On the time for fold surfaces to order during the crystallization of polyethylene from the melt and its dependence on molecular parameters

New experiments underpin the interpretation of the basic division in crystallization behaviour of polyethylene in terms of whether or not there is time for the fold surface to order before the next molecular layer is added at the growth front. For typical growth rates, in Regime 11, polyethylene lamellae form with disordered {001} fold surfaces then transform, with lamellar thickening and twisting, towards the more-ordered condition found for slower crystallization in Regime 1, in which lamellae form with and retain {201} fold surfaces. Several linear and linear-low-density polyethylenes have been used to show that, for the same polymer crystallized alone or in a blend, the growth rate at which the change in initial lamellar condition occurs is reasonably constant thereby supporting the concept of a specific time for surfaces to attain the ordered {201}) state. This specific time, in the range from milliseconds to seconds, increases with molecular length, and in linear-low-density polymer, for higher branch contents. (c) 2006 Elsevier Ltd. All rights reserved.

Molecular pathology of colorectal cancer.

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently (sessile) serrated adenomas, which can be detected endoscopically and removed. The morphological steps in the adenoma-carcinoma sequence have been elucidated at a molecular level, which has been facilitated by identification of the genes responsible for familial intestinal cancer. However, apart from early detection of familial forms of CRC and its use in genetic counseling, until recently such detailed molecular knowledge has had little impact on clinical management of the disease. This has dramatically changed in the last decade. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Additional genetic tests for mutations in NRAS, BRAF and PIK3CA contribute to determining who to treat, and others will follow. New therapies effective in patients with advanced CRC are under investigation. Remaining burning questions for optimal management are which patients will relapse after resection of the primary tumor and which patients will respond to the standard 5FU-oxaliplatin adjuvant treatment regimen. Predictive tests to address these issues are eagerly awaited. New classifications of CRC, based on molecular parameters, are emerging, and we will be confronted with new subtypes of CRC, for which the definition is based on combinations of gene expression patterns, chromosomal alterations, gene mutations and epigenetic characteristics. This will be instrumental in designing new approaches for therapy but will also be translated into molecular diagnostics. Both will contribute to improved clinical management of CRC.

Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer.

Background The prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing. Methods Tumors from patients (N = 1404) in the PETACC3 adjuvant chemotherapy trial were examined for BRAF and KRAS mutations, microsatellite instability (MSI), chromosome 18q loss of heterozygosity (18qLOH), and SMAD4 expression. Their importance in predicting relapse-free survival (RFS) and overall survival (OS) was assessed by Kaplan-Meier analyses, Cox regression models, and recursive partitioning trees. All statistical tests were two-sided. Results MSI-high status and SMAD4 focal loss of expression were identified as independent prognostic factors with better RFS (hazard ratio [HR] of recurrence = 0.54, 95% CI = 0.37 to 0.81, P = .003) and OS (HR of death = 0.43, 95% CI = 0.27 to 0.70, P = .001) for MSI-high status and worse RFS (HR = 1.47, 95% CI = 1.19 to 1.81, P < .001) and OS (HR = 1.58, 95% CI = 1.23 to 2.01, P < .001) for SMAD4 loss. 18qLOH did not have any prognostic value in RFS or OS. Recursive partitioning identified refinements of TNM into new clinically interesting prognostic subgroups. Notably, T3N1 tumors with MSI-high status and retained SMAD4 expression had outcomes similar to stage II disease. Conclusions Concomitant assessment of molecular and clinical markers in multivariable analysis is essential to confirm or refute their independent prognostic value. Including molecular markers with independent prognostic value might allow more accurate prediction of prognosis than TNM staging alone.

