Miracle-dz/UniFAR-FTUs huggingface dataset:
HSP90: Enabler of Cancer Adaptation

The stability and function of many oncogenic mutant proteins depend on heat shock protein 90 (HSP90). This unique activity has inspired the exploration of HSP90 as an anticancer target for over two decades. Unfortunately, while clinical trials of highly optimized HSP90 inhibitors have demonstrated modest benefit for patients with advanced cancers, most commonly stabilization of disease, no HSP90 inhibitor has demonstrated sufficient efficacy to achieve FDA approval to date. This review discusses potential reasons for the limited success of these agents and how our increasingly sophisticated understanding of HSP90 suggests alternative, potentially more effective strategies for targeting it to treat cancers. First, we focus on insights gained from model organisms that suggest a fundamental role for HSP90 in supporting the adaptability and heterogeneity of cancers, key factors underlying their ability to evolve and acquire drug resistance. Second, we examine how HSP90’s role in promoting the stability of mutant proteins might be targeted in genetically unstable tumor cells to reveal their aberrant, foreign proteome to the immune system. Both of these emerging aspects of HSP90 biology suggest that the most effective use of HSP90 inhibitors may not be at high doses with the intent to kill cancer cells, but rather in combination with other molecularly targeted therapies at modest, non-heat shock-inducing exposures that limit the adaptive capacity of cancers.
Tasks and responsibilities in physical activity promotion of older patients during hospitalization: A nurse perspective

Objective To investigate how nurses perceive tasks and responsibilities in promoting physical activity during hospitalization of older patients and which factors are of influence. Design Observational cohort study Setting and participants One hundred and eight nurse students, nurses and nurse supervisors employed by an academic Dutch teaching hospital participated in a questionnaire survey and 51 nurses took part in a subsequent in-depth interview. Measures Data were collected on tasks and responsibilities in physical activity promotion and their influencing factors as perceived by nurses. Descriptive statistics were used to analyze the data from the questionnaire survey and a deductive approach with directed content analysis was used for the data from the interviews. Results Nurses perceived to have a dominant role in physical activity promotion of older patients during hospitalization. Ninety percent of the nurses stated to be responsible for physical activity promotion and 32 percent stated to be satisfied with the actual level of physical activity of their patients. Influencing factors were low patient motivation, high workload causing priority shifts of tasks and the role of physicians. Conclusion Although their perceived dominant role in physical activity promotion, nurses identified a number of barriers interfering with actual level of physical activity. Improvement strategies should involve physicians, patients and carers.
A Comparative Study of Seed Germination And Seedling Emergence of Two Wild Edible Allium Species Endemic to Zagros Areas

Allium L. is one of the largest and most diversified monocotyledonous genera worldwide. These taxa have wide geographical distribution range mainly occurred in the northern hemisphere with an important center of diversity in the Mediterranean and Irano-Anatolian regions. They include an important number of taxa of high economic values (wild edible, cultivated, medicinal, ornamentals, etc.). These geophytes species exhibit diversified adaptation strategies that permit them to persist under harsh environmental conditions. The present experimental study was designed to understanding better the environmental factors that control the natural regeneration of the two wild edible Allium (A. calocephalum and A. notabile) species endemic to Zagros areas via evaluating the effect of different (i) pre-sowing treatments on seed germination rate and (ii) soil depth on seedling emergence timing. The results of the present study confirmed relatively high seed and bulbs viabilities under the different pre-sowing treatments. In general, both Allium species have a relatively similar germination trend (around 80% without treatments) and seedling emergence (from bulbs at 5 cm) patterns. The high rate of seed germination for A. calocephalum was found under cold stratification for 1 month and soak in water for 3 days and GA3 1500 ppm with 83%, 86%, and 85%, respectively. The different germination pattern was found for A. notabile with 83%, 85%, 84% for soaking water for 2 and 3 days and GA3 1000 ppm, respectively. Whoever, these two threatened species from different taxonomical groups and habitats have different adaptation strategy. A. notabile is Mediterranean species exhibiting an optimum seedling emergence in autumn-early winter with summer underground organ dormancy to avoid the hot-dry conditions; While, A. calocephalum is IranoAnatolian species exhibiting an optimum seedling in late winter-early spring permitting it to persist thanks to its avoidance strategy of the harsh winter climatic conditions. The results of this research support the idea that Allium species from different habitats exhibit different seed germination and seedling emergency strategies allowing it to persist. The evidence of this experimental study enriches our understanding of the diversified adaptation strategy of the plants. In this context, further experimental investigations are needed to evaluate the crucial rule of the seed germination ecology and bulbs dormancy strategies on the population dynamic and persistence.
Integration of open e-learning datasets

