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Abstract—The review presents publications devoted to a promising biopolymer, poly-3-hydroxybutyrate, and composite materials based on it. The structure and properties of the materials are considered. The main focus is on the biomedical application of these biopolymer materials. The main advantage of poly-3-hydroxybutyrate is its biodegradability in nature and living systems, biocompatibility, hemocompatibility, and thromboresistance. This biopolymer also possesses processability. The products and materials based on it can be processed by solution and melt production methods. The review pays great attention to the production of ultrathin fibers by electrospinning. Materials based on poly-3-hydroxybutyrate even now find wide application in medicine, hygiene, packaging, and ecology.

Abstract—Nonwoven fibrous materials based on polylactide (PLA) and ozonide of oleic acid triglyceride (glycero-(9,10-trioxolane)-trialeate) in a range of concentrations of 1–5 wt % intended for hygienic and medical devices are obtained by electrospinning. The introduction of ozonide leads to plasticization of PLA, which manifests itself in the cleavage of the primary jet of the forming solution and appearance of ultrathin nanofibers; here, the porosity and relative elongation at break increase. The optimum weight fraction of ozonide introduced into PLA is determined to be 3 wt %.

AimsCystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with Corynebacteriumspp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases.MethodsBreast specimens diagnosed as granulomatous inflammation between 2010 and 2020 were reviewed to identify a CNGM cohort and a non-CNGM cohort. Polymerase chain reaction-based identification of Corynebacteria by 16S ribosomal RNA (16S rRNA) primers, followed by confirmatory Sanger sequencing (SS), was performed on all cases. Clinical, radiological and microbiology data were retrieved from the electronic patient records.ResultsTwenty-eight CNGM cases and 19 non-CNGM cases were identified. Compared with the non-CNGM cohort, patients in the CNGM cohort were more likely to be multiparous (p=0.01), breast feeding (p=0.01) and presenting with a larger breast mass (p<0.01), spontaneous drainage (p=0.05) and skin irritation (p<0.01). No significant difference in the prevalence of Corynebacteriabetween the cohorts (7% vs 11%, p=0.68) by microbiological culture was identified. Compared with microbiology culture, the sensitivity and specificity of each Corynebacterial detection method were 50% and 81% for Gram stain, and 25% and 100% for 16S rRNA combined with SS. Regardless of the diagnosis, patients positive for Corynebacteriawere more likely to have a persistent disease (p<0.01).ConclusionCNGM presents as a large symptomatic breast mass in multiparous breastfeeding women. The importance of adequate sampling and repeated microbiology culture in conjunction with sequencing on all GM cases with persistent disease is paramount.

Abstract: The principles of creating biomedical materials based on biopolymers and their compositions for various medical applications are considered. The direction of creating materials with antimicrobial activity is especially emphasized using the example of polyhydroxyalkanoates. These biopolymers and composites based on them are most frequently used in the production of medical devices. Polyhydroxyalkanoates as a class of biopolymers, as well as polyhydroxybutyrate, the representative of this class most suitable for biomedical use, are analyzed in the context of increasing resistance to microorganisms. Progress in this direction achieved in recent years is reported. The influence of the supramolecular and molecular structure of the materials on the ability to biodegrade in the environment and a living organism is considered. The advantage of mixtures of biopolymers for achieving high degradation rates in comparison with the original polymers is noted. Promising antiseptics based on porphyrin metal complexes in combination with biopolymer nonwoven fibrous matrices are demonstrated. Characteristic features of preclinical tests of antiseptic materials are considered. A conclusion is drawn that the structural organization of a polymeric material or composite determines the level of intermolecular interactions during the formation of the material and thereby programs the set of functional properties and mechanism of degradation under the influence of aggressive external factors.

