List Of Candidates Research Articles

Metaphors for Očaj ‘Despair’ in Croatian

This study examines the role of metaphor in the conceptualization of očaj ‘despair’ based on the Croatian corpus hrWaC. The study also considers some non-figurative aspects. Employing “metaphorical pattern analysis” (Stefanowitsch 2006) and MIP (Pragglejaz Group 2007) methods, the paper scrutinizes corpus examples that contain the target-domain word očaj ‘despair’, looking for metaphorical patterns. These patterns were extracted from a random sample of 1,000 citations and additional corpus citations that were retrieved based on a list of collocation candidates. The analysis shows that the metaphorical conceptualization of očaj ‘despair’ in Croatian in the data examined relates to approximately forty source domains, out of which the most frequently utilized is container, followed by object. The source domains identified in the conceptualization of očaj illustrate similarities between the metaphors for očaj in Croatian and those identified for sadness and depression in various languages, and point toward universal features of metaphorical conceptualization of some emotions and emotional states.

Explanation of Tong Shaowen's Local Examination Zhu-juan Today

Based on a specific analysis of a person's Zhu-juan (red-ink copy of test papers used in imperial examinations) in the late Qing Dynasty, it includes personal resume, teacher-student relationship, the content and answers of the exam questions, and the examiner's comments. It should be said that the study of Zhujuan has important historical value for studying historical figures and regional historical culture. Tong Shaowen’s Zhu-juan written in Provincial examination originates from The Collection of Zhu-juan in the Qing Dynasty, which was compiled by Gu Tinglong and published by Taipei Chengwen Publishing House in 1992. Tong Shaowen (1816-1860) , also known as Ziyin and Jianqin, was born in Lanxi, Zhejiang Province today. He was the Zengguang scholar at prefectural school in JinHua, the civilian in registered residence in Lanxi County. This Zhu-juan is Zhejiang provincial examination paper written in 1846. Tong ranked 54th in the list of successful candidates. In the third year of Xianfeng (1853) , Tong Obtained first class in the Datiao examination selecing excellent candidates to become officials and served as the Supervisor of the County in Henan Province for trial use. He died while serving as an official. Tong was born on the eleventh day of the first month in the third year of the Jiaqing reign (1816) at Maoshi, and died on the twelfth day of the third month in the Gengshen year of the Xianfeng reign (1860) at Youshi. In combination with the Huanggang Tong's Genealogy (1949) from Hongnishan Village, Nubu Street, Lanxi City, Zhejiang Province, this paper annotates Tong’s Zhu-juan, including the personal resume, the teacher-student relationship, and the political ideas. The purpose is to highlight its historical and cultural value and historical data value, so as to provide an important reference for the study of imperial examination history, local history and family history.

Interactome Analysis Reveals a Link of the Novel ALMS1-CEP70 Complex to Centrosomal Clusters

Alström syndrome (ALMS) is a very rare autosomal-recessive disorder, causing a broad range of clinical defects most notably retinal degeneration, type 2 diabetes, and truncal obesity. The ALMS1 gene encodes a complex and huge ∼0.5MDa protein, which has hampered analysis in the past. The ALMS1 protein is localized to the centrioles and the basal body of cilia and is involved in signaling processes, for example, TGF-β signaling. However, the exact molecular function of ALMS1 at the basal body remains elusive and controversial. We recently demonstrated that protein complex analysis utilizing endogenously tagged cells provides an excellent tool to investigate protein interactions of ciliary proteins. Here, CRISPR/Cas9-mediated endogenously tagged ALMS1 cells were used for affinity-based protein complex analysis. Centrosomal and microtubule-associated proteins were identified, which are potential regulators of ALMS1 function, such as the centrosomal protein 70kDa (CEP70). Candidate proteins were further investigated in ALMS1-deficient hTERT-RPE1 cells. Loss of ALMS1 led to shortened cilia with no change in structural protein localization, for example, acetylated and ɣ-tubulin, Centrin-3, or the novel interactor CEP70. Conversely, reduction of CEP70 resulted in decreased ALMS1 at the ciliary basal body. Complex analysis of CEP70 revealed domain-specific ALMS1 interaction involving the TPR-containing C-terminal (TRP-CT) fragment of CEP70. In addition to ALMS1, several ciliary proteins, including CEP135, were found to specifically bind to the TPR-CT domain. Data are available via ProteomeXchange with the identifier PXD046401. Protein interactors identified in this study provide candidate lists that help to understand ALMS1 and CEP70 function in cilia-related protein modification, cell death, and disease-related mechanisms.

