Miracle-dz/UniFAR-FTUs huggingface dataset:
SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms.

SL651498 (6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one) was identified as a drug development candidate from a research program designed to discover subtype-selective GABA(A) receptor agonists for the treatment of generalized anxiety disorder and muscle spasms. The drug displays high affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and alpha(2) (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing GABA(A) receptors (K(i) = 117 nM). Studies on recombinant rat GABA(A) receptors confirm these findings and indicate intermediate affinity for the alpha(3)beta(2)gamma(2) subtype. SL651498 behaves as a full agonist at recombinant rat GABA(A) receptors containing alpha(2) and alpha(3) subunits, and as a partial agonist at recombinant GABA(A) receptors expressing alpha(1) and alpha(5) subunits. SL651498 produced anxiolytic-like and skeletal muscle relaxant effects qualitatively similar to those of benzodiazepines (BZs) [minimal effective dose (MED): 1 to 10 mg/kg, i.p. and 3 to 10 mg/kg, p.o. ]. However, unlike these latter drugs, SL651498 induced muscle weakness, ataxia or sedation at doses much higher than those having anxiolytic-like activity (MED: 30 to 100 mg/kg, i.p. or p.o.). Moreover, in contrast to BZs, SL651498 did not produce tolerance to its anticonvulsant activity or physical dependence. It was much less active than BZs in potentiating the depressant effects of ethanol or impairing cognitive processes in rodents. The differential profile of SL651498 as compared to BZs may be related to its selective efficacy at the alpha(2)- and alpha(3)-containing GABA(A) receptors. This suggests that selectively targeting GABA(A) receptor subtypes can lead to drugs with increased clinical specificity. SL651498 represents a promising alternative to agents currently used for the treatment of anxiety disorders and muscle spasms without the major side effects seen with classical BZs.
Bibliometric analysis of entrepreneurial orientation

Purpose The remarkable concept of entrepreneurial orientation (EO) has attracted scholars’ attention for its relevance to a firm’s performance. Based on bibliometric and distance-based visualization of similarities (VOS) analysis, the purpose of this paper is to outline a broad-spectrum perspective of the structure of research in EO across more than 20 years of publications, identifying the most prominent journals, authors and articles in this field. Design/methodology/approach The paper uses the Web of Science Core Collection and the VOS viewer software. The analysis searches for all the documents connected to EO available in the database from 1976 to 2017. The graphical visualization maps the bibliographic data using both bibliographic coupling and co-citation data. Findings Entrepreneurship Theory and Practice Journal, Journal of Business Venturing and Family Business Review are the most relevant journals in the field. Among the many important authors in the EO literature, key contributors are Lumpkin, Payne, Short, Covin, Dess and Wiklund. Three different streams of research are linked to the EO concept; strategy and entrepreneurship, family business and miscellaneous work in psychometrics, methods, marketing and knowledge/capability-based approaches to organizations. Originality/value This paper contributes to EO research by providing a global perspective on the concept’s investigation, using bibliometric data and graphical networks.
On-farm phenotypic characterization of Mursi cattle in its production environment in South Omo Zone, Southwest Ethiopia.

This study was conducted to characterize the morphological peculiarities and performance characteristics of Mursi cattle in its production environment managed by Bodi and Mursi pastoral communities in Southern Ethiopia. A structured questionnaire survey, group discussion, cattle morphological measurements and morphological descriptions were used to collect data. One hundred and two household heads were selected to administer the questionnaire and 201 adult cattle were selected for morphological description and body measurements. The Mursi cattle population was found to have variable coat colour type (85.9 percent) and coat colour pattern (51.3 percent). Body length, chest girth, withers height, rump width and rump length of Mursi cattle were 122.1 ± 0.9, 144.5 ± 0.9, 113 ± 0.1. 1, 36.9 ± 0.3 and 20.4 ± 0.3 cm, respectively. Morphological measurements of most linear traits show no difference in the two locations but all measurements vary (P < 0.001) between males and females. Estimated age at first calving was 4.6 years and was significantly (P < 0.0001) higher in the Mursi area, while the calving interval (14.5 months) and cow reproductive life (14.2 years) were the same in both locations. Average daily milk yield (2.1 litres) and lactation length (7.8 months) of Mursi cattle in the two locations were similar. Cattle production was constrained by high disease prevalence, seasonal feed availability, and water shortage, with frequent drought. Trypanosomosis, black leg, anthrax and skin diseases are major cattle diseases reported in the two study areas. Because of its peculiar morphological characteristics, including large body frame, higher production performance, and survivability in the harsh environment, the Mursi cattle can be used as an alternative genetic resource for production improvement programs.
Coping strategies to water shortages in central Sudan; Almanagil locality

