Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequent inactivation of the BAP1 gene in epithelioid‐type malignant mesothelioma

In the present study, we analyzed genomic alterations of BRCA1‐associated protein 1 (BAP1) in 23 malignant mesotheliomas (MMs), 16 epithelioid and seven non‐epithelioid, consisting of 18 clinical specimens and five established cell lines. In examining these samples for homozygous deletions and sequence‐level mutations, we found biallelic BAP1 gene alterations in 14 of 23 MMs (61%). Seven of these 14 MMs had homozygous deletions of the partial or entire BAP1 gene, another five had sequence‐level mutations, including small deletions, a nonsense mutation, and missense mutations with additional monoallelic deletions, and the remaining two had homozygous mutations without allelic loss. All but one of the 14 BAP1 gene mutations were found in the epithelioid‐type MMs; BAP1 mutations were found in 13 of 16 epithelioid‐type MMs, but in only one of seven non‐epithelioid‐type MMs (13/16 vs 1/7; P = 0.005). There was no BAP1 mRNA expression in MMs with biallelic deletion and repressed expression was confirmed in MM specimens with deletion/mutation as compared with Met5a, SV40‐transformed normal mesothelial cells. Western blot showed that seven of eight epithelioid MMs analyzed were BAP1 negative. Immunostaining with anti‐BAP1 antibody in normal lung tissues revealed clear nuclear staining of normal mesothelial cells. No nuclear staining was observed among BAP1 mutation‐positive MM tumors, whereas nuclear staining was observed among BAP1 mutation‐negative MM tumors. These results suggest that the lack of the tumor suppressor BAP1 may be more specifically involved in the pathogenesis of epithelioid MM rather than non‐epithelioid MM, and would be useful for diagnosis of epithelioid‐type MM. (Cancer Sci 2012; 103: 868–874)
From newspeak to cyberspeak: a history of Soviet cybernetics

In this book Slava Gerovitch argues that Soviet cybernetics was not just an intellectual trend but a social movement for radical reform in science and society as a whole. Followers of cybernetics viewed computer simulation as a universal method of problem solving and the language of cybernetics as a language of objectivity and truth. With this new objectivity, they challenged the existing order of things in economics and politics as well as in science.
The pig as a model for the study of radiation effects on the lung.

PURPOSE The treatment of thoracic malignancies is frequently limited by the 'tolerance' of normal lung tissue. In order to learn more about the factors that influence lung tolerance an animal model that closely mimics the clinical exposure situation is required. The lungs of pigs are similar to those of man in a variety of ways and the animal's size permits the irradiation of partial tissue volumes comparable with those used clinically; very rarely in man is the whole lung irradiated. In this report, the available data for the effects of irradiation on pig lung are reviewed as they relate to the key issues in radiotherapy. RESULTS The dose-effect relationships for exposure to single doses indicate that for a significant impairment in both early and late lung function and for the histological detection of fibrosis, the dose-related changes in pig and man are similar. Studies with dose-fractionation using X-rays indicate a large dependence of the iso-effective dose on fraction number and fraction size, and the parameters obtained were not significantly influenced by the time of assessment after irradiation. A simple power-law function fitted the whole data set better than the linear-quadratic model, with a fraction number exponent (N) of 0.44+/-0.06 for treatments given in 1-30 fractions. The alpha/beta values ranged from 0.6 to 4.86 Gy, tending to increase with the length of the follow-up period; however; the majority of these alpha/beta values were not significantly different from zero at the 5% level. Studies of the effect of changes in the volume of lung tissue irradiated indicated the need for care in the use of the terms 'tolerance' and 'iso-effective' dose. Doses that were iso-effective for the severity of regional damage were not matched by those for total lung function. The same level of damage in a small volume compared with a large volume had less effect, i.e. was better tolerated in terms of changes in total lung function. CONCLUSION Iso-effective doses in pig and humans are lower than those for the more common laboratory animal species. This observation may be related to the differences in anatomical structure of the lungs in the different species.
Loss of tubedown expression as a contributing factor in the development of age-related retinopathy.