The scarcity and the heterogeneity of publicly available e-learning datasets are some of the main concerns for Learning Analytics research. For this reason, a common framework is needed to provide researchers with a richer information and a general schema, in which new datasets can be collected. The educational context can vary depending on educational level, national policies and cultural characteristics, so the integration of datasets is challenging and requires a dynamic approach. The thesis work focuses on the design of UNIFORM, an integrated open relational database for education, which guarantees modularity and flexibility: its structure can be dynamically edited, to allow the integration of new datasets. The schema contains attributes and tables representing the data of learning datasets; it is designed to be general enough in order to include information from different learning institutions.
Stably expressed genes in single-cell RNA-sequencing

Motivation In single-cell RNA-sequencing (scRNA-seq) experiments, RNA transcripts are extracted and measured from isolated cells to understand gene expression at the cellular level. Measurements from this technology are affected by many technical artifacts, including batch effects. In analogous bulk gene expression experiments, external references, e.g., synthetic gene spike-ins often from the External RNA Controls Consortium (ERCC), may be incorporated to the experimental protocol for use in adjusting measurements for technical artifacts. In scRNA-seq experiments, the use of external spike-ins is controversial due to dissimilarities with endogenous genes and uncertainty about sufficient precision of their introduction. Instead, endogenous genes with highly stable expression could be used as references within scRNA-seq to help normalize the data. First, however, a specific notion of stable expression at the single cell level needs to be formulated; genes could be stable in absolute expression, in proportion to cell volume, or in proportion to total gene expression. Different types of stable genes will be useful for different normalizations and will need different methods for discovery. Results We compile gene sets whose products are associated with cellular structures and record these gene sets for future reuse and analysis. We find that genes whose final product are associated with the cytosolic ribosome have expressions that are highly stable with respect to the total RNA content. Notably, these genes appear to be stable in bulk measurements as well. Supplementary information The Supplement is available on bioRxiv, and the gene set database is available through GitHub. Contact johanngb@umich.edu
Evaluating the CALIOPE air quality modelling system: dynamics and chemistry over Europe and Iberian Peninsula for 2004 at high horizontal resolution

The present contribution describes a thorough quantitative evaluation study performed for a reference year (2004). The CALIOPE modelling system is configured with 38 vertical layers reaching up to 50 hPa for the meteorological core. Atmospheric initial and boundary conditions are obtained from the NCEP final analysis data. The vertical resolution of the CMAQ chemistry-transport model for gas-phase and aerosols has been increased from 8 to 15 layers in order to simulate vertical exchanges more accurately. Gas phase boundary conditions are provided by the LMDz-INCA2 global climate-chemistry model (see Hauglustaine et al., 2004). The DREAM model simulates long-range transport of mineral dust over the domains under study. For the European simulation, emissions are disaggregated from the EMEP expert emission inventory for 2004 to the utilized resolution using the criteria implemented in the HERMES emission model (Baldasano et al., 2008b). The HERMES model system, using a bottom-up approach, was adopted to estimate emissions for the Iberian Peninsula simulation at 4 km horizontal resolution, every hour. In order to evaluate the performances of the CALIOPE system, model simulations were compared with ground-based measurements from the EMEP and Spanish air quality networks. For the European domain, 45 stations have been used to evaluate NO2, 60 for O3, 39 for SO2, 25 for PM10 and 16 for PM2.5. On the other hand, the Iberian Peninsula domain has been evaluated against 75 NO2 stations, 84 O3 stations, 69 for SO2, and 46 for PM10. Such large number of observations allows us to provide a detailed discussion of the model skills over quite different geographical locations and meteorological situations.
Thermal Properties of Disordered Organic Solids and Interfaces Involving Organics.

Thermal Properties of Disordered Organic Solids and Interfaces involving Organics by Yansha Jin Co-Chair: Professor Max Shtein and Professor Kevin P. Pipe Research interest in energy conversion in organic materials has been growing steadily, driven in part by the potential advantages of light weight, mechanical flexibility, scalability and low-cost manufacturing capability. Among the unique properties of these materials is the strong coupling between charge carriers and phonons. Under this strong coupling, the organic molecules deform and rearrange in the presence of the charge carrier; the resulting carrier accompanied by local polarization of the solid is termed “Polaron”. The detailed physics of the polaronic behavior in organic materials is still relatively poorly understood, particularly at the interfaces between the organic semiconductor and the inorganic phase in energy conversion devices. Thus, there remain vast possibilities for future leaps in the development of new materials and device architectures. This thesis is aimed to generate some of this needed knowledge, focusing on phonon dynamics and heat transport in van der Waals bonded organic thin films, especially at organic-inorganic interfaces. Thermal Boundary Conductance (TBC) values are reported here for interfaces between several metals and small molecule organic semiconductors. Both experimen-
Antidepressant treatment modulates the gut microbiome and metabolome during pregnancy and lactation in rats with a depressive-like phenotype

