A Statistical Approach to Biological Factors of Safety: Bending and Shearing inPsilotumAxes

A method is presented to calculate the factor of safety (basedon any criterion of failure) for populations of equivalent biologicalstructures that normally sustain mechanical loads (e.g. stemsof the same order of branching). The method uses the empiricallydetermined mean and standard deviation of the actual loads andthe load capabilities provided that both types of loads arenormally distributed in the population. The factor of safetySiscalculated from the formulaS     

Computer assisted management of warfarin treatment.

Maintenance of anticoagulation is laborious and costly, and the results are often indifferent. An automatic system which adjusts the dose of warfarin has been designed using a formula devised after a survey of prescribing habits. Programs running on a microcomputer maintain a file of the necessary information and deal with the bulk of the weekly clinic. Dosage is advised, the date of the next visit determined, and the file updated. A doctor uses the console to advise some 10% of patients reserved for special reasons. The system produces clinic and ambulance lists, copies of the advice sent to patients, and, as a protection against machine failure, a weekly copy of the updated file. The results after 16 months are at least as good as those achieved manually. Medical and secretarial time is saved, and statistics about the clinic and its efficacy are made available.     

Putting the Biological Species Concept to the Test: Using Mating Networks to Delimit Species

Although interfertility is the key criterion upon which Mayr’s biological species concept is based, it has never been applied directly to delimit species under natural conditions. Our study fills this gap. We used the interfertility criterion to delimit two closely related oak species in a forest stand by analyzing the network of natural mating events between individuals. The results reveal two groups of interfertile individuals connected by only few mating events. These two groups were largely congruent with those determined using other criteria (morphological similarity, genotypic similarity and individual relatedness). Our study, therefore, shows that the analysis of mating networks is an effective method to delimit species based on the interfertility criterion, provided that adequate network data can be assembled. Our study also shows that although species boundaries are highly congruent across methods of species delimitation, they are not exactly the same. Most of the differences stem from assignment of individuals to an intermediate category. The discrepancies between methods may reflect a biological reality. Indeed, the interfertility criterion is an environment-dependant criterion as species abundances typically affect rates of hybridization under natural conditions. Thus, the methods of species delimitation based on the interfertility criterion are expected to give results slightly different from those based on environment-independent criteria (such as the genotypic similarity criteria). However, whatever the criterion chosen, the challenge we face when delimiting species is to summarize continuous but non-uniform variations in biological diversity. The grade of membership model that we use in this study appears as an appropriate tool.     

Testing of antiviral compounds against Mengo virus infection of mice. A 2-step procedure of in vivo screening.

A 2-step procedure of screening of antiviral compounds in vivo is presented on the basis of standardized methods of both experimental examination and statistical analysis. The procedure uses the "rate of protection" R as the sole criterion of activity. In the first step, requiring a total of 40 mice, compounds with significant R are detected. Drugs producing R less than 15% are discarded. Compounds eliciting R larger than or equal to 15%, without significance, are examined in a second step, using again 40 mice, to decide whether the protective activity becomes significant employing a greater number of animals. The procedure works with relatively less expense with regard of the number of animals used and the time required. The procedure can be applied to test systems based on lethal infections as well as to test models for which the use of the "rate of protection" is relevant.     

Predicting the structural integrity of bone defects repaired using bone graft materials

Bone defects create stress concentrations which can cause fracture under impact or cyclic loading. Defects are often repaired by filling them with a bone graft material; this will reduce the stress concentration, but not completely, because these materials have lower stiffness than bone. The fracture risk decreases over time as the graft material is replaced by living bone. Many new bone graft materials are being developed, using tissue engineering and other techniques, but currently there is no rational way to compare these materials and predict their effectiveness in repairing a given defect. This paper describes, for the first time, a theoretical model which can be used to predict failure by brittle fracture or fatigue, initiating at the defect. Preliminary results are presented, concentrating on the prediction of stress fracture during the crucial post-operative period. It is shown that the likelihood of fracture is strongly influenced by the shape of the defect as well as its size, and also by the level of post-operative exercise. The most important finding is that bone graft materials can be successful in preventing fracture even when their mechanical properties are greatly inferior to those of bone. Future uses of this technique include pre-clinical assessment of bone replacement materials and pre-operative planning in orthopaedic surgery.     

