Effort estimation of FLOSS projects: A study of the Linux kernel

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 SpringerEmpirical research on Free/Libre/Open Source Software (FLOSS) has shown that developers tend to cluster around two main roles: “core” contributors differ from “peripheral” developers in terms of a larger number of responsibilities and a higher productivity pattern. A further, cross-cutting characterization of developers could be achieved by associating developers with “time slots”, and different patterns of activity and effort could be associated to such slots. Such analysis, if replicated, could be used not only to compare different FLOSS communities, and to evaluate their stability and maturity, but also to determine within projects, how the effort is distributed in a given period, and to estimate future needs with respect to key points in the software life-cycle (e.g., major releases). This study analyses the activity patterns within the Linux kernel project, at first focusing on the overall distribution of effort and activity within weeks and days; then, dividing each day into three 8-hour time slots, and focusing on effort and activity around major releases. Such analyses have the objective of evaluating effort, productivity and types of activity globally and around major releases. They enable a comparison of these releases and patterns of effort and activities with traditional software products and processes, and in turn, the identification of company-driven projects (i.e., working mainly during office hours) among FLOSS endeavors. The results of this research show that, overall, the effort within the Linux kernel community is constant (albeit at different levels) throughout the week, signalling the need of updated estimation models, different from those used in traditional 9am–5pm, Monday to Friday commercial companies. It also becomes evident that the activity before a release is vastly different from after a release, and that the changes show an increase in code complexity in specific time slots (notably in the late night hours), which will later require additional maintenance efforts

About curvature, conformal metrics and warped products

We consider the curvature of a family of warped products of two pseduo-Riemannian manifolds $(B,g_B)$ and $(F,g_F)$ furnished with metrics of the form $c^{2}g_B \oplus w^2 g_F$ and, in particular, of the type $w^{2 \mu}g_B \oplus w^2 g_F$, where $c, w \colon B \to (0,\infty)$ are smooth functions and $\mu$ is a real parameter. We obtain suitable expressions for the Ricci tensor and scalar curvature of such products that allow us to establish results about the existence of Einstein or constant scalar curvature structures in these categories. If $(B,g_B)$ is Riemannian, the latter question involves nonlinear elliptic partial differential equations with concave-convex nonlinearities and singular partial differential equations of the Lichnerowicz-York type among others.Comment: 32 pages, 3 figure

Characterization of HMGA2 variants expands the spectrum of Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation. HMGA2 variants are a rare cause of SRS and its functional role in human linear growth is unclear. Patients with suspected SRS negative for 11p15LOM/mUPD7 underwent whole-exome and/or targeted-genome sequencing. Mutant HMGA2 protein expression and nuclear localization were assessed. Two Hmga2-knockin mouse models were generated. Five clinical SRS patients harbored HMGA2 variants with differing functional impacts: 2 stop-gain nonsense variants (c.49G>T, c.52C>T), c.166A>G missense variant, and 2 frameshift variants (c.144delC, c.145delA) leading to an identical, extended-length protein. Phenotypic features were highly variable. Nuclear localization was reduced/absent for all variants except c.166A>G. Homozygous knockin mice recapitulating the c.166A>G variant (Hmga2K56E) exhibited a growth-restricted phenotype. An Hmga2Ter76-knockin mouse model lacked detectable full-length Hmga2 protein, similarly to patient 3 and 5 variants. These mice were infertile, with a pygmy phenotype. We report a heterogeneous group of individuals with SRS harboring variants in HMGA2 and describe the first Hmga2 missense knockin mouse model (Hmga2K56E) to our knowledge causing a growth-restricted phenotype. In patients with clinical features of SRS but negative genetic screening, HMGA2 should be included in next-generation sequencing testing approaches

5-Formylcytosine can be a stable DNA modification in mammals.

5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA modification. These results suggest that 5fC has functional roles in DNA that go beyond being a demethylation intermediate.This work was supported by the Cancer Research UK (C14303/A17197, S.B.), The Wellcome Trust (WT099232, S.B.; WT095645/Z/11/Z, W.R.) and the BBSRC (BB/K010867/1, W.R.).This is the accepted manuscript. It is currently embargoed pending publication

Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

<p>Abstract</p> <p>Background</p> <p>GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver) in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats.</p> <p>Methods</p> <p>Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old); untreated old rats (O, 103 weeks old); and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight^-1* day^-1) for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland). Serum levels of hormones (testosterone, IGF-I and insulin) were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states). ATP synthesis in isolated mitochondria was determined by an enzymatic method.</p> <p>Results</p> <p>Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS). IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations.</p> <p>Conclusions</p> <p>We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and IGF-I levels.</p

Fusion between Leishmania amazonensis and Leishmania major Parasitophorous Vacuoles: Live Imaging of Coinfected Macrophages

Protozoan parasites of the genus Leishmania alternate between flagellated, elongated extracellular promastigotes found in insect vectors, and round-shaped amastigotes enclosed in phagolysosome-like Parasitophorous Vacuoles (PVs) of infected mammalian host cells. Leishmania amazonensis amastigotes occupy large PVs which may contain many parasites; in contrast, single amastigotes of Leishmania major lodge in small, tight PVs, which undergo fission as parasites divide. To determine if PVs of these Leishmania species can fuse with each other, mouse macrophages in culture were infected with non-fluorescent L. amazonensis amastigotes and, 48 h later, superinfected with fluorescent L. major amastigotes or promastigotes. Fusion was investigated by time-lapse image acquisition of living cells and inferred from the colocalization of parasites of the two species in the same PVs. Survival, multiplication and differentiation of parasites that did or did not share the same vacuoles were also investigated. Fusion of PVs containing L. amazonensis and L. major amastigotes was not found. However, PVs containing L. major promastigotes did fuse with pre-established L. amazonensis PVs. In these chimeric vacuoles, L. major promastigotes remained motile and multiplied, but did not differentiate into amastigotes. In contrast, in doubly infected cells, within their own, unfused PVs metacyclic-enriched L. major promastigotes, but not log phase promastigotes - which were destroyed - differentiated into proliferating amastigotes. The results indicate that PVs, presumably customized by L. major amastigotes or promastigotes, differ in their ability to fuse with L. amazonensis PVs. Additionally, a species-specific PV was required for L. major destruction or differentiation – a requirement for which mechanisms remain unknown. The observations reported in this paper should be useful in further studies of the interactions between PVs to different species of Leishmania parasites, and of the mechanisms involved in the recognition and fusion of PVs

TET family dioxygenases and DNA demethylation in stem cells and cancers

The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine methylation, and also serve as stable epigenetic modifications that exert distinctive regulatory roles. It is becoming increasingly obvious that TET proteins and their catalytic products are key regulators of embryonic development, stem cell functions and lineage specification. Over the past several years, the function of TET proteins as a barrier between normal and malignant states has been extensively investigated. Dysregulation of TET protein expression or function is commonly observed in a wide range of cancers. Notably, TET loss-of-function is causally related to the onset and progression of hematologic malignancy in vivo. In this review, we focus on recent advances in the mechanistic understanding of DNA methylation-demethylation dynamics, and their potential regulatory functions in cellular differentiation and oncogenic transformation

'Then look!' Unborn attachments and the half-moving image

This article explores the emotional impact on the viewer of disturbing and disorienting images of infant-caregiver relationality in four “melo-horror” films: Imitation of Life (Stahl, 1934), Imitation of Life (Sirk, 1959), The Brood (Cronenberg, 1979), and Beloved (Demme, 1998). Comparing some of these filmic images with the infant performances of “disorganized” attachment styles captured on videotape by attachment researchers such as Mary Main, the author argues that the filmed audiovisual enactment of relational trauma, whether in the context of scientific research or cinematic art, offers the spectator an opportunity to work consciously and unconsciously with representations of unbearable psychic and psychosocial experience—both her own and that of others—that may hitherto have been thought unrepresentable or simply not thought at all

From Pinot to Xinomavro in the world's future wine-growing regions

Predicted impacts of climate change on crops—including yield declines and loss of conservation lands—could be mitigated by exploiting existing diversity within crops. Here we examine this possibility for wine grapes. Across 1,100 planted varieties, wine grapes possess tremendous diversity in traits that affect responses to climate, such as phenology and drought tolerance. Yet little of this diversity is exploited. Instead many countries plant 70–90% of total hectares with the same 12 varieties—representing 1% of total diversity. We outline these challenges, and highlight how altered planting practices and new initiatives could help the industry better adapt to continued climate change