The complexity of the overlap method for sequencing biopolymers

The problem of trying to reconstruct the sequence of a biopolymer by using overlapping fragments obtained from cleaving agents is shown to be computationally intractable. This strongly suggests that any computer program for overlap sequencing, even though it may work well for a limited number of inputs, will not work sufficiently for all inputs. However, if the problem is restricted so that certain crucial fragments are known, called prime strings, a sequence can be found efficiently in all cases. Graph theory techniques for doing so can also be used to count the number of sequences consistent with the fragment data to determine whether a unique sequence has been obtained.     

Culture and decontamination methods affecting enumeration of phages infecting Bacteroides fragilis in sewage.

A new medium has been adapted for the growth of Bacteroides fragilis so that its phages can be recovered from environmental samples, and its efficiency has been assessed. Polyvinylidene difluoride membranes allow significantly higher recoveries among different membrane filters used to decontaminate the samples. In all cases, a number of phages remain in the filters and a percentage of them can be recovered by treatment with an eluant.     

Culture and decontamination methods affecting enumeration of phages infecting Bacteroides fragilis in sewage.

A new medium has been adapted for the growth of Bacteroides fragilis so that its phages can be recovered from environmental samples, and its efficiency has been assessed. Polyvinylidene difluoride membranes allow significantly higher recoveries among different membrane filters used to decontaminate the samples. In all cases, a number of phages remain in the filters and a percentage of them can be recovered by treatment with an eluant.     

A semiparametric two-component "compound" mixture model and its application to estimating malaria attributable fractions

Malaria remains a major epidemiologic problem in many developing countries. Malaria is defined as the presence of parasites and symptoms (usually fever) due to the parasites. In endemic areas, an individual may have symptoms attributable either to malaria or to other causes. From a clinical viewpoint, it is important to correctly diagnose an individual who has developed symptoms so that the appropriate treatments can be given. From an epidemiologic and economic viewpoint, it is important to determine the proportion of malaria-affected cases in individuals who have symptoms so that policies on intervention program can be developed. Once symptoms have developed in an individual, the diagnosis of malaria can be based on the analysis of the parasite levels in blood samples. However, even a blood test is not conclusive as in endemic areas many healthy individuals can have parasites in their blood slides. Therefore, data from this type of study can be viewed as coming from a mixture distribution, with the components corresponding to malaria and non-malaria cases. A unique feature in this type of data, however, is the fact that a proportion of the non-malaria cases have zero parasite levels. Therefore, one of the component distributions is itself a mixture distribution. In this article, we propose a semiparametric likelihood approach for estimating the proportion of clinical malaria using parasite-level data from a group of individuals with symptoms. Our approach assumes the density ratio for the parasite levels in clinical malaria and nonclinical malaria cases can be modeled using a logistic model. We use empirical likelihood to combine the zero and nonzero data. The maximum semiparametric likelihood estimate is more efficient than existing nonparametric estimates using only the frequencies of zero and nonzero data. On the other hand, it is more robust than a fully parametric maximum likelihood estimate that assumes a parametric model for the nonzero data. Simulation results show that the performance of the proposed method is satisfactory. The proposed method is used to analyze data from a malaria survey carried out in Tanzania.     

Optimal design of fair layouts

A relevant logistic issue in the organization of a fair is to determine how stands have to be placed in the exhibition space so as to satisfy all constraints on security, ease of access, services, and so on, while maximizing the revenues coming from the exhibitors. We consider in particular the problem of allocating the maximum number of stands by satisfying all the constraints required by practical implementations. We examine a number of real-world cases, and show how basic mathematical programming models can be improved to handle specific requests from the organizers. We report the solutions obtained through an original decision support system, that embeds a number of algorithms to solve the various cases by reduction to one or more linear programs.     

Evaluation of a decision support system in a medical environment

This paper describes the impact of a decision support system on the quality of recorded diagnoses and the completeness of medical records. The assumption is that for quality assessment purposes enough data have to be recorded in an electronic medical record so that diagnostic decisions can be justified. The hypotheses were tested that active decision support will lead to better quality recorded diagnoses and more complete medical records. Three groups of ten GPs were presented with 10 cases each. The GPs had to enter the data about these cases in a GP information system. One group of GPs was not supported. The second group was presented with the ICHPPC-II-Defined criteria that had to be fulfilled when a diagnosis was entered. In a third group, the GPs were asked those data that were needed to justify an entered diagnosis (active support). It could be shown that the last group of GPs entered better quality diagnoses than the other two groups. These latter groups also entered so little data that most of their diagnoses could not be justified. It is concluded from the study that only active decision support will lead to better diagnoses and a more complete medical record that can be used for quality assessment.     

