Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits.

A nicotinic cholinergic antagonist, mecamylamine (MEC), was administered to rabbits tested on eyeblink classical conditioning (EBCC) in the 750-msec delay paradigm for 10 90-trial sessions. Nicotinic receptors were measured in 3 brain regions in S treatment groups: paired conditioned stimulus–unconditioned stimulus (CS–UCS) presentations with (1) vehicle, young; (2) vehicle, older; (3) 0.5 mg/kg MEC, young; unpaired CS–UCS with (4) 0.5 mg/kg MEC, young; and (5) vehicle, young. Daily MEC injections disrupted acquisition in young rabbits (769 trials to learning criterion vs 323 trials for vehicle-treated young rabbits). MEC-treated young rabbits learned similarly to older rabbits. Brain nicotinic receptors were not affected by 10 daily MEC injections. To our knowledge, this experimental protocol, using a low MEC dose to selectively inhibit nicotinic cholinergic receptors, is the first to demonstrate a role for nicotinic cholinergic receptors in EBCC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chaos based key expansion function for block ciphers

The Key Expansion Function is a vital constituent component of any block cipher. Many of Key Expansion Functions generate subkeys through the algorithms which are based on Feistel or Substitution Permutation Network (SPN) structures against which cryptanalytic methods have been well researched. In this very paper, an efficient method for generating subkeys based on chaotic maps has been suggested. The phenomenon behind the proposed Key Expansion Function is the mixing property of Tent Map. Using chaotic binary sequences, the proposed Key Expansion Function satisfies the specific statistical and cryptographic properties of chaotic generators. A new Bit Extraction Technique based on IEEE-754 Floating-point Standard (binary32) is used to extract the bits of subkeys from the chaotic binary sequences. The generated subkeys are then analyzed. The results show that the given Chaos-based Key Expansion Function is well protected and fully strengthened in all respects.     

Theranostic Interpolation of Genomic Instability in Breast Cancer

Breast cancer is a diverse disease caused by mutations in multiple genes accompanying epigenetic aberrations of hazardous genes and protein pathways, which distress tumor-suppressor genes and the expression of oncogenes. Alteration in any of the several physiological mechanisms such as cell cycle checkpoints, DNA repair machinery, mitotic checkpoints, and telomere maintenance results in genomic instability. Theranostic has the potential to foretell and estimate therapy response, contributing a valuable opportunity to modify the ongoing treatments and has developed new treatment strategies in a personalized manner. “Omics” technologies play a key role while studying genomic instability in breast cancer, and broadly include various aspects of proteomics, genomics, metabolomics, and tumor grading. Certain computational techniques have been designed to facilitate the early diagnosis of cancer and predict disease-specific therapies, which can produce many effective results. Several diverse tools are used to investigate genomic instability and underlying mechanisms. The current review aimed to explore the genomic landscape, tumor heterogeneity, and possible mechanisms of genomic instability involved in initiating breast cancer. We also discuss the implications of computational biology regarding mutational and pathway analyses, identification of prognostic markers, and the development of strategies for precision medicine. We also review different technologies required for the investigation of genomic instability in breast cancer cells, including recent therapeutic and preventive advances in breast cancer.     

Acid–base and dyeing properties of Nigerian Merino,Yankasa, and Merino–Yankasa crossbred wools

The acid–base titration curves of three wools, Merino, Yankasa, and a ?–? Merino–Yankasa crossbred wool, grown in Nigeria, were measured at 25°C in the presence of varying amounts of sodium chloride. Amino acid analysis was carried out on these wools and correlated with the acid–base properties. The isoionic point and titration curves of Merino and the crossbred wool are similar, while those of Yanakasa are somewhat different. The acid–base behavior was interpreted by the Gibbs–Donnan treatment for the acid titrations and the pK₀¹ values for the carboxyl groups obtained, showing the existence of normal and salt-linked carboxyl groups in these wools. Dyeing tests with acidic and basic dyes have shown that the crossbred wool responds almost as well as Merino. Together with the similarity of its mechanical properties, it seems that this crossbred wool is suitable for all the textile applications for which Merino wool is normally preferred.     

