bluuebunny/crossref_metadata_2025 huggingface dataset:
The designed and the ad hoc: dynamic remakings of street space in New York City
Authors: Snyder Alison B , Montgomery Jason
Published: October 2022

Most people in the United States began to alter their decisions and actions beginning in March 2020 due to the Covid-19 pandemic, when the closures and ‘pause’ on most work were established. Studying the transforming urban conditions in New York City specifically presents a lens through which to understand how we quickly adapted to new spatial conditions as measures were put in place for keeping people healthy and encouraging businesses to stay open and approachable. Immediately, the need for social distancing asked us to consider how to navigate exposure as we moved beyond the home. Necessities for businesses to survive became a priority for the city and coalesced with people’s desire for seeking ways to do things outdoors. A focus on using city streets as urban public spaces resulted. Policies such as Open Restaurants and Open Streets were developed by the Department of Transportation to mitigate pandemic circumstances and to stir dynamic and optimistic possibilities for street use. Open Restaurants called for food/drink establishments to quickly reimagine their adjacent pavement or available street space. Open Streets initiated new ways for creating pedestrian zones in previously trafficked areas. This article highlights fieldwork documentation comparing a Cluster and Line of food/drink establishments with a newly pedestrian Avenue, in connected Brooklyn neighbourhoods. Diagrams, photographs and maps document the ingenious street constructions and the observed and felt psychological or phenomenal transformations taking place. An urban interiorism grew out of the imposed formalisation of rules for movement patterns and compact constructions, while the ad hoc or serendipitous conditions allowed for other intimate conditions. Notions of ‘village cafés’ or ‘urban beaches’ evolved through myriad forms and materials inviting unusual seating configurations and interactions. Speculations on what these internal/external spatial experiences, changing identities and continued urban freedoms are teaching us are also explored through a multidisciplinary set of voices.
Evaluation of Total Hardness and Qualitative Analysis of Boiler Water at the Food Jam Industry, Tangerang, Indonesia
Authors: Kuntolaksono Satrio , Wicaksono Imam , Emilia Febrianty , Enjarlis Enjarlis , Yoshi Linda Aliffia
Published: October 2022

Food industry is one of the most crucial and rapidly growing economic sectors in Indonesia. One of the examples is the food jam industry. This industry was located in Tangerang, Indonesia. The majority of the food jam industry uses its own source of water, so this part is also important to water producers in Indonesia. Water used in the food jam industry should meet the requirements of at least drinking water quality, so the factories need to treat the water. Good quality water is water that requires good physical, chemical, and bacteriology properties. Hard water is a term known for water that contains a high concentration of minerals such as Calcium (Ca) and Mag-nesium (Mg). Moreover, water with very high degrees of hardness is harmful to health. In this study, we want to evaluate and determine the pH, total hardness, and total dissolved solids (TDS) at three different times namely morning, midday, and afternoon. The results obtained in the range of pH analysis are 6.98 to 7.99 with all cover times. The total hardness in the boiler water and the TDS are around 252.6 to 388.2 mg/L and 310 to 406 mg/L, respectively. These results indicated that it has fulfilled the requirements for total hardness values under the Minister of Health Regulations (Permenkes) No. 492/Menkes/Per/IV/2010.
The Effect of Green Supply Chain Management, Green Intellectual Capital, and Green Information System on Environmental Performance and Financial Performance
Authors: Renaldo Nicholas , Augustine Yvonne
Published: October 2022

Environmental degradation is increasing and resource depletion has become a problem. Based on the results of the preliminary survey, the majority of respondents are more concerned with financial performance than environmental performance. This study aims to examine the effect of green supply chain management (GSCM), green intellectual capital (GIC), and green information system (GIS) on environmental performance (EnvP) and financial performance (FinP). The sample in this study was 219 respondents who came from manufacturing companies in Riau Province. Data analysis used structural equation analysis with SMART PLS application. The results show that only green supply chain management has a positive effect on financial performance. Then green intellectual capital and environmental performance each have a positive effect on financial performance. This research develops a new measurement for green supply chain management and green information system variables. Companies can develop systems and information technology that can reduce waste so that their environmental and financial performance can be better.
Does plantar skin abrasion affect cutaneous mechanosensation?
Authors: Wynands Bert , Zippenfennig Claudio , Holowka Nicholas B. , Lieberman Daniel E. , Milani Thomas L.
Published: October 2022

In humans, plantar cutaneous mechanoreceptors provide critical input signals for postural control during walking and running. Because these receptors are located within the dermis, the mechanical properties of the overlying epidermis likely affect the transmission of external stimuli. Epidermal layers are highly adaptable and can form hard and thick protective calluses, but their effects on plantar sensitivity are currently disputed. Some research has shown no effect of epidermal properties on sensitivity to vibrations, whereas other research suggests that vibration and touch sensitivity diminishes with a thicker and harder epidermis. To address this conflict, we conducted an intervention study where 26 participants underwent a callus abrasion while an age‐matched control group (n = 16) received no treatment. Skin hardness and thickness as well as vibration perception thresholds and touch sensitivity thresholds were collected before and after the intervention. The Callus abrasion significantly decreased skin properties. The intervention group exhibited no change in vibration sensitivity but had significantly better touch sensitivity. We argue that touch sensitivity was impeded by calluses because hard skin disperses the monofilament's standardized pressure used to stimulate the mechanoreceptors over a larger area, decreasing indentation depth and therefore stimulus intensity. However, vibration sensitivity was unaffected because the vibrating probe was adjusted to reach specific indentation depths, and thus stimulus intensity was not affected by skin properties. Since objects underfoot necessarily indent plantar skin during weight‐bearing, calluses should not affect mechanosensation during standing, walking, or running.
Association between Economic Growth, Mortality, and Healthcare Spending in 31 High-Income Countries
Authors: Sanmarchi Francesco , Esposito Francesco , Bucci Andrea , Toscano Fabrizio , Golinelli Davide
Published: October 2022