Nonwoven fibers from biodegradable polymers such as polylactide and poly-3-hydroxybutyrate were obtained by electrospinning. The fiber morphology was studied by optical microscopy. The fiber materials were used like the substrates for the plant growing. The sowing qualities of the "Athena"winter wheat (triticum aestivum L.) and biometric indicators of the plants were determined. The biometric indicators of wheat plants grown on polymer substrates are higher compared with the GOST technique. Eco-friendly fiber materials are promising for the agricultural application. Polylactide and poly-3-hydroxybutyrate undergo a hydrolysis process. They are destroyed to form nutrients for the growth and development of wheat plants.

A new material with hydrophobic-hydrophilic properties is obtained based on ultrathin poly(3-hydroxybutyrate) (PHB) fibers modified with poly(2-hydroxyethyl methacrylate). The supramolecular structure of the samples is investigated by structurally dynamic methods: scanning electron microscopy, differential scanning calorimetry, and electron paramagnetic resonance. The equilibrium-kinetic characteristics of water sorption by the material are determined. Evidence is obtained by the method of 1H NMR (proton nuclear magnetic resonance spectroscopy) for the chemical modification of the PHB surface due to the participation of its terminal groups in the transesterification reaction of 2-hydroxyethyl methacrylate.

AimsTo assess the utility of a three-antibody immunohistochemistry panel to classify muscle invasive bladder cancers (MIBCs) in correlation with morphological features and p53 status.MethodsA retrospective review of 243 chemotherapy nai¨ve MIBC cystectomy specimens was performed to assess morphological features. A tissue microarray was sequentially stained with CK5/6, GATA-3 and p16. Subgroups were assigned as basal-like (CK5/6+, GATA3−) and luminal (CK5/6−, GATA3+), with the latter subdivided into genomically unstable (GU, p16+) and urothelial like (Uro, p16−) subgroups. p53 staining was assessed as abnormal/wild type. Cases from the The Cancer Genome Atlas (TCGA) portal were assessed as external validation.ResultsWe identified 78.8% luminal, 21.2% basal cases within our cohort and 63.4% luminal, 36.6% basal in the TCGA dataset. Divergent differentiation (p<0.001) was significantly associated with basal-subtype cases in both cohorts. Within the luminal subgroup (n=186), 81 cases were classified as GU and 105 as Uro. Abnormal p53 staining was noted in 48.0% of basal, 80.2% GU and 38.1% Uro cases. Further, basal-subtype tumours significantly correlated with disease-specific death compared with Uro cases in multivariate survival analysis.ConclusionsThis retrospective study demonstrates the potential utility of a three-antibody immunohistochemistry panel to differentiate luminal and basal MIBC.

Foaming of the biodegradable polymer composites and melting of the gas-filled materials were studied using thermal microscopy. Composite materials under investigation were based on the low density polyethylene and natural products used as the polymer composite fillers: wood flour and corn starch. Porous structure of the composite material was obtained using a chemical porogen “Hydrocerol BIF”. It has been shown that the foaming and melting processes occur differently in the polymer composite samples containing either different amount of the fillers or the same content of the filler with different particle size fractions. Thermal behavior of the composite samples was shown to be different from the behavior of pure polyethylene, which indicates non-additivity (superadditivity) of the contribution of the above components to the thermal behavior of the final composite material. All the results obtained using heating stage (hot stage) microscopy were in good agreement with the SEM and DSC data.

AimsThe advent of immune checkpoint inhibitor therapy has proven beneficial in a subset of high-grade urothelial carcinomas (HGUC) of the bladder. Although treatment selection is currently largely determined by programmed death-ligand 1 (PD-L1) status, multiple factors in the immune system may modulate the host immune response to HGUC and immunotherapy. In this pilot study, we used a transcriptomic approach to identify the immune milieu associated with PD-L1 expression to enhance our understanding of the HGUC immune evasion network.MethodsThe immune transcriptome of 40 HGUC cystectomy cases was profiled using the NanoString nCounter Human V.1.1 PanCancer Panel. All cases were assessed for associated PD-L1 status (SP263) using whole tissue sections. PD-L1 status was determined as high or low using 25% tumour and/or immune cell staining.ResultsThe most significantly differentially expressed gene was PD-L1 messenger RNA (CD274), which strongly correlated with protein expression (r=0.720, p<0.001). The sensitivity, specificity, positive and negative predictive values of CD274for PD-L1 expression were 85%, 96%, 92% and 93%, respectively. The PD-L1 associated gene signature also included complement components C1QAand CD46and NOD2(innate immune system), proinflammatory cytokines CXCL14, CXCL16, CCL3, CCL3L1and OSMalong with the immune response mediator SMAD3,among others. Pathway analysis determined enrichment of these genes in interleukin-10 production, lymphocyte chemotaxis and aberrant IFNγ, NF-κB and ERK signalling networks.ConclusionsWe report key genes and pathways in the immune transcriptome and their association with PD-L1 status, which may be involved in immune evasion of HGUC and warrants further investigation.

Supplemental Digital Content is available in the text.CTNNB1mutations and aberrant β-catenin expression have adverse prognosis in endometrial endometrioid carcinoma, and recent evidence suggests a prognostic role of β-catenin in ovarian endometrioid carcinoma. Thus, we aimed to determine the prognostic value of the CTNNB1mutational status, and its correlation with β-catenin expression, in a well-annotated cohort of 51 ovarian endometrioid carcinomas. We performed immunohistochemistry for β-catenin and developed an 11-gene next-generation sequencing panel that included whole exome sequencing of CTNNB1and TP53. Results were correlated with clinicopathologic variables including disease-free and disease-specific survival. Tumor recurrence was documented in 14 patients (27%), and cancer-related death in 8 patients (16%). CTNNB1mutations were found in 22 cases (43%), and nuclear β-catenin in 26 cases (51%). CTNNB1mutation highly correlated with nuclear β-catenin (P<0.05). Mutated CTNNB1status was statistically associated with better disease-free survival (P=0.04, log-rank test) and approached significance for better disease-specific survival (P=0.07). It also correlated with earlier International Federation of Gynecology and Obstetrics stage (P<0.05). Nuclear β-catenin, TP53mutations, age, ProMisE group, surface involvement, tumor grade and stage also correlated with disease-free survival. There was no association between membranous β-catenin expression and disease-free or disease-specific survival. CTNNB1mutations and nuclear β-catenin expression are associated with better progression-free survival in patients with OEC. This relationship may be in part due to a trend of CTNNB1-mutated tumors to present at early stage. β-catenin immunohistochemistry may serve as a prognostic biomarker and a surrogate for CTNN1Bmutations in the evaluation of patients with ovarian endometrioid neoplasia, particularly those in reproductive-age or found incidentally without upfront staging surgery.

This article considers experimental data on the surface charge propagation along the dielectric polymer fibers. Nonwoven polymer materials based on polyhydroxybutyrate obtained by electrospinning technique were used as an example of dielectric fibers in our experiments. Polymer fiber charging was investigated under the electron beam in a vacuum chamber of the scanning electron microscope. The fiber electric response registration was performed in a TV mode and in dynamic conditions using oscilloscopic sectioning visualization. Digitized images were processed using specialized software by Sobel-Feldman operator (Sobel filter), visualizing isopotential lines of the electron beam-induced emission. The results obtained were analyzed in the framework of the Roll’s cable model, which has been extrapolated from the electrical signal transduction along the nerve fibers to the charge propagation along the dielectric polymer fibers.

