Source Lines Counter (SLiC) Version 4.0

Source Lines Counter (SLiC) is a software utility designed to measure software source code size using logical source statements and other common measures for 22 of the programming languages commonly used at NASA and the aerospace industry. Such metrics can be used in a wide variety of applications, from parametric cost estimation to software defect analysis. SLiC has a variety of unique features such as automatic code search, automatic file detection, hierarchical directory totals, and spreadsheet-compatible output. SLiC was written for extensibility; new programming language support can be added with minimal effort in a short amount of time. SLiC runs on a variety of platforms including UNIX, Windows, and Mac OSX. Its straightforward command-line interface allows for customization and incorporation into the software build process for tracking development metrics.

Cerebrospinal metastases in malignant childhood astrocytomas

Over a period of five years, antemortem diagnosis of leptomeningeal spread was made in six of thirteen children with high grade astrocytomas. These included four of seven children with hemispheral tumors and two of six children with malignant brainstem gliomas. Leptomeningeal spread was diagnosed by the clinical picture and CSF profile. Meningeal spread occurred an average of 5 months (range 0–16) after initial diagnosis of tumor was made. Several patients responded well to local radiation and/ or chemotherapy. Mean survival after evidence of meningeal spread was 7 months (range 2–16) with one patient still alive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45379/1/11060_2004_Article_BF00177897.pd

The influence of haemoglobin and iron on in vitro mycobacterial growth inhibition assays.

The current vaccine against tuberculosis, live attenuated Mycobacterium bovis BCG, has variable efficacy, but development of an effective alternative is severely hampered by the lack of an immune correlate of protection. There has been a recent resurgence of interest in functional in vitro mycobacterial growth inhibition assays (MGIAs), which provide a measure of a range of different immune mechanisms and their interactions. We identified a positive correlation between mean corpuscular haemoglobin and in vitro growth of BCG in whole blood from healthy UK human volunteers. Mycobacterial growth in peripheral blood mononuclear cells (PBMC) from both humans and macaques was increased following the experimental addition of haemoglobin (Hb) or ferric iron, and reduced following addition of the iron chelator deferoxamine (DFO). Expression of Hb genes correlated positively with mycobacterial growth in whole blood from UK/Asian adults and, to a lesser extent, in PBMC from South African infants. Taken together our data indicate an association between Hb/iron levels and BCG growth in vitro, which may in part explain differences in findings between whole blood and PBMC MGIAs and should be considered when using such assays

Improving Requirements-Test Alignment by Prescribing Practices that Mitigate Communication Gaps

The communication of requirements within software development is vital for project success. Requirements engineering and testing are two processes that when aligned can enable the discovery of issues and misunderstandings earlier, rather than later, and avoid costly and time-consuming rework and delays. There are a number of practices that support requirements-test alignment. However, each organisation and project is different and there is no one-fits-all set of practices. The software process improvement method called Gap Finder is designed to increase requirements-test alignment. The method contains two parts: an assessment part and a prescriptive part. It detects potential communication gaps between people and between artefacts (the assessment part), and identifies practices for mitigating these gaps (the prescriptive part). This paper presents the design and formative evaluation of the prescriptive part; an evaluation of the assessment part was published previously. The Gap Finder method was constructed using a design science research approach and is built on the Theory of Distances for Software Engineering, which in turn is grounded in empirical evidence from five case companies. The formative evaluation was performed through a case study in which Gap Finder was applied to an on-going development project. A qualitative and mixed-method approach was taken in the evaluation, including ethnographically-informed observations. The results show that Gap Finder can detect relevant communication gaps and seven of the nine prescribed practices were deemed practically relevant for mitigating these gaps. The project team found the method to be useful and supported joint reflection and improvement of their requirements communication. Our findings demonstrate that an empirically-based theory can be used to improve software development practices and provide a foundation for further research on factors that affect requirements communicatio

Microenvironment‐induced restoration of cohesive growth associated with focal activation of P ‐cadherin expression in lobular breast carcinoma metastatic to the colon

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1 /E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1 /E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth

ActEarly: a City Collaboratory approach to early promotion of good health and wellbeing

Economic, physical, built, cultural, learning, social and service environments have a profound effect on lifelong health. However, policy thinking about health research is dominated by the ‘biomedical model’ which promotes medicalisation and an emphasis on diagnosis and treatment at the expense of prevention. Prevention research has tended to focus on ‘downstream’ interventions that rely on individual behaviour change, frequently increasing inequalities. Preventive strategies often focus on isolated leverage points and are scattered across different settings. This paper describes a major new prevention research programme that aims to create City Collaboratory testbeds to support the identification, implementation and evaluation of upstream interventions within a whole system city setting. Prevention of physical and mental ill-health will come from the cumulative effect of multiple system-wide interventions. Rather than scatter these interventions across many settings and evaluate single outcomes, we will test their collective impact across multiple outcomes with the goal of achieving a tipping point for better health. Our focus is on early life (ActEarly) in recognition of childhood and adolescence being such critical periods for influencing lifelong health and wellbeing

The spatial pattern of premature mortality in Hong Kong: how does it relate to public housing?

Research into understanding the relationship between access to housing, health and wellbeing in cities has yielded mixed evidence to date and has been limited to case studies from Western countries. Many studies appear to highlight the negative effects of public housing in influencing the health of its residents. Current trends in the urban housing markets in cities of advanced Asian economies and debates surrounding the role of government in providing housing underscore the need for more focused research into housing and health. In this paper, we investigate Hong Kong as an example of a thriving Asian city by exploring and comparing the intra-urban geographies of premature mortality and public housing provision in the city. Using a fully Bayesian spatial structural model, we estimate associations between public housing provision and different types of premature mortality. We find significant geographic variations in premature mortality within Hong Kong during the five-year period 2005–2009, with positive associations between the residents of public housing and premature mortality risk. But the associations attenuate or are even reversed for premature mortality of injuries and non-communicable diseases after controlling for local deprivation, housing instability, access to local amenities and other neighbourhood characteristics. The results indicate that public housing may have a protective effect on community health, which contradicts the findings of similar studies carried out in Western cities. We suggest reasons why the association between public housing and health differs in Hong Kong and discuss the implications for housing policy in Hong Kong and other Asian cities

Inter-domain Communication Mechanisms in an ABC Importer: A Molecular Dynamics Study of the MalFGK2E Complex

ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is “transmitted” to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK2E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the “EAA motif” (especially in the “coupling helices” region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the “coupling helices”

Molecular dynamics simulations reveal that AEDANS is an inert fluorescent probe for the study of membrane proteins

Computer simulations were carried out of a number of AEDANS-labeled single cysteine mutants of a small reference membrane protein, M13 major coat protein, covering 60% of its primary sequence. M13 major coat protein is a single membrane-spanning, α-helical membrane protein with a relatively large water-exposed region in the N-terminus. In 10-ns molecular dynamics simulations, we analyze the behavior of the AEDANS label and the native tryptophan, which were used as acceptor and donor in previous FRET experiments. The results indicate that AEDANS is a relatively inert environmental probe that can move unhindered through the lipid membrane when attached to a membrane protein