This study aims to investigate the association between gross domestic product (GDP), mortality rate (MR) and current healthcare expenditure (CHE) in 31 high-income countries. We used panel data from 2000 to 2017 collected from WHO and OECD databases. The association between CHE, GDP and MR was investigated through a random-effects model. To control for reverse causality, we adopted a test of Granger causality. The model shows that the MR has a statistically significant and negative effect on CHE and that an increase in GDP is associated with an increase of CHE (p < 0.001). The Granger causality analysis shows that all the variables exhibit a bidirectional causality. We found a two-way relationship between GDP and CHE. Our analysis highlights the economic multiplier effect of CHE. In the debate on the optimal allocation of resources, this evidence should be taken into due consideration.
M2 macrophages-derived exosomal miR-3917 promotes the progression of lung cancer via targeting GRK6
Authors: Song Sinuo , Zhao Yunping , Wang Xiaoxing , Tong Xinghe , Chen Xiaobo , Xiong Qiuxia
Published: October 2022

Macrophages in the tumor microenvironment (TME) can serve as potential targets for therapeutic intervention. The aim of this study was to investigate the molecular mechanism by which M2 macrophage-derived exosomes (M2-Ex) affect lung cancer progression through miRNA transport. The THP-1 cells were differentiated into M0 and M2 macrophages. M2-Ex were isolated and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Cancer tissues and adjacent tissues of non-small-cell lung cancer (NSCLC) patients were collected. H1299 and A549 cells were co-cultured with M2-Ex. Subcutaneous xenograft mouse model was established. miR-3917 is highly expressed in lung cancer tissues and M2-Ex. Interference of miR-3917 in M2-Ex inhibits H1299 cell proliferation, migration and invasion, while overexpression of miR-3917 had the opposite effect in A549 cells. M2-Ex promote tumor growth by delivering miR-3917 in vivo. miR-3917 could target G protein-coupled receptor kinase 6 (GRK6), and interference of miR-3917 in M2-Ex inhibits H1299 cells proliferation, migration and invasion by up-regulating GRK6 level, while overexpression of miR-3917 had the opposite effect in A549 cells. M2-Ex can transfer miR-3917 into lung cancer cells and promote lung cancer progression, providing theoretical basis for the diagnosis and effective treatment of lung cancer.
Membrane binding and pore forming insertion of PEX5 into horizontal lipid bilayer
Authors: Blum Daniel , Reuter Maren , Schliebs Wolfgang , Tomaschewski Jana , Erdmann Ralf , Wagner Richard
Published: October 2022

The assembly of the peroxisomal translocon involves the transition of a soluble form of the peroxisomal targeting receptor PEX5 into a membrane-bound form, which becomes an integral membrane component of the import pore for peroxisomal matrix proteins. How this transition occurs is still a mystery. We addressed this question using a artificial horizontal bilayer in combination with fluorescence time-correlated single photon counting (TCSPC) and electrophysiological channel recording. Purified human isoform PEX5L and truncated PEX5L(1–335) lacking the cargo binding domain were selectively labeled with thiol-reactive Atto-dyes. Diffusion coefficients of labeled protein in solution show that PEX5L is monomeric with a rather compact spherical conformation, while the truncated protein appeared in a more extended conformation. Labeled PEX5L and the truncated PEX5L(1–335) bind stably to horizontal bilayer thereby accumulating around 100-fold. The diffusion coefficients of the membrane-bound PEX5L forms are 3–4 times lower than in solution, indicating the formation of larger complexes. Electrophysiological single channel recording shows that membrane-bound labeled and non-labeled PEX5L, but not the truncated PEX5L(1–335), can form ion conducting membrane channels. The data suggest that PEX5L is the pore-forming component of the oligomeric peroxisomal translocon and that spontaneous PEX5L membrane surface binding might be an important step in its assembly.
Experimental assessment on the contact characteristics of 3D printed flexible poly lactic acid (PLA) soft fingertips
Authors: Yuvaraj S. , Venkatesh Raja K. , Bakkiyaraj M. , Malayalamurthi R. , Magibalan S. , Thavasilingam K. , Muralidharan K.
Published: October 2022

This purpose of this research work primarily focuses on assessing the contact characteristics of a novel 3D printed flexible poly lactic acid (PLA) fingertip exposed to a normal load ranging from 1–750 N. The 3D printed fingertip is pressed against three different target surfaces having concave, convex and flat profiles to facilitate a rational comparison. The growth of contact area is recorded for a wide range of applied normal force against the fingertip on logging sheets and the same is converted in vector format for facilitating digital measurements. From close examination of the results, it may be noted that the rate of growth of contact area follows the parametric relationshipa=cNγ. A weighted least squares fit algorithm is used to formulate the parametric relationship based on experimental data. Further, the contact characteristics of the 3D printed fingertip follows the same pattern of soft neoprene fingertip, and it is well in line with the expected results. Hence, it is evident that 3D printed fingertips could be utilized for handling fragile to hard objects and capable of handling multi-profiled objects in dexterous robotic manipulation. Moreover, complex profiled fingertips can easily be manufactured by 3D printing, and it can be considered as a better alternative for conventionally manufactured anthropomorphic robotic grippers. Practical implications of this research will be highly useful for development of soft-fingered robotic grippers for dexterous robotic manipulations.
Coordinated target tracking in sensor networks by maximizing mutual information
Authors: Wang Yintao , Xie Fuchao
Published: October 2022