Molecular and isotopic characterization of organic samples from the wreck of the Saint-Etienne merchant ship (XVIIIth century): Identification of pitch, fat, hair and sulfur

The wreck U Pezzo, excavated within the Saint Florent Gulf in northern Corsica was identified as the pink, Saint Etienne, a merchant ship which sank on January 31, 1769. In order to determine the composition of organic materials used to coat the hull or to waterproof different parts of the pink, a study of several samples, using molecular biomarker and carbon isotopic analysis, was initiated. The results revealed that the remarkable yellow coat, covering the outside planks of the ship's bottom under the water line, is composed of sulfur, tallow (of ox and not of cetacean origin) and black pitch which corresponds to a mixture called ``couroi'' or ``stuff'. Onboard ropes had been submitted to a tarring treatment with pitch. Hairs mixed with pitch were identified in samples collected between the two layers of the hull or under the sheathing planking. The study also provides a key model for weathering of pitch, as different degrees of degradation were found between the surface and the heart of several samples. Accordingly, molecular parameters for alteration were proposed. Furthermore novel mixed esters between terpenic and diterpenic alcohols and the free major fatty acids (C(14:0), C(16:0), C(18:0)) were detected in the yellow coat. (C) 2009 Elsevier Ltd. All rights reserved.

Basin-internal derivation of hydrocarbons in the Witwatersrand Basin, South Africa: evidence from bulk and molecular δ13C data

Gold in the quartz-pebble conglomerates of the late Archean Witwatersrand Basin, South Africa, is often intimately associated with carbonaceous matter of organic/biogenic origin which occurs in the form of stratiform carbon seams and paragenetically late bitumen nodules. Both carbon forms are believed to be formed by solidification of migrating hydrocarbons. This paper presents bulk and molecular chemical and stable carbon isotope data for the carbonaceous matter, all of which are used to provide a clue to the source of the hydrocarbons. These data are compared with those from intra-basinal shales and overlying dolostone of the Transvaal Supergroup. The delta C-13 values of the extracts from the Witwatersrand carbonaceous material show small differences (up to 2.4 parts per thousand) compared to the associated insoluble organic matter. This suggests that the auriferous rocks were stained by mobile hydrocarbons produced by thermal and oxidative alteration of indigenous bitumens, a contribution from hydrocarbons derived from intra-basinal Witwatersrand shales cannot be excluded. Individual aliphatic hydrocarbons of the various carbonaceous materials were subjected to compound specific isotope analysis using on-line gas chromatography/combustion/stable isotope ratio mass spectrometry (GC/C/IRMS). The limited variability of the molecular parameters and uniform delta C-13 values of individual n-alkanes (-31.1 +/- 1.7 parts per thousand) and isoprenoids (-30.7 +/- 1.1 parts per thousand) in the Witwatersrand samples exclude the mixing of oils from different sources. Carbonaceous matter in the dolostones shows distinctly different bulk and molecular isotope characteristics and thus cannot have been the source of the hydrocarbons in the Witwatersrand deposits. All the various forms of Witwatersrand carbon appear indigenous to the Witwatersrand Basin, and the differences between them are explained by variable, in general probably short (centimeter- to meter-scale) hydrocarbon migration during diagenesis and subsequent hydrothermal infiltration. (C) 2001 Elsevier Science B.V. All rights reserved.

Phylogeny of snake trypanosomes inferred by SSU rDNA sequences, their possible transmission by phlebotomines, and taxonomic appraisal by molecular, cross-infection and morphological analysis

Blood examination by microhaematocrit and haemoculture of 459 snakes belonging to 37 species revealed 24% trypanosome prevalence in species of Viperidae (Crotalus durissus and Bothrops jararaca) and Colubridae (Pseudoboa nigra). Trypanosome cultures from C. durissus and P. nigra were behaviourally and morphologically indistinguishable. In addition, the growth and morphological features of a trypanosome from the sand fly Viannaniyia tuberculata were similar to those of snake isolates. Cross-infection experiments revealed a lack of host restriction, as snakes of 3 species were infected with the trypanosome from C. durissus. Phylogeny based on ribosomal sequences revealed that snake trypanosomes clustered together with the sand fly trypanosome, forming a new phylogenetic lineage within Trypanosoma closest to a clade of lizard trypanosomes transmitted by sand flies dagger. The clade of trypanosomes from snakes and lizards suggests an association between the evolutionary histories of these trypanosomes and their squamate hosts. Moreover, data strongly indicated that these trypanosomes are transmitted by sand flies. The flaws of the current taxonomy of snake trypanosomes are discussed, and the need for molecular parameters to be adopted is emphasized. To our knowledge, this is the first molecular phylogenetic study of snake trypanosomes.

Molecular structures and vibrational frequencies for cis-[PdCl2(tmen)] and cis-[Pd(N-3)(2)(tmen)]: A DFT study

Theoretical molecular structures of the complexes cis-[PdCl2(tmen)] and cis-[Pd(N-3)(2)(tmen)] (tmen = N,N,N',N'-tetramethylethylenediamine) were investigated using B3LYP/DFT method. The calculated molecular parameters, bond distances and angles, revealed a square-planar geometry around the metallic center for both compounds with the azide being linear. The theoretical infrared spectra of C, symmetry (electronic state (1)A) of the compounds are in agreement with the experimental data. (C) 2007 Elsevier B.V. All rights reserved.

Molecular and Cytogenetic Analyses on Brazilian Youths with Pervasive Developmental Disorders

The Pervasive Developmental Disorders (PDDs) constitute a group of behavioral and neurobiological impairment conditions whose main features are delayed communicative and cognitive development. Genetic factors are reportedly associated with PDDs and particular genetic abnormalities are frequently found in specific diagnostic subgroups such as the autism spectrum disorders. This study evaluated cytogenetic and molecular parameters in 30 youths with autism or other PDDs. The fragile X syndrome was the most common genetic abnormality detected, presented by 1 patient with autism and 1 patient with PPD not-otherwise specified (PPD-NOS). One girl with PDD-NOS was found to have tetrasomy for the 15q11-q13 region, and one patient with autism exhibited in 2/100 metaphases an inv(7)(p15q36), thus suggesting a mosaicism 46,XX/46,XX,inv(7)(p15q36) or representing a coincidental finding. The high frequency of chromosomopathies support the hypothesis that PDDs may develop as a consequence to chromosomal abnormalities and justify the cytogenetic and molecular assessment in all patients with PDDs for establishment of diagnosis.

Histomorphometrical and molecular evaluation of endosseous dental implants sites in humans: Correlation with clinical and radiographic aspects

Objective: To evaluate the correlations between clinical-radiographical aspects and histomorphometric-molecular parameters of endosseous dental implant sites in humans. Material and methods: The study sample consisted of bone implant sites from the jawbones of 32 volunteers, which were classified according to two different systems: (1) based only on periapical and panoramic images (PP); (2) as proposed by Lekholm & Zarb (L&Z). Bone biopsies were removed using trephine during the first drilling for implant placement. Samples were stained with haematoxylin-eosin (HE), and histomorphometric analysis was performed to obtain the following parameters: trabecular thickness (Tb.Th), trabecular number, bone volume density (BV/TV), bone specific surface (BS/BV), bone surface density and trabecular separation (Tb.Sp). In addition, immunohistochemistry analysis was performed on bone tissue samples for the proteins, Receptor activator of nuclear factor kappa-B (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and Osteocalcin (OC). Also, the determination of the relative levels of gene expression was performed using Reverse transcription-real-time Polymerase Chain Reaction (RT-PCR). Results: PP and L&Z classification systems revealed a moderate correlation with BV/TV, BS/BV, Tb.Th and Tb.Sp. L&Z's system identified differences among bone types when BV/TV, BS/BV, Tb.Th and Tb.Sp were compared. A weak correlation between PP/L&Z classifications and the expression of bone metabolism regulators (RANK, RANKL, OPG e OC) was found. The analysis of mRNA expression showed no difference between the bone types evaluated. Conclusions: Our results suggest that PP and L&Z subjective bone-type classification systems are related to histomorphometric aspects. These data may contribute to the validation of these classifications. Bone remodelling regulatory molecules do not seem to influence morphological aspects of the jawbone © 2011 John Wiley & Sons A/S.

Caracterização biológica e molecular de quatro cepas de Trypanosoma cruzi Chagas,1909 (Kinetoplastida, Trypanosomatidae) isoladas de pacientes chagásicos crônicos

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Molecular dynamics simulations of sheared brush-like systems

Mit Hilfe von Molekulardynamik-Simulationen untersuchen wir bürstenartige Systeme unter guten Lösungsmittelbedingungen. Diese Systeme sind, dank ihren vielfältigen Beschaffenheiten, die von Molekularparametern und äußeren Bedingungen abhängig sind, wichtig für viele industrielle Anwendungen. Man vermutet, dass die Polymerbürsten eine entscheidende Rolle in der Natur wegen ihrer einzigartigen Gleiteigenschaften spielen. Ein vergröbertes Modell wird verwendet, um die strukturellen und dynamischen Eigenschaften zweier hochkomprimierter Polymerbürsten, die eine niedrige Reibung aufweisen, zu untersuchen. Allerdings sind die Lubrikationseigenschaften dieser Systeme, die in vielen biologischen Systemen vorhanden sind, beeinflußt. Wir untersuchen so-genannte "weiche Kolloide", die zwischen den beiden Polymerbürsten eingebettet sind, und wie diese Makroobjekte auf die Polymerbürsten wirken.rnrnNicht-Gleichgewichts-Molekulardynamik-Simulationen werden durchgeführt, in denen die hydrodynamischen Wechselwirkungen durch die Anwendung des DPD-Thermostaten mit expliziten Lösungsmittelmolekülen berücksichtigt werden. Wir zeigen, dass die Kenntnis der Gleichgewichtseigenschaften des Systems erlaubt, dynamische Nichtgleichgewichtsigenschaften der Doppelschicht vorherzusagen.rnrnWir untersuchen, wie die effektive Wechselwirkung zwischen kolloidalen Einschlüßen durch die Anwesenheit der Bürsten (in Abhängigkeit der Weichheit der Kolloide und der Pfropfdichte der Bürsten) beeinflußt wird. Als nächsten Schritt untersuchen wir die rheologische Antwort von solchen komplexen Doppelschichten auf Scherung. Wir entwickeln eine Skalen-Theorie, die die Abhängigkeit der makroskopischen Transporteigenschaften und der lateralen Ausdehnung der verankerten Ketten von der Weissenberg Zahl oberhalb des Bereichs, in dem die lineare Antwort-Theorie gilt, voraussagt. Die Vorhersagen der Theorie stimmen gut mit unseren und früheren numerischen Ergebnissen und neuen Experimenten überein. Unsere Theorie bietet die Möglichkeit, die Relaxationszeit der Doppelschicht zu berechnen. Wenn diese Zeit mit einer charakteristischen Längenskala kombiniert wird, kann auch das ''transiente'' (nicht-stationäre) Verhalten beschrieben werden.rnrnrnWir untersuchen die Antwort des Drucktensors und die Deformation der Bürsten während der Scherinvertierung für grosse Weissenberg Zahlen. Wir entwickeln eine Vorhersage für die charakteristische Zeit, nach der das System wieder den stationären Zustand erreicht.rnrnrnElektrostatik spielt eine bedeutende Rolle in vielen biologischen Prozessen. Die Lubrikationseigenschaften der Polymerbürsten werden durch die Anwesenheit langreichweitiger Wechselwirkungen stark beeinflusst. Für unterschiedliche Stärken der elektrostatischen Wechselwirkungen untersuchen wir rheologische Eigenschaften der Doppelschicht und vergleichen mit neutralen Systemen. Wir studieren den kontinuierlichen Übergang der Systemeigenschaften von neutralen zu stark geladenen Bürsten durch Variation der Bjerrumlänge und der Ladungsdichte.

Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates

The gastrin-releasing peptide receptor (GRPR) has emerged as an attractive target for both therapeutic and diagnostic appliances, but has only insufficiently been characterized in the human prostate so far. The aim of this study is to profile GRPR in a large cohort and correlate it with clinicopathologic and molecular parameters.

IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival

BACKGROUND Low-grade gliomas (LGGs) are rare brain neoplasms, with survival spanning up to a few decades. Thus, accurate evaluations on how biomarkers impact survival among patients with LGG require long-term studies on samples prospectively collected over a long period. METHODS The 210 adult LGGs collected in our databank were screened for IDH1 and IDH2 mutations (IDHmut), MGMT gene promoter methylation (MGMTmet), 1p/19q loss of heterozygosity (1p19qloh), and nuclear TP53 immunopositivity (TP53pos). Multivariate survival analyses with multiple imputation of missing data were performed using either histopathology or molecular markers. Both models were compared using Akaike's information criterion (AIC). The molecular model was reduced by stepwise model selection to filter out the most critical predictors. A third model was generated to assess for various marker combinations. RESULTS Molecular parameters were better survival predictors than histology (ΔAIC = 12.5, P< .001). Forty-five percent of studied patients died. MGMTmet was positively associated with IDHmut (P< .001). In the molecular model with marker combinations, IDHmut/MGMTmet combined status had a favorable impact on overall survival, compared with IDHwt (hazard ratio [HR] = 0.33, P< .01), and even more so the triple combination, IDHmut/MGMTmet/1p19qloh (HR = 0.18, P< .001). Furthermore, IDHmut/MGMTmet/TP53pos triple combination was a significant risk factor for malignant transformation (HR = 2.75, P< .05). CONCLUSION By integrating networks of activated molecular glioma pathways, the model based on genotype better predicts prognosis than histology and, therefore, provides a more reliable tool for standardizing future treatment strategies.

Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: Efficacy of tributyrin, a butyric acid prodrug

Hepatocellular carcinoma (HCC) ranks in prevalence and mortality among top 10 cancers worldwide. Butyric acid (BA), a member of histone deacetylase inhibitors (HDACi) has been proposed as an anticareinogenic agent. However, its short half-life is a therapeutical limitation. This problem could be circumvented with tributyrin (TB), a proposed BA prodrug. To investigate TB effectiveness for chemoprevention, rats were treated with the compound during initial phases of ""resistant hepatocyte"" model of hepatocarcinogenesis, and cellular and molecular parameters were evaluated. TB inhibited (p < 0.05) development of hepatic preneoplastic lesions (PNL) including persistent ones considered HCC progression sites. TB increased (p < 0.05) PNL remodeling, a process whereby they tend to disappear. TB did not inhibit cell proliferation in PNL, but induced (p < 0.05) apoptosis in remodeling ones. Compared to controls, rats treated with TB presented increased (P < 0.05) hepatic levels of BA indicating its effectiveness as a prodrug. Molecular mechanisms of TB-induced hepatocarcinogenesis chemoprevention were investigated. TB increased (p < 0.05) hepatic nuclear histone H3K9 hyperacetylation specifically in PNL and p21 protein expression, which could be associated with inhibitory HDAC effects. Moreover, it reduced (p < 0.05) the frequency of persistent PNL with aberrant cytoplasmic p53 accumulation, an alteration associated with increased malignancy. Original data observed in our study support the effectiveness of TB as a prodrug of BA and as an HDACi in hepatocarcinogenesis chemoprevention. Besides histone acetylation and p21 restored expression, molecular mechanisms involved with TB anticarcinogenic actions could also be related to modulation of p53 pathways. (C) 2008 Wiley-Liss, Inc.