Background: Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during and after pregnancy to manage mood disorders, with possible implications for the developing offspring. The microbiota within the gastrointestinal tract contributes to the regulation of serotonin synthesis. However, the interaction between maternal depression, SSRI use, bacterial community composition, and availability of microbiota-derived metabolites during pregnancy and lactation is not clear and may be consequential to the long-term health of mother and offspring. To determine the impact of SSRI treatment on maternal microbial community dynamics, we conducted these studies in a rat model of maternal vulnerability (MV). All MV females are on a background of genetic vulnerability, where rats exposed to early life stress (sMV) develop a depressive-like phenotype. In adulthood, sMV- and control (cMV) females were treated with either the SSRI fluoxetine (FLX) or the vehicle (Veh) throughout pregnancy and lactation. High-resolution 16S ribosomal RNA gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Results: The diversity, structure, and composition of the fecal bacterial community differed between pregnancy and lactation. Shifts in microbiota composition were accompanied by changes in fecal metabolite availability. FLX altered some key features of the transition from pregnancy to lactation, but only in females exposed to early life stress (sMV-Veh vs sMV-FLX). For instance, sMV-FLX females had lower fecal availability of the amino acids serine, proline, and aspartic acid than sMV-Veh females. These metabolite concentrations correlated negatively with the relative abundance of bacterial taxa Prevotella, Ruminococcus, and Oscillospira. Conclusions: Our studies demonstrate an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in sMV rats, possibly through parallel changes in the maternal gut microbiome. Since maternal microbial metabolites contribute to health outcomes in offspring, insults to the maternal microbiome by SSRIs might have inter-generational consequences.
Environment perception and road boundary detection from LiDAR data

Self-driving cars are in continuous development and they will give us a safer and most powerful way of moving. The research, in the autonomous vehicles field, is working all the time in order to meet all the requirements in terms of real-time, safety and traffic congestion optimization. To do these, three different development areas are the most crucial: environment perception for mapping and localization, planning and decision-making for the behavioral part and vehicle control in order to give the vehicle the proper input. The environment perception is one of the critical parts because the car has to know what there is in its surroundings: if there something moving like other cars, bikes or people and if there are some fixed obstacles to avoid the collision with them. This is crucial also because the localization of a vehicle cannot be done using only the Global Positioning System or the Inertia Measurements, thus it becomes more and more challenging to have a really good estimate of the mapping environment with high precision. In this thesis work, I proposed a SLAM approach using data coming from the LiDAR sensor. The main strategy is to use a scan-matching algorithm in order to give to the tracker the transformation between consecutive scans, that computes the relative position and then map the entire car surrounding into a single map with the track of the vehicle trajectory. This is done thanks to the Iterative Closest Point algorithm that is a powerful point-set registration process that gives excellent results in terms of accuracy, compared to other methods, for the estimate of the transformation from a moving scan to a reference one. The overall SLAM method has been carried out taking a cue from some other techniques and testing time to time different parameters setups: the car can be larger or smaller, the perceived environment can change based on the road we are on and sometimes we need improved real-time response. The boundary construction problem is strongly related to the environment perception because the car has to know also where it can go without making any damage to things or people, and what the behavioral planner has to command to the controller in order to make a turn or avoid an obstacle. With my work for this part, the vehicle has a free area in which it can move defined, in fact, through the lines of the boundaries obtained thanks to an interpolation method. The idea is to discretize the processed scan into shapes and then obtain the front free space of the vehicle. This boundary construction process is entirely made through point cloud processing and shapes analyzing. The overall coding and algorithms have been developed using MATLAB and related toolbox and they have been tested with some experimental data took with a Velodyne VLP-16 LiDAR.
Physiological Characterization and Genetic Diversity Assessment of the Rhizobial Populations Inhabiting Gliricidia sepium in selected Locations of Ampara District, Sri Lanka

