Robust Pitching Disturbance Force Attenuation for Tractor Considering Functional Constraints

This is the final version. Available on open access from IEEE via the DOI in this recordelectro-hydraulic hitch system, to carry out various farm operations. Forces arising during travel with the lifted implement on uneven terrain, generate disturbance forces on the hitch system. In this study, the electro-hydraulic system was controlled such that the disturbance forces are attenuated. A second order transfer function model of the hitch system was obtained using experimental data. In order to account for the nonlinearities in the system, an advanced Sliding Mode Controller with Power Rate Exponential Reaching Law was developed to control the hitch system to attenuate the disturbance forces. Variation in system parameters due to change of implements was taken into account by making the system adaptive using a Recursive Least Squares (RLS) parameter estimator, which was used to estimate and update the system parameters in the controller. Position regulation was incorporated to prevent the implement from reaching its mechanical limits. Valve deadzone and operating input limits were incorporated into this design. Also, considering the presence of two valves to supply fluid to the same cylinder, a trigger logic was developed to suitably choose the valve to be operated. The controller was found to provide an average disturbance force attenuation of 82.9% while being robust to a random variation in each parameter up to ±80%

Synthesis and crystal structures of 5'-phenylspiro[indoline-3, 2'-pyrrolidin]-2-one derivatives

<p>Abstract</p> <p>Background</p> <p>The spiro- indole-pyrrolidine ring system is a frequently encountered structural motif in many biologically important and pharmacologically relevant alkaloids. The derivatives of spirooxindole ring systems are used as antimicrobial, antitumour agents and as inhibitors of the human NKI receptor besides being found in a number of alkaloids like horsifiline, spirotryprostatin and (+) elacomine. The recently discovered small-molecule MDM2 inhibitor MI-219 and its analogues are in advanced preclinical development as cancer therapeutics.</p> <p>Results</p> <p>In the crystal structures of the two organic compounds, 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl)- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one, N-H···O hydrogen bonds make the R²₂(8) ring motif. Further, the structures are stabilized by intermolecular hydrogen bonds.</p> <p>Conclusion</p> <p>The crystal structures of 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl)- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one have been investigated in detail. In both the compounds, the R²₂(8) motif is present. Due to the substitution of methoxyphenyl instead of phenyl ring, the entire configuration is inverted with respect to the 2-oxyindole ring.</p

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci

Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity. High-risk patients typically have widely disseminated disease at diagnosis and a poor survival probability, but low-risk patients frequently have localized tumors that are almost always cured with little or no chemotherapy. Our genome-wide association study (GWAS) has identified common variants within FLJ22536, BARD1, and LMO1 as significantly associated with neuroblastoma and more robustly associated with high-risk disease. Here we show that a GWAS focused on low-risk cases identified SNPs within DUSP12 at 1q23.3 (P = 2.07×10−6), DDX4 and IL31RA both at 5q11.2 (P = 2.94×10−6 and 6.54×10−7 respectively), and HSD17B12 at 11p11.2 (P = 4.20×10−7) as being associated with the less aggressive form of the disease. These data demonstrate the importance of robust phenotypic data in GWAS analyses and identify additional susceptibility variants for neuroblastoma

Increased HSF1 expression predicts shorter disease-specific survival of prostate cancer patients following radical prostatectomy

Bjork, Johanna K Ahonen, Ilmari Mirtti, Tuomas Erickson, Andrew Rannikko, Antti Butzow, Anna Nordling, Stig Lundin, Johan Lundin, Mikael Sistonen, Lea Nees, Matthias Akerfelt, Malin eng Oncotarget. 2018 Jul 27;9(58):31200-31213. doi: 10.18632/oncotarget.25756. eCollection 2018 Jul 27.Prostate cancer is a highly heterogeneous disease and the clinical outcome is varying. While current prognostic tools are regarded insufficient, there is a critical need for markers that would aid prognostication and patient risk-stratification. Heat shock transcription factor 1 (HSF1) is crucial for cellular homeostasis, but also a driver of oncogenesis. The clinical relevance of HSF1 in prostate cancer is, however, unknown. Here, we identified HSF1 as a potential biomarker in mRNA expression datasets on prostate cancer. Clinical validation was performed on tissue microarrays from independent cohorts: one constructed from radical prostatectomies from 478 patients with long term follow-up, and another comprising of regionally advanced to distant metastatic samples. Associations with clinical variables and disease outcomes were investigated. Increased nuclear HSF1 expression correlated with disease advancement and aggressiveness and was, independently from established clinicopathological variables, predictive of both early initiation of secondary therapy and poor disease-specific survival. In a joint model with the clinical Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score, nuclear HSF1 remained a predictive factor of shortened disease-specific survival. The results suggest that nuclear HSF1 expression could serve as a novel prognostic marker for patient risk-stratification on disease progression and survival after radical prostatectomy.Peer reviewe

The role country of birth plays in receiving disability pensions in relation to patterns of health care utilisation and socioeconomic differences: a multilevel analysis of Malmo, Sweden

