The Effects of Halo Reduction Training on Individuals Varying in Cognitive Complexity

The effects of training in halo reduction on cognitively complex and noncomplex individuals were studied. Three main hypotheses were tested: 1) There would be a significant negative relationship between cognitive complexity and halo. 2) Training would significantly reduce halo. 3) Training would significantly reduce the amount of halo in the ratings of cognitively noncomplex individuals, but not in the ratings of complex individuals. Forty undergraduate students were given a cognitive complexity test, and high and low complexity groups were identified. Subjects were randomly assigned to either the Training or the No-Training condition. The training groups participated in a lecture-discussion session aimed at rating improvement. The No-Training groups worked on a Sentence-Completion exercise. All subjects viewed a videotaped discussion and rated two discussion participants. The relationship between halo and complexity was not significant for either of the rates; however, for one rate, the results were in the expected negative direction (the product moment correlation coefficient between the rating variance and complexity was .3987, .0

Design and Development of the Space Shuttle Tail Service Masts

The successful launch of a space shuttle vehicle depends on the proper operation of two tail service masts (TSMs). Reliable TSM operation is assured through a comprehensive design, development, and testing program. The results of the concept verification test (CVT) and the resulting impact on prototype TSM design are presented. The design criteria are outlined, and the proposed prototype TSM tests are described

Patient Empowerment through Summarization of Discussion Threads on Treatments in a Patient Self-Help Forum

Self-help patient fora are widely used for information acquisition and exchange of experiences, e.g., on the effects of medical treatments for a disease. However, a new patient may have difficulties in getting a fast overview of the information inside a large forum. We propose TinnitusTreatmentMonitor, a prototype tool for the summarization and sentiment characterization of postings on medical treatments. We report on applying TinnitusTreatmentMonitor on the platform TinnitusTalk1, a self-help platform for tinnitus patients

Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity

The endoplasmic reticulum (ER) is responsible for folding secretory and membrane proteins, but disturbed ER proteostasis may lead to protein aggregation and subsequent cellular and clinical pathologies. Chemical chaperones have recently emerged as a potential therapeutic approach for ER stress-related diseases. Here, we identified 2-phenylimidazo[2,1-b]benzothiazole derivatives (IBTs) as chemical chaperones in a cell-based high-throughput screen. Biochemical and chemical biology approaches revealed that IBT21 directly binds to unfolded or misfolded proteins and inhibits protein aggregation. Finally, IBT21 prevented cell death caused by chemically induced ER stress and by a proteotoxin, an aggression-prone prion protein. Taken together, our data show the promise of IBTs as potent chemical chaperones that can ameliorate diseases resulting from protein aggregation under ER stress

Comprehensive fitness maps of Hsp90 show widespread environmental dependence

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard conditions and under five stress conditions. To our knowledge, these are the largest determined comprehensive fitness maps of point mutants. The growth of many variants differed between conditions, indicating that environment can have a large impact on Hsp90 evolution. Multiple variants provided growth advantages under individual conditions; however, these variants tended to exhibit growth defects in other environments. The diversity of Hsp90 sequences observed in extant eukaryotes preferentially contains variants that supported robust growth under all tested conditions. Rather than favoring substitutions in individual conditions, the long-term selective pressure on Hsp90 may have been that of fluctuating environments, leading to robustness under a variety of conditions

Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts

Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.Project ON.2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000021), co-funded by North Portugal Regional Operational Program (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund (ERDF) and also supported by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014)info:eu-repo/semantics/publishedVersio

Development Traceability Systems for Agricultural products in India

Food safety has become a major concern in India, after the adulterated milk scam, usage of toxic chemicals in food and change the essential ingredient with something lesser value were found on large extent in recent years. Thus, there is a need of proper traceability systems in the Indian food industry, for reducing the cases of food safety incidents and fraudulence. With purpose in mind, in the beginning of this PhD thesis, there is a review of the existing traceability techniques in India which include RFID, Holograms, Barcode and other tracking media to monitor production processes. There are some Indian initiatives of food traceability system from APEDA in association with GS, that have created Anarnet, Peanut.net, Meat.net and Grapenet that control traceability for certain products. Also, there are some experiences with barcoding and several ICTs initiatives that are actively working in many states of India, that try to control the food safety and protect the consumers. However, several problems are extensively affecting the Indian food sectors that unbalanced their routine activities. The current traceability systems are behaving abnormally due to number of factors like the high level of illiteracy and lack of proper infrastructures. These situations block the implementation and adoption of ICT initiatives in rural India. In this framework, the objectives of the thesis are: 1) To evaluate current food traceability systems in India and assess the level of ICT adoption in rural India; 2) To analyze the shortcomings of ICT initiatives amongst the smallholders’ farmers in India 3) To support local food systems in India and direct sourcing of raw material from farmers to customer, retailer, food business operator, and exporter in India. 4) To increase the net income of smallholder farmers by providing market facility at the farm gate through web-based traceability portal in India. For achieving these objectives, two experimental studies were done. The first one (section 5.1), was focused in the adoption of ICT tools for tracking and tracing banana batches, in a case study in Jalgaon district (India). To test the hypothesis a field survey was conducted, where 115 respondents were interviewed including smallholder banana farmers and traders. The responses obtained through field survey were analyzed to get information related to knowledge of ICT tools, comfortable in using of local language for ICT, awareness and need for ICT in banana farming production. Hence it has been concluded that majority of traders don’t have effective traceability system and farmers are completely unresponsive about ICT tools. The second experimental study (in section 5.2) is dedicated to provide Indian farmers a new type of online web-based traceability portal, which would be useful for food operators, logistic providers and consumers. This portal as explained in the chapter, would save time and cost in building up traceability system for Indian food sector, wherein tracking and tracing information of food products using webserver and web API technology can be easily obtained. Thus, with the help of this portal, the country’s smallholder farmer will raise their annual income, and it improves the processes of fresh food products supply chain in India. The chapter titled as “Final Conclusions” provides a summary of what has been covered in this thesis and highlights the findings. Being the most important, that direct selling of farm produce is the best way to increase the income for the farmers which has found in survey area in Jalgaon district. And the web based traceability portal provides farmer with access to business opportunities at farm gate without linkage of any brokers in India. Finally, some suggestions for future research are presented. For keeping improving food traceability systems in India; guidance should be provided for small-scale food producers on internal control and development of effective risk management. Also, efforts need to be made to increase awareness on the ways to use and access product traceability information with the help of digital technology; and finally, focus should be made on the installation and development of the public web server and web APIs for an effective traceability control

Paralog dependency indirectly affects the robustness of human cells

Abstract The protective redundancy of paralogous genes partly relies on the fact that they carry their functions independently. However, a significant fraction of paralogous proteins may form functionally dependent pairs, for instance, through heteromerization. As a consequence, one could expect these heteromeric paralogs to be less protective against deleterious mutations. To test this hypothesis, we examined the robustness landscape of gene loss‐of‐function by CRISPR‐Cas9 in more than 450 human cell lines. This landscape shows regions of greater deleteriousness to gene inactivation as a function of key paralog properties. Heteromeric paralogs are more likely to occupy such regions owing to their high expression and large number of protein–protein interaction partners. Further investigation revealed that heteromers may also be under stricter dosage balance, which may also contribute to the higher deleteriousness upon gene inactivation. Finally, we suggest that physical dependency may contribute to the deleteriousness upon loss‐of‐function as revealed by the correlation between the strength of interactions between paralogs and their higher deleteriousness upon loss of function