLA methodology. We experimentally show that both our first- and second-order masked implementation is hardened against univariate and multivariate attacks using 100 million traces, for each mode of operation

Dilemmas in the Management of an Infant with Neuroblastoma Metastasized to the Muscles

The risk stratification of infants with metastatic neuroblastoma (NB) has evolved over time from stage 4/M or IVs/4S/MS/Ms according to various staging systems. Despite these developments for some genetic aberrations, the prognostic value and the impact of soft tissue metastases in infants are not fully understood, nor well described in the different classification systems, hampering the definitions to uniformly treat patients and predict prognosis. A literature review on staging of infants with M/MS disease was performed at the occasion of the diagnosis of NB in an 8-month-old boy who presented with atypical metastatic sites in soft tissue and an aberrant tumor biology. The definitions of stage 4/4S/4s/M/MS/Ms were evaluated and compared to enable tumor risk stratification and inform management. International NB groups use different criteria for defining stage of infants with metastasized NB, resulting in differences in management. Limited literature is available on soft tissue metastases, especially muscular metastases, and is poorly incorporated into management guidelines mainly due to the lack of data. The uncertain prognosis of rare genetic aberrancies may add to the difficulties in treatment decisions. In some rare cases of NB in infants, the international treatment classification is not sufficient for staging and treatment decisions. Based on tumor progression, biology of unknown significance and a lack of evidence to classify a child under 12 months with NB and multiple muscular metastases, the patient was treated as stage 4/M and intermediate-risk protocols with a favorable outcome

Future paradigms for precision oncology

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