Parallelisation Technique for Serial 3D Seismic Codes: SMS Approach

We investigate a fast and easy way to parallelise seismological serial codes mainly oriented for simulating the seismic wave propagation through anelastic dissipative media. Having an efficient modelling tool is important in both assessing strong ground motion and mitigation of seismic hazard when the site effects are considered, and in crustal propagation when the crustal geological structures are of interest. Our chosen case study is repre- sentative of a set of such seismological 3D problems. The Scalable Modelling System (SMS) tool for paralleliza- tion is considered. The IBM SP5 native compiler has been used. Results such as Speed-Up and Efficiency are shown and discussed. SMS can run both in shared and distributed memory environments. The greater advantages of using SMS in such environments become apparent with the utilisation of a higher number of multiprocessor machines arranged in a cluster. We also demonstrate how successful porting from serial to parallel codes is re- alised by way of minimal instructions (6% of the serial original code only) provided that an ad hoc profiling analysis of the serial code is first performed

Propene Polymerization Promoted by C2-Symmetric Metallocene Catalysts: From Atactic to Isotactic Polypropene in Consequence of an Isotope Effect

We studied the polymerization of propene-2-d promoted by the prototypical isotactic-specific catalyst system rac-ethylenebis(4,5,6,7-tetrahydro-1-indenyl)ZrCl2/MAO. In this communication, we report the results of our investigation, documenting a large isotope effect on the balance between polyinsertion and epimerization and, therefore, on the stereospecificity. The mechanistic implications of such results are also discusse

Gastroenteropancreatic High-Grade Neuroendocrine Neoplasms: Histology and Molecular Analysis, Two Sides of the Same Coin

Background: In gastroenteropancreatic (GEP) high-grade neuroendocrine neoplasms (H-NENs), Ki-67 threshold of 55% defines three prognosis subclasses: neuroendocrine tumor (NET) G3, neuroendocrine carcinoma (NEC) <55%, and NEC ≥55%. We investigated whether the molecular profiling of H-NENs differs among these subcategories and evaluated potential therapeutic targets, including PD-L1. Methods: In GEP-NEN patients, we evaluated: (i) 55% threshold for Ki-67 labeling index for further stratifying NEC and (ii) immunoreactivity and gene mutations by immunohistochemistry and targeted next-generation sequencing (T-NGS). Results: Fifteen NETs G3 and 39 NECs were identified. Ki-67 labeling index was <55% in 9 NECs and ≥55% in 30 NECs. Gene mutations by NGS (TP53, 32.9%; KRAS, 5.5%; BRAF, 4.1%) were detected in 46.6% NENs, significantly enriched in NEC ≥55% (76.7%) compared to NEC <55% (55.6%) or NET (20.0%). PD-L1 staining in tumor-infiltrating lymphocytes was observed in NEC ≥55% (36.7%; p = 0.03). Median OS was 4.3 years in NET G3, 1.8 years in NEC <55%, and 0.7 years in NEC ≥55% (p <0.0001); it was 2.3 years with NGS wild-type, 0.7 years with ≥1 mutation (p <0.0001), 0.8 years in PD-L1-positive patients, and 1.7 years in PD-L1-negative subjects (p = 0.0004). In multivariate analysis, only the proposed subclassification approach yielded statistically significant differences between groups (NEC <55% vs. NET G3, HR 14.1, 95% CI 2.2-89.8, p = 0.005; NEC ≥55% vs. NET G3, HR 25.8, 95% CI 3.9-169, p = 0.0007). Conclusions: These findings identify NEC ≥55% as a biologically and prognostically distinct subtype and pave the way for more personalized treatment

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front

Hantavirus transmission in the United States.

In 1996, investigation of a hantavirus pulmonary syndrome (HPS) outbreak in southern Argentina found evidence of person-to-person transmission of a hantavirus. The infection control ramifications of this finding led to this review of hantavirus epidemiology in the United States; the review suggests that Sin Nombre virus infection is rarely, if ever, transmitted from person to person and that existing guidelines for prevention of HPS remain appropriate for North America

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SMO mutations confer poor prognosis in malignant pleural mesothelioma

Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor but approximately 12% of patients survive more than 3 years. The biological differences underlying better outcomes are not known. Several targeted agents and immunotherapy have been ineffective. Hedgehog (Hh) is one emerging pathway. We compared the biological profiles of patients with different survival, investigating the most frequently altered genes, including the Hh pathway. Methods: We analyzed 56 MPM. A 36-month overall survival (OS) cut-off divided patients into 32 normo (NS) and 24 long (LS) survivors. We used next generation sequencing to test 21 genes, immunohistochemistry to evaluate SMO expression. Mutation differences between NS and LS and their associations with clinical features were analysed by Fisher's test, OS with the Kaplan-Meier method and its association with mutations by univariate and multivariate Cox proportional hazard models. Results: Clinical features were similar in both groups. Eighteen out of 56 patients (32%) were wild-type for the genes analysed. At least five had mutations in BAP1, NF2, TP53, SMO and PTCH1 with no significant differences between the groups except for SMO. SMO, a member of the Hh pathway, was mutated only in NS (15.6%) and only SMO mutations were significantly associated with poor prognosis at univariate (HR =4.36, 95% CI: 2.32-8.18, P<0.0001) and multivariate (HR =9.2, 95% CI: 3.0-28.4, P=0.0001) analysis. All SMO mutated patients expressed high protein levels. Conclusions: SMO mutations were clearly associated with worse prognosis. SMO may be a therapeutic target but this needs to be confirmed in a prospective trial

A thermophysical study of the melting process in alkyl chain metal n-alkanoates: The thallium (I) series

The peculiar thermal behavior of the thallium(I) n-alkanoates series (consisting in several transitions between polymorphic and mesomorphic phases) in comparison with other metallic n-alkanoates series is stated. The allowance of highly accurate adiabatic heat capacity data permits a study of the CH2CH2 contributions to the lattice heat capacity curve at low temperature. Moreover, in this series an anomalous gradual enhancement of the lattice heat capacity has been interpreted from vibrational spectroscopy results as a noncooperative effect due to the internal hindered rotation of the alkyl chain (formation of gauche defects, even in the solid state). The thermodynamics of the “stepwise melting process” from the totally ordered solid at low temperature to the isotropic liquid is based on a revised lattice heat-capacity curve. This was used to evaluate the energy and entropy not only of the clear first order transitions present in the series but also of the described noncooperative effect. The CH2CH2 enthalpy and entropy contribution for this series is estimated and a comparison with the published values for other series is carried out. Moreover, the texture of the mesophases is revealed by polarized light microscopy. © 1999 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69602/2/JCPSA6-111-8-3590-1.pd

Negative hyperselection of patients with RAS and BRAF wild-type metastatic colorectal cancer who received panitumumab-based maintenance therapy

PURPOSE We assessed the prognostic/predictive role of primary tumor sidedness and uncommon alterations of anti\u2013epidermal growth factor receptor (EGFR) primary resistance (primary resistance in RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies [PRESSING] panel) in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who were randomly assigned to panitumumab plus fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without fluorouracil (FU) plus leucovorin (LV); Valentino trial (ClinicalTrials.gov identifier: NCT02476045). PATIENTS AND METHODS This prespecified retrospective analysis included 199 evaluable patients with RAS/ BRAF wt. The PRESSING panel included the following: immunohistochemistry (IHC) and in situ hybridization for HER2/MET amplification, IHC with or without RNA sequencing for ALK/ROS1/NTRKs/RET fusions, next-generation sequencing for HER2/PIK3CAex.20/PTEN/AKT1 and RAS mutations with low mutant allele fraction, and multiplex polymerase chain reaction for microsatellite instability. PRESSING status (any positive biomarker v all negative) and sidedness were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in the study population and by treatment arm. RESULTS Overall, left- and right-sided tumors were 85.4% and 14.6%, respectively, and PRESSING-negative and -positive tumors were 75.4% and 24.6%, respectively. At a median follow-up of 26 months, inferior outcomes were consistently observed in right- versus left-sided tumors for ORR (55.2% v 74.1%; P = .037), PFS (8.4 v 11.5 months; P = .026), and OS (2-year rate: 50.2% v 65.1%; P = .062). Similar results were observed in the PRESSING-positive versus PRESSING-negative subgroup for ORR (59.2% v 75.3%; P = .030), PFS (7.7 v 12.1 months; P, .001), and OS (2-year rate: 48.1% v 68.1%; P = .021). The PFS benefit of FU plus LV added to panitumumab maintenance, reported in the study, was independent from sidedness and PRESSING status (interaction for PFS P = .293 and .127, respectively). However, outcomes were extremely poor in patients who received single-agent panitumumab and had right-sided tumors (median PFS, 7.7 months; 2-year OS, 38.5%) or PRESSING-positive tumors (median PFS, 7.4 months; 2-year OS, 47.0%). CONCLUSION The combined assessment of sidedness and molecular alterations of anti-EGFR primary resistance identified a consistent proportion of patients with RAS/BRAF\u2013wt mCRC who had inferior benefit from initial anti-EGFR\u2013based regimens, particularly after maintenance with single-agent anti-EGFRs