GARP and EARP are required for efficient BoHV-1 replication as identified by a genome wide CRISPR knockout screen.

The advances in gene editing bring unprecedented opportunities in high throughput functional genomics to animal research. Here we describe a genome wide CRISPR knockout library, btCRISPRko.v1, targeting all protein coding genes in the cattle genome. Using it, we conducted genome wide screens during Bovine Herpes Virus type 1 (BoHV-1) replication and compiled a list of pro-viral and anti-viral candidates. These candidates might influence multiple aspects of BoHV-1 biology such as viral entry, genome replication and transcription, viral protein trafficking and virion maturation in the cytoplasm. Some of the most intriguing examples are VPS51, VPS52 and VPS53 that code for subunits of two membrane tethering complexes, the endosome-associated recycling protein (EARP) complex and the Golgi-associated retrograde protein (GARP) complex. These complexes mediate endosomal recycling and retrograde trafficking to the trans Golgi Network (TGN). Simultaneous loss of both complexes in MDBKs resulted in greatly reduced production of infectious BoHV-1 virions. We also found that viruses released by these deficient cells severely lack VP8, the most abundant tegument protein of BoHV-1 that are crucial for its virulence. In combination with previous reports, our data suggest vital roles GARP and EARP play during viral protein packaging and capsid re-envelopment in the cytoplasm. It also contributes to evidence that both the TGN and the recycling endosomes are recruited in this process, mediated by these complexes. The btCRISPRko.v1 library generated here has been controlled for quality and shown to be effective in host gene discovery. We hope it will facilitate efforts in the study of other pathogens and various aspects of cell biology in cattle.

Ozonation products of purine derivatives, the basic structures of antiviral micropollutants

Purine and its nucleobases adenine and guanine are the basic structures of a large group of antiviral agents such as acyclovir and penciclovir. Hence, their ozonation is of interest with regard to wastewater treatment due to the formation of products that could affect the aquatic environment.In this study, the transformation products of the mentioned substances are investigated under different defined reaction conditions in order to gain insight into the ozonation characteristics of this compound class.Results show that examining related molecules significantly improves product screening by compiling known products and analogues leading to comprehensive candidate lists, for the purines with a total number of >120 candidates (including possible duplicates for several purines) of which 49 were detected for the derivatives studied. One product, cyanuric acid, which was previously postulated for adenine, was tentatively confirmed and quantified for the first time for the reaction of purine and adenine with ozone. In addition, two prioritisation approaches are presented to identify the major products that are either formed under specific reaction conditions or are potentially relevant for structurally related pollutants. First, principal component analysis allowed the prioritisation of the products formed according to reaction conditions. In the analysis of guanine and the two antivirals, this approach showed that at neutral and basic pH the 2-imino-5-oxoimidazoline products dominated while at acidic pH either analogues of 5-amino-2,4-imidazolidinedione or 2,4-diamino-1,3-oxazol-5-(2H)-one were abundant. A second approach prioritising common products in the ozonation of all three basic structures revealed the formation of two products that had not been reported before: C4H8O3 and C3H2N2O3, presumably oxalylurea. Both molecules or their analogues may also be formed from related micropollutants. Overall, examining basic structures and exemplary micropollutants in combination was shown to be a worthwhile approach to gain knowledge on the ozonation of a whole range of compounds.

Adaptive Ant Colony Optimization With Node Clustering for the Multidepot Vehicle Routing Problem

