Ichnofossils, cracks or crystals? A test for biogenicity of stick-like structures from vera rubin ridge, mars

New images from Mars rover Curiosity display millimetric, elongate stick- like structures in the fluvio-lacustrine deposits of Vera Rubin Ridge, the depositional environment of which has been previously acknowledged as habitable. Morphology, size and topology of the structures are yet incompletely known and their biogenicity remains untested. Here we provide the first quantitative description of the Vera Rubin Ridge structures, showing that ichnofossils, i.e., the product of life-substrate interactions, are among their closest morphological analogues. Crystal growth and sedimentary cracking are plausible non-biological genetic processes for the structures, although crystals, desiccation and syneresis cracks do not typically present all the morphological and topological features of the Vera Rubin Ridge structures. Morphological analogy does not necessarily imply biogenicity but, given that none of the available observations falsifies the ichnofossil hypothesis, Vera Rubin Ridge and its sedimentary features are here recognized as a privileged target for astrobiological research

A test of analog-based tools for quantitative prediction of large-scale fluvial architecture

Outcrop analogs are routinely used to constrain models of subsurface fluvial sedimentary architecture built through stochastic modeling or inter-well sandbody correlations. Correlability models are analog-based quantitative templates for guiding the well-to-well correlation of sand-bodies, whereas indicator variograms used as input to reservoir models can be parameterized from data collected from analogs, using existing empirical relationships. This study tests the value and limitations of adopting analog-informed correlability models and indicator-variogram models, and assesses the impact and significance of analog choice in subsurface workflows for characterizing fluvial reservoirs. A 3.2 km long architectural panel based on a Virtual Outcrop from the Cretaceous Blackhawk Formation (Wasatch Plateau, Utah, USA) has been used to test the methodologies: vertical 'dummy' wells have been constructed across the panel, and the intervening fluvial architecture has been predicted using correlability models and sequential indicator simulations. The correlability and indicator-variogram models employed to predict the outcrop architecture have been compiled using information drawn from an architectural database. These models relate to: (i) analogs that partially match with the Blackhawk Formation in terms of depositional setting, and (ii) empirical relationships relating statistics on depositional-element geometries and spatial relations to net-to-gross ratio, based on data from multiple fluvial systems of a variety of forms. The forecasting methods are assessed by quantifying the mismatch between predicted architecture and outcrop observations in terms of the correlability of channel complexes and static connectivity of channel deposits. Results highlight the effectiveness of correlability models as a check for the geologic realism of correlation panels, and the value of analog-informed indicator variograms as a valid alternative to variogram-model parameterization through geostatistical analysis of well data. This work has application in the definition of best-practice use of analogs in subsurface workflows; it provides insight into the typical degree of realism of analog-based predictions of reservoir architecture, as well as on the impact of analog choice, and draws attention to associated pitfalls

A hierarchical multiple-point statistics simulation procedure for the 3D reconstruction of alluvial sediments

A correct representation of the heterogeneity of porous formations and of their preferential flow paths is crucial for a reliable modelization of the contaminant transport processes. Several geostatistical tools have been developed to tackle this challenge. Many of these tools are often applied in a multi-scale framework, where the geostatistical simulation is applied fist trying to reproduce the big scale features of the sedimentary formations, and finally to reproduce their small scale features. However, many of the developed multi-scale and hierarchical techniques have a quite complex work-flow and rely on diverse simulation methods. Here a simplified hierarchical simulation procedure is proposed, where only multiple-point statistics (MPS) is used to simulate the target heterogeneities at different scales. The simulation procedure is organized in a tree-like frame, where MPS is applied at each simulation branch using a simplified binary training image and the corresponding available conditioning data. At each simulation branch, the MPS simulation is performed in a sub- domain defined by one of the two facies codes simulated at the parent branch. The proposed procedure is tested in the three-dimensional (3D) reconstruction of two model blocks of alluvial sediments, using the available two-dimensional (2D) outcrop information as training images. It is compared against a non hierarchical MPS simulation procedure in terms of connectivity indicators and breakthrough curves obtained from 3D particle tracking numerical experiments. All the aforementioned tests are performed considering 100 equiprobable realizations for each simulation technique. This allows to make statistically reliable comparisons, and to extract statistical distributions of the transport parameters by fitting analytical curves to the results of the particle tracking experiments. These statistical distributions are used to perform one-dimensional transport experiments on spatial scales ten times bigger than the block scale using the Kolmogorov-Dmitriev approach in a Monte Carlo framework

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Aquifer architecture of the Quaternary alluvial succession of the southern lambro basin (Lombardy-Italy)