PURPOSE Tubedown (Tbdn), a cortactin-binding acetyltransferase subunit, regulates retinal vascular permeability and homeostasis in adulthood. Here the authors explore whether Tbdn loss during aging might contribute to the mechanisms underlying age-related neovascular retinopathy. METHODS A conditional endothelial-specific transgenic model of Tbdn loss was compared with aged mouse and human specimens from 5- to 93-year-old individuals. Specimens were analyzed by morphometric measurements and for functional markers using immunohistochemistry and Western blot analysis. RESULTS An age-dependent decrease in Tbdn expression in endothelial cells of the posterior pole of the eye correlated with pathologic changes in choroidal and retinal tissues of aged mice. In humans, aged specimens without eye disease exhibited a moderate decrease in retinal and choroidal endothelial Tbdn expression compared with younger persons, whereas a greater decrease in choroid vascular Tbdn expression was observed in patients with age-related macular degeneration. In mice, Tbdn loss resulting from old age or conditional Tbdn knockdown was associated with retinal lesions showing significant extravascularly localized albumin and correlated with increased activity of senescence-associated β-galactosidase in the retinal pigment epithelium. A range of abnormalities in RPE, Bruch's membrane, and choriocapillaris observable at the ultrastructural level in Tbdn-knockdown eyes recapitulate those present in human AMD. CONCLUSIONS This work provides evidence that the marked decrease in the level of expression of Tbdn in the retinal and choroidal vasculature during aging contributes to the multifactorial process that leads to the development of age-related retinopathy and choroidopathy.
Timing of Flowering: Opposed Selection on Different Fitness Components and Trait Covariation

The timing of reproduction influences how organisms interact with the environment and can have important fitness effects. In plants, the evolution of flowering phenology is often interpreted as the response to selection from mutualists, although antagonistic interactions may also be important. We examined direct and indirect phenotypic selection on the start of flowering via mutualistic and antagonistic interactions in the perennial herb Lathyrus vernus over 7 years. Flowering start influenced seed set, predispersal seed predation, and risk of grazing. These effects were in opposed directions and partly influenced different components of fitness. Combining information about effects on fitness components with information about links between fitness components and average lifetime fitness, in terms of population growth rate, showed that earlier flowering was associated with higher lifetime fitness in all years. These relationships were, however, mediated largely by variation in flower number, and direct selection on first flowering date was more variable among years. We conclude that long‐term studies correcting for indirect selection and environmental covariance are needed to understand selection on reproductive phenology and that demographic approaches are necessary to assess selection mediated by several agents and influencing several components of fitness.
Nondeclarative learning in children with Specific Language Impairment: Predicting regularities in the visuomotor, phonological, and cognitive domains

Ullman (2004) suggested that Specific Language Impairment (SLI) results from a general procedural learning deficit. In order to test this hypothesis, we investigated children with SLI via procedural learning tasks exploring the verbal, motor, and cognitive domains. Results showed that compared with a Control Group, the children with SLI (a) were unable to learn a phonotactic learning task, (b) were able but less efficiently to learn a motor learning task and (c) succeeded in a cognitive learning task. Regarding the motor learning task (Serial Reaction Time Task), reaction times were longer and learning slower than in controls. The learning effect was not significant in children with an associated Developmental Coordination Disorder (DCD), and future studies should consider comorbid motor impairment in order to clarify whether impairments are related to the motor rather than the language disorder. Our results indicate that a phonotactic learning but not a cognitive procedural deficit underlies SLI, thus challenging Ullmans’ general procedural deficit hypothesis, like a few other recent studies.
Stigma and discrimination against people with schizophrenia related to medical services

Objective: To investigate whether people with schizophrenia experience discrimination when using health care services. Methods: A cross-sectional survey in 27 countries in centres affiliated to the INDIGO Research Network, using face-to-face interviews with 777 participants with schizophrenia (62% male and 38% female). We analysed the data related to health issues, including health care, disrespect of mental health staff, and also personal privacy, safety and security, starting a family, pregnancy and childbirth. Discrimination was measured by the Discrimination and Stigma Scale (DISC), which consists of 36 items comprising three sub-scales: positive experienced discrimination; negative experienced discrimination; and anticipated discrimination. Results: More than 17% of patients experienced discrimination when treated for physical health care problems. More than 38% of participants felt disrespected by mental health staff, with higher ratings in the post-communist countries. Conclusions: Mental health service providers have a key role in decreasing stigma in their provision of health care, and by doing more against stigmatizing and discriminating practices on the therapeutic and organizational level. This will require a change of attitudes and practices among mental and physical health care staff.
Determination of metformin in human plasma and urine by high-performance liquid chromatography using small sample volume and conventional octadecyl silane column.

