A human carboxypeptidase E/NF-alpha 1 gene mutation in an Alzheimer's disease patient leads to dementia and depression in mice

Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-alpha 1 (NF-alpha 1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ. Expression of CPE-QQ in Neuro2a cells demonstrated that it was not secreted, but accumulated in the endoplasmic reticulum and was subsequently degraded by proteasomes. Expression of CPE-QQ in rat hippocampal neurons resulted in cell death, through increased ER stress and decreased expression of pro-survival protein, BCL-2. Transgenic mice expressing CPE-QQ did not show any difference in the processing enzyme activity of CPE compared with wild-type mice. However, the transgenic mice exhibited poor memory, depressive-like behavior, severely decreased dendrites in the hippocampal CA3 region and medial prefrontal cortex indicative of neurodegeneration, hyperphosphorylation of tau at Ser(396), and diminished neurogenesis in the dentate gyrus at 50 weeks old. All these pathologies are associated with AD and the latter with depression and were observed in 50-week-old mice. Interestingly, the younger CPE-QQ mice (11 weeks old) did not show deficits in dendrite outgrowth and neurogenesis. This study has uncovered a human CPE/NF-alpha 1 gene mutation that could lead to comorbidity of dementia and depression, emphasizing the importance of this gene in cognitive function

Focusing of geodesic congruences in an accelerated expanding Universe

We study the accelerated expansion of the Universe through its consequences on a congruence of geodesics. We make use of the Raychaudhuri equation which describes the evolution of the expansion rate for a congruence of timelike or null geodesics. In particular, we focus on the space-time geometry contribution to this equation. By straightforward calculation from the metric of a Robertson-Walker cosmological model, it follows that in an accelerated expanding Universe the space-time contribution to the Raychaudhuri equation is positive for the fundamental congruence, favoring a non-focusing of the congruence of geodesics. However, the accelerated expansion of the present Universe does not imply a tendency of the fundamental congruence to diverge. It is shown that this is in fact the case for certain congruences of timelike geodesics without vorticity. Therefore, the focusing of geodesics remains feasible in an accelerated expanding Universe. Furthermore, a negative contribution to the Raychaudhuri equation from space-time geometry which is usually interpreted as the manifestation of the attractive character of gravity is restored in an accelerated expanding Robertson-Walker space-time at high speeds.Comment: 11 pages, 2 figures. Final version changed to match published version in JCAP. References updated. Conclusions unchange

Experimental evaluation of digitally verifiable photonic computing for blockchain and cryptocurrency

As blockchain technology and cryptocurrency become increasingly mainstream, photonic computing has emerged as an efficient hardware platform that reduces ever-increasing energy costs required to verify transactions in decentralized cryptonetworks. To reduce sensitivity of these verifications to photonic hardware error, we propose and experimentally demonstrate a cryptographic scheme, LightHash, that implements robust, low-bit precision matrix multiplication in programmable silicon photonic networks. We demonstrate an error mitigation scheme to reduce error by averaging computation across circuits, and simulate energy-efficiency-error trade-offs for large circuit sizes. We conclude that our error-resistant and efficient hardware solution can potentially generate a new market for decentralized photonic blockchain

Improving the tokenisation of identifier names

Identifier names are the main vehicle for semantic information during program comprehension. For tool-supported program comprehension tasks, including concept location and requirements traceability, identifier names need to be tokenised into their semantic constituents. In this paper we present an approach to the automated tokenisation of identifier names that improves on existing techniques in two ways. First, it improves the tokenisation accuracy for single-case identifier names and for identifier names containing digits, which existing techniques largely ignore. Second, performance gains over existing techniques are achieved using smaller oracles, making the approach easier to deploy. Accuracy was evaluated by comparing our algorithm to manual tokenizations of 28,000 identifier names drawn from 60 well-known open source Java projects totalling 16.5 MSLOC. Moreover, the projects were used to perform a study of identifier tokenisation features (single case, camel case, use of digits, etc.) per object-oriented construct (class names, method names, local variable names, etc.), thus providing an insight into naming conventions in industrial-scale object-oriented code. Our tokenisation tool and datasets are publicly available

Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study

Background Anemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia. Methods A cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson\u27s correlations and ordinary least-squares regressions were calculated. Results Median (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was \u3c15 μg/L in 18.6% of the women. Only one woman had α-1-acid glycoprotein (AGP) \u3e1.0 g/L; four women (2%) had \u3e 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferring receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%. Conclusion Iron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem

Combining machine learning and spatial data processing techniques for allocation of large-scale nature-based solutions