This article deals with the novel metaheuristic algorithm based on the Ant Colony Optimization (ACO) principle. It implements several novel mechanisms that improve its overall performance, lower the optimization time, and reduce the negative behavior which is typically connected with ACO-based algorithms (such as prematurely falling into local optima, or the impact of setting of control parameters on the convergence for different problem configurations). The most significant novel techniques, implemented for the first time to solve the Multi-Depot Vehicle Routing Problem (MDVRP), are as follows: (a) node clustering where transition vertices are organized into a set of candidate lists called clusters; (b) adaptive pheromone evaporation which is adapted during optimization according to the diversity of the population of ant solutions (measured by information entropy). Moreover, a new termination condition, based also on the population diversity, is formulated. The effectiveness of the proposed algorithm for the MDVRP is evaluated via a set of experiments on 23 well-known benchmark instances. Performance is compared with several state-of-the-art metaheuristic methods; the results show that the proposed algorithm outperforms these methods in most cases. Furthermore, the novel mechanisms are analyzed and discussed from points of view of performance, optimization time, and convergence. The findings achieved in this article bring new contributions to the very popular ACO-based algorithms; they can be applied to solve not only the MDVRP, but also, if adapted, to related complex NP-hard problems.

The Proportional Electoral Systems in the Western Balkans Countries: A Comparative Approach

Representative democracy is closely related to elections and voting. Electoral systems can influence not just the number of minority candidates elected but also how majority parties seek to appeal to or marginalize minority voters, and how inclusive candidate lists will be. Electoral systems can be defined and categorized concerning - How many representatives are elected from each constituency? Is the formula used a plurality, majority, or type of proportionality? What is the threshold for representation for parties and candidates? These elements determine the seats in the parliament and the winning parties. This paper does not aim to be an exhaustive one about the wide topic of electoral systems. It aims at presenting an overview of electoral systems in Western Balkans, focusing on the presentation of the main features of the proportional electoral systems in these countries. Proportional representation systems are applied in the countries under consideration, therefore analytical and comparative research will be the focus of the paper. From the short comparative analysis of this paper on the electoral systems in the countries of the Western Balkans, similarities and differences between them are observed. As a result, we will try to understand which of the criteria and formulas used provides better representation and governance for these countries.
 
 Received: 25 September 2023 / Accepted: 26 October 2023 / Published: 23 November 2023

The multifunctional LBC-Corpora: different aims depending on the user

Abstract Corpora are nowadays the primary source of many dictionaries and the core element of various platforms and information systems. Lexicographers have therefore a variety of new possibilities which were unthinkable in the past with different types of corpora available for use in the data collection phase of the lexicographic process (Flinz 2021). Not only lexicographers, but also other types of users (academics, translators, teachers, students etc.) can profit from them, especially when corpora are public and can be accessed using corpus linguistic tools (Ballestracci/Buffagni/Flinz 2020; Flinz/Farina 2020). The LBC-corpora are monolingual specialized comparable corpora, already online (http://corpora.lessicobeniculturali.net/) and, as monitor corpora (Lemnitzer/Zinsmeister 2015: 140), they will be augmented over time. They can be analysed using the open source tool NoSketchEngine (Billero 2020). The LBC-Corpora are also the lexicographic primary source of the LBC multilingual dictionary, which is in preparation: the provisional entry lists of different languages (Spanish, German, and French) are now ready (Billero/Farina/Nicolás Martínez 2020) and together with a selection of KWICS, which have been carefully selected following a quantitative-qualitative procedure (for German see Buffagni/Flinz/Ballestracci in prep.), will soon be online (Flinz et al. in prep.). The purpose of this paper is to reflect on the LBC-corpora from a double perspective: from the user of the LBC-platform and from the lexicographic team. In the first case following an overview of the principal characteristics of the LBC-Platform, the focus will be on the accessible corpora showing the tools which can be used (§ 2). In the second case the LBC-corpora will be examined in their function as a data basis for the LBC-Dictionary (§ 3). The attention will be on the data preparation phase: after discussing the procedure for the realization of the LBC-provisional lemma candidate lists, the focus will be on the adopted procedure for finding equivalence relations and for the individuation of other types of relations between the entries (synonymy, belonging to the same semantic field etc.). In § 4 the focus will be on the LBC-provisional lemma candidate lists and their related KWICs. Conclusions and an outlook to the future can be found in the last section (§ 5).

Using a Quench Level Approximation to Estimate the Effect of Metallicity on the Abundances of N-bearing Species in H2-dominated Atmospheres

Variations in atmospheric elemental nitrogen can considerably affect the abundance of major nitrogen-bearing species such as NH3 and HCN. Also, due to vertical mixing and photochemistry, their abundance deviates from thermochemical equilibrium. The goal of this study is to understand the effect of atmospheric metallicity on the composition of NH3, N2, and HCN over a large parameter space in the presence of vertical mixing, which when combined with the work on CHO-bearing species in Soni & Acharyya can provide a comprehensive understanding of the effect of atmospheric metallicity. We used quenching approximations and a full chemical kinetics model for the calculations, and a comparison between these two methods was made. To generate thermal profiles, the petitRADTRANS code was used. Chemical timescales of NH3 and N2 are found to be complex functions of metallicity, while HCN is inversely proportional. Using quenched abundances of NH3 and CO, the quenched abundance of HCN can be constrained since it remains in equilibrium with NH3, CO, and H2O. Quenched NH3 increases with increasing K zz until a particular point, after which it becomes independent of vertical mixing. There is a sweet spot in the K zz parameter space to maximize the quenched HCN for a given T int and T equi; the parameter space moves toward a lower equilibrium temperature, and the abundance of HCN increases with metallicity. Finally, we used a data set of quenched abundances to provide a list of potential candidates in which the observation of HCN is possible.

The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug (http://adhdrug.cibr.ac.cn/). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

Promoting Women’s Political Participation in Tanzania: Assessing Voluntary Gender Quotas in CCM’s and CHADEMA’s Constitutions

In response to the low numbers of women in elected positions of power, Tanzania reserves special seats for women in parliament and local governance structures. Consequently, the special seats system remains one of the main pathways for women’s access to political seats. Despite political parties’ role in nominating women for special seats, concerns linger regarding their internal commitment to advancing women’s political participation. This article inspects the constitutions of Chama cha Mapinduzi (CCM, the Revolutionary Party) and Chama cha Demokrasia na Maendeleo (CHADEMA, Party of Democracy and Development) to assess whether there are voluntary gender quotas for increasing women’s political participation in political parties’ leadership positions and elections. While the two parties’ constitutions include principles of gender equality and non-discrimination, they contain minimal and inconsistent measures for women to attain positions in the party leadership, its decision-making organs and candidate lists. Various constraints, including the competition caused by the First Past the Post electoral system, challenges associated with the implementation of the special seats system, loopholes in the legal framework, weaknesses of women’s political parties’ wings, lack of competition from other political parties, and gendered social norms account for CCM and CHADEMA’s reluctance to adopt voluntary gender quotas.

Associations between home environmental factors and childhood eczema and related symptoms in different cities in China

Previous studies have shown significant associations between home environmental factors and childhood eczema. However, few studies have compared how associations differ in different regions. This study investigated associations between home environmental factors and childhood eczema ever, and related symptoms including itchy rash (IR) and being awakened by itchy rash at night (awake by IR) in 4 cities located in different regions of China, based on cross-sectional investigations during 2010–2012. We used two-step analysis to explore the associations between influencing factors and eczema/related symptoms: first, group Least Absolute Shrinkage and Selection Operator (LASSO) was conducted to identify important factors among a list of candidates; then, the associations in total study population and in each city were estimated using logistic regression. We found these home environmental factors to be risk factors for eczema or related symptoms: large residence size, shared room, air cleaner at home, abnormal smell, perceived dry air, visible mold or damp stains, cooking with coal or wood, painted wall, incense, mice, new furniture during pregnancy, abnormal smell at birth, window condensation at birth and environmental tobacco smoke at birth. Environmental protective factors were rural house location and window ventilation. Associations of factors with eczema/related symptoms differed across cities. For example, air conditioning was protective for eczema in Beijing and awakening by IR in Shanghai with ORs of 0.70 (95%CI: 0.52, 0.95) and 0.33 (95%CI: 0.14, 0.81) respectively, but not significant in other cities. Our results have implications for improving home environments to reduce the risk of childhood eczema/related symptoms in different regions of China.

