AVMf: An Open-Source Framework and Implementation of the Alternating Variable Method

The Alternating Variable Method (AVM) has been shown to be a fast and effective local search technique for search-based software engineering. Recent improvements to the AVM have generalized the representations it can optimize and have provably reduced its running time. However, until now, there has been no general, publicly-available implementation of the AVM incorporating all of these developments. We introduce AVMf, an object-oriented Java framework that provides such an implementation. AVMf is available from http://avmframework.org for configuration and use in a wide variety of projects

Abdominal Ultrasound and Abdominal Radiograph to Diagnose Necrotizing Enterocolitis in Extremely Preterm Infants

Necrotizing enterocolitis (NEC) is an important contributor towardmortality in extremely premature infants and Very Low Birth Weight(VLBW) infants. The incidence of NEC was 9% in VLBW infants(birth weight 401 to 1,500 grams) in the Vermont Oxford Network(VON, 2006 to 2010, n = 188,703).1 The incidence of NEC was 7%in 1993, increased to 13% in 2008, and decreased to 9% in extremelypreterm infants (22 to 28 weeks gestation) in the Neonatal ResearchNetwork Centers (1993 to 2012).2 The incidence of surgically treatedNEC varies from 28 to 50% in all infants who develop NEC.3 SurgicalNEC occurred in 52% in the VON cohort.1 In this cohort, the odds ofsurgery decreased by 5% for each 100 gram increase in birth.The incidence of surgical NEC has not decreased in the pastdecade.4 The mortality from NEC is significantly higher in infantswho need surgery compared to those who did not (35% versus 21%).1The case fatality rate among patients with NEC is higher in thosesurgically treated (23 to 36%) compared to those medically treated (5to 24%).3 In addition to surgery, NEC mortality rates are influencedby gestational age, birth weight,1,2,5 assisted ventilation on the day ofdiagnosis of NEC, treatment with vasopressors at diagnosis of NEC,and black race.6,7Extremely preterm infants who survive NEC are at risk for severeneurodevelopmental disability and those with surgical NEC have asignificantly higher risk of such delays (38% surgical NEC versus 24%medical NEC).8 Diagnosis of necrotizing enterocolitis is challengingand it is usually suspected based on non-specific clinical signs. Bell’scriteria and Vermont-Oxford Network criteria help in the diagnosisof NEC.Bell’s criteria, commonly used for diagnosis, staging, and planningtreatment of NEC, were described in 1978 and modified in 1986.9,10Bell’s stage I signs are non-specific: temperature instability, lethargy,decreased perfusion, emesis or regurgitation of food, abdominal distension,recurrent apnea, and on occasion, increased support withmechanical ventilation. Abdominal distension and emesis are morecommon than bloody stools in very preterm infants compared to terminfants.7 Abdominal radiographic findings are an integral part of Bell’scriteria. Identification of Bell’s stage I NEC (early NEC) with abdominalradiograph is challenging, as the features on abdominal radiograph(normal gas pattern or mild ileus) are non-specific. With progressionof NEC to Bell Stage IIA, the symptoms (grossly bloody stools,prominent abdominal distension, absent bowel sounds) and featureson abdominal radiographs (one or more dilated loops and focal pneumatosis)are more specific.On the other hand, the Vermont Oxford Network criteria for NECconsist of at least one physical finding (bilious gastric aspirate oremesis, abdominal distension or occult/gross blood in the stool inthe absence of anal fissure) and at least one feature on abdominalradiograph (pneumatosis intestinalis, hepatobiliary gas, or pneumoperitoneum).1 These features correspond to Bell Stage IIA or StageIIB and are not features of early NEC. Thus relying solely on abdominalradiograph for diagnosis of early NEC, as is practiced currently,has significant drawbacks especially in extremely premature infants.7Ultrasound has been suggested to improve the percentage of infantsdiagnosed with early NEC.11 However, this imaging modality is notused routinely in the diagnosis or management of NEC.As the incidence of surgical NEC and mortality from NEC continuesto be high, the literature to demonstrate the shortcomings ofabdominal radiographs and promise of abdominal ultrasound in diagnosisof NEC is reviewed

Multiple inducers of the Drosophila heat shock locus 93D (hsr omega): inducer-specific patterns of the three transcripts

The Drosophila hsr omega locus produces one of the largest and most active heat shock puffs, yet it does not encode a heat shock protein. Instead, this locus produces a distinctive set of three transcripts, all from the same start site. The largest transcript, omega 1, is limited to the nucleus and appears to have a role there. A second nuclear transcript, omega 2, is produced by alternative termination and contains the sequence found in the 5' 20-25% of omega 1 (depending on the Drosophila species). The cytoplasmic transcript, omega 3, is produced by removal of a 700-bp intron from omega 2. All three hsr omega RNAs are produced constitutively and production is enhanced by heat shock. In addition to being a member of the set of heat shock puffs, the hsr omega puff is induced by agents that do not affect other heat shock loci, suggesting that hsr omega is more sensitive to environmental changes than other loci. We report here that agents that induce puffing of hsr omega loci in polytene nuclei also lead to an increase in hsr omega transcripts in diploid cells. We also show that the relative levels of omega 1 and omega 3 can be modulated independently by several agents. All drugs that inhibit translation, either initiation or elongation, stabilize the omega 3 transcript, which normally turns over within minutes in control cells. Drugs (such as benzamide and colchicine) that induce puffing of hsr omega, but not other heat shock loci, lead to large increases in omega 1. Although the constitutive level of omega 1 is relatively stable, the drug-induced excess is lost rapidly when the drug is withdrawn. The relative levels of hsr omega transcripts may reflect different states in cellular metabolism