BACKGROUND: People of low socioeconomic status have worse health and a higher probability of being granted a disability pension than people of high socioeconomic status. It is also known that public and private general physicians and public and private specialists have varying practices for issuing sick leave certificates (which, if longstanding, may become the basis of disability pensions). However, few studies have investigated the influence of a patient's country of birth in this context. METHODS: We used multilevel logistic regression analysis with individuals (first level) nested within countries of birth (second level). We analysed the entire population between the ages of 40 and 64 years (n = 80 212) in the city of Malmo, Sweden, in 2003, and identified 73% of that population who had visited a physician at least once during that year. We studied the associations between individuals and country of birth socioeconomic characteristics, as well as individual utilisation of different kinds of physicians in relation to having been granted a disability pension. RESULTS: Living alone (OR(women )= 1.72, 95% CI: 1.62–1.82; OR(men )= 2.64, 95% CI: 2.46–2.83) and having limited educational achievement (OR(women )= 2.14, 95% CI: 2.00–2.29; OR(men )= 2.12, 95% CI: 1.98–2.28) were positively associated with having a disability pension. Utilisation of public specialists was associated with a higher probability (OR(women )= 2.11, 95% CI: 1.98–2.25; OR(men )= 2.16, 95% CI: 2.01–2.32) and utilisation of private GPs with a lower probability (OR(men )= 0.76, 95% CI: 0.69–0.83) of having a disability pension. However, these associations differed by countries of birth. Over and above individual socioeconomic status, men from middle income countries had a higher probability of having a disability pension (OR(men )= 1.61, 95% CI: 1.06–2.44). CONCLUSION: The country of one's birth appears to play a significant role in understanding how individual socioeconomic differences bear on the likelihood of receiving a disability pension and on associated patterns of health care utilisation

Integration of gene expression data with prior knowledge for network analysis and validation

<p>Abstract</p> <p>Background</p> <p>Reconstruction of protein-protein interaction or metabolic networks based on expression data often involves in silico predictions, while on the other hand, there are unspecific networks of in vivo interactions derived from knowledge bases.</p> <p>We analyze networks designed to come as close as possible to data measured in vivo, both with respect to the set of nodes which were taken to be expressed in experiment as well as with respect to the interactions between them which were taken from manually curated databases</p> <p>Results</p> <p>A signaling network derived from the TRANSPATH database and a metabolic network derived from KEGG LIGAND are each filtered onto expression data from breast cancer (SAGE) considering different levels of restrictiveness in edge and vertex selection.</p> <p>We perform several validation steps, in particular we define pathway over-representation tests based on refined null models to recover functional modules. The prominent role of the spindle checkpoint-related pathways in breast cancer is exhibited. High-ranking key nodes cluster in functional groups retrieved from literature. Results are consistent between several functional and topological analyses and between signaling and metabolic aspects.</p> <p>Conclusions</p> <p>This construction involved as a crucial step the passage to a mammalian protein identifier format as well as to a reaction-based semantics of metabolism. This yielded good connectivity but also led to the need to perform benchmark tests to exclude loss of essential information. Such validation, albeit tedious due to limitations of existing methods, turned out to be informative, and in particular provided biological insights as well as information on the degrees of coherence of the networks despite fragmentation of experimental data.</p> <p>Key node analysis exploited the networks for potentially interesting proteins in view of drug target prediction.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Quality of Life and Related Factors among HIV-Positive Spouses from Serodiscordant Couples under Antiretroviral Therapy in Henan Province, China

OBJECTIVE: To describe the quality of life and related factors in HIV-positive spouses undergoing ART from discordant couples. METHODS: A cross-sectional study was conducted among 1,009 HIV-positive spouses from serodiscordant couples in Zhumadian, Henan Province, between October 1, 2008 and March 31, 2009. HIV-positive spouses were interviewed by local health professionals. Quality of life was evaluated by WHOQOL (Chinese Version). A multiple linear regression model was used to analyze the related factors. RESULTS: The majority of subjects were female (56.39%), had received a high school education (44%), were of Han ethnicity (98.41%), and were farmers (90.09%); the median time period of receiving ART was 3.92 years. The physical, psychological, social, and environmental QOL scores of the subjects were 12.91±1.95, 12.35±1.80, 13.96±2.43, and 12.45±1.91 respectively. The multiple linear regression model identified the physical domain related factors to be CD4 count, educational level, and occupation; psychological domain related factors include age, educational level, and reported STD symptom; social domain related factors included education level; and environmental domain related factors included education level, reported STD symptoms, and occupation. CONCLUSION: Being younger, a farmer, having a lower level of education, a reported STD symptom, or lower CD4 count, could decrease one's quality of life, suggesting that the use of blanket ART programs alone may not necessarily improve quality of life. Subjects received lower scores in the psychological domain, suggesting that psychological intervention may also need to be strengthened

Genetic and Proteomic Approaches to Identify Cancer Drug Targets

While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification