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The field of immunotherapy holds clear promise not only for the development of new approaches to cancer and other diseases, but also for providing fundamental insight into the human immune response. In order for this promise to be realized, however, the scientific community must overcome an array of challenges. These challenges reflect not only the difficulties inherent in conducting investigations in human patients, but also difficulties created by the culture and practice of our own institutions, reward structure, and funding mechanisms. We suggest steps to be taken to reinvigorate basic research in human subjects as part of the mainstream of science. 相似文献
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The need for a planned response to a deliberate introduction of smallpox has recently become urgent. We constructed a stochastic simulator of the spread of smallpox in structured communities to compare the effectiveness of mass vaccination versus targeted vaccination of close contacts of cases. Mass vaccination before smallpox introduction or immediately after the first cases was more effective than targeted vaccination in preventing and containing epidemics if there was no prior herd immunity (that is, no prior immunologic protection within the population). The effectiveness of postrelease targeted and mass vaccinations increased if we assumed that there was residual immunity in adults vaccinated before 1972, but the effectiveness of targeted vaccination increased more than that of mass vaccination. Under all scenarios, targeted vaccination prevented more cases per dose of vaccine than did mass vaccination. Although further research with larger-scale structured models is needed, our results suggest that increasing herd immunity, perhaps with a combination of preemptive voluntary vaccination and vaccination of first responders, could enhance the effectiveness of postattack intervention. It could also help targeted vaccination be more competitive with mass vaccination at both preventing and containing a deliberate introduction of smallpox. 相似文献
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A NOVEL,REMOVABLE, CERROBEND,BEAM‐BLOCKING DEVICE FOR RADIATION THERAPY OF THE CANINE HEAD AND NECK: PILOT STUDY 
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下载免费PDF全文 Michael S. Kent Davide Berlato Isabelle Vanhaezebrouck Ira K. Gordon Katherine S. Hansen Alain P. Theon Randall W. Holt Earl A. Trestrail 《Veterinary radiology & ultrasound》2017,58(1):100-105
Radiation therapy of the head and neck can result in mucositis and other acute affects in the oral cavity. This prospective pilot study evaluated a novel, intraoral, beam‐blocking device for use during imaging and therapeutic procedures. The beam‐blocking device was made from a metal alloy inserted into a coated frozen dessert mold (Popsicle® Mold, Cost Plus World Market, Oakland, CA). The device was designed so that it could be inserted into an outer shell, which in turn allowed it to be placed or removed depending on the need due to beam configuration. A Farmer type ionization chamber and virtual water phantom were used to assess effects of field size on transmission. Six large breed cadaver dogs, donated by the owner after death, were recruited for the study. Delivered dose at the dorsal and ventral surfaces of the device, with and without the alloy block in place, were measured using radiochromic film. It was determined that transmission was field size dependent with larger field sizes leading to decreased attenuation of the beam, likely secondary to scatter. The mean and median transmission on the ventral surface without the beam‐blocking device was 0.94 [range 0.94–0.96]. The mean and median transmission with the beam‐blocking device was 0.52 [range 0.50–0.57]. The mean and median increase in dose due to backscatter on the dorsal surface of the beam‐blocking device was 0.04 [range 0.02–0.04]. Findings indicated that this novel device can help attenuate radiation dose ventral to the block in dogs, with minimal backscatter. 相似文献
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William Christian Kayser Gordon E Carstens Ira Loyd Parsons Kevin E Washburn Sara D Lawhon William E Pinchak Eric Chevaux Andrew L Skidmore 《Journal of animal science》2021,99(9)
The objective of this experiment was to determine if statistical process control (SPC) procedures coupled with remote continuous data collection could accurately differentiate between animals experimentally inoculated with a viral–bacterial (VB) challenge or phosphate buffer solution (PBS). Crossbred heifers (N = 38; BW = 230 ± 16.4 kg) were randomly assigned to treatments by initial weight, average daily gain (ADG), bovine herpes virus 1, and Mannheimia haemolytica serum titers. Feeding behavior, dry matter intake (DMI), animal activity, and rumen temperature were continuously monitored remotely prior to and following VB challenge. VB-challenged heifers exhibited decreased (P < 0.01) ADG and DMI, as well as increased (P < 0.01) neutrophils and rumen temperature consistent with a bovine respiratory disease (BRD) infection. However, none of the heifers displayed overt clinical signs of disease. Shewhart and cumulative summation (CUSUM) charts were evaluated, with sensitivity and specificity computed on the VB-challenged heifers (n = 19) and PBS-challenged heifers (n = 19), respectively, and the accuracy was determined as the average of sensitivity and specificity. To address the diurnal nature of rumen temperature responses, summary statistics (mean, minimum, and maximum) were computed for daily quartiles (6-h intervals), and these quartile temperature models were evaluated separately. In the Shewhart analysis, DMI was the most accurate (95%) at deciphering between PBS- and VB-challenged heifers, followed by rumen temperature (94%) collected in the 2nd and 3rd quartiles. Rest was most the accurate accelerometer-based traits (89%), and meal duration (87%) and bunk visit (BV) frequency (82%) were the most accurate feeding behavior traits. Rumen temperature collected in the 3rd quartile signaled the earliest (2.5 d) of all the variables monitored with the Shewhart, followed by BV frequency (2.8 d), meal duration (2.8 d), DMI (3.0 d), and rest (4.0 d). Rumen temperature and DMI remained the most accurate variables in the CUSUM at 80% and 79%, respectively. Meal duration (58%), BV frequency (71%), and rest (74%) were less accurate when monitored with the CUSUM analysis. Furthermore, signal day was greater for DMI, rumen temperature, and meal duration (4.4, 5.0, and 3.7 d, respectively) in the CUSUM compared to Shewhart analysis. These results indicate that Shewhart and CUSUM charts can effectively identify deviations in feeding behavior, activity, and rumen temperature patterns for the purpose of detecting sub-clinical BRD in beef cattle. 相似文献
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Inflammation in pulp tissue is caused by caries bacteria. Most bacteria found are Lactobacillus acidophilus. Propolis is a sticky resin material that is derived from the bees and the surrounding plants, which are reported to have several biological effects including anti-bacterial and anti-inflammatory. This study will prove the effectiveness of propolis against proinflammatory cytokines on odontoblast-like cells in human dental pulp. This study was performed on cultured odontoblast-like cells in pulp. Cell culture was derived from the pulp tissue of human M3 teeth that had been extracted. Odontoblast pulp culture was divided in three groups： group one, cultured cells with propolis; group two, cultured cells induced with inactive Lactobacillus acidophilus; group three, cultured cells induced with inactive Lactobacillus acidophilus and exposed to 3 μg/mL propolis. A measurement of TNF-α and TGF-β1 expression was done using the immunocytochemical technique to determine the effectiveness of propolis extracts from East Java Indonesia against proinfalmmatory cytokines. Data were analyzed using the analysis of variance （ANOVA） test （P = 0.05）. Propolis extract can inhibit the expression of TNF-α and increase the expression of TGF-β1 on odontoblast-like cell in human dental pulp. Anti-inflammatory effects of East Java propolis extract are associated with cytokine modulation. 相似文献
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Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate 总被引：2，自引：0，他引：2
Delamarre L Pack M Chang H Mellman I Trombetta ES 《Science (New York, N.Y.)》2005,307(5715):1630-1634
Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes systemically for purposes of tolerance and immunity. 相似文献