Miracle-dz/UniFAR-FTUs huggingface dataset:
Coordination of Gene Expression and Growth-Rate in Natural Populations of Budding Yeast

Cells adapt to environmental changes through genetic mutations that stabilize novel phenotypes. Often, this adaptation involves regulatory changes which modulate gene expression. In the budding yeast, ribosomal-related gene expression correlates with cell growth rate across different environments. To examine whether the same relationship between gene expression and growth rate is observed also across natural populations, we measured gene expression, growth rate and ethanol production of twenty-four wild type yeast strains originating from diverse habitats, grown on the pentose sugar xylulose. We found that expression of ribosome-related genes did not correlate with growth rate. Rather, growth rate was correlated with the expression of amino acid biosynthesis genes. Searching other databases, we observed a similar correlation between growth rate and amino-acid biosyntehsis genes in a library of gene deletions. We discuss the implications of our results for understanding how cells coordinate their translation capacity with available nutrient resources.
Endometriosis Cost Assessment (the EndoCost Study): A Cost-of-Illness Study Protocol

Aims: The EndoCost study aims to calculate the costs of endometriosis from a societal perspective. Methods: This multicentre, prevalence-based cost-of-illness analysis aggregates data on endometriosis costs and quality of life from a prospective hospital questionnaire and from both retrospective and prospective patient questionnaires. The EndoCost study comprises 12 representative tertiary care centres involved in the care of women with endometriosis in 10 countries. The sample includes patients with a laparoscopic and/or histological diagnosis of endometriosis and with at least 1 patient contact related to endometriosis during 2008. The EndoCost study measures direct healthcare costs (e.g. costs of medication, physician visits), direct non-healthcare costs (e.g. transportation costs), and indirect costs of productivity loss. Cost questions are developed specifically for the purpose of the EndoCost study. Quality of life is measured using the EuroQol-5D and relevant parts of the Global Study of Women’s Health instruments. Both aggregate analyses and country-specific analyses are planned for total costs per patient. Costs are broken down into cost drivers and into the various payers that incur costs. Conclusions: The cost estimates provided by the EndoCost cost-of-illness analysis may be used to justify the prioritisation of future research in endometriosis.
Realization and characterization of a 77 GHz reconfigurable liquid crystal reflectarray

A tunable microstrip reflectarray with beam reconfiguration capability at 77 GHz is presented. Tunablility is achieved by using anisotropic liquid crystal as RF-substrate, tunable by a biasing voltage below 15V. The reflector has been characterized by utilizing a lens setup forming a gaussian beam. The reflector properties has been extracted in terms of its reflected phase and magnitude: While it is possible to tune about 280. of phase, the associated losses are still quite high. Nevertheless, pattern measurements of the reflectarray showed distinct beam collimation towards different angles when appropriate DC control voltages are applied.
Targeting enzyme inhibitors in drug discovery

Drugs that function as enzyme inhibitors constitute a significant portion of the orally bioavailable therapeutic agents that are in clinical use today. Likewise, much of drug discovery and development efforts at present are focused on identifying and optimizing drug candidates that act through inhibition of specific enzyme targets. The attractiveness of enzymes as targets for drug discovery stems from the high levels of disease association (target validation) and druggability (target tractability) that typically characterize this class of proteins. In this expert opinion the authors describe the existing practices and future directions in drug discovery enzymology, with emphasis on how a detailed understanding of the catalytic mechanism of specific targets can be used to identify and optimize small-molecule compounds that interact with conformationally distinct forms of the enzyme, thus resulting in high potency, high selectivity inhibitors.
Underreporting of Dengue-4 in Brazil Due to Low Sensitivity of the NS1 Ag Test in Routine Control Programs

We have identified fifty-eight samples that were positive for Dengue-4 among 119 samples with negative diagnoses for dengue via the Platelia™ dengue NS1 Ag in Aracaju, State of Sergipe, Brazil. We determined that the low sensitivity of the NS1 Ag test could be related to secondary dengue infections in the studied population. Therefore, we concluded that the sensitivity and specificity of the Platelia™ dengue NS1 Ag test as a screening method for monitoring circulating dengue serotypes must be reevaluated. In addition, regional endo-epidemic profiles should also be considered due to the prevalence of secondary responses.
SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na+/Cl−-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy. Furthermore, psychostimulants such as cocaine and amphetamines have the SLC6 NTTs as primary targets. Beginning with the determination of a high-resolution structure of a prokaryotic homolog of the mammalian SLC6 transporters in 2005, the understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly. Furthermore, intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights. This review provides an update of these advances and their implications for the current understanding of the SLC6 NTTs.
Assessment of the Eye Irritating Properties of Chemicals by Applying Alternatives to the Draize Rabbit Eye Test: The Use of QSARs and In Vitro Tests for the Classification of Eye Irritation