The article studies the supramolecular structure of polymer matrices for sustained isolation of drugs based on ultrathin fibers of polyhydroxybutyrate obtained by electrospinning method. Dipyridamole was chosen as a model drug. The concentration of dipyridamole in the fibers ranged from 1 to 5%. The morphology of nonwoven fibrous materials was investigated by scanning electron microscopy, differential scanning calorimetry, electron paramagnetic resonance. It was shown that the addition of the dipyridamole leads to a change in the fiber geometry. Fibers based on polyhydroxybutyrate are characterized by non-equilibrium molecular structure. In the current work, it was found that the addition of dipyridamole causes extra crystallization processes and the molecular mobility in the amorphous regions of the polymer slows down

After diagnosis of prostate cancer is confirmed by a positive biopsy, the tumor may be surgically removed via radical prostatectomy (RP). However, many prostate cancer patients experience biochemical recurrence after surgery and/or undergo salvage radiotherapy or hormone therapy. Timely treatment is required to prevent the spread of disease in these cases, and biopsy tissue may hold potential for disease prognostication before surgery is ever performed. We previously developed a prognostic multigene methylation panel in RP specimens, including APC, CRIP3, HOXD3, and TGFB2. In the current study, this panel was applied to a cohort of biopsy specimens (n= 86), which were assessed for DNA methylation using the real-time quantitative PCR–based multiplex MethyLight. The biopsy-based methylation panel is significantly associated with biochemical recurrence when combined with the current clinical parameter of prostate-specific antigen (PSA) levels at diagnosis and is able to prognosticate the initiation of salvage radiotherapy, where it outperforms PSA, and/or hormone therapy after RP. In addition, this methylation panel is significantly associated with late recurrence occurring within 5 and 7 years after surgery, when combined with PSA at diagnosis. Combining DNA methylation and clinicopathologic markers at the biopsy stage will not only increase their prognostic ability but will also ensure effective patient management.

Supplemental Digital Content is available in the text.The PROMISE diagnostic algorithm, which uses p53, mismatch repair (MMR) protein immunohistochemistry, and DNA polymerase ε (POLE) exonuclease domain mutation testing, is a reliable surrogate of the molecular group in endometrial carcinoma. Its prognostic value has been validated in endometrial carcinoma and ovarian endometrioid carcinoma. Moreover, a similar prognostic grouping has been recently documented in endometrial clear cell carcinoma. Thus, we aimed to explore the role of these markers in ovarian clear cell carcinoma, another endometriosis-associated malignancy. A total of 90 cases were identified and confirmed after secondary review. Immunohistochemistry for p53, MLH1, MSH2, MSH6, and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. POLEmutational analysis was performed in 47 cases. Results were correlated with clinicopathologic variables including disease-free survival (DFS), overall survival, and disease-specific survival (DSS). Endometriosis was found in 67 (74%) cases. Six (7%) tumors were p53 abnormal, 82 (91%) were p53 normal, and 2 (2%) tumors had MMR deficiency (1 MSH6 loss and 1 MSH2/6 loss; both were p53 normal). Several POLEvariants of unknown significance were detected, but no pathogenic mutations. The mean follow-up period was 43 months (median: 34, range: 1 to 189). Abnormal p53 status was associated with advanced Federation of Gynecology and Obstetrics stage, lymph node metastases, DFS and DSS (P<0.05, Fisher exact test). In univariate analysis, abnormal p53 and positive lymph node status had worse DFS, whereas bilaterality, surface involvement, and advanced stage were associated with worse DFS, overall survival and DSS (P<0.05, Cox regression). On multivariate analysis, only stage retained statistical association with survival. Using a molecular-based approach designed for endometrial carcinoma, most ovarian clear cell carcinomas fall into the copy-number-low molecular subgroup. However, a small but important subset has an abnormal p53 expression (copy-number-high group). This subset is associated with adverse features including extrapelvic disease, nodal metastases, and recurrence similar to endometrial and ovarian endometrioid cancer. Thus, testing for this marker has potential prognostic significance. The role of other markers in the PROMISE algorithm remains to be elucidated, as we found a low frequency of MMR abnormalities and no pathogenic POLEmutations in our series.

Gas-filled composite materials were obtained by foaming of low density polyethylene (PE) and introduction of natural components. Particulate chemical gas-generating agent hydrocerol was used for the polyethylene porosity. Particulate biodegradable filler, wood flour, and corn starch were used as the natural components. Investigation of structure, physical, and physicomechanical properties of the materials was performed. It is shown that the polyethylene structure became inhomogeneous: pores and foreign inclusions were observed. The density and physicomechanical properties decreased. It is noted that such peculiarities of the material as low density and the presence of pores and particles of the hydroscopic filler increase the capacity for biodegradation. Evaluation of the capacity of the material to degrade in the environment was conducted. Results of the evaluation demonstrate the weight loss of the samples with the biodegradable filler, which may be explained by the destructive effect of microorganisms, partial washing of the filler, and fragmentation of the sample. The samples of the gas-filled composite materials, with reduced performance properties but retained at a sufficient level, proved the promising outlook for their application as packaging materials and sealing packaging elements for the nonfood goods.

The International Federation of Obstetrics and Gynecology (FIGO) grading system for endometrial carcinoma is currently applied to ovarian endometrioid carcinoma (OEC) in many practices. However, previous reports claim superior prognostication by using the Silverberg grading system for ovarian carcinoma. Thus, a thorough comparison between FIGO and Silverberg in OEC is still warranted. A total of 72 OECs diagnosed at our institution were independently graded using both systems. Grade (G) following Silverberg was based on combined scores for architecture, nuclear atypia, and mitotic activity. FIGO grading was based on the % of nonsquamous solid component; severe atypia warranted upgrade to the architectural FIGO grade (G1 to G2 or G2 to G3). Case grouping by grade was correlated with disease-free (DFS), disease-specific (DSS), and overall (OS) survival. Eleven (15.3%) OECs were bilateral, 26 (36.1%) had ovarian surface involvement, and 12 (16.7%) had lymphovascular space invasion. Forty-seven OECs were stage I (65%), 16 (22%) stage II, and 9 (13%) stage III. Median follow-up period was 62 months (range: 1 to 179 mo). Median DFS was 60.5 months (1 to 179 mo); median OS was 61 months (1 to 179 mo). Sixteen (22%) OECs recurred and 9 (13%) patiets died of disease. In univariate analysis, both FIGO and Silverberg correlated significantly with DFS, DSS, and OS (all with P<0.05). However, when compared in multivariate analysis, only Silverberg retained statistical correlation with survival (P<0.05). G1+G2 OEC by Silverberg had significantly better DFS, DSS, and OS compared with G3; such separation was not seen with FIGO. Survival was similar in Silverberg G1 and G2 tumors even 5 years after diagnosis, whereas FIGO G2 tumors had survival approaching G1 in the first 5 years, but declined after the 5-year mark approaching G3 tumors. Tumor laterality, lymphovascular space invasion, and stage also correlated with outcome. Stage showed prognostication superior to all other variables in multivariate analysis. As currently defined, the Silverberg grading system is a better predictor of survival than FIGO. Such differences may be explained by the G2 OEC groups, with G2 Silverberg clustering with G1 tumors, and having a more favorable behavior compared with G2 FIGO. Thus, Silverberg may be preferable in order to stratify patients in low and high-risk categories for prognosis and disease management.