Predicting the structural integrity of bone defects repaired using bone graft materials

Bone defects create stress concentrations which can cause fracture under impact or cyclic loading. Defects are often repaired by filling them with a bone graft material; this will reduce the stress concentration, but not completely, because these materials have lower stiffness than bone. The fracture risk decreases over time as the graft material is replaced by living bone. Many new bone graft materials are being developed, using tissue engineering and other techniques, but currently there is no rational way to compare these materials and predict their effectiveness in repairing a given defect. This paper describes, for the first time, a theoretical model which can be used to predict failure by brittle fracture or fatigue, initiating at the defect. Preliminary results are presented, concentrating on the prediction of stress fracture during the crucial post-operative period. It is shown that the likelihood of fracture is strongly influenced by the shape of the defect as well as its size, and also by the level of post-operative exercise. The most important finding is that bone graft materials can be successful in preventing fracture even when their mechanical properties are greatly inferior to those of bone. Future uses of this technique include pre-clinical assessment of bone replacement materials and pre-operative planning in orthopaedic surgery.     

Evaluation of bone cement failure criteria with applications to the acetabular region

A Strain energy density (SED) criterion based on a fracture mechanics approach was used to assess the possible failure of acetabular bone cement after total hip replacement. Stress distributions in the cement at the bone-cement interface were calculated using two-dimensional finite element analyses. The results indicate that increasing the thickness of bone cement reduces the risk of cement fracture. The addition of a metal backing to the polyethylene cup and retention of the subchondral bone further reduces the risk of failure. The SED criterion was found to predict the same critical regions as zones of possible cement failure as the von Mises' criterion. Although either criterion can be used for predicting failure in this acetabular analysis both criteria are excessively conservative in predicting failure in regions where high principal compressive stresses are present. Further development of cement failure criteria are indicated.     

Optimal Investment in Multi-species Protection: Interacting Species and Ecosystem Health

This article uses an ecological-economic approach to study optimal investment in multi-species protection when species interact in an ecosystem. The analysis is based on a model of stochastic species extinction in which survival probabilities are interdependent. Individual species protection plans can increase a species survival probability within certain limits and contingent upon the existence or absence of other species. Protection plans are costly and the conservation budget is fixed. It is assumed that human well-being depends solely on the services provided by one particular species, but other species contribute to overall ecosystem functioning and thus influence the first species survival probability. One result is that it may be optimal to invest in the protection of those species that do not directly contribute to human well-being, even if biological conservation decisions are exclusively derived from such a utilitarian framework. Another result is that the rank ordering of spending priorities among different species protection plans, as obtained under the assumption of independent species, may be completely reversed by taking species interaction into account. The conclusion is that effective species protection should go beyond targeting individual species, and consider species relations within whole ecosystems as well as overall ecosystem functioning. Ecosystem health is identified as a necessary prerequisite for successful species protection in situ.     

Determining hypoxic fraction in a rat glioma by uptake of radiolabeled fluoromisonidazole

The usefulness of radiolabeled nitroimidazoles for measuring hypoxia will be clarified by defining the relationship between tracer uptake and radiobiologically hypoxic fraction. We determined the radiobiologically hypoxic fraction from radiation response data in 36B10 rat gliomas using the paired cell survival curve technique and compared the values to the radiobiologically hypoxic fraction inferred from mathematical modeling of time-activity data acquired by PET imaging of [(18)F]FMISO uptake. Rats breathed either air or 10% oxygen during imaging, and timed blood samples were taken. The uptake of [(3)H]FMISO by 36B10 cells in vitro provided cellular binding characteristics of this radiopharmaceutical as a function of oxygen concentration. The radiobiologically hypoxic fraction determined for tumors in air-breathing rats using the paired survival curve technique was 6.1% (95% CL = 4.3- 8.6%), which agreed well with that determined by modeling FMISO time-activity data (7. 4%; 95% CL = 2.5-17.3%). These results are consistent with the agreement between the two techniques for measuring radiobiologically hypoxic fraction in Chinese hamster V79 cell spheroids. In contrast, the FMISO-derived radiobiologically hypoxic fraction in rats breathing 10% oxygen was 13.1% (95% CL 7.9-8.3%), much lower than the radiobiologically hypoxic fraction of 43% determined from the radiation response data. This discrepancy may be due to the failure of FMISO to identify hypoxic cells residing at or above an oxygen level of 2-3 mmHg that will still confer substantial protection against radiation. The presence of transiently hypoxic cells in rats breathing reduced oxygen may also be under-reported by nitroimidazole binding, which is strongly dependent on time and concentration.     

Two modified techniques for flexor tendon repair.

The aim of this article is to present two new techniques for digital flexor tendon repair: a modification to the conventional Kessler technique (wrap core suture) and tendon splints (H-shaped splint). These techniques were aimed at enhancing the biomechanical properties of such repairs as related to resistance to both gap formation and repair failure. Comparing (in an ex vivo study) the tensiometric properties (gap formation and failure strengths) of 24 flexor digitorum profundus tendons repaired with the described techniques (12 repairs per each technique) and the conventional Kessler repair (24 repairs), we found that the former provided significantly stronger repairs than the latter in vitro. A statistically significant difference (p < 0.001) was found between each of the two presented techniques and the Kessler repair. The wrap core suture increased the load at which a visible (1 mm) gap formed by 22.6 percent when compared with the conventional Kessler suture. The mean gap strength of the wrap core repair was 6.5 N, whereas that of the conventional Kessler was 5.3 N. The failure loads (ultimate strength) of the wrap core suture were 33.8 percent higher than those of the conventional Kessler. The mean breaking load of the wrap core repair was 19.4 N, whereas that of the conventional Kessler was 14.5 N. The H-splint repair increased the load at which a visible gap formed and the failure loads (ultimate strength) by 158.5 and 333.1 percent, respectively, when compared with the conventional Kessler suture. The mean gap strength of the H-splint repair was 13.7 N, and its mean breaking load was 62.8 N.     

Anisotropic yield behavior of bone under combined axial force and torque

In this study the yield behavior of cortical bone was determined under combined loading conditions involving tension, compression and torsion. The axis of each test sample coincided with the long bone axis. To minimize viscoelastic behavior, tests were conducted using an effective strain rate in the range of 0.01-0.06 s-1. Experimental yield loci for bovine and human cortical bone were determined using a strain offset technique to determine the 'common yield point' for combined loading. Several failure criteria which have been used for composite materials were examined for applicability to the experimental results. Data were obtained for bovine and human tibial and femoral bone. The Tsai-Wu criterion was in best agreement to the test data, although Hill's criterion could describe the individual compression-torsion or tension-torsion regimes with good accuracy.     

Multiscale Mechanics and Optimization of Gastropod Shells

A vast majority of mollusks grow a hard shell for protection.The structure of these shells comprises several levels of hierarchy that increase their strength and their resistance to natural threats.This article focuses on nacreous shells,which are composed of two distinct layers.The outer layer is made of calcite,which is a hard but brittle material,and the inner layer is made of nacre,a tough and ductile material.The inner and outer layers are therefore made of materials with distinct structures and properties.In this article,we demonstrate that this system is optimum to defeat attacks from predators.A two-scale modeling and optimization approach was used.At the macroscale,a two-layer finite element model of a seashell was developed to capture shell geometry.At the microscale,a representative volume element of the microstructure of nacre was used to model the elastic modulus of nacre as well as a multiaxial failure criterion,both expressed as function of microstructural parameters.Experiments were also performed on actual shells of red abalone to validate the results obtained from simulations and gain insight into the way the shell fails under sharp perforation.Both optimization and experimental results revealed that the shell displays optimum performance when two modes of failure coincide within the structure.Finally,guidelines for designing two-layer shells were proposed to improve the performance of engineered protective systems undergoing similar structural and loading conditions.     

基于系统保护规划的黄河流域湿地优先保护格局

黄河流域湿地为我国生物多样性维持提供了重要生境.本研究基于黄河流域气候分区、地貌单元及湿地遥感数据,构建黄河流域生态地理综合湿地分类系统.在系统保护规划理论框架下,将湿地气候-地貌分类单元作为生态系统层次保护对象,结合黄河流域鸟类分布范围作为物种层次的保护对象,设定30%湿地优化目标,将公路、铁路、城镇、农村居民点、水坝等作为度量因子创建黄河流域保护代价图层,并利用系统保护规划工具--Marxan软件构建黄河流域湿地保护优化格局,识别湿地保护空缺.结果表明: 黄河流域大部分沼泽湿地集中在黄河上游区域,目前源区保护区覆盖面积大,在内蒙古、甘肃及四川部分区域一些稀有湿地类型游离在保护体系外;黄河中游湿地类型以河道和河滩湿地类型为主,保护覆盖率极低,保护空缺严重,经优化保护网络体系后,保护成效可分别得到29.1%、37.6%的提升.黄河下游湿地主要集中在黄河三角洲区域,目前保护体系完整,保护空缺面积极小.总体上,黄河流域中游河流湿地的保护空缺比例最高,亟需重视.本研究基于湿地保护格局优化结果分区分析黄河流域湿地保护模式,为黄河流域湿地的保护规划管理提供了科学性建议,从宏观层面上为黄河流域水生态保护奠定了基石.     

LBA technique in the detection of chromosome variants

Summary A method is described (LBA method) which uses DNA replication pattern in the detection of chromosome variants in man. In Part I, results on chromosomes with known sites of Q-variants, i.e., 5 pairs of acrocentrics, as well as 3 and 4, were presented.Fourty-one variants were detected in a total of 40 acrocentrics. Twentyeight of them were detected only by the LBA technique; 11 of them being in short arms and 17 of them in centromeres. Seven variants, including 4 of those in satellites, were detected only in QFQ-stained metaphases. Six short-arm variants were observed by both methods. It appears that a sequential QFQ-LBA technique is very useful in the detection of variants in D- or G-group chromosomes.     

A comparison of outcomes using three different methods of breast reconstruction.

In a review of 325 postmastectomy breast reconstructions, the aesthetic quality of the result and the risk of unsuccessful outcome were compared for three techniques: tissue expansion (105 breasts), latissimus dorsi myocutaneous flap (47 breasts), and TRAM flap (173 breasts). The aesthetic successes achievable with the three methods were similar, and some excellent results were achieved with each of them. The failure rate after tissue expansion (21 percent) was significantly higher than those observed with the TRAM (3 percent) and latissimus (9 percent) flaps. Tissue expansion also was not as aesthetically successful as other techniques in obese patients. For immediate breast reconstruction, the TRAM flap was the most aesthetically successful technique. Although tissue expansion has advantages and may be the best choice for some patients, methods that used autogenous tissue provided more consistent success.     

Protective role of zinc-metallothionein (Zn-MT) in iron nitrilotriacetate (Fe-NTA)-induced renal oxidative damage

Several studies have shown the role of thiol-rich proteins especially metallothionein (MT) in the therapeutic interventions against oxidative damage. Previously, we have provided strong evidence for the involvement of ROS in iron nitrilotriacetate (Fe-NTA)-induced renal toxicity, which may have relevance to its carcinogenicity. The purpose of this study was to evaluate the role of zinc metallothionein (Zn-MT) on the protection against Fe-NTA-induced renal oxidative damage. The results demonstrate that Zn-MT pretreatment provided protection against Fe-NTA-induced mortality in mice (40% protection). Similarly, Zn-MT pretreatment also provided protection against Fe-NTA-induced lipid peroxidation (26% inhibition, P < 0.001). It is proposed that Zn-MT protects kidney tissue against the noxious effect of Fe-NTA primarily by interference with lipid peroxides. It is concluded that Zn-MT may serve as an excellent physiological antioxidant against Fe-NTA-mediated renal oxidative damage.     

Culture of fetal mouse liver in plastic chambers: a new technique for organ culture.

A new technique for organ culture which uses plastic culture chambers and the advantages of the cellophane-sheet technique is described with the results of a study of cultivations of fetal mouse liver. Two chambers, each containing cells, were placed in gas permeable roller tubes and rotated at 0.1 rpm in a CO2-air gassed incubator. The fetal mouse liver cells developed electron microscopic features similar to those of the in vivo adult liver by 9 days of cultivation. The albumin content and tyrosine aminotransferase (TAT) activity were detected in the cultivated liver. TAT activity was further induced by prednisolone. These results indicate that potential of this culture method for the study of physiological and pathological processes.     

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.     

45S rDNA基因的不稳定性及其与转录的相关性

45S rDNA基因由串联重复序列构成,是遗传不稳定性的热点区域,易于发生DNA断裂和重组。以Hela和CHO细胞系为研究对象,运用荧光原位杂交技术检测有丝分裂不同时期的45S rDNA基因的不稳定性表型。结果表明,位点特异性的染色体浓缩失败是其在中期染色体上不稳定性的主要表型。具有这种表型的染色体在后期可能会出现落后或粘连现象,甚至有可能引发断裂,形成卫星核。同时,免疫荧光双染色技术检测表明DNA双链断裂的标记蛋白(γH2AX)和RNA聚合酶I的上游结合因子(UBF)在有丝分裂的不同时期都存在共定位现象。该结果为探讨45S rDNA基因的不稳定性与转录的关系提供了直观的细胞学证据。     

A TLR5 agonist inhibits acute renal ischemic failure

Reperfusion of ischemic organs induces a potent inflammatory response initiated by the generation of reactive oxygen species that directly damage tissue and promote leukocyte infiltration and activation that also mediate tissue injury. We recently found that radiation-induced tissue injury, which is caused by radiation-induced reactive oxygen species, is attenuated by administration of CBLB502, a pharmacologically optimized derivative of the TLR5 agonist flagellin. Therefore, we tested the ability of CBLB502 to attenuate injury in a murine model of acute ischemic renal failure. CBLB502 given 30 min before imposition of bilateral renal pedicle occlusion provided marked protection against the renal dysfunction and inflammation that follows reperfusion of ischemic kidneys, including marked decreases in leukocyte infiltration, proinflammatory cytokine production, and tubular injury. Importantly, CBLB502 given within 30 min after ischemic kidney reperfusion reproduced the protective effects of pretreatment with the TLR5 agonist, indicating a window following reperfusion in which CBLB502 administration abrogates acute renal ischemic failure. Bone marrow-reconstituted chimeras were used to show that the protective effects of CBLB502 could be delivered by intact MyD88 signaling on renal parenchymal cells. Consistent with this, Ab staining of kidney sections indicated that cells lining the renal vasculature expressed TLR5. Overall, these results indicate the use of TLR5 agonists as mitigators and protectants of acute renal ischemic failure.