Potentiation of chlorambucil cytotoxicity in B-cell chronic lymphocytic leukemia by inhibition of DNA-dependent protein kinase activity using wortmannin

In this study, we examined the ability of wortmannin to modulate chlorambucil (CLB) cytotoxicity in lymphocyte samples from patients with B-cell chronic lymphocytic leukemia (B-CLL). It has been suggested previously that enhanced cross-link repair is a primary mechanism of resistance to nitrogen mustards (NMs) in B-CLL. DNA-dependent protein kinase (DNA-PK) is involved in the repair of double-strand breaks and in rejoining steps in recombination mechanisms. Mutants defective in this process are hypersensitive to alkylating agents. We have recently demonstrated that the activity of DNA-PK is a determinant in the cellular response of B-CLL to CLB. The DNA-PK gene has homology to the P110 phosphatidylinositol 3-kinase (PI 3-K). Wortmannin, an inhibitor of P110 PI 3-K, also inhibits DNA-PK activity in vitro. We investigated the effect of wortmannin on DNA-PK activity and CLB toxicity in the lymphocytes from 11 patients with B-CLL. Our results demonstrate that DNA-PK activity is decreased after exposure to wortmannin in a dose-dependent manner. Wortmannin, at nontoxic concentrations, synergistically sensitized B-CLL lymphocytes to the effects of CLB. Moreover, we observed a significant correlation when we compared the fold decrease in DNA-PK activity and the synergistic value (I), obtained when wortmannin was used at 0.1 microM. In the resistant B-CLL lymphocyte samples, there was a highly significant correlation between the ability of wortmannin at 0.1 and 0.25 microM to decrease the level of DNA-PK activity and to increase CLB sensitivity. In a model of primary human tumor cells, our findings suggest that the inhibition of DNA-PK activity may be a powerful way to overcome resistance to NMs such as CLB and point to new possibilities to improve the effectiveness of NM therapy.     

Investigation of the Heterogeneity of Disruptive Behaviour in Elementary-Age Children.

We evaluated parent and teacher ratings of a large sample (N=1579) of elementary-school children in Canada to determine how different conceptualizations of disruptive behaviour are co-related and related to other measures of functioning. Parent and teacher ratings were consistent, and suggested three separate but correlated aspects of disruptive behaviour in children: (1) reactive/oppositional behaviour, (2) proactive/callous behaviour; and (3) inattention-impulsive-overactive behaviour. These were uniquely and significantly related to DSM-IV diagnostic scores and to other measure of impairment, indicating that they measure distinct aspects of disruptive behaviour in children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use of intravenous intermediate dose melphalan and dexamethasone as induction treatment in the management of de novo multiple myeloma

The variable absorption of melphalan from the gastrointestinal tract results in response rates between 40 and 60%. High dose melphalan increases response rates but at the cost of increased morbidity and mortality. We have investigated intravenous intermediate dose melphalan and dexamethasone in the treatment of patients presenting with de novo multiple myeloma with the object of reducing toxicity while preserving an improved response rate compared to oral melphalan and prednisolone. The results show that this treatment can be delivered safely on an outpatient basis in patients up to the age of 78 yr; 82% of patients achieved an objective response and 30% a complete haematological and clinical remission. Median overall survival for the whole group is 37 months.     

Improving Routine Immunization Coverage Through Optimally Designed Predictive Models

Routine immunization (RI) of children is the most effective and timely public health intervention for decreasing child mortality rates around the globe. Pakistan being a low-and-middle-income-country (LMIC) has one of the highest child mortality rates in the world occurring mainly due to vaccine-preventable diseases (VPDs). For improving RI coverage, a critical need is to establish potential RI defaulters at an early stage, so that appropriate interventions can be targeted towards such population who are identified to be at risk of missing on their scheduled vaccine uptakes. In this paper, a machine learning (ML) based predictive model has been proposed to predict defaulting and non-defaulting children on upcoming immunization visits and examine the effect of its underlying contributing factors. The predictive model uses data obtained from Paigham-e-Sehat study having immunization records of 3,113 children. The design of predictive model is based on obtaining optimal results across accuracy, specificity, and sensitivity, to ensure model outcomes remain practically relevant to the problem addressed. Further optimization of predictive model is obtained through selection of significant features and removing data bias. Nine machine learning algorithms were applied for prediction of defaulting children for the next immunization visit. The results showed that the random forest model achieves the optimal accuracy of 81.9% with 83.6% sensitivity and 80.3% specificity. The main determinants of vaccination coverage were found to be vaccine coverage at birth, parental education, and socio-economic conditions of the defaulting group. This information can assist relevant policy makers to take proactive and effective measures for developing evidence based targeted and timely interventions for defaulting children.     

Peripheral mRNA Expression and Prognostic Significance of Emotional Stress Biomarkers in Metastatic Breast Cancer Patients

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes (5-HTT, NR3C1, OXTR, and FKBP5) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients–short form (QSC-R10). A survival database, the Kaplan–Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT (p = 0.02) and OXTR (p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II (p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis.