91 research outputs found
Using leprosy elimination campaign on leprosy case finding: Case series study in Kurdistan, Iran
BACKGROUND: Because of the long incubation period of leprosy and disability caused by it, even mother to fetus transmission has been reported. Thus, this disease causes much alarm. Kurdistan Province, which is located in the Western part of Iran, is one of the regions that have previously suffered from endemic leprosy. The aim of the present study was to investigate the effects of the leprosy elimination campaign (LEC) on leprosy case finding in Baneh, Iran, in 2012. METHODS: This case series study was conducted in Baneh District. Case finding was performed via LEC method, which is a recommended method for leprosy case finding in endemic areas. The performed steps included public education, and screening families of ex-patients through careful examination, identification of suspected cases, and diagnosis based on specialistâs examination. RESULTS: The families of ex-patients were assessed and 76 people who had prolonged exposure to ex-patients were invited to be examined by a trained general physician. Subsequently, 50 people were referred to a dermatologist for further examinations, 5 of whom and 1 unexposed person underwent bacteriological test for further evaluation. The results of all the tests were negative. CONCLUSION: Active leprosy case finding and use of LEC method require a great deal of money and efforts to identify a small number of patients. Because a district like Baneh is in the process of eliminating leprosy and since the economic and social situation has changed greatly over the past two decades, LEC method is no longer cost effective
Distinct neurocomputational mechanisms support informational and socially normative conformity
A change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive, and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of 2 different social roles and 2 different social partners revealed distinct behavioural and neural markers for informational and normative conformity. Dorsal anterior cingulate cortex (dACC) BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with humans. A network of brain areas (dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ)) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind
Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I
Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs) Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia.
Methods: The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC) from Ph + ALL-patients.
Results: Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner.
Conclusions: Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors
Three-Dimensional Design of Axial Flow Compressor Blades Using the Ball-Spine Algorithm
Recently a new inverse design algorithm has been developed for the design of ducts, called ball-spine (BS). In the BS algorithm, the duct walls are considered as a set of virtual balls that can freely move along some specified directions, called âspinesâ. Initial geometry is guessed and the flow field is analyzed by a flow solver. Comparing the computed pressure distribution (CPD) with the target pressure distribution (TPD), new balls positions for the modified geometry are determined. This procedure is repeated until the target pressure is achieved. In the present work, the ball-spine algorithm is applied to three-dimensional design of axial compressor blades. The design procedure is tested on blades based on NACA65-410 and NACA65-610 profiles and the accuracy of the method is shown to be very good. As an application, the pressure distribution of the blade with NACA65-610 profiles is modified and the pressure gradient in the aft part of the blade is decreased and selected as target pressure distribution. The corresponding geometry which satisfies the target
pressure is determined using the BS design algorithm
Robust Walking Using Peicewise Linear Spring
Having a direct impact on the energy efficiency has made the compliance a favorable element in the robotic systems. Moreover, legged system can benefit from compliance for stability, speed, adaptability and robustness. Recently, we have studied the effects of compliant spine in quadrupedal robots. We have observed that having nonlinearity in the spine compliance can set a better trade-off between speed and energy efficiency. Similar to the spine in quadruped robots, compliance at the hip joint of bipedal robots can also improve the walking performance such as robustness. Here, we test the efficacy of piecewise linear hip compliance for robust bipedal walking
Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism
ABSTRACT: BACKGROUND: Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias. Despite high rates of clinical response, Ph (+) patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein. Of special interest is the 'gatekeeper' T315I mutation, which confers complete resistance to Abl kinase inhibitors. Recently, GNF-2, Abl allosteric kinase inhibitor, was demonstrated to possess cellular activity against Bcr-Abl transformed cells. Similarly to Abl kinase inhibitors (AKIs), GNF-2 failed to inhibit activity of mutated Bcr-Abl carrying the T315I mutation.
METHODS: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs.
RESULTS: In this study, we report a cooperation between AKIs and GNF-2 in inhibiting proliferation and clonigenicity of Ba/F3 cells carrying T315I mutated Bcr-Abl. Interestingly, cooperation was most evident between Dasatinib and GNF-2. Furthermore, we showed that GNF-2 was moderately active in inhibiting the activity of JAK2 kinase, and presence of AKIs augmented GNF-2 activity.