PURPOSE To develop a selective and sensitive high-performance liquid chromatographic method for the determination of metformin in human plasma and urine, using a conventional reverse phase column and low specimen volume. METHODS Extraction of metformin and ranitidine (as internal standard) from plasma and urine samples (100 µL) was performed with a 1-butanol-hexane (50:50, v/v) mixture under alkaline conditions followed by back-extraction into diluted acetic acid. Chromatography was carried out using a C18 column (250 mm×4.6 mm, 5 μm). A mobile phase consisting of acetonitrile and KH2PO4 (34:66, v/v) and sodium dodecyl sulphate (3 mM) was pumped at an isocratic flow rate of 0.7 mL/min. RESULTS The calibration curves were linear (>0.995) in the concentration ranges of 10-5000 and 2-2000 μg/mL for metformin in plasma and urine respectively. The mean absolute recoveries for 100 and 1000 ng/mL metformin in plasma using the present extraction procedure were 93.7 and 88.5%, respectively. The intra- and inter-day coefficients of variation in plasma and urine were <20% at the lowest, and <16% at other concentrations. The percent error values were less than 2% in plasma while it reached ~9% in urine. The lower limits of quantification were 7.8 ng/mL and 1.6 μg/mL of metformin base in plasma and urine respectively. CONCLUSION The method showed high calibers of sensitivity and selectivity for monitoring therapeutic concentrations of metformin in both plasma and urine based on a 0.1 ml sample size. _____________________________________________________________________________________
Stochastic Resource Provisioning for Containerized Multi-Tier Web Services in Clouds

Under today's bursty web traffic, the fine-grained per-container control promises more efficient resource provisioning for web services and better resource utilization in cloud datacenters. In this paper, we present Two-stage Stochastic Programming Resource A llocator (2SPRA). It optimizes resource provisioning for containerized n-tier web services in accordance with fluctuations of incoming workload to accommodate predefined SLOs on response latency. In particular, 2SPRA is capable of minimizing resource over-provisioning by addressing dynamics of web traffic as workload uncertainty in a native stochastic optimization model. Using special-purpose OpenOpt optimization framework, we fully implement 2SPRA in Python and evaluate it against three other existing allocation schemes, in a Docker-based CoreOS Linux VMs on Amazon EC2. We generate workloads based on four real-world web traces of various traffic variations: AOL, WorldCup98, ClarkNet, and NASA. Our experimental results demonstrate that 2SPRA achieves the minimum resource over-provisioning outperforming other schemes. In particular, 2SPRA allocates only 6.16 percent more than application's actual demand on average and at most 7.75 percent in the worst case. It achieves 3x further reduction in total resources provisioned compared to other schemes delivering overall cost-savings of 53.6 percent on average and up to 66.8 percent. Furthermore, 2SPRA demonstrates consistency in its provisioning decisions and robust responsiveness against workload fluctuations.
trp RNA-binding Attenuation Protein-mediated Long Distance RNA Refolding Regulates Translation of trpE inBacillus subtilis *

Expression of the trpEDCFBA operon is regulated at both the transcriptional and translational levels by thetrp RNA-binding attenuation protein (TRAP) ofBacillus subtilis. When cells contain sufficient levels of tryptophan to activate TRAP, the protein binds to trpoperon transcripts as they are being synthesized, most often causing transcription termination. However, termination is never 100% efficient, and transcripts that escape termination are subject to translational control. We determined that TRAP-mediated translational control of trpE can occur via a novel RNA conformational switch mechanism. When TRAP binds to the 5′-untranslated leader segment of a trp operon read-through transcript, it can disrupt a large secondary structure containing a portion of the TRAP binding target. This promotes refolding of the RNA such that thetrpE Shine-Dalgarno sequence, located more than 100 nucleotides downstream from the TRAP binding site, becomes sequestered in a stable RNA hairpin. Results from cell-free translation, ribosome toeprint, and RNA structure mapping experiments demonstrate that formation of this structure reduces TrpE synthesis by blocking ribosome access to the trpE ribosome binding site. The role of the Shine-Dalgarno blocking hairpin in controlling translation oftrpE was confirmed by examining the effect of multiple nucleotide substitutions that abolish the structure without altering the Shine-Dalgarno sequence itself. The possibility of protein-mediated RNA refolding as a general mechanism in controlling gene expression is discussed.
Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma*