This is the final version. Available on open access from IWA Publishing via the DOI in this recordData availability statement: All relevant data are available from an online repository or repositories: (https://developers.google.com/earth-engine/datasets; https://search.asf.alaska.edu/#/; https://geo.gob.bo/; https://www.openstreetmap.org/#map=7/52.154/5.295; https://rsis.ramsar.org/; https://www.arcgis.com/apps/mapviewer/index.html?layers=cfcb7609de5f478eb7666240902d4d3d; https://land.copernicus.eu/en/products/corine-land-cover; https://worldcover2020.esa.int/viewer).The escalating impacts of climate change trigger the necessity to deal with hydro-meteorological hazards. Nature-based solutions (NBSs) seem to be a suitable response, integrating the hydrology, geomorphology, hydraulic, and ecological dynamics. While there are some methods and tools for suitability mapping of small-scale NBSs, literature concerning the spatial allocation of large-scale NBSs is still lacking. The present work aims to develop new toolboxes and enhance an existing methodology by developing spatial analysis tools within a geographic information system (GIS) environment to allocate large-scale NBSs based on a multi-criteria algorithm. The methodologies combine machine learning spatial data processing techniques and hydrodynamic modelling for allocation of large-scale NBSs. The case studies concern selected areas in the Netherlands, Serbia, and Bolivia, focusing on three large-scale NBS: rainwater harvesting, wetland restoration, and natural riverbank stabilisation. Information available from the EC H2020 RECONECT project as well as other available data for the specific study areas was used. The research highlights the significance of incorporating machine learning, GIS, and remote sensing techniques for the suitable allocation of large-scale NBSs. The findings may offer new insights for decision-makers and other stakeholders involved in future sustainable environmental planning and climate change adaptation.European Union Horizon 202

Statistička analiza nanokapsuliranja niskomolekularnog heparina

The objective of this study was to use Box-Behnken design (BBD) to investigate the influence of formulation variables on the properties of heparin-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit-RLPO (E-RLPO) nanoparticles (NP) in terms of mean diameter (as size) and drug encapsulation efficiency. The NPs were prepared by the double emulsion solvent evaporation method. The independent variables were: X1 olymer mass ratio (PLGA:E-RLPO) in the oil phase, X2 concentration of polyvinyl alcohol (PVA) as emulsion stabilizer, and X3 volume of the external aqueous phase (W2). Particle size (analyzed by dynamic light scattering) and encapsulation efficiency (EE, estimated by spectrophotometry) were the investigated responses. The polynomial equation obtained from regression analysis of the reduced model (p = 0.0002, F = 25.7952 and R2 = 0.96) provided an excellent fit. The optimal size for the NP was found to be 134.2 ± 16.5 nm with formulation variables of 48.2:61.8, 0.321 (%, m/V) and 263 mL for X1, X2 and X3, respectively. Probably, due to electrostatic interaction between the negatively charged drug and the positively charged E-RLPO, the percent EE of heparin was between 74.4 ± 6.5 % (lowest value) and 92.1 ± 5.3 % (highest value). The data suggest that BBD is a useful tool in rational design of heparin-loaded NPs.Box-Behnkenovo dizajniranje (BBD) primijenjeno je za praćenje utjecaja formulacijskih varijabli na svojstva nanočestica (NP) s heparinom. Za izradu nanočestica korišten je kopolimer mliječne i glikolne kiseline (PLGA) i Eudragit-RLPO (E-RLPO). Nanočestice su pripravljene metodom dvostruke evaporacije otapala iz emulzije. Nezavisne varijable bile su: X1 omjer masa polimera (PLGA : E-RLPO) u uljnoj fazi, X2 koncentracija polivinil alkohola (PVA) kao stabilizatora emulzije i X3 volumen vanjske vodene faze (W2). Zavisne varijable bile su veličina čestica (analizirana pomoću dinamičkog rasapa svjetlosti) i učinkovitost inkapsuliranja (EE) (praćena spektrofotometrijski). Polinomska jednadžba dobivena regresijskom analizom reduciranog modela odlično je odgovarala (p = 0,0002, F = 25,7952 i R2 = 0,96). Optimalna veličina nanočestica bila je 134,2 ± 16,5 nm s formulacijskim varijablama 48,2:61,8, 0,321 (%, m/V) i 263 mL for X1, X2 odnosno X3. Vjerojatno je zbog elektrostatskih interakcija između negativno nabijene ljekovite tvari i pozitivno nabijenog E-RLPO učinkovitost inkapsuliranja heparina varirala od 74,4 ± 6,5 % (najniža vrijednost) do 92,1 ± 5,3 % (najviša vrijednost). Rezultati sugeriraju da je BBD vrlo korisno u racionalnom dizajniranju nanočestica s heparinom

