Simulation as experiment: a philosophical reassessment for biological modeling

Some scientific modelers suggest that complex simulation models that mimic biological processes should have a limited place in ecological and evolutionary studies. However, complex simulation models can have a role that is different from that of simpler models that are designed to be fit to data. Simulation can be viewed as another kind of experimental system and should be analyzed as such. Here, I argue that current discussions in the philosophy of science and in the physical sciences fields about the use of simulation as an experimental system have important implications for biology, especially complex sciences such as evolution and ecology. Simulation models can be used to mimic complex systems, but unlike nature, can be manipulated in ways that would be impossible, too costly or unethical to do in natural systems. Simulation can add to theory development and testing, can offer hypotheses about the way the world works and can give guidance as to which data are most important to gather experimentally.     

A computerized database-management system for curriculum analysis.

This report describes a computerized database-management system designed to allow users to retrieve and report information on the curriculum of an undergraduate pathophysiology course. With the system the user can locate where and in what context a topic is covered in the course and can answer queries and prepare reports concerning, for example, format and duration of sessions, teaching aids used and instructors. The system is a unique tool that can be used to optimize course structure and content. It can easily be expanded to include other undergraduate medical courses, and the techniques can be applied to other disciplines.     

Interactions of liposomes with serum proteins

The interactions of serum proteins are diverse, complex and can lead to dramatic effects on liposome stability and in vivo behavior; conversely lipids can modify the biological activities of serum proteins. Serum lipoproteins can potentially destabilize bilayer membranes leading to vesicle disruption and loss of contents; irregularities in the lipid bilayer, such as those which exist at phase boundaries, promote the destabilizing effects of lipoproteins. Other serum components such as fibronectin, immunoglobulins and C reactive protein can modify the biological properties of liposomes by promoting interactions with reticuloendothelial cells and/or activation of the complement system. Liposomes can avidly bind certain serum clotting factors, a process which can lead to dramatic effects on the clotting cascade. Thus the interactions of liposomes with serum proteins can reciprocally effect both components involved.     

Modification of commerical and custom-built slab gel electrophoresis units for two-dimensional polyacrylamide gel electrophoresis

Many commercial and custom-built slab gel electrophoresis units can be modified to function as two-dimensional polyacrylamide gel electrophoresis units with the insertion of Plexiglas adapters. These adapters can be made for about $50 a pair and can be used for either temporary or permanent modification of the slab gel units. The physical dimensions of the adapters can be varied to permit great flexibility in the diameter of cylinder gels and the thickness of slab gels that can be run together. For example, proteins from 6-mm cylinder gels can be easily separated on 1-mm slab gels, which can then be dried for autoradiography.     

Marine yeasts as biocontrol agents and producers of bio-products

As some species of marine yeasts can colonize intestine of marine animals, they can be used as probiotics. It has been reported that β-glucans from marine yeast cells can be utilized as immuno-stimulants in marine animals. Some siderophores or killer toxins produced by marine yeasts have ability to inhibit growth of pathogenic bacteria or kill pathogenic yeasts in marine animals. The virulent factors from marine pathogens can be genetically displayed on marine yeast cells, and the yeast cells displaying the virulent factors can stimulate marine animals to produce specific antibody against the pathogens. Some marine yeast cells are rich in proteins and essential amino acids and can be used in nutrition for marine animals. The marine yeast cells rich in lipid can be used for biodiesel production. Recently, it has been reported that some strains of Yarrowia lipolytica isolated from marine environments can produce nanoparticles. Because many marine yeasts can remove organic pollutants and heavy metals, they can be applied to remediation of marine environments. It has been shown that the enzymes produced by some marine yeasts have many unique properties and many potential applications.     

The chemoinvasion assay: a method to assess tumor and endothelial cell invasion and its modulation

Invasive and metastatic cells, as well as endothelial cells, must cross basement membranes (BMs) in order to disseminate or to form new blood vessels. The chemoinvasion assay using the reconstituted BM Matrigel in Boyden blind-well chambers is a very rapid, easy, inexpensive and flexible test that can be used to quantify the invasive potential of most cell types; it can be applied to detect the migratory activity associated with matrix degradation and can also be adapted to study the selective degrading activity on different matrix substrates. Transwell inserts can also be used. Once the optimal experimental conditions are empirically determined for specific cellular models, the chemoinvasion assay can be used for the screening of inhibitors of invasiveness and angiogenesis, or to select for invasive cellular populations. This protocol can be completed in 9 h.     