Rapid Cervical Cytology Screening

2030 Papanicolaou-stained cervical smears were submitted for rapid screening prior to routine screening; 30 seconds were allowed for each slide, and those thought to be abnormal were identified. The results were compared with those of conventional screening. All severe and moderately dyskaryotic cases were detected by the rapid technique, as were the majority of mild dyskaryosis and borderline cases. When a laboratory has a backlog it may be worth rapid-screening all slides in addition to routine screening, so that patients most at risk can receive prompt treatment.     

Electron microscopy of fine needle aspiration biopsies of mediastinal and paramediastinal lesions

The ultrastructural cytologic study of fine needle aspiration (FNA) biopsies from eight cases with mediastinal and paramediastinal lesions is reported. In these cases, electron microscopy (EM) was essential in cytologically determining the correct type of the cancer cells. The results in these cases suggest that portions of FNA biopsies from deep sites, where aspiration is difficult or requires computed tomographic scanning, should be routinely processed for plastic embedding, so that EM examination can be performed if the cells are undifferentiated, scanty or poorly preserved by light microscopic examination. The proper cytologic identification of the cell might, in fact, have a major bearing on the therapeutic choices and on the prognosis.     

Microbial transformation of azaarenes and potential uses in pharmaceutical synthesis

Pyridine, quinoline, acridine, indole, carbazole, and other heterocyclic nitrogen-containing compounds (azaarenes) can be transformed by cultures of bacteria and fungi to produce a variety of new derivatives, many of which have biological activity. In many cases, the microbial biotransformation processes are regio- and stereoselective so that the transformation products may be useful for the synthesis of new candidate drugs.     

Equilibria of idealized confined astral microtubules and coupled spindle poles

Positioning of the mitotic spindle through the interaction of astral microtubules with the cell boundary often determines whether the cell division will be symmetric or asymmetric. This process plays a crucial role in development. In this paper, a numerical model is presented that deals with the force exerted on the spindle by astral microtubules that are bent by virtue of their confinement within the cell boundary. It is found that depending on parameters, the symmetric position of the spindle can be stable or unstable. Asymmetric stable equilibria also exist, and two or more stable positions can exist simultaneously. The theory poses new types of questions for experimental research. Regarding the cases of symmetric spindle positioning, it is necessary to ask whether the microtubule parameters are controlled by the cell so that the bending mechanics favors symmetry. If they are not, then it is necessary to ask what forces external to the microtubule cytoskeleton counteract the bending effects sufficiently to actively establish symmetry. Conversely, regarding the cases with asymmetry, it is now necessary to investigate whether the cell controls the microtubule parameters so that the bending favors asymmetry apart from any forces that are external to the microtubule cytoskeleton.     

On dependent repeated screening tests

A screening test is applied n times to a person with known true status. If more than k tests have positive outcomes, then the person is assigned to be screen-positive; otherwise, the person is assigned to be screen-negative. Assuming that the tests are exchangeable, we can characterize the possible dependence among tests by at most n parameters called canonical moments, which can be estimated from the data. The performance characteristics of the composite test (such as likelihood ratios, sensitivity, and specificity) can be computed based on these estimates. Thus, we can choose n and k so that the desired levels of likelihood ratios, sensitivity, and specificity can be achieved. We study the cases n = 2 and n = 3 in detail.     

Systematic detection of polygenic cis-regulatory evolution

The idea that most morphological adaptations can be attributed to changes in the cis-regulation of gene expression levels has been gaining increasing acceptance, despite the fact that only a handful of such cases have so far been demonstrated. Moreover, because each of these cases involves only one gene, we lack any understanding of how natural selection may act on cis-regulation across entire pathways or networks. Here we apply a genome-wide test for selection on cis-regulation to two subspecies of the mouse Mus musculus. We find evidence for lineage-specific selection at over 100 genes involved in diverse processes such as growth, locomotion, and memory. These gene sets implicate candidate genes that are supported by both quantitative trait loci and a validated causality-testing framework, and they predict a number of phenotypic differences, which we confirm in all four cases tested. Our results suggest that gene expression adaptation is widespread and that these adaptations can be highly polygenic, involving cis-regulatory changes at numerous functionally related genes. These coordinated adaptations may contribute to divergence in a wide range of morphological, physiological, and behavioral phenotypes.     

On the design of closed recapture experiments

We propose a method to plan the number of occasions of recapture experiments for population size estimation. We do so by fixing the smallest number of capture occasions so that the expected length of the profile confidence interval is less than or equal to a fixed threshold. In some cases, we solve the optimization problem in closed form. For more complex models we use numerical optimization. We detail models assuming homogeneous, time‐varying, subject‐specific capture probabilities, behavioral response to capture, and combining behavioral response with subject‐specific effects. The principle we propose can be extended to plan any other model specification. We formally show the validity of the approach by proving distributional convergence. We illustrate with simulations and challenging examples in epidemiology and ecology. We report that in many cases adding as few as two sampling occasions may substantially reduce the length of confidence intervals.     