The study focused on Almanagil plateau, located in central Sudan, within three states of Gezira, Sennar, and White Nile, which was excluded from the Geizera Agricultural Scheme. Various coping strategies carried by inhabitants were studied as means of climate change adaptation. A structured questionnaire (50 small-scale farmers), key-informant interview and group discussions were undertaken in seven villages within this plateau. Questions covered coping strategies with drought and flood shocks, suggestions for water shed managements, improving surface, subsurface and ground water availability, in addition to willingness to participate in adaptation and mitigation activities. Secondary data included meteorological rainfall data for the last 6 years (20052010), expectations for water requirements for the next coming 10 years (20102016). Sources of water and quantities consumed by households and animals were studied. Remote sensing and GIS and GPS survey level data were used to provide information on potentialities for improving water sources for human consumption and irrigation. All of the surveyed villages lie within S2 with moderate suitability for irrigation but with different soil characteristics, generally slightly calcareous, susceptible to erosion. All respondents in all villages expressed shortages in water availability for both human and animal consumptions. Coping strategies with drought or floods reported were temporal migration, selling part of their animals or properties, turning to other activities. Willingness to participate in natural resource conservation was expressed by all respondents. Suggestions to improve water resources included building dams on streams, terracing, extending water pipes from canals to farmers’ field, ponds construction, enlarging and deepening of streams beds, establishing water pumps. It was concluded that the concept of multi water use services could meet farmers’ needs for cooking and sanitation and promote small enterprises as livestock raising, horticulture and crop production. In areas with gentle sloping, surface run-off could be collected and used for supplementary irrigation during dry spells.
Trends in Temperature in Thailand from 1964 to 2013

Globally, minimum temperatures are increasing at a faster rate than maximum ones. In this study, Thailand’s trends in daily maximum surface air temperature (Tmax), minimum surface air temperature (Tmin), and the diurnal temperature range (DTR) from 1964 to 2013 were observed and interpolated. The results were compared with other studies and demonstrate that the trends in Tmax and Tmin are increasing, whereas the DTR is most often decreasing due to the increase of Tmin at a faster rate than that of Tmax. As surface air temperature changes can be seen as indicators of climate change, the findings indicate that Easter, Central and West Thailand appear to be the most impacted areas of Thailand over the past 50 years (1964-2013) regarding rapid surface air temperature changes. To further understand the changes in Thailand’s climate, trends in precipitation intensities should be evaluated.
ON THE RELATIONSHIP BETWEEN HUMAN CAPITAL INEQUALITY AND GLOBALIZATION

This study attempts to tackle the inequality and globalization issue by departing from the usual convention and studying the effect of globalization on another distribution, which is the distribution of human capital. We would like to investigate whether globalization helps to alleviate or worsen inequality in education and benefit everyone in the observed population in the same way in terms of education. Moreover, we would also like to analyze whether the benefit or loss experienced by countries differ across the level of development. Our focus is on the impact of the composite index of globalization as well as its three different dimensions on education inequality. The study shows that the developing countries (low and middle-income countries) do not necessarily benefit from globalization, which clearly contradicts the standard trade theory. This is because we observe the existence of variation of effects within the developing countries itself. Globalization narrows the education gap in low-income countries but it widens the gap in middle-income countries. Additionally, the study also show the importance of social and political globalization, which is often ignored in existing literature. The results are robust to different measures of globalization, exclusion of countries from different regions and inclusion of several control variables.Keywords: Globalization; Human Capital Inequality; System GMM.
A window on The International Environmetrics Society: The first 25 international conferences

The 25th international conference of The International Environmetrics Society (TIES) was held in 2015. The conferences have been an integral part of the development of TIES and of the society's official journal, Environmetrics, since the concurrent inception of the society and journal at the first conference in 1989. The conferences are documented in chronological order, with more description of the early conferences because many features were set at these conferences. Some common features are included for all conferences, and only new or particularly relevant components are mentioned for later conferences. This development is then drawn on to discuss the character, contributors, and evolution of the conferences in the context of TIES as a society with the aim of fostering the development and use of quantitative methods in solving environmental problems through collaboration among individuals in different disciplines and types of organizations.
Global Positioning inside Tunnels Using Camera Pose Estimation and Point Clouds

This master thesis aims to solve the positioning problem in the absence of an accurate GPS solution. We will show how high density tunnel model in 3D point clouds, together with only a single vehicle-mounted camera, can estimate the vehicle’s position throughout tunnels without the assistance of other positioning systems. We developed a solution by analysing an image sequence where feature detection and image to point cloud backprojection were used to generate an accurate positioning system. The feature detection was performed using the well-known SIFT algorithm and back-projection onto the point cloud is done through repeated closest-neighbour search along a ray we build from the feature’s coordinates. Multiple post-processed GPS runs within the tunnel are used to generate a ground truth which is used as the reference for evaluating the solution. For this end, we developed a new software architecture where the software could ultimately be placed on top of any existing positioning method and then provide an easy comparison between the two. An experimental result is provided to show that accurate positioning can be achieved under the right circumstances, reaching a drift distance of below ten centimeters.
Enhanced pro-apoptotic activity of rituximab through IBTK silencing in non-Hodgkin lymphoma B-cells