Huggins has reported on the current situation relating to the development of alternatives to the Draize eye irritation test with rabbits, and an ECVAM Working Group have reviewed the efforts needed in order to replace this animal test within the next 10 years by using the results of non-animal assessment methods. Our report reviews regulatory experience gained over the last 20 years with the EU chemicals notification procedure with respect to the assessment of eye lesions observed in Draize tests. The nature of eye lesions and their importance for classification and labelling of possible hazards to human eyes are evaluated and discussed, with a view to promoting the development of specific in vitro assays which are able to discriminate between eye damage, moderate eye irritation, and minor irritation effects which are completely reversible within a few days. Structural alerts for the prediction of eye irritation/corrosion hazards to be classified and labelled according to international classification criteria, are presented, which should be validated in accordance with internationally agreed (OECD) principles for (Q)SAR system validation. Physicochemical limit values for prediction of the absence of any eye irritation potential relevant for human health can make available a definition of the applicability domains of alternative methods developed for the replacement of the Draize eye irritation test.
Epigenetic Control of Gene Expression in the Alcoholic Brain

Chronic alcohol exposure causes widespread changes in brain gene expression in humans and animal models. Many of these contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. There is an emerging appreciation for the role of epigenetic processes in alcohol-induced changes in brain gene expression and behavior. For example, chronic alcohol exposure produces changes in DNA and histone methylation, histone acetylation, and microRNA expression that affect expression of multiple genes in various types of brain cells (i.e., neurons and glia) and contribute to brain pathology and brain plasticity associated with alcohol abuse and dependence. Drugs targeting the epigenetic “master regulators” are emerging as potential therapeutics for neurodegenerative disorders and drug addiction.
Immunocytochemical characterization of extracellular matrix proteins expressed by cultured glioma cells.

The immunolocalization of type I, III and IV collagens and fibronectin in two rat glioma cell lines in vitro (BT4C and BT4Cn) is described. In addition, antibodies against denatured type I and III collagens were used to study breakdown products of native type I and III collagens. For the BT4C cells, the extracellular matrix expression in monolayer cultures and in multicellular tumor spheroids was compared. Type IV collagen was strongly expressed in BT4C tumor spheroids but was negative in the corresponding monolayer cultures. Denatured type I collagen was found both in monolayers and in spheroids of BT4C, suggesting either a rapid turnover (i.e., synthesis and immediate breakdown) of type I collagen or an altered collagen gene transcription. Both cell lines were negative for native type I and III and denatured type III collagen. Fibronectin was strongly expressed in both cell lines. Supporting the immunofluorescence data, the hydroxyproline content in the tumor spheroids was twice the amount found in monolayer cultures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunoblotting also verified the immunostaining experiments, showing that glioma spheroids and injected tumor cells have the potential for fibronectin and collagen production, given the appropriate growth conditions.
Layout-Accurate Design and Implementation of a High-Throughput Interconnection Network for Single-Chip Parallel Processing

A mesh of trees (MoT) on-chip interconnection network has been proposed recently to provide high throughput between memory units and processors for single-chip parallel processing (Balkan et al., 2006). In this paper, we report our findings in bringing this concept to silicon. Specifically, we conduct cycle-accurate Verilog simulations to verify the analytical results claimed in (Balkan et al., 2006). We synthesize and obtain the layout of the MoT interconnection networks of various sizes. To further improve throughput, we investigate different arbitration primitives to handle load and store, the two most common memory operations. We also study the use of pipeline registers in large networks when there are long wires. Simulation based on full network layout demonstrates that significant throughput improvement can be achieved over the original proposed MoT interconnection network. The importance of this work lies in its validation of performance features of the MoT interconnection network, as they were previously shown to be competitive with traditional network solutions. The MoT network is currently used in an eXplicit multi-threading (XMT) on-chip parallel processor, which is engineered to support parallel programming. In that context, a 32-terminal MoT network could support up to 512 on-chip XMT processors. Our 8-terminal network that could serve 8 processor clusters (or 128 total processors), was also accepted recently for fabrication.
A feasibility study of self-heating concrete utilizing carbon nanofiber heating elements

This paper presents the development of an electric, self-heating concrete system that uses embedded carbon nanofiber paper as electric resistance heating elements. The proposed system utilizes the conductive properties of carbon fiber materials to heat a surface overlay of concrete with various admixtures to improve the concrete’s thermal conductivity. The development and laboratory scale testing of the system were conducted for the various compositions of concrete containing, separately, carbon fiber, fly ash, and steel shavings as admixtures. The heating performances of these concrete mixtures with the carbon fiber heating element were experimentally obtained in a sub-freezing ambient environment in order to explore the use of such a system for deicing of concrete roadways. Analysis of electric power consumption, heating rate, and obtainable concrete surface temperatures under typical power loads was performed to evaluate the viability of a large scale implementation of the proposed heating system for roadway deicing applications. A cost analysis is presented to provide a comparison with traditional deicing methods, such as salting, and other integrated concrete heating systems.
Fertility programs for lactating dairy cows, their physiological basis, and the factors that are critical for their success