Mitochondrial targeting sequences may form amphiphilic helices.

Twenty three mitochondrial targeting sequences have been analysed with regard to their potential for forming amphiphilic helices. It is shown that most if not all of these sequences can be expected to form helices with high hydrophobic moments in a suitable environment. In the few cases studied so far, the segments of maximal hydrophobic moment coincide closely with 'critical' regions defined by deletions and point mutations.     

Physiological and ecological significance of biological ice nucleators

When a pure water sample is cooled it can remain in the liquid state at temperatures well below its melting point (0 degrees C). The initiation of the transition from the liquid state to ice is called nucleation. Substances that facilitate this transition so that it takes place at a relatively high sub-zero temperature are called ice nucleators. Many living organisms produce ice nucleators. In some cases, plausible reasons for their production have been suggested. In bacteria, they could induce frost damage to their hosts, giving the bacteria access to nutrients. In freeze-tolerant animals, it has been suggested that ice nucleators help to control the ice formation so that it is tolerable to the animal. Such ice nucleators can be called adaptive ice nucleators. There are, however, also examples of ice nucleators in living organisms where the adaptive value is difficult to understand. These ice nucleators might be structures with functions other than facilitating ice formation. These structures might be called incidental ice nucleators.     

PROTEIN COAGULATION AND ITS REVERSAL : SERUM ALBUMIN

1. It is possible to prepare crystalline, soluble, heat-coagulable serum albumin from coagulated serum albumin. 2. In the cases so far studied, the more soluble a denatured protein, the more easily its denaturation can be reversed.     

The value of needle aspiration cytology of the breast, with an emphasis on the diagnosis of breast disease in young women below the age of 30

Our experience with 4,739 needle aspirations of the breast was reviewed, with an emphasis on the diagnosis of carcinoma in young women under the age of 30 years. Among benign diseases, fibroadenomas were most frequently seen in younger women (24.3% of 919 cases) while cysts were most frequently seen in women 30 years of age and older (20.0%). Fibrocystic conditions were identified in approximately 30% of the women in each group. All younger women with suspicious diagnoses had fibrocystic disease at biopsy; in older women, 75% of the suspicious cases proved to be carcinomas while 25% proved to be fibrocystic diseases. Carcinomas were diagnosed cytologically in 1.3% of younger women and in 9.7% of older women. In young women, in whom breast carcinoma is a rare disorder, it is important that carcinoma be diagnosed without delay so that an appropriate plan of management can be adopted. These findings suggest that needle aspiration cytology can accurately make that diagnosis.     

Likelihood and Inconsistency

Parsimony can be inconsistent, but not maximum likelihood—likelihood advocates often say. This difference and conclusions drawn from it have provided the main reasons advanced by likelihoodists against the use of parsimony. Recent statistical research, however, shows that maximum likelihood estimation of phylogenetic trees can become inconsistent in all but the simplest cases, so that under realistic conditions the consistency of maximum likelihood cannot be assured. If likelihoodists wish to dispose of parsimony, they will have to find another argument.     

甲下外生性骨疣的临床病理分析

目的阐述甲下外生性骨疣的临床、影像、病理特征。方法收集中国医科大学附属盛京医院2006年1月～2011年12月甲下外生性骨疣14例进行分析,并参阅文献。结果14例患者平均年龄13岁,11例位于拇趾,病程2个月～3年,临床上出现甲下或甲旁的结节、疼痛、感染、趾甲异常。x线多表现为趾骨远端的骨性突起,基底与趾骨相连,大小0．5～1．2厘米。组织学上,表现为基底的成熟骨组织表面被覆纤维软骨。有随访结果的6例中1例术后1年复发。结论甲下外生性骨疣有典型的临床、影像、病理特点。手术时应确认肿物和甲床的关系,做到既将肿物完全切除以防止复发,同时又保护甲床,对甲床进行精确的修复以尽量避免指甲变形或丧失。     

Developmental disorders: what can be learned from cognitive neuropsychology?

The discipline of cognitive neuropsychology has been important for informing theories of cognition and describing the nature of acquired cognitive disorders, but its applicability in a developmental context has been questioned. Here, we revisit this issue, asking whether the cognitive neuropsychological approach can be helpful for exploring the nature and causes of developmental disorders and, if so, how. We outline the key features of the cognitive neuropsychological approach, and then consider how some of the major challenges to this approach from a developmental perspective might be met. In doing so, we distinguish between challenges to the methods of cognitive neuropsychology and those facing its deeper conceptual underpinnings. We conclude that the detailed investigation of patterns of both associations and dissociations, and across both developmental and acquired cases, can assist in describing the cognitive deficits within developmental disorders and in delineating possible causal pathways to their acquisition.