The Art of Data Science

To flourish in the new data-intensive environment of 21st century science, we need to evolve new skills. These can be expressed in terms of the systemized framework that formed the basis of mediaeval education - the trivium (logic, grammar, and rhetoric) and quadrivium (arithmetic, geometry, music, and astronomy). However, rather than focusing on number, data is the new keystone. We need to understand what rules it obeys, how it is symbolized and communicated and what its relationship to physical space and time is. In this paper, we will review this understanding in terms of the technologies and processes that it requires. We contend that, at least, an appreciation of all these aspects is crucial to enable us to extract scientific information and knowledge from the data sets which threaten to engulf and overwhelm us.Comment: 12 pages, invited talk at Astrostatistics and Data Mining in Large Astronomical Databases workshop, La Palma, Spain, 30 May - 3 June 2011, to appear in Springer Series on Astrostatistic

Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia – case report

BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies

Structure and Molecular Evolution of CDGSH Iron-Sulfur Domains

The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into seven major types with a wide distribution throughout the three domains of life. The type 1 protein mitoNEET has been shown to fold into a dimer with the signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of all other types of CISDs were unknown. Here we report the crystal structures of type 3, 4, and 6 CISDs determined at 1.5 Å, 1.8 Å and 1.15 Å resolution, respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a dimeric structure. Although similar to each other, the two structures have permutated topologies, and both are distinct from the type 1 structure. The type 6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an internal pseudo dyad symmetry. All currently known CISD structures share dual iron-sulfur binding modules and a β-sandwich for either intermolecular or intramolecular dimerization. The iron-sulfur binding module, the β-strand N-terminal to the module and a proline motif are conserved among different type structures, but the dimerization module and the interface and orientation between the two iron-sulfur binding modules are divergent. Sequence analysis further shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings suggest that all CISDs share common ancestry and diverged into three primary folds with a characteristic phylogenetic distribution: a eukaryote-specific fold adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3, 4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our comprehensive structural, sequential and phylogenetic analysis provides significant insight into the assembly principles and evolutionary relationship of CISDs

The role of c-FLIP splice variants in urothelial tumours

Deregulation of apoptosis is common in cancer and is often caused by overexpression of anti-apoptotic proteins in tumour cells. One important regulator of apoptosis is the cellular FLICE-inhibitory protein (c-FLIP), which is overexpressed, for example, in melanoma and Hodgkin's lymphoma cells. Here, we addressed the question whether deregulated c-FLIP expression in urothelial carcinoma impinges on the ability of death ligands to induce apoptosis. In particular, we investigated the role of the c-FLIP splice variants c-FLIPlong (c-FLIPL) and c-FLIPshort (c-FLIPS), which can have opposing functions. We observed diminished expression of the c-FLIPL isoform in urothelial carcinoma tissues as well as in established carcinoma cell lines compared with normal urothelial tissues and cells, whereas c-FLIPS was unchanged. Overexpression and RNA interference studies in urothelial cell lines nevertheless demonstrated that c-FLIP remained a crucial factor conferring resistance towards induction of apoptosis by death ligands CD95L and TRAIL. Isoform-specific RNA interference showed c-FLIPL to be of particular importance. Thus, urothelial carcinoma cells appear to fine-tune c-FLIP expression to a level sufficient for protection against activation of apoptosis by the extrinsic pathway. Therefore, targeting c-FLIP, and especially the c-FLIPL isoform, may facilitate apoptosis-based therapies of bladder cancer in otherwise resistant tumours

Possible Novel Therapy for Malignant Gliomas with Secretable Trimeric TRAIL

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas

Insights into the chemical composition of Equisetum hyemale by high resolution Raman imaging

Equisetaceae has been of research interest for decades, as it is one of the oldest living plant families, and also due to its high accumulation of silica up to 25% dry wt. Aspects of silica deposition, its association with other biomolecules, as well as the chemical composition of the outer strengthening tissue still remain unclear. These questions were addressed by using high resolution (<1 μm) Confocal Raman microscopy. Two-dimensional spectral maps were acquired on cross sections of Equisetum hyemale and Raman images calculated by integrating over the intensity of characteristic spectral regions. This enabled direct visualization of differences in chemical composition and extraction of average spectra from defined regions for detailed analyses, including principal component analysis (PCA) and basis analysis (partial least square fit based on model spectra). Accumulation of silica was imaged in the knobs and in a thin layer below the cuticula. In the spectrum extracted from the knob region as main contributions, a broad band below 500 cm−1 attributed to amorphous silica, and a band at 976 cm−1 assigned to silanol groups, were found. From this, we concluded that these protrusions were almost pure amorphous, hydrated silica. No silanol group vibration was detected in the silicified epidermal layer below and association with pectin and hemicelluloses indicated. Pectin and hemicelluloses (glucomannan) were found in high levels in the epidermal layer and in a clearly distinguished outer part of the hypodermal sterome fibers. The inner part of the two-layered cells revealed as almost pure cellulose, oriented parallel along the fiber