CONCLUSIONS: Our data illustrated the ability of allosteric inhibitors such as GNF-2 to cooperate with AKIs to overcome T315I mutation by Bcr-Abl-independent mechanisms, providing a possibility of enhancing AKIs efficacy and overcoming resistance in Ph+ leukemia cells
Changes in Aflatoxin Content During the Processing of Vinegar Obtained From Grape
Mycotoxins are known to be one of the most important food contaminants that pose potential health risks to humans. This study aimed to investigate the changes in total aflatoxin (TAF) content during grape vinegar production. Different types of aflatoxins including aflatoxin B1 (AFB1 ), B2 (AFB2 ), G1 (AFG1 ), and G2 (AFG2 ) were spiked into washed grape samples in the level of 5 ÎŒg/kg. Then grape samples were converted to vinegar. After different stages of vinegar processing including juicing, alcoholic fermentation, acetic acid fermentation, and pasteurization, sampling was performed and the level of each aflatoxin was measured using high performance liquid chromatography with fluorescence detector (HPLC-FD). Among different processing steps, the pasteurization operation had the least effect on the removal of aflatoxin. After juicing, the amount of AFB1 , AFB2 , AFG1 and AFG2 decreased by 14%, 11.18%, 13.77%, and 18.56%, respectively. Alcoholic fermentation had the greatest effect on the removal of aflatoxin so that it could reduce the levels of AFB1 , AFB2 , AFG1 and AFG2 by 41.87%, 45.34%, 45.37%, and 46.52%, respectively. Overall, during processing and conversion of grapes to vinegar, the values of AFB1 , AFB2 , AFG1 and AFG2 were reduced by 76.20%, 71.06%, 69.26%, and 75.85%, respectively. Processing grapes to vinegar can have a significant effect on the aflatoxin reduction
The Impact of an Instructional Model with Assistive Technology on Achievement Satisfaction of People with Physical-Motor Impairments
Background: The use of new technologies in education is a topic that has attracted the attention of educational experts over the past two decades. The purpose of this study was to investigate the effect of an instructional model enriched with assistive technology on the achievement satisfaction of people with physical-motor impairments in learning English. Methods: The research method is semi-experimental, with a pre-test/post-test design using a control group. The statistical population consisted of male individuals with physical mobility impairments studying at Imam Ali Educational Center in Tehran. To determine the sample size,Cohenâs (1986) table was used. Based on the sample size table, 16 people were selected. In this method, after drawing up a student list with a random number table, the sample was selected after checking criteria for entry and exit. The experimental group was trained in six sessions using an instructional model enriched with online and offline assistive technologies, and the control group was trained in the usual way. Results: The mean ± standard deviation (SD) for pre- and post-test in the experimental group were 75.50 ± 5.90 and 82.25 ± 6.29, respectively, and was 75.38 ± 11 and 77.37 ± 11.91 in the control group. The results of the analysis of covariance between adjusted means of both groups for variable of academic satisfaction show a significant difference between the two groups (F =20.06, P < 0.01). The effect size was 0.60. Conclusion: Using an instructional model enriched with assistive technology can be useful in teaching English to individuals with physical-motor impairments
Piecewise linear spine for speed-energy efficiency trade-off in quadruped robots
We compare the effects of linear and piecewise linear compliant spines on locomotion performance of quadruped robots in terms of energy efficiency and locomotion speed through a set of simulations and experiments. We first present a simple locomotion system that behaviorally resembles a bounding quadruped with flexible spine. Then, we show that robots with linear compliant spines have higher locomotion speed and lower cost of transportation in comparison with those with rigid spine. However, in linear case, optimal speed and minimum cost of transportation are attained at very different spine compliance values. Moreover, it is verified that fast and energy efficient locomotion can be achieved together when the spine flexibility is piecewise linear. Furthermore, it is shown that the robot with piecewise linear spine is more robust against changes in the load it carries. Superiority of piecewise linear spines over linear and rigid ones is additionally confirmed by simulating a quadruped robot in Webots and experiments on a crawling two-parts robot with flexible connection. (C) 2013 Elsevier B.V. All rights reserved
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