The miniJPAS survey quasar selection

Aims. Quasar catalogues from photometric data are used in a variety of applications including those targeting spectroscopic follow-up, measurements of supermassive black hole masses, Baryon Acoustic Oscillations, or non-Gaussianities. Here, we present a list of quasar candidates including photometric redshift estimates from the miniJPAS Data Release constructed using SQUEzE. miniJPAS is a small proof-of-concept survey covering 1 deg2 with the full J-PAS filter system, consisting of 54 narrow filters and 2 broader filters covering the entire optical wavelength range. Methods. This work is based on the machine-learning classification of photometric data of quasar candidates using SQUEzE. It has the advantage that its classification procedure can be explained to some extent, making it less of a ‘black box’ when compared with other classifiers. Another key advantage is that the use of user-defined metrics means the user has more control over the classification. While SQUEzE was designed for spectroscopic data, we have adapted it for multi-band photometric data; that is we treat multiple narrow-band filters as very low-resolution spectra. We trained our models using specialised mocks. We estimated our redshift precision using the normalised median absolute deviation, σNMAD, applied to our test sample. Results. Our test sample returns an f1 score (effectively the purity and completeness) of 0.49 for high-z quasars (with z ≥ 2.1) down a to magnitude of r = 24.3 and 0.24 for low-z quasars (with z < 2.1), also down to a magnitude of r = 24.3. For high-z quasars, this goes up to 0.9 for magnitudes of r < 21.0. We present two catalogues of quasar candidates including redshift estimates: 301 from point-like sources and 1049 when also including extended sources. We discuss the impact of including extended sources in our predictions (they are not included in the mocks), as well as the impact of changing the noise model of the mocks. We also give an explanation of SQUEzE reasoning. Our estimates for the redshift precision using the test sample indicate a σNMAD = 0.92% for the entire sample, reduced to 0.81% for r < 22.5 and 0.74% for r < 21.3. Spectroscopic follow-up of the candidates is required in order to confirm the validity of our findings.

The Involvement of Women’s Instant Politics in the Legislative Candidates From 2019-2024 Base on Gender Justice in Jambi City

In the 2019 legislative elections, the issue of women's representation in politics, as much as 30%, is interesting to study. Law No.7 of 2017 in article 245 states that the list of prospective candidates contains at least 30% women. The problem now is the lack of women's interest in politics and the lack of female cadres. Political parties need to find an instant way to make women more than only commodities to fulfill the party's qualification requirements. This study aims to explore the dynamics of women's involvement in legislative nominations in Jambi City and the government's participation in maximizing women's involvement. This research was conducted in Jambi City using a case study approach. The selection of the data was from political party officials and at the same time, they became the research informants. In addition, the General Election Commission (KPU) of the City of Jambi was a supplementary informant. Data collection was done through brainstorming and interviews. This research uses the theory of liberal feminism and the theory of gender politics. Furthermore, this research will find a model of gender equality in politics based on gender justice in terms of representation in the political world by showing partiality to be on the agenda and the issues of women.

Transmembrane protein 184B (TMEM184B) promotes expression of synaptic gene networks in the mouse hippocampus

In Alzheimer’s Disease (AD) and other dementias, hippocampal synaptic dysfunction and loss contribute to the progression of memory impairment. Recent analysis of human AD transcriptomes has provided a list of gene candidates that may serve as drivers of disease. One such candidate is the membrane protein TMEM184B. To evaluate whether TMEM184B contributes to neurological impairment, we asked whether loss of TMEM184B in mice causes gene expression or behavior alterations, focusing on the hippocampus. Because one major risk factor for AD is age, we compared young adult (5-month-old) and aged (15-month-old) wild type and Tmem184b-mutant mice to assess the dual contributions of age and genotype. TMEM184B loss altered expression of pre- and post-synaptic transcripts by 5 months and continued through 15 months, specifically affecting genes involved in synapse assembly and neural development. Wnt-activated enhancer elements were enriched among differentially expressed genes, suggesting an intersection with this pathway. Few differences existed between young adult and aged mutants, suggesting that transcriptional effects of TMEM184B loss are relatively constant. To understand how TMEM184B disruption may impact behaviors, we evaluated memory using the novel object recognition test and anxiety using the elevated plus maze. Young adult Tmem184b-mutant mice show normal object discrimination, suggesting a lack of memory impairment at this age. However, mutant mice showed decreased anxiety, a phenotype seen in some neurodevelopmental disorders. Taken together, our data suggest that TMEM184B is required for proper synaptic gene expression and anxiety-related behavior and is more likely to be linked to neurodevelopmental disorders than to dementia.

P10.24.B SCREENING NON-ONCOLOGICAL DRUGS IN A PATIENT-DERIVED GLIOBLASTOMA MODEL IDENTIFIES PITAVASTATIN WITH POTENTIAL ANTITUMOR ACTIVITY

Abstract BACKGROUND Glioblastoma (GBM) is a malignancy which is in dire need of novel treatment options. Repurposing non-oncological drugs has become of great interest in GBM research. Non-oncological drugs have many advantages over their oncological counterparts including a well-established safety and toxicity profile, possibilities to perform dose escalation studies, and combinations with oncological drugs (e.g. temozolomide, TMZ). Making use of our patient-derived in vitro model which has been shown to recapitulate GBM in terms of genetic make-up and heterogeneity, we aim at identifying non-oncological drugs that exhibit potent antitumor activity. MATERIAL AND METHODS Drug screening was performed using an NIH clinical compound selection consisting of 446 non-oncological drugs on 2 patient-derived GBM cell lines. Viability 5 days post treatment was assessed using the ATP-based Cell Titer Glo assay. Validation studies were performed on a panel of 25 GBM cultures. Nanostring analysis using the Pan Cancer gene panel, flow cytometry, Western Blotting and immunofluorescence were employed to gain insight into drug mechanism of action. The zero-interaction potential method was used to quantify synergy with TMZ. Dose-modifying factors (DMF) were calculated to quantify synergy with irradiation. RESULTS Screening of 446 non-oncological drugs yielded a top 10 list of candidates which were evaluated on an additional cell panel. Based on safety and efficacy, pitavastatin, an HMG-CoA reductase inhibitor, was selected for further analysis. Compared to 8 other registered statins, pitavastatin revealed the most potent anti-tumor activity, with IC50 values in the low micromolar range. Pitavastatin efficacy was validated in a panel of 25 GBM cultures derived from various GBM subtypes in terms of primary/recurrence, MGMT and IDH status (IC50 ranging from 0.1 - 5.0 µM). GBM cultures derived from patients using statins for cholesterol management did not reveal resistance to pitavastatin. Combination treatment of pitavastatin with either TMZ or irradiation showed synergy with TMZ in 5/8 cultures and radiosensitizing effects in 3/5 cultures (DMF >2.0). Importantly, no antagonism was observed with TMZ or irradiation. Mechanistic studies demonstrated that pitavastatin treatment led to induction of autophagy, perturbations in GBM cell cycle and attenuation of GSC stemness through downregulation of SOX2 and CD133. CONCLUSION Drug screening on patient derived GBM cultures identified pitavastatin as a potent inhibitor of GBM cell viability and revealed its chemo- and radiosensitizing effects. Mechanistic studies suggest that its antitumor effects could be a consequence of autophagy induction, cell cycle arrest and loss of GBM cell stemness. Currently we are exploring strategies to ensure optimal intratumoral delivery in vivo.

Drug repurposing on Alzheimer's disease through modulation of NRF2 neighborhood

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of cognitive decline. The alarming epidemiological features of Alzheimer's disease, combined with the high failure rate of candidate drugs tested in the preclinical phase, impose more intense investigations for new curative treatments. NRF2 (Nuclear factor-erythroid factor 2-related factor 2) plays a critical role in the inflammatory response and in the cellular redox homeostasis and provides cytoprotection in several diseases including those in the neurodegeneration spectrum. These roles suggest that NRF2 and its directly associated proteins may be novel attractive therapeutic targets in the fight against AD. In this study, through a systemics perspective, we propose an in silico drug repurposing approach for AD, based on the NRF2 interactome and regulome, with the aim of highlighting possible repurposed drugs for AD. Using publicly available information based on differential expressions of the NRF2-neighborhood in AD and through a computational drug repurposing pipeline, we derived to a short list of candidate repurposed drugs and small molecules that affect the expression levels of the majority of NRF2-partners. The relevance of these findings was assessed in a four-step computational meta-analysis including i) structural similarity comparisons with currently ongoing NRF2-related drugs in clinical trials ii) evaluation based on the NRF2-diseasome iii) comparison of relevance between targeted pathways of shortlisted drugs and NRF2-related drugs in clinical trials and iv) further comparison with existing knowledge on AD and NRF2-related drugs in clinical trials based on their known modes of action. Overall, our analysis yielded in 5 candidate repurposed drugs for AD. In cell culture, these 5 candidates activated a luciferase reporter for NRF2 activity and in hippocampus derived TH22 cells they increased NRF2 protein levels and the NRF2 transcriptional signatures as determined by increased expression of its downstream target heme oxygenase 1. We expect that our proposed candidate repurposed drugs will be useful for further research and clinical translation for AD.

Experimental validation of thermochemical water-sorption materials for thermal energy storage: Building application

Salt hydrates for seasonal heat storage have emerged as an important research topic due to their potential to fulfil the heat demand in the residential and commercial building sector. However, the research undertaken has not yet covered key aspects of their fundamental thermal behaviour understanding e.g. experimentally validation, characterisation methodologies or material screening. The present investigation is aimed to identify promising thermochemical materials in the temperature range of 25–150°C, which are suitable for building applications and waste heat recovery. A list of ten salt hydrates has been screened through an experimental validation, which was developed and optimized for the specific working conditions. The salt hydrates were tested under operational conditions and key properties are assessed (thermal conductivity, specific heat, volume change, etc). Different case studies were used to narrow down to a list of final salts candidates under three theoretical working conditions scenarios for both open and closed systems. The cases of study prioritised high energy density (after one hydration/dehydration cycle), acceptable volume expansion and stability, which led to the final candidates. Magnesium sulphate was selected in the case of high energy density (>2 MJ/m3) and low cost (1 €/MJ), when lowering the energy density to 1 MJ/m3 calcium sulphate and copper sulphate were revealed as promising candidates for open and closed systems. While calcium nitrate was identified as a candidate along with magnesium sulphate when considering closed systems.

Pairing Optical and Atomic Hydrogen Detections to Assess Newly-Discovered Galaxy Candidates

As optical telescopes become more advanced, their detections begin to unveil very faint, previously unobserved extragalactic objects in the night sky – some of which could be among the smallest and most diffuse galaxies ever discovered. Many of the objects detected appear to be comprised of young, blue stars which seem to exist in isolation from any parent galaxies. In this research, we attempt to connect the very faint optical detections with atomic hydrogen, HI, detections from archival surveys, in order to assess the likelihood that they are newly-discovered galaxies and whether they are actively forming stars. Using the Systematically Measuring Ultra-diffuse Galaxies (SMUDGes) catalog to generate a list of potential candidates, the HI profile corresponding to each candidate’s coordinates was generated and smoothed, ensuring the detection of subtle emissions. Out of the 48 candidates analyzed, 2 very promising candidates emerged and properties like the object’s recessional velocity and HI mass were determined. While the lack of emissions detected may point to radio surveys not being deep enough to detect subtle HI emissions, observing these successful candidates may allow for the formation, origins and evolution of these objects to be studied, thus expanding our knowledge of the universe and galaxy formations.

Completeness of the NASA/IPAC Extragalactic Database (NED) Local Volume Sample

Abstract We introduce the NASA/IPAC Extragalactic Database (NED) Local Volume Sample (NED-LVS), a subset of ∼1.9 million objects with distances out to 1000 Mpc. We use UV and IR fluxes available in NED from all-sky surveys to derive physical properties, and estimate the completeness relative to the expected local luminosity density. The completeness relative to near-IR luminosities (which traces a galaxy’s stellar mass) is roughly 100% at D < 30 Mpc and remains moderate (70%) out to 300 Mpc. For brighter galaxies (≳L *), NED-LVS is ∼100% complete out to ∼400 Mpc. When compared to other local Universe samples (GLADE and HECATE), all three are ∼100% complete below 30 Mpc. At distances beyond ∼80 Mpc, NED-LVS is more complete than both GLADE and HECATE by ∼10%–20%. NED-LVS is the underlying sample for the NED gravitational-wave follow-up service (NED-GWF), which provides prioritized lists of host candidates for GW events within minutes of alerts issued by the LIGO–Virgo–KAGRA collaboration. We test the prioritization of galaxies in the volume of GW170817 by three physical properties, where we find that both stellar mass and inverse specific star formation rate place the correct host galaxy in the top 10. In addition, NED-LVS can be used for a wide variety of other astrophysical studies: galaxy evolution, star formation, large-scale structure, galaxy environments, and more. The data in NED are updated regularly, and NED-LVS will be updated concurrently. Consequently, NED-LVS will continue to provide an increasingly complete sample of galaxies for a multitude of astrophysical research areas for years to come.