Fluorescence in situ hybridization on vibratome sections of plant tissues

This protocol describes the application of fluorescence in situ hybridization (FISH) to three-dimensionally (3D) preserved tissue sections derived from intact plant structures such as roots or florets. The method is based on the combination of vibratome sectioning with confocal microscopy. The protocol provides an excellent tool to investigate chromosome organization in plant nuclei in all cell types and has been used on tissues of both monocot and dicot plant species. The visualization of 3D well-preserved tissues means that cell types can be confidently identified. For example, meiocytes can be clearly identified at all stages of meiosis and can be imaged in the context of their surrounding maternal tissue. FISH can be used to localize centromeres, telomeres, repetitive regions as well as unique regions, and total genomic DNAs can be used as probes to visualize chromosomes or chromosome segments. The method can be adapted to RNA FISH and can be combined with immunofluorescence labeling. Once the desired plant material is sectioned, which depends on the number of samples, the protocol that we present here can be carried out within 3 d.     

microRNA在乙型肝炎病毒感染及相关疾病中的作用

乙型肝炎病毒(hepatitis B virus,HBV)是一种嗜肝性DNA病毒,感染后可导致急性和慢性肝炎,而慢性感染是导致肝硬化、肝癌和肝衰竭的主要病因。在乙型肝炎病毒复制、转录和相关疾病进程中,microRNA(miRNA)扮演着重要的角色。乙型肝炎病毒感染肝细胞后能引起细胞内microRNA表达谱的改变:一方面,microRNA能促进乙型肝炎病毒的转录和诱导宿主细胞向肿瘤细胞转化;另一方面,microRNA也能抑制乙型肝炎病毒包装和复制。重要的是,乙型肝炎病毒的感染能影响宿主血清microRNA的表达。因此,这类特殊的microRNA今后可成为乙型肝炎病毒相关疾病诊断的潜在生物标记物。将对乙型肝炎病毒与宿主microRNA之间相互作用及其相关生物学效应作一综述。     

The use of biomarkers in surveillance, medical screening, and intervention

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.     

Fiber optic array biosensors

Optical fiber arrays provide a powerful substrate for creating high-density sensing systems that can address a variety of biological problems. The fiber substrate can be used to create femtoliter wells that can be loaded with individual beads to create high-density arrays for multiplexed screening and analysis. In addition, living cells can be loaded into the arrays, and their individual responses monitored over long time periods, enabling functional screening of biologically active compounds. Adherent cells can be attached to the fiber substrate to provide a rapid method for observing cell migration and for screening anti-migratory compounds. Finally, individual enzyme molecules can be loaded into the array wells enabling single molecule detection via enzyme-catalyzed signal amplification.     

Management of alcoholism in the primary care setting.

Primary care physicians can play an important role in managing alcoholic patients. Identifying and treating alcoholism early, before it has interfered with patients'' relationships and work, may increase the likelihood of prolonged recovery. Simple office interventions can help motivate patients to abstain and seek treatment. People who abuse alcohol and are unwilling to abstain can benefit from a recommendation to reduce their intake of alcohol. For alcohol-dependent patients who decide to stop drinking, primary care physicians often can manage withdrawal on an outpatient basis. Selecting an appropriate treatment program for each alcoholic patient is important, and referral to a specialist to assist in matching patients to treatments is often necessary. Primary care physicians also can help prevent relapse. Although disulfiram is of limited value, primary care physicians can support recovery by identifying coexistent psychosocial problems, helping patients to restructure their lives, and ensuring continuity of care.     

Late-life Onset Bipolar Disorder Presenting as a Case of Pseudo-Dementia: A Case Discussion and Review of Literature

Depression and comorbid cognitive impairment in the elderly can be difficult to distinguish from dementia. Adding to the complex differential is that depression may be part of a bipolar illness rather than a unipolar mood disorder. A diligent workup and close monitoring of patients can inform appropriate treatment and can make the difference between recovery and persistence of symptoms. The present case will illustrate how a comprehensive workup utilizing extensive data gathering, laboratory workup, use of neuropsychological testing, neuroimaging, and timely treatment can lead to successful clinical outcomes that can be sustained for many years.     

Protein φ and ψ dihedral restraints determined from multidimensional hypersurface correlations of backbone chemical shifts and their use in the determination of protein tertiary structures

The chemical shifts of the backbone atoms of proteins can be used to obtainrestraints that can be incorporated into structure determination methods. Eachchemical shift can be used to define a restraint and these restraints can besimultaneously used to define the local, secondary structure features. Theglobal fold can be determined by a combined use of the chemical shift basedrestraints along with the long-range information present in the NOEs ofpartially deuterated proteins or the amide–amide NOEs but not from suchlimited NOE data sets alone. This approach has been demonstrated to be capableof determining the overall folding pattern of four proteins. This suggeststhat solution-state NMR methods can be extended to the structure determinationof larger proteins by using the information present in the chemical shifts ofthe backbone atoms along with the data that can be obtained on a small numberof labeled forms.     

