An integrative approach to CTL epitope prediction: a combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions

Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and C-terminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method.The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php.     

Neuromuscular function and mechanical efficiency of human leg extensor muscles during jumping exercises

The influence of prestretch amplitude on the mechanical efficiency was examined with 5 subjects, who performed 5 different series of vertical jumps, each of which differed with respect to the mechanics of the knee joint action during the prestretch (eccentric) phase of the contact on the floor. Electromyographic activity was recorded from the major extensor muscles during the entire work period of 1 min per series. In addition, expired air was collected during the test and recovery for determination of energy expenditure. Mechanical work was calculated from the vertical displacement of the body during the jumps. The results indicated that high net efficiency of 38.7% was observed in condition where amplitude of knee bending in eccentric phase was small. In large range motion the corresponding net efficiency was 30.1%. In jumps where no prestretching of extensor muscles ocurred the net efficiency was 19.7%. The high efficiency of small amplitude jumps was characterized by low myoelectrical activity of the leg extensor muscles during the positive (concentric) work phase. In addition, the small amplitude jumps had shorter transition time in the stretch-shortening cycle, high average eccentric force and high stretching speed. Therefore the results suggest that the restitution of elastic energy, which was also related to the length change and stiffness of the muscles during stretch, plays an important role in regulating the mechanical efficiency of work.     

珍珠散协同爱宝疗治疗重度宫颈糜烂的临床疗效与药物经济学研究

目的观察中药珍珠散协同爱宝疗浓缩液治疗重度官颈糜烂临床疗效和药物经济学效益。方法将有生育要求的Ⅲ度官颈糜烂患者111例随机分为治疗组和对照组，治疗组用中药珍珠散联合爱宝疗浓缩液治疗，对照组则单用爱宝疗浓缩液治疗，均每3d治疗一次。45d后，比较两组疗效、疗程及治疗费用。结果治疗组治愈率明显高于对照组（67．9％vs36．4％），差异有统计学意义（P〈0．05）。治疗组费用明显低于对照组[（371．6±138．4）vs（483．6±36．6）]元（P〈0．01）。治疗组治疗时间比对照组显著缩短[（32．4±12．1）vs（44．0±3．3）]d（P〈0．01）。治疗组中提前结束治疗患者多于对照组（35／56vs6／55，P〈0．05）。治疗组与对照组均未见副作用发生。结论珍珠散协同爱宝疗浓缩液治疗重度官颈糜烂疗效好，药物经济学效益高，值得临床推广。     

二维视觉搜索的计算机模拟

视觉搜索的模拟算法考虑两个交互作用的过程:覆盖过程(“看”)和视觉过程(“看见”)。搜索场景包含有靶,假目标和背景噪声;一个视力角模型按一定的搜索策略去覆盖场景。对模拟程序的输入是场景和靶的空间大小,随机分布的靶和假目标的数目。靶探测几率和识别几率均为物体在场景中对比度和物体离视力角中心的距离的函数。本模拟程序的目的是比较系统搜索和随机搜索的性能,验证关于计算最佳视窗宽度的公式,进而鉴别影响靶探测和识别能力的覆盖过程和视觉过程的参数,阐明它们之间的相互作用。     

Escape efficiency of diploid and polyploid frogs: A comparison ofOdontophrynus cultripes (2n=22) andO. americanus (4n=44)

The escape efficiency of two closely related species of frogs,Odontophrynus cultripes(2n=22) and the tetraploidO. americanus (4n=44), were compared in a shuttle box and under simulated naturalistic conditions.O. americanus was generally superior toO. cultripes, and females tended to outperform males within both species. The relative inefficiency ofO. cultripes escape behavior was examined in light of the animals' having an elaborate, passive defense mechanism in the form of well-marked venom glands. Escape efficiency was highly variable in both species. Possessing twice the amount of DNA, the tetraploid behavioral variation was paradoxically less than that of the diploid, but compatible with what has been found for morphological characters in other organisms.This research was carried out at the Instituto Butantan with the support of ongoing grants from the Brazilian CNPq, FAPESP, FEDIB, and PNUD while the first author was a visiting professor in the Departamento de Genética Humana, Instituto de Biociências, Universidade de São Paulo, under the auspices of the Programa Multinacional de Genética, Organization of American States.     

Gross efficiency of muscular work during step exercise at -15°C and 21 °C

In an effort to assess the effect of ambient temperature on the gross efficiency (Eff_g) of step exercise 12 subjects performed a modified step test either at —15 °C or 21°C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min^-1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Eff_g is altered in a contradictory manner. At —15°C Eff_g increased with increasing work load, whereas at 21°C it decreased when the work load increased. The highest Eff_g (heavy work at —15°C and light work at 21°C) values are reflected as rather similar rectal temperatures (37.4–37.7°C) and identical mean skin temperatures (32.8 °C) as well as the same (slightly warm) thermal sensation of the legs. At — 15 °C the lowest Eff_g in light work was probably hue to the need to warm up the muscles. At 21°C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Eff_g in heavy work.     

Supra-maximal cycling efficiency assessed in humans by using a new protocol

This study proposed a non-invasive method to determine the gross (GE, no baseline correction), net (NE, resting metabolism as the baseline correction) and work (WE, unloaded cycling as the baseline correction) efficiencies during cycling at an intensity higher than the maximal aerobic power (MAP). Twelve male subjects performed two exercises consisting of 4 min at 50% MAP followed either by 8 min at 63% MAP or by 8 sequences of 60 s divided into 10 s at 130% MAP and 50 s at 50% MAP (i.e., 63% MAP on average). Oxygen uptake was continuously measured to calculate GE, NE and WE at 50%, 63% and 130% MAP, and the data presented as the means and standard deviations. The GE values were 18.2%, 19.1%, 22.7%, the NE values were 22.4%, 22.8%, 24.3% and the WE values were 34.2%, 31.4% and 27.2% at 50%, 63% and 130% MAP, respectively. The GE and NE increased (P<0.001) whereas the WE decreased (P<0.001) with each increment in power output. The GE was lower than the NE (P<0.001) at 50% and 63% MAP and than the WE (P<0.001) at all intensities. The NE was lower (P<0.001) than the WE at 50% and 63% MAP. These results showed that (1) efficiency index values obtained during supra-maximal exercise were consistent with previous proposals and (2) the efficiency-power output relationships were not limited to sub-maximal intensity levels but were confirmed at higher power output.     

The efficacy and efficiency of an in-vitro fertilization programme including embryo cryopreservation: a cohort study

A cohort of 485 couples starting their first in-vitro fertilization(IVF) attempt between January, 1989 and February, 1991 inclusive,were followed until June 1, 1992. A total of 1086 treatmentcycles were initiated (mean 2.2, range 1–6). Of these,235 (21.8%) cycles were cancelled, giving a total of 851 embryoreplacements (mean 1.7, range 1–5). After IVF treatment,189 women have either delivered or have an ongoing pregnancyin the second or third trimester. This gives a baby take-homerate of 17.4% per started cycle and 22.2% per embryo replacement.For 91 (18.6%) of the couples, the treatment was abandoned priorto completion of the three scheduled IVF attempts and 57 (11.7%)of these had no completed IVF cycles. In the group of coupleswith reduced sperm quality, the delivery rate was significantlylower than that of the other groups. A total of 193 women hadembryos cryopreserved in at least one IVF cycle; 124 of thesewomen started a frozen embryo replacement cycle and 88 had atleast one cycle with replacement of frozen/thawed embryos, resultingin 25 deliveries/ongoing pregnancies. Due to the Norwegian lawon assisted procreation 65 (33.7%) of the women have had theirfrozen embryos thawed and discarded after 12 months of storage.The cryopreservation programme, with the limitations of theNorwegian law, gives a 5.2% increase in the baby take-home ratefor women entering the IVF programme, an increase of 13.2% inthe number of ongoing pregnancies/deliveries and an 11.6% increasein number of children/viable fetuses. A total of 214 women havedelivered or have ongoing pregnancies in the second or thirdtrimester. This represents 44.1% of the 485 women accepted forIVF treatment, irrespective of whether they were treated ornot, and 50.0% of those couples who completed at least one IVFcycle.     

An energy balance of front crawl

With the aim of computing a complete energy balance of front crawl, the energy cost per unit distance (C= v^–1, where is the metabolic power and v is the speed) and the overall efficiency (_o=W_tot/C, where W_tot is the mechanical work per unit distance) were calculated for subjects swimming with and without fins. In aquatic locomotion W_tot is given by the sum of: (1) W_int, the internal work, which was calculated from video analysis, (2) W_d, the work to overcome hydrodynamic resistance, which was calculated from measures of active drag, and (3) W_k, calculated from measures of Froude efficiency (_F). In turn, _F=W_d/(W_d+W_k) and was calculated by modelling the arm movement as that of a paddle wheel. When swimming at speeds from 1.0 to 1.4 m s^–1, _F is about 0.5, power to overcome water resistance (active body drag × v) and power to give water kinetic energy increase from 50 to 100 W, and internal mechanical power from 10 to 30 W. In the same range of speeds increases from 600 to 1,200 W and C from 600 to 800 J m^–1. The use of fins decreases total mechanical power and C by the same amount (10–15%) so that _o (overall efficiency) is the same when swimming with or without fins [0.20 (0.03)]. The values of _o are higher than previously reported for the front crawl, essentially because of the larger values of W_tot calculated in this study. This is so because the contribution of W_int to W_tot was taken into account, and because _F was computed by also taking into account the contribution of the legs to forward propulsion.     

A comparison of three methods for titration of poliovirus vaccines

Two methods for in vitro endpoint titration of poliovirus — the roller tube and the microtitration assay — were compared with each other and with the plaque assay, using secondary vervet monkey kidney cells and Vero cells as indicators. The roller tube method is the most reliable under difficult working conditions, but is otherwise cumbersome and expensive. The microtitre method is the most economical and the plaque assay the most sensitive. By suspending freshly trypsinized indicator cells with the virus dilutions before planting, it was possible to simplify the microtitre method considerably. The sensitivity of the plaque assay was improved for Vero cells by absorbing the virus onto freshly planted monolayers. The method was scaled down to a semi-micro level by using 24-well cell culture trays. The slower rate of plaque development under a low calcium overlay medium facilitated a more accurate plaque count.