Rituximab is a commonly used chemotherapeutic drug for patients with aggressive lymphomas, such as non-Hodgkin’s lymphoma (NHL). Currently, the combination of Rituximab and chemotherapy (R-CHOP) stands as the most prevalent first-line therapy for NHL. Nevertheless, the development of new therapeutic approaches remains imperative. An increasing body of evidence highlights a novel role for IBTK in tumorigenesis and cancer growth. In this study, we aim to broaden our understanding of IBTK’s function in B-lymphoma, with a particular focus on its impact on the expression of the oncogene MYC. Here, we assessed the effects of combining Rituximab with IBTK silencing on cell viability through cell cycle analysis and Annexin V assays in vitro. Furthermore, we leveraged the transplantability of Eμ-myc lymphomas to investigate whether the inhibition of IBTK could elicit anti-tumor effects in the treatment of lymphomas in vivo. Our data suggests that IBTK silencing may serve as an effective anti-tumor agent for aggressive B-Lymphomas, underscoring its role in promoting apoptosis when used in combination with Rituximab, both in in vitro and in vivo settings.
Probabilistic investigations on the watertightness of jet-grouted ground considering geometric imperfections in diameter and position

The effect of geometric imperfections in both diameter and position of jet-grouted columns on the watertightness of an underground cement-treated slab is investigated in this study. A three-dimensional discretized algorithm is proposed to facilitate the detection and measurement of untreated zones that penetrate the treated slab. The normalized flow rate of a cement-treated slab is then evaluated by calculating the harmonic average area of the penetrated defect. Statistical evaluation of the gross flow rate through the penetrated defects is carried out via Monte Carlo simulations. The results show that a more economic design is obtainable if intracolumn variation of diameter is considered or multi-shaft jet-grouting is used. Based on the statistical results, a reliability-based design method is proposed for designers to strike a balance among various design parameters, including slab thickness, depth, column diameter, and column spacing.
Flexural uplift of the Transantarctic Mountains

The Transantarctic Mountains have formed at the continent-continent boundary between East and West Antarctica. High heat flow, thin crust, normal faulting, and past and present volcanism indicate that this approximately 3000-km-long boundary is divergent in character. Three principal structures have developed at and adjacent to the boundary: the Transantarctic Mountains, the Wilkes Basin, and the Victoria Land Basin. The Transantarctic Mountains form the east edge of East Antarctica and consist of a block-tilted mountain range up to 4500 m high. Running parallel but 400–500 km behind, or to the west of, the Transantarctic Mountains is the Wilkes Basin. This is a broad subglacial basin where the bedrock surface is now as much as 1 km below sea level. East of and immediately adjacent to the Transantarctic Mountain front is an area of extension called the Victoria Land Basin where at least 4–5 km of Cenozoic sediments have been interpreted from seismic reflection data. The wavelengths and amplitudes of these three structures can be accounted for by the elastic flexure of two cantilevered lithospheric plates if the boundary between East and West Antarctica is taken as a stress-free edge. Specifically, the Wilkes Basin is modeled as a flexural “outer low” coupled to uplift of the Transantarctic Mountains. Similarly, subsidence within the Victoria Land Basin is also linked to uplift of the Transantarctic Mountains via the Vening Meinesz uplift-subsidence mechanism and sediment loading. The maximum flexural rigidity for East Antarctica is estimated to be about 1025 N m (or effective elastic thickness, Te, of 115±10 km), one of the highest values for continental rigidity from long-term loads. Flexural rigidity for the Ross Embayment in West Antarctica is, on the other hand, found to be more than 2 orders of magnitude less at 4×1022 N m (Te = 19 ± 5 km). This rigidity variation suggests a marked contrast in effective thermal age, and hence geotherms, between East Antarctica and the western Ross Embayment. Accordingly, one of the principal uplift mechanisms for the Transantarctic Mountains is considered to be a thermal uplift associated with lateral heat conduction from the extended and thinned West Antarctic lithosphere into the thicker lithosphere of East Antarctica. Augmenting thermal uplift of the Transantarctic Mountains are the effects of erosion and the Vening Meinesz uplift effect.
Urinary Acidification Does Not Explain the Absence of Nephrocalcinosis in a Mouse Model of Familial Hypomagnesaemia with Hypercalciuria and Nephrocalcinosis (FHHNC)

Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) which can lead to renal insufficiency. Mice lacking claudin-16 show hypomagnesemia and hypercalciuria, but no nephrocalcinosis. Calcium oxalate and calcium phosphate are the most common insoluble calcium salts that accumulate in the kidney in the case of nephrocalcinosis, however, the formation of these salts is less favored in acidic conditions. Therefore, urine acidification has been suggested to limit the formation of calcium deposits in the kidney. Assuming that urine acidification is causative for the absence of nephrocalcinosis in the claudin-16-deficient mouse model, we aimed to alkalinize the urine of these mice by the ablation of the subunit B1 of the vesicular ATPase in addition to claudin-16. In spite of an increased urinary pH in mice lacking claudin-16 and the B1 subunit, nephrocalcinosis did not develop. Thus, urinary acidification is not the only factor preventing nephrocalcinosis in claudin-16 deficient mice.
Utilization of Recycled Brick Powder as Supplementary Cementitious Materials—A Comprehensive Review

Over the past two decades, extensive research has been conducted to explore alternative supplementary cementitious materials (SCMs) in order to address the environmental concerns associated with the cement industry. Bricks, which are frequently preferred in the construction sector, generate a lot of waste during the production and demolition of existing buildings, requiring environmentally sustainable recycling practices. Therefore, many studies have been carried out in recent years on the use of brick waste as supplementary cementitious materials (SCMs) in cement mortar and concrete production. This critical review evaluates the impact of waste brick powder (WBP) on the mechanical and durability properties of mortar and concrete when used as a partial replacement for cement. It was observed that the properties of WBP-blended cement mortar or concrete depend on several factors, including WBP particle size, replacement ratio, pozzolanic activity, and mineralogical structure. The findings indicate that WBP with a particle size range of 100 µm to 25 µm, with a maximum cement replacement level of 10–20%, exhibits a positive impact on the compressive strength of both mortars and concretes. However, it is crucial to emphasize that a minimum curing duration of 28 days is imperative to facilitate the development of a pozzolanic reaction. This temporal requirement plays a vital role in realizing the optimal benefits of utilizing waste brick powder as a supplementary cementitious material in mortars and concretes.
Temperature Dependence of Platelet Metabolism

Temperature plays a fundamental role in biology, influencing cellular function, chemical reaction rates, molecular structures, and interactions. While the temperature dependence of many biochemical reactions is well defined in vitro, the effect of temperature on metabolic function at the network level is poorly understood, and it remains an important challenge in optimizing the storage of cells and tissues at lower temperatures. Here, we used time-course metabolomic data and systems biology approaches to characterize the effects of storage temperature on human platelets (PLTs) in a platelet additive solution. We observed that changes to the metabolome with storage time do not simply scale with temperature but instead display complex temperature dependence, with only a small subset of metabolites following an Arrhenius-type relationship. Investigation of PLT energy metabolism through integration with computational modeling revealed that oxidative metabolism is more sensitive to temperature changes than glycolysis. The increased contribution of glycolysis to ATP turnover at lower temperatures indicates a stronger glycolytic phenotype with decreasing storage temperature. More broadly, these results demonstrate that the temperature dependence of the PLT metabolic network is not uniform, suggesting that efforts to improve the health of stored PLTs could be targeted at specific pathways.
Cardiac Sarcoidosis: A Comprehensive Clinical Review

Sarcoidosis is an inflammatory multisystemic disease of unknown etiology characterized by the formation of non-caseating granulomas. Sarcoidosis can affect any organ, predominantly the lungs, lymphatic system, skin and eyes. While > 90% of patients with sarcoidosis have lung involvement, an estimated 5% of patients with sarcoidosis have clinically manifest cardiac sarcoidosis (CS), whereas approximately 25% have asymptomatic, clinically silent cardiac involvement verified by autopsy or imaging studies. CS can present with conduction disturbances, ventricular arrhythmias, heart failure or sudden cardiac death. Approximately 30% of < 60-year-old patients presenting with unexplained high degree atrioventricular (AV) block or ventricular tachycardia are diagnosed with CS, therefore CS should be strongly considered in such patients. CS is the second leading cause of death among patients affected by sarcoidosis after pulmonary sarcoidosis, therefore its early recognition is important, because early treatment may prevent death from cardiovascular involvement. The establishment of isolated CS diagnosis sometimes can be quite difficult, when extracardiac disease cannot be verified. The other reason for the difficulty to diagnose CS is that CS is a chameleon of cardiology and it can mimic (completely or almost completely) different cardiac diseases, such as arrhythmogenic cardiomyopathy, giant cell myocarditis, dilated, restrictive and hypertrophic cardiomyopathies. In this review article we will discuss the current diagnosis and management of CS and delineate the potential difficulties and pitfalls of establishing the diagnosis in atypical cases of isolated CS.