Purpose: Gliricidia sepium is a wide spread multipurpose legume plant which is effective in nitrogen fixation and host to many Rhizobial strains. However, few studies have been carried out to identify and characterize the Rhizobial populations inhabiting G. sepium in Sri Lanka. The main objective of this study was to isolate and identify the stress tolerant Rhizobial strains in G. sepium. Research Method: Root nodules of G. sepium were collected from seven locations in Ampara district, which belongs to dry zone in Sri Lanka. Total of 35 isolates were screened for the tolerance for different pH, salinity, drought conditions and temperatures separately as well as in combinations. Genetic diversity of stress tolerant isolates was assessed using ERIC fingerprinting. Findings: All isolates were grown under wide range of stress conditions. The Rhizobial strains isolated from the site closer to the coast showed a high tolerance for all salinity levels as they are adapted to the high salt stress experienced in their natural habitat. The growth response to drought conditions and temperature was variable. Moreover, 14 isolates showed a high tolerance for more than two extreme stress conditions. When extreme conditions were combined, 12 isolates among 14 were survived. These 14 isolates grouped in to ten clusters at 69% similarity coefficient that make them genetically diverse. Research Limitation: The stress tolerance was observed under laboratory conditions and it does not provide enough evidence for the effectiveness of selected isolates in field. Original Value: The 14 stress tolerant Rhizobial isolates can be used to cross inoculate crop legumes to identify possible cross inoculation groups in order to reduce nitrogen fertilizer usage.
Short-Term Effects on Diversity and Biomass on Grasslands from Artificial Dykes under Grazing and Mowing Treatments

Summary Few studies document the impacts of conservation management practices such as extensive grazing or mowing on the new ecosystems created by industrial conversions. In southern France, the Rhône channelling led to the construction of dykes to protect the Tricastin industrialized area from floods. Aiming to control plant dynamics for safety reasons and to favour plant biodiversity, mowing or extensive grazing by cattle were recently tested. Monitoring from both permanent plots and aerial photographs shows that three years of extensive grazing and annual mechanical mowing have modified plant composition, significantly increasing plant species richness, evenness and heterogeneity. The increase in evenness and beta-diversity from grazing was significantly higher than from mowing. Only grazing was able to reduce the height and cover of the dominant tussock perennial grass species (Brachypodium phoenicoides), while increasing bare soil cover and thus the contribution of annual species. The Normalized Difference Vegetation Index (NDVI) obtained through aerial photographic analyses confirmed the correlation between NDVI, aboveground biomass and plant species richness for the grazed site alone, allowing the results obtained from quadrats to be generalized to the scale of the grazed site. On the Rhône’s artificial dykes, extensive grazing appears to be a better management tool than mowing to enhance plant biodiversity and meet safety objectives.
Maintenance and distribution of mammalian mitochondrial nucleoids

Mitochondria derive from the capture of an ancestral α-proteobacteria within an archaeal cell about 2 billion years ago. Since then mitochondria have retained a small proportion of genes within their multi-copy genome mitochondrial DNA (mtDNA) that encode proteins essential to the oxidative phosphorylation system. They have also evolved into a major metabolic hub in eukaryotic cells. Many biosynthetic pathways require mitochondria such as the synthesis of iron-sulfur clusters, heme, lipids and coenzyme Q. However, mitochondria are best known for their efficient ATP production through aerobic metabolism. The mitochondrial network is a dynamic structure. Through coordinated actions of membrane fusion and fission, mitochondria are able to remodel their shapes and sizes, but also their distribution within the cell. Mitochondrial dynamics is an essential process that impacts mammalian physiology in many different ways. One of the clearest examples is the relationship between mitochondrial fusion and mtDNA maintenance. In animal studies, the absence of mitochondrial fusion proteins resulted in severe reduction in mtDNA copy number. Moreover, loss of mitochondrial fusion proteins, mitofusins, was also associated with an increase in mtDNA point mutations and deletions. However, the molecular basis of these findings is poorly understood. The research presented in this thesis aims to address the underlying link between mitochondrial fusion and mtDNA maintenance. We report that inactivation of mitofusin 1 and 2 leads to mtDNA depletion and nucleoid clustering in mouse embryonic fibroblasts and heart tissue. With super-resolution microscopy and fluorescent in situ hybridization, we show that clustered nucleoids have normal diameters and are transcribed. We report that the loss of mtDNA accounts for the reduction in transcription and bioenergetic defects. Moreover, we demonstrate that the profound mtDNA depletion is not explained by genome instability, but instead it is caused by altered stoichiometry of protein components of the mtDNA replisome. Lastly, we show that outer membrane fusion is necessary to sustain rapid mtDNA replication in MEFs recovering from mtDNA depletion and in the mouse heart during postnatal development. We thus report an unexpected link between OMM fusion and replication and distribution of mtDNA in mammalian cells.