Aquifer stratigraphy of the sector of the Pleistocene - Holocene alluvial plain of Lombardy, run by the Lambro valley system south of Milan, has been reconstructed on the basis of geological mapping at 1:10.000 and subsurface interpretation and correlation of more than 150 among water wells, boreholes and deep excavations. The Middle (?) - Late Pleistocene sedimentary evolution of this sector includes four major progradation cycles of alluvial depositional systems that migrated from the alpine northern side towards the axial palaeo-Po depositional system. These cycles were governed by Pleistocene glacial cycles, in combination with ramp-folding of the San Colombano - Salerano apenninic anticlines and minor uplift of the alpine side. Every major cycle is soled by an erosion surface, and is shaped by minor fining upward sequences. Both major and minor sequences record at first the advance of coarse-grained units (distal braided alluvial fan or sandy braid plain) which fringe-out south-eastwards into meandering fluvial systems, and are replaced upwards by alluvial plain fines, which close the sequences. Physical stratigraphy and geomorphology, analysis of facies associations, characterisation of gravel composition, radiocarbon dating on 4 peat and plant relic samples and findings of transported artefacts allowed the correlation of the four cycles with the regional evolution. The Post Glacial meandering depositional systems of the deeply entrenched Lambro valley system (Unit 4, Holocene; Unit 5, historical), are cut into the braided stream to meandering depositional systems that developed during L.G.M. times, at present outside the Lambro valley (Unit 3, Late Pleistocene). These represent the uppermost aquifer unit, i.e. the phreatic - non saturated zone. The underlying Unit 2 (Late Pleistocene) can be correlated with the Besnate Allogroup, and therefore developed during the corresponding glaciations. It is formed by three stacked sequences, controlled by glacial cycles, which are deeply scoured into the lowermost succession that could be studied (Unit 1 Middle ? - Late Pleistocene ?). It represents the most important and permeable intermediate aquifer unit, that is only partly confined by the flood-plain fines of the uppermost sub-unit 2C

Origin of mud in turbidites and hybrid event beds: Insight from ponded mudstone caps of the Castagnola turbidite system (north‐west Italy)

The partitioning of different grain‐size classes in gravity flow deposits is one of the key characteristics used to infer depositional processes. Turbidites have relatively clean sandstones with most of their clay deposited as part of a mudstone cap or as a distal mudstone layer, whereas sand‐bearing debrites commonly comprise mixtures of sand grains and interstitial clay; hybrid event beds develop alternations of clean and dirty (clay‐rich) sandstones in varying proportions. Analysis of co‐genetic mudstone caps in terms of thickness and composition is a novel approach that can provide new insight into gravity flow depositional processes. Bed thickness data from the ponded Castagnola system show that turbidites contain more clay overall than do hybrid event beds. The Castagnola system is characterized by deposits of two very different petrographic types. Thanks to this duality, analyses of sandstone and mudstones composition allow inference of which proportion of the clay in each of the deposit types was acquired en route. In combination with standard sedimentological observations the new data allow insight into the likely characteristics of their parent flows. Clean turbidites were deposited by lower concentration, long duration, erosive, muddy turbidity currents which were more efficient at fractionating clay particles away from their basal layer. Hybrid event beds were deposited by shorter duration, higher‐concentration, less‐erosive sandier flows which were less efficient at clay fractionation. The results are consistent with data from other turbidite systems (for example, Marnoso‐arenacea). The approach represents a new method to infer the controls on the degree of clay partitioning in gravity flow deposits

Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m–2): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18–34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28–40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing. © 2000 Cancer Research Campaig

Antibodies reacting with Simian virus 40 mimotopes in serum samples from patients with thalassaemia major

Background. Simian virus 40 (SV40) is a small DNA tumour virus. Footprints of the virus have been detected in different humam lymphoproliferative disorders and in blood specimens of blood from healthy blood donors. This study was carried out to verify whether SV40 antibodies can be detected in serum samples from multiply transfused patients with thalassaemia major.Materials and methods. An indirect enzyme-linked immunosorbent assay was employed, using SV40 specific synthetic peptides mimicking the antigens of the viral capsid proteins 1-2-3, to test for the presence of antibodies to SV40 in serum samples taken from patients affected by transfusiondependent thalassaemia major (n=190) and healthy blood donors (n=251).Results. The prevalence of antibodies against SV40 was higher in patients than in controls (24% vs 17%). The prevalence increased and was significantly higher in the older age group of patients affected by thalassemia major than in controls (38% vs 20%, p<0.04).Discussion. The higher prevalence of serum antibodies against simian virus 40 in older, multiply transfused patients with thalassamia major than in controls suggests that this virus, or a closely related yet unknown human polyomavirus, could have been transmitted in the past by transfusion with whole blood. At the same time, our data indicate no significant differences in prevalence of SV40 antibodies in patients and controls of younger age thus suggesting that current transfusion methods with leucodepletion and filtered red cells are safe

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.</p> <p>Methods</p> <p>Overall, 95 patients received pemetrexed 500 mg/m²i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria.</p> <p>Results</p> <p>Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression.</p> <p>Conclusion</p> <p>Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.</p