Search mechanism of a stream grazer in patchy environments: the role of food abundance

The search behavior of the grazing stream insect Baetis tricaudatus (Ephemeroptera: Baetidae) was examined in field and laboratory experiments. Regardless of food abundance in experimental habitats, nymphs spent significantly more time in food patches than predicted if they had moved randomly with respect to patches. A significant reduction in movement rate within patches relative to movement rate between patches largely accounted for these results. The movement pattern within patches was highly systematic and in agreement with predictions of optimal foraging theory since food was uniformly distributed within patches. Between-patch search movements were affected by food abundance in the most recently grazed patch. Search intensity after departure from a patch was positively related to food abundance in the patch while movement rate after patch departure was inversely related to patch food level. These effects produced between-patch movement patterns that were suboptimal in the experimental habitats because they resulted in revisitation of previously depleted patches. However, differences between experimental and natural habitats in the spatial occurrence of patch types suggest that Baetis between-patch search behavior may be adaptive in natural habitats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47752/1/442_2004_Article_BF00379015.pd

Factors predicting hospital length-of-stay and readmission after colorectal resection: a population-based study of elective and emergency admissions

<p>Abstract</p> <p>Background</p> <p>The impact of developments in colorectal cancer surgery on length-of-stay (LOS) and re-admission have not been well described. In a population-based analysis, we investigated predictors of LOS and emergency readmission after the initial surgery episode.</p> <p>Methods</p> <p>Incident colorectal cancers (ICD-O2: C18-C20), diagnosed 2002-2008, were identified from the National Cancer Registry Ireland, and linked to hospital in-patient episodes. For those who underwent colorectal resection, the associated hospital episode was identified. Factors predicting longer LOS (upper-quartile, > 24 days) for elective and emergency admissions separately, and whether LOS predicted emergency readmission within 28 days of discharge, were investigated using logistic regression.</p> <p>Results</p> <p>8197 patients underwent resection, 63% (n = 5133) elective and 37% (n = 3063) emergency admissions. Median LOS was 14 days (inter-quartile range (IQR) = 11-20) for elective and 21 (15-33) for emergency admissions. For both emergency and elective admissions, likelihood of longer LOS was significantly higher in patients who were older, had co-morbidities and were unmarried; it was reduced for private patients. For emergency patients only the likelihood of longer LOS was lower for patients admitted to higher-volume hospitals. Longer LOS was associated with increased risk of emergency readmission.</p> <p>Conclusions</p> <p>One quarter of patients stay in hospital for at least 25 days following colorectal resection. Over one third of resected patients are emergency admissions and these have a significantly longer median LOS. Patient- and health service-related factors were associated with prolonged LOS. Longer LOS was associated with increased risk of emergency readmission. The cost implications of these findings are significant.</p

Structure and dynamics of the shark assemblage off recife, northeastern Brazil

Understanding the ecological factors that regulate elasmobranch abundance in nearshore waters is essential to effectively manage coastal ecosystems and promote conservation. However, little is known about elasmobranch populations in the western South Atlantic Ocean. An 8-year, standardized longline and drumline survey conducted in nearshore waters off Recife, northeastern Brazil, allowed us to describe the shark assemblage and to monitor abundance dynamics using zero-inflated generalized additive models. This region is mostly used by several carcharhinids and one ginglymostomid, but sphyrnids are also present. Blacknose sharks, Carcharhinus acronotus, were mostly mature individuals and declined in abundance throughout the survey, contrasting with nurse sharks, Ginglymostoma cirratum, which proliferated possibly due to this species being prohibited from all harvest since 2004 in this region. Tiger sharks, Galeocerdo cuvier, were mostly juveniles smaller than 200 cm and seem to use nearshore waters off Recife between January and September. No long-term trend in tiger shark abundance was discernible. Spatial distribution was similar in true coastal species (i.e. blacknose and nurse sharks) whereas tiger sharks were most abundant at the middle continental shelf. The sea surface temperature, tidal amplitude, wind direction, water turbidity, and pluviosity were all selected to predict shark abundance off Recife. Interspecific variability in abundance dynamics across spatiotemporal and environmental gradients suggest that the ecological processes regulating shark abundance are generally independent between species, which could add complexity to multi-species fisheries management frameworks. Yet, further research is warranted to ascertain trends at population levels in the South Atlantic Ocean.State Government of Pernambuco, Brazil; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/37065/2007]info:eu-repo/semantics/publishedVersio