The use of library technologies for the generation of affinity proteins often includes an affinity maturation step, based on the construction of secondary libraries from which second generation ...variants with improved affinities are selected. Here, we describe for the first time the affinity maturation of affibody molecules based on step-wise in vitro molecular evolution, involving cycles of error-prone PCR (epPCR) amplification for the introduction of diversity over the entire 58-residue three-helix bundle structure and ribosome display (RD) for the selection of improved variants. The model affibody molecule for the process was ZRAF322, binding with a 1.9μm equilibrium dissociation constant (KD) to human Raf-1 (hRaf-1), a protein kinase of central importance in the MAPK/ERK proliferation pathway. The molecular evolution process was followed on both gene and protein levels via DNA sequencing and a biosensor-based binding analysis of pools of selected variants. After two cycles of diversification and selection, a significant increase in binding response of selected pools was seen. DNA sequencing showed that a dominant alanine to valine substitution had been effectively enriched, and was found in 83% of all selected clones, either alone or in combination with other enriched substitutions. The evolution procedure resulted in variants showing up to 26-fold increases in affinity to the hRaf-1 target. Noteworthy, for the two variants showing the highest affinities, substitutions were also found in affibody framework positions, corresponding to regions of the protein domain not addressed by traditional affibody molecule affinity maturation strategies. Interestingly, thermal melting point (Tm) analyses showed that an increased affinity could be associated with both higher and lower Tm values. All investigated variants showed excellent refolding properties and selective binding to hRaf-1, as analysed using a multiplexed bead-based binding assay, making them potentially valuable affinity reagents for cell biology studies.
The aim of this study is to compare the dose in various soft tissues in brachytherapy with photon emitting sources.
(103)Pd, (125)I, (169)Yb, (192)Ir brachytherapy sources were simulated with MCNPX ...Monte Carlo code, and their dose rate constant and radial dose function were compared with the published data. A spherical phantom with 50 cm radius was simulated and the dose at various radial distances in adipose tissue, breast tissue, 4-component soft tissue, brain (grey/white matter), muscle (skeletal), lung tissue, blood (whole), 9-component soft tissue, and water were calculated. The absolute dose and relative dose difference with respect to 9-component soft tissue was obtained for various materials, sources, and distances.
There was good agreement between the dosimetric parameters of the sources and the published data. Adipose tissue, breast tissue, 4-component soft tissue, and water showed the greatest difference in dose relative to the dose to the 9-component soft tissue. The other soft tissues showed lower dose differences. The dose difference was also higher for (103)Pd source than for (125)I, (169)Yb, and (192)Ir sources. Furthermore, greater distances from the source had higher relative dose differences and the effect can be justified due to the change in photon spectrum (softening or hardening) as photons traverse the phantom material.
The ignorance of soft tissue characteristics (density, composition, etc.) by treatment planning systems incorporates a significant error in dose delivery to the patient in brachytherapy with photon sources. The error depends on the type of soft tissue, brachytherapy source, as well as the distance from the source.
Introduction: About 5% of visits to emergency departments are made up of conversion disorder cases. This study was designed with the aim of comparing the effectiveness of quetiapine and haloperidol ...in controlling conversion disorder symptoms. Methods: The present single-blind clinical trial has been performed on patients with conversion disorder (based on the DSM-IV definition) presenting to emergency department of 9-Day Hospital, Torbat Heydariyeh, Iran, from January 2017 until May 2018. Results: 73 patients were allocated to haloperidol and 71 to quetiapine group. Mean age of these patients was 32.03 ± 12.80 years (62.50% female). Two groups were similar regarding the baseline characteristics. Within 30 minutes, 90.41% of haloperidol cases and 91.55% of quetiapine cases were relieved (p=0.812). The most common side effects after 30 minutes were extrapyramidal symptoms (9.59%) in the haloperidol group and fatigue and sleepiness (7.04%) in the quetiapine group. Extrapyramidal symptoms was significantly higher than the quetiapine group (p=0.013). Conclusion: The results of the present study showed that although quetiapine and haloperidol have a similar effect in relieving the patients from conversion disorder symptoms, the prevalence of extrapyramidal symptoms is significantly lower in the group under treatment with quetiapine. Therefore, it seems that quetiapine is a safer drug compared to haloperidol.
In this paper, the dynamical moving mesh method is merged with the local time stepping technique and the new method is applied for blow-up problems. It has some benefit in approximating an accurate ...blow-up time by starting at any positive initial time (
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Our numerical experiment shows that without applying the local time stepping method, wrong blow-up time will be obtained, if the equation integrates from
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Background and aims: Survay of the particulates, biological molecules and other harmful materials which enter into Earthchr('39')s atmosphere as airborn agents is one of research intrest of health ...sciences. Animal housing laboratories for producing malodor especially near residential, educational and official areas can cause neighbors complainant. In order to overcome this challenge qualitative and quantitative evaluation of airborn contaminants of Iran university of medical scienses animal housing had been done. Method: In order to sampling and evaluation of the airborne contaminants in the animal housing the ASTM D3686-95 (for VOCs), ASTM D 4490-90 (for NH3, CO2 and, H2S) and, NIOSH 0500 (for total dusts) standard methods had been used. According to the survey goals apparatus and equipment were prepared and calibrated. Results: According to the results, the unspesified mixed dusts need controling measures and, also showed the presence of the toxic substances like xylene and ethyl benzene, 1, 2, 3-trimethyl Benzene. However the analyses of these show trace concentration of mixture exposure in the air. High number of animals in the small areas and large animal such as rabbits are responsible for more ammonia production. Conclusion: More frequently passing through the salons and geographical condition of the building and also natural ventilation of the laboratory all are good methods reducing the concentration of pollutions. In the other hand long times presence of employees in the laboratory could cause reduce sensitively. Nevertheless in order to increase employees and researcher welfare the implementation of general ventilation is recommended
We consider a population of mobile agents able to make noisy observation of the environment and communicate their observation by production and comprehension of signals. Individuals try to align ...their movement direction with their neighbors. Besides, they try to collectively find and travel towards an environmental direction. We show that, when the fraction of informed individuals is small, by increasing the noise in communication, similarly to the Viscek model, the model shows a discontinuous order-disorder transition with strong finite size effects. In contrast, for large fraction of informed individuals, it is possible to go from the ordered phase to the disordered phase without passing any phase transition. The ordered phase is composed of two phases separated by a discontinuous transition. Informed collective motion, in which the population collectively infers the correct environmental direction, occurs for high fraction of informed individuals. When the fraction of informed individuals is low, misinformed collective motion, where the population fails to find the environmental direction becomes stable as well. Besides, we show that an amount of noise in the production of signals is more detrimental for the inference capability of the population, and increases the density fluctuations and the probability of group fragmentation, compared to the same amount of noise in the comprehension.
In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design ...a guideline to manage patients with colorectal cancers during the COVID-19pandemic.
To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline.
This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B.
This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.
Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was ...performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.
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