This paper addresses the problem of coordinated target tracking in sensor networks. For a typical target tracking scene with nonlinear bearing-only measurements, we first investigate the mutual information between multiple sensors and the target state. To improve the performance of target tracking, we analyzed the relative positions between sensor agents and the target to be tracked and derived the optimal positions for sensors in the network by mutual information maximization. Simulation results are presented and discussed to demonstrate that the performance of estimated target states could be improved by the proposed method.
Deutsch im Beruf – eine Untersuchung der psychometrischen Güte des Goethe-Test PRO
Authors: Fink Aron , Frey Andreas , Klein Katharina
Published: October 2022

Deutsch im Beruf ist mit zunehmender Migration und Mobilität ein zentrales Thema im DaF/DaZ-Bereich. Berufsbezogene Sprachkenntnisse können mithilfe von verschiedenen Tests für den Beruf diagnostiziert werden. Ein Test zum Nachweis berufsbezogener Sprachkenntnisse ist der Goethe-Test PRO: Deutsch für den Beruf (GTP). Der vorliegende Beitrag widmet sich zunächst der berufsorientierten Ausrichtung, dem Testformat sowie dem adaptiven Testverfahren des GTP. Der zweite Teil dieses Beitrags beschäftigt sich mit der Beschreibung seiner psychometrischen Güte. Abschließend werden die Ergebnisse mit Blick auf die Relevanz von berufsbezogenen Tests für Deutsch als Fremdsprache diskutiert.
Comparative analysis of written corrective feedback strategies: a linear growth modeling approach
Authors: Shin Hye Won
Published: October 2022

The purpose of this study was to examine the development of English article accuracy in second language writing following direct or indirect corrective feedback (CF). Participants were 56 middle-school-aged learners of English nested within four classrooms who were studying for the writing portion of the Secondary School Admission Test. In this longitudinal analysis, each student completed four essays, with a weekly gap between each assignment. On the measures of writing accuracy, adolescent students in the direct CF group demonstrated increasing trajectories of accuracy with English article usage compared to the indirect CF group. Additionally, there was a significant difference in improvement by proficiency level: for lower proficiency learners, but not higher proficiency learners, both indirect and direct corrective feedback resulted in improvement in English article accuracy. The findings suggest that CF treatments designed to enhance a learner’s accuracy can be influenced by the learner’s existing proficiency, at least among adolescents.
A Harmonized Net Wealth Tax in the European Union
Authors: Krenek Alexander , Schratzenstaller Margit
Published: October 2022

While taxes on wealth for a long time played only a marginal role in the public finance and taxation literature, the increase of wealth inequality and concentration in many EU countries has spurred new interest in wealth taxation. At the same time, recurrent net wealth taxes have almost completely disappeared in Europe, inter alia due to fears of asset and taxpayer migration. The paper provides estimates of the revenue that could be raised from an EU-wide net wealth tax enabling the containment of migration responses, using data from the Household, Finance and Consumption Survey (HFCS). To account for differential non-response, we augment the HFCS with data from the Forbes rich list as well as national rich lists and replace the top tail of the wealth distribution according to the HFCS by an estimated Pareto distributed top tail. To account for under-reporting we scale aggregate financial assets in the HFCS to match their counterparts outlined in the National Accounts. We estimate that a moderately progressive net wealth tax levied at a rate of 1% on net wealth between € 1 and € 5 million, and 1.5% on wealth above € 5 million, could raise between € 165 and € 177 billion after accounting for avoidance and evasion responses. Such an EU harmonized net wealth tax would affect only a small fraction of households, ranging between 0.41% in Latvia and 8.65% in Belgium.
Propagation properties of cosh-Airy beams in an inhomogeneous medium with Gaussian PT-symmetric potentials
Authors: Deng Yangbao , Wen Bing , Chen Liezun , Zhang Saiwen , Zhang Guangfu , Xiong Cuixiu , Leng Xiaoling
Published: October 2022

We numerically investigate and statistically analyze the impact of medium parameters (modulation depth P, modulation factor ω, and gain/loss strength W
0) and beam parameters (truncation coefficient a and distribution factor χ
0) on the propagation characteristics of a cosh-Airy beam in the Gaussian parity-time (PT)-symmetric potential. It is demonstrated that the main lobe of a cosh-Airy beam is captured as a soliton, which varies periodically during propagation. The residual beam self-accelerates along a parabolic trajectory due to the self-healing property. With increment in P, the period of a trapped soliton decreases almost monotonically, while the peak power of a trapped soliton increases monotonically. With the increase in ω or decrease in the absolute value of W
0, the period and peak power of a trapped soliton decrease rapidly and then almost remain unchanged. Moreover, it is indicated that the period of a trapped soliton remains basically unchanged no matter a and χ
0 increase or decrease. The peak power of a trapped soliton increases with increment of a, but the peak power of a trapped soliton stays relatively constant irrespective of variation in χ
0.
Der lange Weg der Stabilisierungspolitik
Authors: Landmann Oliver
Published: October 2022

Zweimal im frühen 21. Jahrhundert waren Regierungen und Zentralbanken mit drastischen Wirtschaftseinbrüchen konfrontiert und haben resolut stabilisierend eingegriffen. Dies war keine Selbstverständlichkeit. Denn Theorie und Praxis der Stabilisierungspolitik haben in den zurückliegenden 100 Jahren vielfache Wandlungen durchlaufen, in deren Zuge sich grenzenloses Vertrauen auf die Möglichkeiten der Stabilisierungspolitik immer wieder mit tiefer Skepsis abwechselte. In seinem Aufsatz gibt Oliver Landmann einen knappen Abriss dieser turbulenten Historie. Als Leitmotiv dient ihm dabei die von Keynes ins Zentrum gerückte Frage, ob die Marktwirtschaft eine inhärente Tendenz zur Selbststabilisierung („self-adjustment“) besitzt. Unterschiedliche Ansichten hierüber, geformt durch Empirie und Theorie, behielten zu unterschiedlichen Zeiten die Oberhand.
Effects of motorcycle group membership on the ride experience and travel motivators: A comparison between the USA, the UK, and Turkey
Authors: Ertaş Mehmet , Sykes Diane , Cater Carl
Published: October 2022

Due to the global prevalence of motorcycle tourism, this study considers the travel motivators among riders from Turkey, the United States of America, and the United Kingdom. This study adds the previously unexplored factor of group membership and its influence on travel motivators. The study used quantitative analysis of a survey that was disseminated via Google forms. The primary factors are: sense of pleasure, passion for adrenaline, and ease of riding and travel activities. Group membership was used to examine the difference among the factors. All motorcyclists ranked the factors as high as travel motivators. There were some differences among riders from different countries. Turkish riders ranked their participation in group activities higher than did the US and UK. While the US and UK and Turkey had significant differences on the sense of pleasure. This study has importance to governments, travel agencies, and businesses that serve motorcyclists.
Semana Santa en Cañadas de Nanchititla, Luvianos, Estado de México. Análisis de los impactos del turismo a partir del índice de irritabilidad de Doxey
Authors: Dominguez Cortez Zarahid , Ramírez Hernández Omar Ismael , Osorio González Rebeca
Published: October 2022

El presente trabajo tiene como objetivo analizar, a través del modelo de irritación Doxey, los impactos del turismo en la población de Cañadas de Nanchititla, con respecto al evento religioso de Semana Santa. Se trabajó bajo un enfoque metodológico mixto que consistió en realizar entrevistas con personas vinculadas directa e indirectamente con la festividad, además de aplicar un cuestionario a residentes de la localidad. Los principales hallazgos indican que varios pobladores se encuentran en la primera etapa del modelo, debido a los impactos económicos que tiene la festividad en la localidad, aunque existen algunos casos en etapa de apatía. De esta manera, se concluye la utilidad del modelo para el estudio de los impactos y actitudes de la comunidad local, pero este modelo no se puede aplicar de forma lineal; además, se tiene que agregar algunos elementos como la tipología turística y la temporalidad de las actividades turísticas.
Wellness Aging Model Related to Inactivity, Illness, and Injury (WAMI-3): A Tool to Encourage Prevention in Practice
Authors: Billek-Sawhney Barbara , Criss Michelle G. , Galantino Mary Lou , Sawhney Rajiv
Published: October 2022

It is a steep challenge to fully implement the wide range of evidence that supports rehabilitation interventions for the prevention of chronic disease. Proactive physical activity (PA) promotion can lead to increased PA levels to improve and maintain physical function. Higher levels of PA throughout the lifespan lead to better overall population health, wellness, aging, disease prevention, and chronic condition management. This article introduces the Wellness Aging Model related to Inactivity, Illness, and Injury (WAMI-3) as a simple visual tool to educate patients on the importance of PA and exercise for primary, secondary, and tertiary prevention. As a clinical construct, the WAMI-3 can be applied to all body systems affected by aging, inactivity, illness, and/or injury and exemplifies the concept of Exercise is Medicine®. The WAMI-3 framework is intended for easy integration into clinical practice; a clinician-friendly resource, based on health promotion, is provided to serve as a catalyst for enhancing the patient interview and education on the importance of PA and exercise.

Video Abstract available: For more insight from the authors, see Supplemental Digital Content 1 (available at: http://links.lww.com/JGPT/A115)
Dysregulation of Synaptic and Developmental Transcriptomic/Proteomic Profiles upon Depletion of MUNC18-1
Authors: Van Berkel Annemiek A. , Koopmans Frank , Gonzalez-Lozano Miguel Angel , Lammertse Hanna C. A. , Feringa Femke , Bryois Julien , Sullivan Patrick F. , Smit August B. , Toonen Ruud F. , Verhage Matthijs
Published: October 2022

Absence of presynaptic protein MUNC18-1 (gene:Stxbp1) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immatureStxbp1knock-out (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi ofStxbp1KO mice showed cell type-specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response. To further investigate direct, neuron-specific effects of MUNC18-1 depletion, a proteomic screen was performed on murine neuronal cultures at two developmental timepoints before onset of neuron degeneration. 399 proteins were differentially expressed, which were primarily involved in synaptic function (especially synaptic vesicle exocytosis) and neuron development. We further show that many of the downregulated proteins on loss of MUNC18-1 are normally upregulated during this developmental stage. Thus, absence of MUNC18-1 extensively dysregulates the transcriptome and proteome, primarily affecting synaptic and developmental profiles. Lack of synaptic activity is unlikely to underlie these effects, as the changes were observed in immature neurons without functional synapses, and minimal overlap was found to activity-dependent proteins. We hypothesize that presence of MUNC18-1 is essential to advance neuron development, serving as a “checkpoint” for neurons to initiate cell death in its absence.
TheSYNGAP13′UTR Variant in ALS Patients Causes AberrantSYNGAP1Splicing and Dendritic Spine Loss by Recruiting HNRNPK
Authors: Yokoi Satoshi , Ito Takuji , Sahashi Kentaro , Nakatochi Masahiro , Nakamura Ryoichi , Tohnai Genki , Fujioka Yusuke , Ishigaki Shinsuke , Udagawa Tsuyoshi , Izumi Yuishin , Morita Mitsuya , Kano Osamu , Oda Masaya , Sone Takefumi , Okano Hideyuki , Atsuta Naoki , Katsuno Masahisa , Okada Yohei , Sobue Gen
Published: October 2022

Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 (Syngap1) mRNA at its 3′ untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified theSYNGAP13′UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with theSYNGAP1variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform γ levels, which caused dendritic spine loss. Moreover, theSYNGAP1variant excessively recruited FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK), and antisense oligonucleotides (ASOs) blocking HNRNPK altered aberrant splicing and ameliorated dendritic spine loss. These data suggest that excessive recruitment of RNA-binding proteins, especially HNRNPK, as well as changes inSYNGAP1isoforms, are crucial for spine formation in motor neurons.

SIGNIFICANCE STATEMENTIt is not yet known which RNAs cause the pathogenesis of amyotrophic lateral sclerosis (ALS). We previously reported that Fused in sarcoma (FUS), a pathogenic RNA-binding protein in ALS, stabilizes synaptic Ras-GTPase activating protein 1 (Syngap1) mRNA at its 3′ untranslated region (UTR) and maintains dendritic spine maturation. To elucidate whether this mechanism is crucial for ALS, we identified theSYNGAP13′UTR variant rs149438267 at the FUS binding site. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with theSYNGAP1variant showed aberrant splicing, which caused dendritic spine loss along with excessive recruitment of FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK). Our findings that dendritic spine loss is because of excess recruitment of RNA-binding proteins provide a basis for the future exploration of ALS-related RNA-binding proteins.
Neurexin-β Mediates the Synaptogenic Activity of Amyloid Precursor Protein
Authors: Cvetkovska Vedrana , Ge Yuan , Xu Qin , Li Shaokun , Zhang Peng , Craig Ann Marie
Published: October 2022

In addition to its role in Alzheimer's disease, amyloid precursor protein (APP) has physiological roles in synapse development and function. APP induces presynaptic differentiation when presented to axons, but the mechanism is unknown. Here we show that APP binds neurexin to mediate this synaptogenic activity. APP specifically binds β not α neurexins modulated by splice site 4. Binding to neurexin heparan sulfate glycan and LNS protein domains is required for high-affinity interaction and for full-length APP to recruit axonal neurexin. The synaptogenic activity of APP is abolished by triple knockdown of neurexins in hippocampal neurons pooled from male and female rats. Based on these and previous results, our model is that a dendritic-axonaltransdimer of full-length APP binds to axonal neurexin-β to promote synaptic differentiation and function. Furthermore, soluble sAPPs also bind neurexin-β and inhibit its interaction with neuroligin-1, raising the possibility that disruption of neurexin function by altered levels of full-length APP and its cleavage products may contribute to early synaptic deficits in Alzheimer's disease.

SIGNIFICANCE STATEMENTThe prevailing model for the basis of Alzheimer's disease is the amyloid cascade triggered by altered cleavage of amyloid precursor protein (APP). APP also has physiological roles at the synapse, but the molecular basis for its synaptic functions is not well understood. Here, we show that APP binds the presynaptic organizing protein neurexin-β and that neurexin is essential for the synaptogenic activity of APP. Furthermore, soluble APP forms generated by APP cleavage also bind neurexin-β and can block interaction with transmembrane synaptogenic ligands of neurexin. These findings reveal a role for neurexin-APP interaction in synapse development and raise the possibility that disruptions of neurexin function may contribute to synaptic and cognitive deficits in the critical early stage of Alzheimer's disease.
An arrayed genome‐wide perturbation screen identifies the ribonucleoprotein Hnrnpk as rate‐limiting for prion propagation
Authors: Avar Merve , Heinzer Daniel , Thackray Alana M , Liu Yingjun , Hruska‐Plochan Marian , Sellitto Stefano , Schaper Elke , Pease Daniel P , Yin Jiang‐An , Lakkaraju Asvin KK , Emmenegger Marc , Losa Marco , Chincisan Andra , Hornemann Simone , Polymenidou Magdalini , Bujdoso Raymond , Aguzzi Adriano
Published: October 2022

A defining characteristic of mammalian prions is their capacity for self‐sustained propagation. Theoretical considerations and experimental evidence suggest that prion propagation is modulated by cell‐autonomous and non‐autonomous modifiers. Using a novel quantitative phospholipase protection assay (QUIPPER) for high‐throughput prion measurements, we performed an arrayed genome‐wide RNA interference (RNAi) screen aimed at detecting cellular host‐factors that can modify prion propagation. We exposed prion‐infected cells in high‐density microplates to 35,364 ternary pools of 52,746 siRNAs targeting 17,582 genes representing the majority of the mouse protein‐coding transcriptome. We identified 1,191 modulators of prion propagation. While 1,151 modified the expression of both the pathological prion protein, PrPSc, and its cellular counterpart, PrPC, 40 genes selectively affected PrPSc. Of the latter 40 genes, 20 augmented prion production when suppressed. A prominent limiter of prion propagation was the heterogeneous nuclear ribonucleoprotein Hnrnpk. Psammaplysene A (PSA), which binds Hnrnpk, reduced prion levels in cultured cells and protected them from cytotoxicity. PSA also reduced prion levels in infected cerebellar organotypic slices and alleviated locomotor deficits in prion‐infected Drosophila melanogaster expressing ovine PrPC. Hence, genome‐wide QUIPPER‐based perturbations can discover actionable cellular pathways involved in prion propagation. Further, the unexpected identification of a prion‐controlling ribonucleoprotein suggests a role for RNA in the generation of infectious prions.
Diseño de herramientas pedagógicas mediadas por las TIC para fortalecer procesos de educación inclusiva: Centro de Servicios Financieros SENA
Authors: Guerrero William Alberto , Gómez Miranda Nidia Johana , Portilla Moreno Diana Liceth , Bedoya Salcedo Adelaida
Published: October 2022

Según datos del Ministerio del Interior de la República de Colombia, en la actualidad más de 1 300 000 de ciudadanos presentan algún tipo de discapacidad. No obstante, no ha sido prioridad para el Gobierno Nacional la atención de dicha población, más aún cuando de formación en centros de educación superior se trata. En consecuencia, el imperativo moral de los educadores debe ser velar por la educación inclusiva. El presente trabajo tiene como objetivo principal diseñar herramientas pedagógicas mediadas por las TIC para fortalecer los procesos de educación inclusiva en los instructores del Centro de Servicios Financieros del Servicio Nacional de Aprendizaje (SENA). Esta metodología puede ser usada como guía en otras organizaciones que necesiten implementar la educación inclusiva.
Los sistemas de información como generadores de valor en la gestión educativa: caso de una IES colombiana
Authors: Marrero-Ascanio Eliana Sofía , Ávila-Guerrero Flor Marlen , González-Cortés Cristo Javier
Published: October 2022

El propósito de este ártículo es determinar cómo los sistemas de información (SI) generan valor en la gestión educativa para el caso de una institución de educación superior (IES) colombiana. Para ello, se parte de una descripción de la Institución, se efectúa la matriz de análisis entre los 17 SI y las diferentes dependencias de la Universidad; luego se identifica la cadena de valor generada a partir de la dinámica institucional. El estudio se realizó con un enfoque cualitativo de corte transversal. Los hallazgos demuestran la relevancia de optimizar recursos informáticos para garantizar una mejor atención de los procesos y procedimientos que maneja la Universidad, lo que permite generar eficiencia y eficacia en la interrelación que debe existir entre la docencia, la investigación, la extensión y la internacionalización.
Utilización del catéter venoso central de inserción periférica en la Unidad de Cuidados Intensivos Neonatales del Instituto Nacional de Salud Del Niño Breña, 2017–2019
Authors: Aguilar Ronceros Lisset F. , Abad Bernardo Frida C. , Chávez Rodríguez Miriam N. , La Rosa Solórzano Juana G. , Loayza Escobar Katherine Y. , Ríos Díaz Karen
Published: October 2022

Introducción. Actualmente la tasa de nacimientos a nivel mundial es de 18,8% y en el Perú es de 10%. Las principales causas de mortalidad neonatal son los partos pre termino, infecciones y defectos congénitos. La unidad de cuidados intensivos neonatales es el área que se encarga de la atención de los recién nacidos en estado crítico, siendo indispensable la obtención de una vía de acceso venoso central adecuada para su tratamiento. Objetivo. Describir la utilización del catéter percutáneo de inserción periférica en la Unidad de Cuidados Intensivos Neonatales del Instituto Nacional de Salud del Niño Breña, periodo junio 2017 – junio 2019. Métodos. Estudio descriptivo, observacional, retrospectivo, transversal. La muestra fue intencional conformada aproximadamente por 110 historias clínicas de recién nacidos que estuvieron hospitalizados en la unidad de cuidados intensivos neonatales. La técnica la observación y el instrumento la lista de chequeo. Resultados. El 51,8% fueron neonatos con patología quirúrgica. Asimismo, el 36,4% tuvieron una edad gestacional menor o igual de 32 semanas, la vena más usada fue la basílica con un 27,3%, el 37.,3% de los catéteres fueron retirados por sospecha de sepsis y las puntas enviadas a cultivo. Conclusiones: El cuidado en el procedimiento y mantenimiento del catéter percutáneo fue el adecuado, presentándose un bajo número de complicaciones.
Cybersecurity competence map of Lithuania
Authors:   Vilnius University, Lithuania, Bukauskas Linas , Brilingaitė Agnė ,   Vilnius University, Lithuania, Ikamas Kęstutis ,   Generolo Jono Žemaičio Lietuvos karo akademija, Juozapavičius Aušrius ,   Generolo Jono Žemaičio Lietuvos karo akademija, Lepaitė Daiva ,   Vilnius University, Lithuania
Published: October 2022

This work aims to prepare the first Lithuanian cyber competence map together with recommendations on how to attract specialists to the CS sector and how to advance their competencies. During the research phase, we explored the demand for CS specialists in Lithuania and the world, surveyed the opinions of CS professionals, management and specialists from private and public sector organizations, including national defence sector. Also, we determined the career path of the specialists, analysed job offers, distinguished work roles, and gathered findings and recommendations from scientific research papers and similar reports of other countries. The results of the work include a publicly available database of collected data, expert findings of the research and recommendations for stakeholders, and a submitted scientific article to promote the results.
The Tension between the Problem of Unconceived Alternatives and Epistemic Instrumentalism
Authors: Zorzato Lisa
Published: October 2022

In this paper, I develop a critical assessment of epistemic instrumentalism as advocated by Kyle Stanford (2006). Epistemic instrumentalism is based on the claim that the criterion for the reliability of any theory is the absence of what Stanford calls ‘unconceived alternatives’. This means that the theory is reliable if and only if it does not admit of alternatives. Since most scientific theories do admit of unconceived alternatives, Stanford claims, they cannot be reliable. In contrast, ‘common sense’ claims are not exposed to unconceived alternatives, therefore they are reliable. Here, I analyse the definition of ‘common sense’ and argue that it is equally vulnerable to the ‘problem of unconceived alternatives’, pushing epistemic instrumentalism position to scepticism. The consequence is that the position of epistemic instrumentalist has nothing to stand on.
PENGAWASAN LEGISLASI DAERAH OLEH DPD: TANTANGAN ERA DISRUPSI HUKUM
Authors: Nainggolan Indra L
Published: October 2022

Control authority of the DPD in Article 22D of the 1945 Constitution of the Republic of Indonesia has expanded to include regional law products, both draft regional regulations, and regional regulations. Control referred to in Article 249 paragraph 1 letter j of Law No. 2 of 2018 is not a legislative review or cancellation of regional regulations. Monitoring and evaluation of draft regional regulations and regional regulations by the DPD is a broad interpretation of the legislative function, control function, and representation function. Monitoring and evaluation of regional regulations and regional regulations will ultimately carry out the function of regional representation. Regions in the context of a unitary state have representatives at the center to fight for their aspirations which are outlined in the form of national policies. Such a position makes the DPD have a major role in carrying out its representation as external control of draft regional regulations and regional regulations. The era of legal disruption demands a more responsive and innovative role for the DPD in carrying out various regional aspirations. The control practices carried out should not use the old method which is actually considered to hinder the implementation of the authority it has. The research method used is normative juridical by using library research.Keywords: Control; Draft Regional Regulations; Regional Regulations; Legal Disruption AbstrakKewenangan pengawasan DPD pada pasal 22D UUD NRI 1945 berkembang luas hingga pada produk hukum daerah baik ranperda dan perda. Pengawasan yang dimaksud pada pasal 249 ayat 1 huruf j UU No.2 Tahun 2018 bukanlah legislative review atau pembatalan peraturan daerah. Pemantauan dan evaluasi atas rancangan peraturan daerah dan peraturan daerah oleh DPD merupakan intrepretasi luas dari fungsi legislasi, fungsi pengawasan, dan fungsi representasi. Pemantauan dan evaluasi ranperda dan perda pada akhirnya melaksanakan fungsi keterwakilan daerah. Daerah dalam konteks negara kesatuan memiliki perwakilan di pusat guna memperjuangkan aspirasinya yang dituangkan dalam bentuk kebijakan nasional. Posisi demikian membuat DPD memiliki peran besar dalam menjalankan keterwakilannya sebagai pengawas eksternal terhadap ranperda dan perda. Era disrupsi hukum menuntut peran DPD lebih responsif dan inovatif  dalam menjalankan aspirasi daerah yang beragam. Praktik pengawasan yang dilakukan jangan sampai menggunakan cara lama yang justru dianggap menghambat pelaksanaan kewenangan yang dimilikinya. Metode penelitian yang digunakan yuridis normatif dengan menggunakan studi kepustakaan.Keyword: Pengawasan; Ranperda; Perda; Disrupsi Hukum
Perlindungan Hukum Penerima Fidusia Terhadap Wanprestasi Yang Dilakukan Oleh Pemberi Fidusia Pada Jaminan Fidusia
Authors: Syafrida Syafrida , Hartati Ralang , Sinaga Hasudung
Published: October 2022

Fiduciary rights are material rights that provide guarantees. The purpose of writing is to find out the legal protection for fiduciary recipients if the fiduciary giver is in default. The research method used is library research using secondary data in the form of primary legal materials, secondary legal materials and tertiary legal materials. The research is juridical normative. Fiduciary guarantee certificates provide legal protection for fiduciary recipients if the fiduciary giver defaults. The fiduciary recipient can sell on his own power the object that is the object of the fiduciary guarantee for the settlement of his receivables. Irah Irah's fiduciary certificate "For the sake of Justice Based on God Almighty" has the same legal force as a judge's decision with the power to carry out forced executions. The sale of collateral objects can be carried out under the hand based on the agreement of both parties at a high price that is mutually beneficial to both parties.Keywords: Legal Protection; Fiduciary Recipient; Default AbstrakFidusia merupakan hak kebendaan yang bersifat memberikan jamian. Tujuan penulisan  untuk mengetahui perlindungan hukum terhadap penerima fidusia apabila pemberi Fidusia melakukan wanprestasi. Metode penelitian yang digunakan adalan penelitian kepustakaan menggunaan data sekunder berupa bahan hukum primer, bahan hukum sekunder dan bahan hukum tersier. Penelitian bersifat yuridis normatif. Sertifikat jaminan  fidusia memberikan perlindungan hukum terhadap penerima fidusia apabila pemberi fidusia melakukan wanprestasi. Penerima fidusia dapat menjual atas kekuasaan sendiri benda yang menjadi objek jaminan fidusia untuk pelunasan piutangnya.  Sertifikat fidusia Irah irah “ Demi Keadilan Berdasarkan Ketuhanan Yang Maha Esa” kekuatan hukumnnya sama dengan putusan hakim berkekuatan tetap dilakukan eksekusi paksa. Penjualan objek jaminan dapat dilakukan dibawah tangan berdasarkan kesepakatan kedua belah pihak dengan harga yang tinggi yang saling menguntungkan kedua belah pihak.Kata kunci: Perlindungan Hukum; Penerima Fidusia; Wanprestasi
Dispensasi Nikah Pada Masa Pandemi: Pasca UU Nomor 16 Tahun 2019 dan Undang-Undang Perlindungan Anak di Pengadilan Agama Indramayu-Jawa Barat
Authors: Kamarusdiana Kamarusdiana
Published: October 2022

Penelitian ini bertujuan untuk mengetahui faktor-faktor yang melatar belakangi masyarakat Indramayu mengajukan dispensasi nikah serta dasar hukum hakim dalam menetapkan dispensasi nikah di Pengadilan Agama Indramayu dan menganalisis penetapan putusan perkara dispensasi nikah dari perspektif Undang-Undang Perlindungan anak.. Penelitian ini menggunakan pendekatan undang-undang, data kasus dispensasi nikah dan pendekatan konseptual. Adapun jenis penelitian yang digunakan adalah kualitatif.  Sumber data primer diperoleh dari data putusan perkara dispensasi nikah di Pengadilan Agama Indramayu. Data lain diperoleh dari wawancara hakim dan para ahli dan sumber data lain yang terkait dengan  dispensasi nikah di Pengadilan Agama Indramayu. Sedangkan data sekunder diperoleh dari data-data resmi di Pengadilan Agama Indramayu,  literatur-literatur serta tulisan-tulisan tentang dispensasi nikah.Hasil penelitian ini ditemukan bahwa faktor terbesar penyebab sejumlah masyarakat Indramayu mengajukan dispensasi nikah adalah karena alasan hamil terlebih dahulu, pergaulan intim dan khawatir terjadi perbuatan yang terlarang serta telah mendapat restu dari orang tua dan keluarga. Terdapat tiga pasal  yang mendasar yang menjadi dasar pertimbangan hakim dalam memutuskan perkara dispensasi nikah, yaitu Pasal 8 UU No. 1 tahun 1974 jo Pasal 39 Kompilasi Hukum Islam, Pasal 89 UU No. 7  tahun 1989 sebagaimana telah diubah dengan UU No. 3 Tahun 2006 dan perubahan kedua dengan UU Nomor 50 tahun 2009, dan Pasal 7 ayat (2) UU No. 1 tahun 1974. dalam perspektif Undang-Undang Perlindungan Anak, dispensasi nikah diantaranya melanggar ketentuan Pasal 3 Undang-Undang Nomor 23 tahun 2002.
Legal Certainty in the Application of the Crime of Narcotics Abuse Judging from the Disparity of Judges' Decisions
Authors: Suhendar Suhendar , Rezki Annissa , Yunus Nur Rohim
Published: October 2022

Efforts to eradicate drug crimes present a law that has criminal sanctions, namely Law Number 35 of 2009 concerning Narcotics (abbreviated as the Narcotics Law) that criminal sanctions in the Narcotics Law are one of them with a death penalty. The Narcotics Law regulates the policy of criminal sanctions for drug abusers which are divided into two categories, namely the perpetrators as “Users” and/or “Dealers”. It is possible for perpetrators as dealers to be subject to the most severe criminal sanctions in the form of capital punishment as regulated in Article 114 paragraph (2). The method of legal discovery (rechtsvinding) that is often used by judges is the method of interpretation or interpretation. The results of the study state that the interpretation of the provisions that have been stated expressly must not deviate from the intent of the legislators. The judge has the authority to interpret the law if the content of the article used is unclear or incomplete. Analytical interpretation in the field of criminal law is prohibited insofar as it makes a formulation of the offense to be expanded. Analogous interpretation is permitted if it is used to fill the voids contained in the law because it has not been regulated in the provisions of the law.Keywords: Disparity; Judge; Drugs AbstrakUpaya untuk memberantas kejahatan narkoba menghadirkan sebuah Undang-Undang yang memiliki sanksi pidana yaitu Undang-Undang Nomor 35 Tahun 2009 tentang Narkotika (disingkat UU Narkotika) bahwa Sanksi Pidana dalam Undang-Undang Narkotika salah satunya adalah sanksi pidana mati. Undang-Undang Narkotika mengatur mengenai kebijakan sanksi pidana bagi pelaku penyalahguna narkoba yang dibagi kedalam dua kategori yaitu pelaku sebagai “Pengguna” dan/atau “Pengedar”. Terhadap pelaku sebagai pengedar dimungkinkan dikenakan sanksi pidana yang paling berat berupa pidana mati seperti yang diatur dalam Pasal 114 ayat (2). Metode penemuan hukum (rechtsvinding) yang sering digunakan hakim yaitu metode interpretasi atau penafsiran. Hasil penelitian menyatakan bahwa Penafsiran terhadap ketentuan yang telah dinyatakan dengan tegas tidaklah boleh menyimpang dari maksud pembentuk Undang-Undang. Hakim mempunyai kewenangan untuk melakukan penafsiran hukum apabila isi pasal yang digunakan tidak jelas atau kurang lengkap. Penafsiran secara analogis di dalam lapangan hukum pidana terlarang sejauh ia membuat suatu rumusan delik itu menjadi diperluas.  Penafsiran secara analogi diizinkan apabila digunakan untuk mengisi kekosongan-kekosongan yang terdapat di dalam Undang-Undang karena belum diatur dalam ketentuan Undang-Undang tersebut.Kata Kunci: Disparitas; Hakim; Narkoba