Assessing the impact of integrated community-based management of severe wasting programs in conflict-stricken south Sudan : a multi-dimensional approach to scalability of nutrition emergency response programs

Community-based management of severe wasting (CMSW) programs have solely focused on exit outcome indicators, often omitting data on nutrition emergency preparedness and scalability. This study aimed to document good practices and generate evidence on the effectiveness and scalability of CMSW programs to guide future nutrition interventions in South Sudan. A total of 69 CMSW program implementation documents and policies were authenticated and retained for analysis, complemented with the analyses of aggregated secondary data obtained over five (2016–2020 for CMSW program performance) to six (wasting prevention) years (2014–2019). Findings suggest a strong and harmonised coordination of CMSW program implementation, facilitated timely and with quality care through an integrated and harmonised multi-agency and multidisciplinary approach. There were challenges to the institutionalisation and ownership of CMSW programs: a weak health system, fragile health budget that relied on external assistance, and limited opportunities for competency-based learning and knowledge transfer. Between 2014 and 2019, the prevalence of wasting fluctuated ac-cording to the agricultural cycle and remained above the emergency threshold of 15% during the July to August lean season. However, during the same period, under-five and crude mortality rates (10,000/day) declined respectively from 1.17 (95% confidence interval (CI): 0.91, 1.43) and 1.00 (95% CI: 0.75, 1.25) to 0.57 (95% CI: 0.38, 0.76) and 0.55 (95% CI: 0.39, 0.70). Both indicators remained below the emergency thresholds, hence suggesting that the emergency response was under control. Over a five-year period (2016–2020), a total of 1,105,546 children (52% girls, 48% boys) were admitted to CMSW programs. The five-year pooled performance indicators (mean [standard deviations]) was 86.4 (18.9%) for recovery, 2.1 (7.8%) for deaths, 5.2 (10.3%) for defaulting, 1.7 (5.7%) for non-recovery, 4.6 (13.5%) for medical transfers, 2.2 (4.7%) for relapse, 3.3 (15.0) g/kg/day for weight gain velocity, and 6.7 (3.7) weeks for the length of stay in the program. In conclusion, all key performance indicators, except the weight gain velocity, met or exceeded the Humanitarian Charter and Minimum Standards in Humanitarian Response. Our findings demonstrate the possibility of implementing robust and resilient CMSAM programs in protracted conflict environments, informed by global guidelines and protocols. They also depict challenges to institutionalisation and ownership

An ethnobotanical study of medicinal plants used by local people in the lowlands of Konta Special Woreda, southern nations, nationalities and peoples regional state, Ethiopia

<p>Abstract</p> <p>Background</p> <p>Research was carried out in Konta Special Woreda (District); it is a remote area with lack of infrastructure like road to make any research activities in the area. Therefore, this research was conducted to investigate medicinal plants of the Konta people and to document the local knowledge before environmental and cultural changes deplete the resources.</p> <p>Methods</p> <p>The information was collected between October 2006 and February 2007. Interview-based field study constituted the main data collection method in which the gathering, preparation, use, previous and current status and cultivation practices were systematically investigated. The abundance, taxonomic diversity and distribution of medicinal plants were studied using ecological approach.</p> <p>Results</p> <p>A total of 120 species, grouped within 100 genera and 47 families that are used in traditional medical practices were identified and studied. The Fabaceae and Lamiaceae were the most commonly reported medicinal plants with 16 (13.3%) and 14 (12%) species, respectively. 25.4% of the total medicinal plants are collected from homegardens and the rest (74.6%) are collected from wild habitats. Of the total number of medicinal plants, 108 species (90%) were used to treat human ailments, 6 (5%) for livestock diseases and the remaining 6 (5%) were used to treat both human and livestock health problems. The major threats to medicinal plants reported include harvesting medicinal plants for firewood (24.8%) followed by fire (22.3%) and construction (19%). Of the four plant communities identified in the wild, more medicinal plant species (34) were found in community type-4 (<it>Hyparrhenia cymbaria</it>-<it>Erythrina abyssinica </it>community), which accounted for 61.8%.</p> <p>Conclusion</p> <p>Konta Special Woreda is an important area for medicinal plants and associated local knowledge; the natural vegetation being the most important reservoir for the majority of the medicinal plants. Environmental and cultural changes are in the process of threatening the resources and this signals the need for serious efforts to create public awareness so that measures are taken to conserve the medicinal plants in the natural ecosystems and other suitable environments.</p