Lactating dairy cows have unique reproductive responses compared to when they were heifers that result in distinctly different reproductive measurements and pregnancy outcomes that can be partially overcome with pharmacological strategies. These parameters include circulating progesterone and estradiol concentrations, ovulatory follicle and corpus luteum diameter, incidence of anovulation and double ovulations, time in estrus, pregnancies per artificial insemination and pregnancy losses. Circulating concentrations of progesterone during diestrus are approximately half that in cows compared with heifers. This marked difference in progesterone is likely the explanation for an increased size in diameter of the ovulatory follicle and incidence of double ovulations in cows compared with heifers. Differences in diameter of the ovulatory follicle may explain why cows have greater corpora lutea diameters compared to heifers. The increase in double ovulations appears to be a key driver in the increase in twinning and pregnancy loss as dairy heifers transition to primi- and multiparous cows. Reduced estradiol concentrations in cows at time of estrus helps to explain the decreased duration of estrus in cows compared with heifers. Concentrations of progesterone during growth of the ovulatory follicle may be a key driver in differences in pregnancies per AI in cows compared with heifers. The difference in circulating progesterone may be related to LH overstimulation of the oocyte/cumulus complex in cows compared to when they were heifers. Pharmacological strategies have been developed in lactating dairy cows to manipulate ovarian development to create a hormonal environment similar to that of heifers. Three primary strategies, Presynch-11, G6G and Double Ovsynch appear to enhance fertility of dairy cows. This review discusses how these three strategies manipulate ovarian development similar to that of heifers and why compelling data indicate these programs should be referred to as “fertility programs. ”
Patterns of late spring frost leaf damage and recovery in a European beech (Fagus sylvatica L.) stand in south-eastern Germany based on repeated digital photographs

Damage by late spring frost is a risk deciduous trees have to cope with in order to optimize the length of their growing season. The timing of spring phenological development plays a crucial role, not only at the species level, but also at the population and individual level, since fresh new leaves are especially vulnerable. For the pronounced late spring frost in May 2011 in Germany, we studied the individual leaf development of 35 deciduous trees (mainly European beech Fagus sylvatica L.) at a mountainous forest site in the Bayerischer Wald National Park using repeated digital photographs. Analyses of the time series of greenness by a novel Bayesian multiple change point approach mostly revealed five change points which almost perfectly matched the expected break points in leaf development: (i) start of the first greening between day of the year (DOY) 108–119 (mean 113), (ii) end of greening, and (iii) visible frost damage after the frost on the night of May 3rd/4th (DOY 123/124), (iv) re-sprouting 19–38 days after the frost, and (v) full maturity around DOY 178 (166–184) when all beech crowns had fully recovered. Since frost damage was nearly 100%, individual susceptibility did not depend on the timing of first spring leaf unfolding. However, we could identify significant patterns in fitness linked to an earlier start of leaf unfolding. Those individuals that had an earlier start of greening during the first flushing period had a shorter period of recovery and started the second greening earlier. Thus, phenological timing triggered the speed of recovery from such an extreme event. The maximum greenness achieved, however, did not vary with leaf unfolding dates. Two mountain ashes (Sorbus aucuparia L.) were not affected by the low temperatures of -5°C. Time series analysis of webcam pictures can thus improve process-based knowledge and provide valuable insights into the link between phenological variation, late spring frost damage, and recovery within one stand.
Selective Inhibition of Inward Rectifier K+ Channels (Kir2.1 or Kir2.2) Abolishes Protection by Ischemic Preconditioning in Rabbit Ventricular Cardiomyocytes