Use of bioluminescence in nucleic acid hybridization reactions

Luminescence reactions can be used to detect specific nucleic acid sequences hybridized with a nucleic probe. Different labels such as cytidine sulphone, fluorescein, and biotin can be incorporated into DNA or oligonucleotide molecules and detected by antibody or avidin conjugates coupled to glucose-6P dehydrogenase. On supports such as nitrocellulose filters, sensitivity is not greatly increased using luminescence, but detection is rapid and easy to perform using polaroid film. Moreover, hybridization can be performed with different labelled probes on the same sample. In solution, luminescence can be used to monitor sandwich reactions. The method is less sensitive than detection on filters but can easily be automated. The performance of these assays can be increased considerably by enzymatic amplification of the target catalysed by a thermostable polymerase.     

植被监测及趋势分析——植被数量生态学中几个理论问题的探讨

 系统监测可以对危机发出预警, 是防治灾害的重要手段。生态监测的基础是植被监测。多物种 多样本 多年的植被定位监测数据隐含 着植被变化的信息。该文探索描述植被的数学工具, 提出植被监测数据的趋势分析方法。植被是资源竞争系统, 可以用多维空间的向量来表示 。在向量空间(射影空间), 不是“距离” , 而是“方向”决定区别; 在植被科学, 不是“产量”, 而是“组成”决定区别。新方法用多维空间 的位置向量来表示植被: 向量的方向表示植被的组成、两向量夹角余弦值表示相似、向量长度表示植被总体。在简缩数据时, 用“中心化”滤 去样本噪音、“标准化”滤去系统噪音, 得到状态向量。在趋势分析时, 定义后、前状态向量的比值为变化趋势; 用当年的状态和趋势的乘积 来预报次年的状态。到次年, 再用实测数据修正、更新来自去年的预报, 是为“卡尔曼滤波”。卡尔曼滤波能降低监测成本, 有效地使用历史 数据, 提高分析精度。     

发酵肥与秸杆还田对土壤微生物区系与作物产量的影响

土壤中施入不发酵新鲜粪肥时土壤细菌与放线菌数量明显增加,当施入发酵肥时对土壤微生物活性影响较小;在施发酵肥基础上再进行秸杆还田,土壤微生物活性明显提高,作物获得持续丰产。单一秸杆还田也能提高土壤微生物活性,但当年无增产效果,在秸杆还田时喷雾接种木霉（Ｔｒｉｃｈｏｄｅｍａｋｏｎｉｎｇｉ）４５６—２与固氮菌（Ａｚ．ｖｉｎｅｌａｎｄｉｉ）２３０,当年获得增产效果。     

Allochthonous inputs: integrating population changes and food-web dynamics

Most ecosystems are recipients of allochthonous materials that enhance in situ productivity. Recent theoretical and empirical studies suggest that low to moderate inputs can stabilize food webs. However, depending on the trophic levels that use the resource, food webs can become unstable as inputs increase. Where large amounts of agricultural resources are transferred to natural habitats, trophic dynamics change: trophic cascades can occur and rare or uncommon species can become invasive. Rates of change in species abundances can also be amplified by the effects of changes in legislation and management practices on subsidized consumers.     

ABDOMINAL FASCIAL TRANSPLANTS—Physiological and Psychological Benefits

Even when they cannot restore the ability of a paralyzed patient to walk, fascial transplanting operations to stabilize the trunk, to give firmness to the abdominal wall and to improve the posture can be of great benefit. Well designed and well executed operations can greatly improve respiratory, circulatory and eliminatory function. Often the ability to talk or even to sing is restored. Even the ability to cough effectively can sometimes be a boon.The rewards in improved physical health and in morale can make the pain and the expense of operation well worth while to the patient.     

A note on the occasional instability of detrending in correspondence analysis

When the two first eigenvalues of correspondence analysis are close to each other, their order can be reversed due to random variation in the data. The first axis can actually be in any direction in the plane defined by the two axes. However, the configuration of the points in the plane can remain unchanged but their projections onto any line in the plane can be very variable. The ordering in the first axis is preserved in detrending. The second axis is detrended with respect to the first one and therefore very variable configurations result when the orientation of the first axis in the plane is changed. This can lead to a situation where the detrended solutions are very unstable under random variation and therefore they can be only casually interpretable.     

Adaptive noise

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.