246 research outputs found

    Standard methods for Apis mellifera anatomy and dissection

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    An understanding of the anatomy and functions of internal and external structures is fundamental to many studies on the honey bee Apis mellifera. Similarly, proficiency in dissection techniques is vital for many more complex procedures. In this paper, which is a prelude to the other papers of the COLOSS BEEBOOK, we outline basic honey bee anatomy and basic dissection techniques

    On Uniformly Sampling Traces of a Transition System (Extended Version)

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    A key problem in constrained random verification (CRV) concerns generation of input stimuli that result in good coverage of the system's runs in targeted corners of its behavior space. Existing CRV solutions however provide no formal guarantees on the distribution of the system's runs. In this paper, we take a first step towards solving this problem. We present an algorithm based on Algebraic Decision Diagrams for sampling bounded traces (i.e. sequences of states) of a sequential circuit with provable uniformity (or bias) guarantees, while satisfying given constraints. We have implemented our algorithm in a tool called TraceSampler. Extensive experiments show that TraceSampler outperforms alternative approaches that provide similar uniformity guarantees.Comment: Extended version of paper that will appear in proceedings of International Conference on Computer-Aided Design (ICCAD '20); changed wrong text color in sec 7; added 'extended version

    Nitric Oxide Antagonizes the Acid Tolerance Response that Protects Salmonella against Innate Gastric Defenses

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    Reactive nitrogen species (RNS) derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood.The genetically tractable acid tolerance response (ATR) that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO) donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment.Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses

    Minor Abnormalities of Testis Development in Mice Lacking the Gene Encoding the MAPK Signalling Component, MAP3K1

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    In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans

    An informatics consult approach for generating clinical evidence for treatment decisions.

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    BACKGROUND: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. METHODS: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. RESULTS: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results. CONCLUSION: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service

    Illness causal beliefs in Turkish immigrants

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    <p>Abstract</p> <p>Background</p> <p>People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia.</p> <p>Methods</p> <p>Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness.</p> <p>Results</p> <p>Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness.</p> <p>Conclusion</p> <p>Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies.</p

    The specific surface area and chemical composition of diamond dust near Barrow, Alaska

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95687/1/jgrd17349.pd
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