Volume regulatory Cl− channels are key regulators of ischemic preconditioning (IPC). Because Cl− efflux must be balanced by an efflux of cations to maintain cell membrane electroneutrality during volume regulation, we hypothesize that IK1 channels may play a role in IPC. We subjected cultured cardiomyocytes to 60-minute simulated ischemia (SI) followed by 60-minute of simulated reperfusion (SR) and assessed percent cell death using trypan blue staining. Ischemic preconditioning (10-minute SI/10-minute SR) significantly (P<0.0001) reduced the percent cell death in nontransfected cardiomyocytes [IPCCM 18.0±2.1% versus control (CCM) 48.3±1.0%]. IPC protection was not altered by overexpression of the reporter gene (enhanced green fluorescent protein, EGFP). However, overexpression of dominant-negative Kir2.1 or Kir2.2 genes using adenoviruses (AdEGFPKir2.1DN or AdEGFPKir2.2DN) encoding the reporter gene EGFP prevented IPC protection [both IPCCM+AdEGFPKir2.1DN 45.8±2.3% (mean±SEM) and IPCCM+AdEGFPKir2.2DN 47.9±1.4% versus IPCCM; P<0.0001] in cultured cardiomyocytes (n=8 hearts). Transfection of cardiomyocytes with AdEGFPKir2.1DN or AdEGFPKir2.2DN did not affect cell death in control (nonpreconditioned) cardiomyocytes (both CCM+ AdEGFPKir2.1DN 45.8±0.7% and CCM+AdEGFPKir2.2DN 46.2±1.3% versus CCM; not statistically significant). Similar effects were observed in both cultured (n=5 hearts) and freshly isolated (n=4 hearts) ventricular cardiomyocytes after IK1 blockade with 20 &mgr;mol/L BaCl2 plus 1 &mgr;mol/L nifedipine (to prevent Ba2+ uptake). Nifedipine alone neither protected against ischemic injury nor blocked IPC protection. Our findings establish that IK1 channels play an important role in IPC protection.
Getting Ahead or Getting Along? The Two-Facet Conceptualization of Conscientiousness and Leadership Emergence

We propose a theoretical process model of the social construction of leadership that sheds light on the relationship between conscientiousness and leadership emergence. The socioanalytic theory of personality is invoked to hypothesize different mediational paths linking the two facets of conscientiousness, achievement striving and duty, with leadership emergence. We tested the theoretical model with data from 249 employees matched with data from 40 of their coworkers and 40 supervisors employed in a Fortune 500 organization. Results indicate that the relationship between achievement striving and leadership emergence is partially mediated by competitiveness, providing support for a getting-ahead path to leadership. In contrast, the relationship between duty and leadership emergence is, in part, carried forward by trust, helping role perceptions, and helping behavior, supporting a getting-along path to leadership. Consistent with the self versus other distinction theoretically posited with regard to the facets of conscientiousness, although helping behavior is a predictor of leadership emergence, achievement strivers help only when they perceive helping as being an in-role requirement, whereas dutiful individuals enlarge their helping role perceptions.
Evolutionary multi-objective optimization for mesh simplification of 3D open models

Polygonal surface models are typically used in three dimensional 3D visualizations and simulations. They are obtained by laser scanners, computer vision systems or medical imaging devices to model highly detailed object surfaces. Surface mesh simplification aims to reduce the number of faces used in a 3D model while keeping the overall shape, boundaries and volume. In this work, we propose to deal with the 3D open model mesh simplification problem from an evolutionary multi-objective viewpoint. The quality of a solution is defined by two conflicting objectives: the accuracy and the simplicity of the model. We adapted the Non-Dominated Sorting Genetic Algorithm II NSGA-II and the Multi-Objective Evolutionary Algorithm Based on Decomposition MOEA/D to tackle the problem. We compare their performance with two classic approaches and two single-objective implementations. The comparison has been carried out using six different datasets from six corresponding real-world objects. Experimental results have demonstrated that NSGA-II and MOEA/D performs similarly and obtain the best solutions for the studied problem.
Survival characteristics and prognostic variables of dogs with preclinical chronic degenerative mitral valve disease attributable to myxomatous degeneration.

BACKGROUND Preclinical myxomatous mitral valve degeneration (MMVD) includes a heterogeneous group of dogs. Therefore, identifying risk factors for progression of the disease is of clinical importance. OBJECTIVES To investigate survival time and risk factors for clinical and echocardiographic variables taken at initial examination for clinical progression in preclinical MMVD dogs. ANIMALS A total of 256 dogs with stage B1 or B2 MMVD. MATERIALS AND METHODS Medical records of 256 dogs with preclinical MMVD were reviewed retrospectively. Long-term outcome was assessed by telephone interview. Dogs alive at the time of phone interview were asked to return to the hospital for re-evaluation of their cardiac status. RESULTS Seventy of 256 (27.3%) dogs died during the observation period. The median survival time, regardless of cause of death, was 588 (range 75-1,668) days. The presence of a murmur was associated with an increased risk of death (AHR 2.14; 95% CI 1.12, 4.11; P = 0.022). Thirty (12%) deaths were considered cardiac related. LA/Ao > 1.4 was the only negative predictor (AHR 2.64; 1.13, 6.13; P = 0.024) for cardiac-related deaths. Eighty-three dogs were re-examined, of which 34 progressed to a more advanced stage of MMVD. The presence of Emax > 1.2 (AHR 2.75; 95% CI 1.01, 7.48; P = 0.047) and cough (AHR 7.89; 95% CI 3.18, 20.07; P < 0.001) were significant in the multivariate analysis. CONCLUSIONS AND CLINICAL IMPORTANCE Preclinical MMVD represents a relatively benign condition in dogs. Clinicians might find stratification of this dog population according to risk factors based on clinical and echocardiographic findings helpful in determining treatment.