We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates were independently verified by lectin magnetic bead array-immunoblotting, confirming the validity of the relative quantitation approach. Thus, we have identified candidate biomarkers, which, following large-scale clinical evaluation, can be developed into diagnostic blood tests. A key feature of the pipeline is the potential for rapid translation of the candidate biomarkers to lectin-immunoassays.
Vascular Development in Early Human Embryos and in Teratomas Derived from Human Embryonic Stem Cells1

Abstract During early human embryonic development, blood vessels are stimulated to grow, branch, and invade developing tissues and organs. Pluripotent human embryonic stem cells (hESCs) are endowed with the capacity to differentiate into cells of blood and lymphatic vessels. The present study aimed to follow vasculogenesis during the early stages of developing human vasculature and to examine whether human neovasculogenesis within teratomas generated in SCID mice from hESCs follows a similar course and can be used as a model for the development of human vasculature. Markers and gene profiling of smooth muscle cells and endothelial cells of blood and lymphatic vessels were used to follow neovasculogenesis and lymphangiogenesis in early developing human embryos (4–8 weeks) and in teratomas generated from hESCs. The involvement of vascular smooth muscle cells in the early stages of developing human embryonic blood vessels is demonstrated, as well as the remodeling kinetics of the developing human embryonic blood and lymphatic vasculature. In teratomas, human vascular cells were demonstrated to be associated with developing blood vessels. Processes of intensive remodeling of blood vessels during the early stages of human development are indicated by the upregulation of angiogenic factors and specific structural proteins. At the same time, evidence for lymphatic sprouting and moderate activation of lymphangiogenesis is demonstrated during these developmental stages. In the teratomas induced by hESCs, human angiogenesis and lymphangiogenesis are relatively insignificant. The main source of blood vessels developing within the teratomas is provided by the murine host. We conclude that the teratoma model has only limited value as a model to study human neovasculogenesis and that other in vitro methods for spontaneous and guided differentiation of hESCs may prove more useful.
Home Management of Acute Diarrhoea in Czech Children

Objectives: The aim of the study was to investigate home management of childhood acute diarrhoea. Methods: A cross-sectional questionnaire study was conducted in Prague, Czech Republic. The caregivers of 210 children ages 6 to 59 months were approached in public places and interviewed about the knowledge and use of oral rehydration solution (ORS) and about management of the child's last episode of diarrhoea. Results: Maternal knowledge of ORS (27.6%) and ORS use (1.9% during the child's last episode of diarrhoea) were low. They were positively associated with education level but not with the source of advice. Small volumes of ORS given and its refusal were issues. Increased amounts of fluid offered to 60% of children were significantly associated with higher maternal education and relatives/friends (76%) as a source of advice rather than a paediatrician (57.9%), the most frequent source of advice (78.1%). Black tea was the most common fluid given (86.2%) followed by plain or mineral water (41.9%). Breast-feeding of all breast-fed children was continued; low-lactose formula was given in 1 case only. Withholding food was rare (5.2%), but the diet of 75.2% cases was modified. Drugs were given to 52.4% children, most frequently smectite and/or probiotics, and antimicrobials were given to 6.4% cases.
An approach for classification of health risks based on air quality levels

There is a need to exploit the available data collected on environment for the development of smart cities in order to improve the air quality which in turn can improve the quality of life for a city. Air pollution is becoming a serious concern to the society as the air pollutants are very hazardous in nature. Pollutants affect the health and causes respiratory and cardiac problems. If air pollutants cross the limits it might be life threatening. Software or tool can be developed whose results can be applied for predicting air pollution levels, predicting air pollution related health concerns, monitoring controlling air pollution and this is challenging one. This paper focuses on analysis of air based on the available data of various air pollutants such as NO2, SO2, CO and O3. The dataset is downloaded from Kaggle website which contains air pollutant's with corresponding AQI values. This paper implements Naive Bayes and Decision tree J48 algorithm for predicting the health concern. The categories based on Air Quality Index(AQI) are good, moderate, (unhealthy for sensitive groups) unhealthy_s, unhealthy, very_unhealthy. The result shown that decision tree algorithm gives 91.9978 % accuracy which is more than that of Naïve Bayes algorithm viz. 86.663%.