In vivo effects of traditional ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications

Background: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their “active” components as is done in most current studies. Methods: We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. Results: A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. Conclusions: The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic formulations

Further observation on Hoechst 33258 plus hypotonic treatment induced supercondensation of interphase heterochromatin in Drosophila nasuta cells

Extending our earlier observation [Exp Cell Res, 132 (198I) 423] on the effects of Hoechst 33258 and hypotonic treatments on condensation of heterochromatin in interphase nuclei of D. nasuta, we now show by Feulgen-DNA cytophotometry that the chromocentre heterochromatin in Hoechst 33258 + hypotonic treated interphase cells of D. nasuta is supercondensed. Like the Hoechst 33258 effect, exposure of live embryonic (2 hr) or larval brain cells (16 hr) of D. nasuta to 20 μg/ml Netropsin or Distamycin A (both A-T specific DNA ligands) when followed by a pre-fixation hypotonic treatment, also causes supercondensation of chromocentre in majority of the treated cells; without ihe hypotonic treatment chromocentre is not supercondensed in any of the drug treated cells. A G-C specific DNA ligand, Olivomycin, does not cause any such effect. It is suggested that, only A-T specific ligands can cause the supercondensation of interphase heterochromatin when the treated cells are exposed to hypotonic solution prior to fixation. By reverting 16 hr Hoechst 33258 + 15min hypotonic treated larval brain ganglia to isotonic culture medium for I or 4 hr, the supercondensation of chromocentre can be reversed, although a second hypotonic treatment after 4 hr in Hoechst 33258 free isotonic culture medium restores the supercondensation of chromocentre. It appears that the A-T specific drug binding to DNA modifies the nucleoprotein interactions in interphase heterochromatin in such a way that a hypotonic treatment causes a very rapid but reversible reorganization of chromatin constituents to cause the supercondensation

Specializing Interpreters using Offline Partial Deduction

We present the latest version of the Logen partial evaluation system for logic programs. In particular we present new binding-types, and show how they can be used to effectively specialise a wide variety of interpreters.We show how to achieve Jones-optimality in a systematic way for several interpreters. Finally, we present and specialise a non-trivial interpreter for a small functional programming language. Experimental results are also presented, highlighting that the Logen system can be a good basis for generating compilers for high-level languages

Finding the Optimal Balance between Over and Under Approximation of Models Inferred from Execution Logs

Models inferred from execution traces (logs) may admit more behaviours than those possible in the real system (over-approximation) or may exclude behaviours that can indeed occur in the real system (under-approximation). Both problems negatively affect model based testing. In fact, over-approximation results in infeasible test cases, i.e., test cases that cannot be activated by any input data. Under-approximation results in missing test cases, i.e., system behaviours that are not represented in the model are also never tested. In this paper we balance over- and under-approximation of inferred models by resorting to multi-objective optimization achieved by means of two search-based algorithms: A multi-objective Genetic Algorithm (GA) and the NSGA-II. We report the results on two open-source web applications and compare the multi-objective optimization to the state-of-the-art KLFA tool. We show that it is possible to identify regions in the Pareto front that contain models which violate fewer application constraints and have a higher bug detection ratio. The Pareto fronts generated by the multi-objective GA contain a region where models violate on average 2% of an application's constraints, compared to 2.8% for NSGA-II and 28.3% for the KLFA models. Similarly, it is possible to identify a region on the Pareto front where the multi-objective GA inferred models have an average bug detection ratio of 110: 3 and the NSGA-II inferred models have an average bug detection ratio of 101: 6. This compares to a bug detection ratio of 310928: 13 for the KLFA tool. © 2012 IEEE

The ISWI Chromatin Remodeler Organizes the hsrω ncRNA–Containing Omega Speckle Nuclear Compartments

The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. The Drosophila chromatin remodeling ATPase ISWI plays evolutionarily conserved roles in chromatin organization. Interestingly, ISWI genetically interacts with the hsrω gene, encoding multiple non-coding RNAs (ncRNA) essential, among other functions, for the assembly and organization of the omega speckles. The nucleoplasmic omega speckles play important functions in RNA metabolism, in normal and stressed cells, by regulating availability of hnRNPs and some other RNA processing proteins. Chromatin remodelers, as well as nuclear speckles and their associated ncRNAs, are emerging as important components of gene regulatory networks, although their functional connections have remained poorly defined. Here we provide multiple lines of evidence showing that the hsrω ncRNA interacts in vivo and in vitro with ISWI, regulating its ATPase activity. Remarkably, we found that the organization of nucleoplasmic omega speckles depends on ISWI function. Our findings highlight a novel role for chromatin remodelers in organization of nucleoplasmic compartments, providing the first example of interaction between an ATP-dependent chromatin remodeler and a large ncRNA

A trajectory-based strict semantics for program slicing

We define a program semantics that is preserved by dependence-based slicing algorithms. It is a natural extension, to non-terminating programs, of the semantics introduced by Weiser (which only considered terminating ones) and, as such, is an accurate characterisation of the semantic relationship between a program and the slice produced by these algorithms. Unlike other approaches, apart from Weiser’s original one, it is based on strict standard semantics which models the ‘normal’ execution of programs on a von Neumann machine and, thus, has the advantage of being intuitive. This is essential since one of the main applications of slicing is program comprehension. Although our semantics handles non-termination, it is defined wholly in terms of finite trajectories, without having to resort to complex, counter-intuitive, non-standard models of computation. As well as being simpler, unlike other approaches to this problem, our semantics is substitutive. Substitutivity is an important property becauseit greatly enhances the ability to reason about correctness of meaning-preserving program transformations such as slicing