AimsThe International Endocervical Adenocarcinoma Criteria and Classification (IECC) was recently proposed as an improved method for categorising endocervical adenocarcinoma (EA) into human papillomavirus (HPV)–associated adenocarcinomas (HPVAs) and non-HPV-associated adenocarcinomas (NHPVAs). Such categorisation correlates with patient age and tumour size; however, its association with patient outcome remains to be established.MethodsInstitutional cases of EA with histological material available were selected. Three gynaecological pathologists independently classified all tumours according to the IECC with consensus review used when necessary. Clinicopathologic variables were recorded for each case.ResultsOf a total of 87 EAs, 71 (82%) were classified as HPVA and 16 (18%) as NHPVA. Among HPVA, most were usual type (51/71, 72%) followed by mucinous not otherwise specified (10/71, 14%) and invasive stratified mucin-producing carcinoma (ISMC, 8/71, 11%). Most NHPVAs were of gastric type (12/16, 71%) followed by clear cell and mesonephric (two each, 12%). Compared with HPVAs, NHPVAs were significantly associated with older age (p<0.001), larger horizontal extent (p=0.013), greater depth of invasion (p=0.003), lymphovascular space invasion (p<0.001), advanced stage (p<0.001) and invasive pattern C (p<0.001). On univariate analysis, worse disease-free survival (DFS) and disease-specific survival (DSS) correlated with NHPVA group. Among the HPVA subtypes, ISMC showed worse DFS and DSS compared with other HPVA types.ConclusionsThe simple morphological approach of the IECC appears to be prognostically valuable. NHPVA (in particular gastric type) and ISMC (a recently recognised subset of HPVA) have an adverse outcome and their recognition following the IECC is important. We provide further evidence to replace the current WHO classification with the IECC.

Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.

An effect of small concentrations of nanosized titanium dioxide and silicon particles exerted on the formation of the supramolecular structure of poly-3-hydroxybutyrate fibers is studied. The fibers were obtained by means of electrospinning from a poly-3-hydroxybutyrate solution in chloroform. The structure of fibrous materials is studied by means of DSC, ESR, SEM, and physicomechanical testing. It is established that the fibers have intercrystalline areas with different ordering level. Using a small concentration of nanosized titanium dioxide and silicon particles leads to a slowing down of crystallization processes and to a decrease in the activation energy of the phase transition of PHB fiber melting. At the same time, the average fiber diameter decreases and the packing density increases. The obtained bioresorbable matrices can be successfully used in biomedicine for growing various connective and integumentary tissues of an organism.

Epigenetic changes, including CpG island hypermethylation, occur frequently in bladder cancer (BC) and may be exploited for BC detection and distinction between high-grade (HG) and low-grade (LG) disease. Genome-wide methylation analysis was performed using Agilent Human CpG Island Microarrays to determine epigenetic differences between LG and HG cases. Pathway enrichment analysis and functional annotation determined that the most frequently methylated pathways in HG BC were enriched for anterior/posterior pattern specification, embryonic skeletal system development, neuron fate commitment, DNA binding, and transcription factor activity. We identified 990 probes comprising a 32-gene panel that completely distinguished LG from HG based on methylation. Selected genes from this panel, EOMES, GP5, PAX6, TCF4,and ZSCAN12,were selected for quantitative polymerase chain reaction–based validation by MethyLight in an independent series (n=84) of normal bladder samples and LG and HG cases. GP5and ZSCAN12, two novel methylated genes in BC, were significantly hypermethylated in HG versus LG BC (P≤.03). We validated our data in a second independent cohort of LG and HG BC cases (n=42) from The Cancer Genome Atlas (TCGA). Probes representing our 32-gene panel were significantly differentially methylated in LG versus HG tumors (P≤.04). These results indicate the ability to distinguish normal tissue from cancer, as well as LG from HG, based on methylation and reveal important pathways dysregulated in HG BC. Our findings were corroborated using publicly available data sets from TCGA. Ultimately, the creation of a methylation panel, including GP5and ZSCAN12, able to distinguish between disease phenotypes will improve disease management and patient outcomes.

The structure and transport and diffusion properties of film matrices based on polyamide and polyhydroxybutyrate blends obtained from solutions and melts are studied. Quantitative analysis of the diffusion and sorption of water shows that the dependence of the diffusion mobility of water increases exponentially with increasing content of polyamide as the more hydrophilic component of the system. The developed materials are recommended for the creation of new therapeutic systems of controlled release of drugs.

DNA methylation plays an important role in carcinogenesis and is being recognized as a promising diagnostic and prognostic biomarker for a variety of malignancies including Prostate cancer (PCa). The human kallikrein-related peptidases (KLKs) have emerged as an important family of cancer biomarkers, with KLK3, encoding for Prostate Specific Antigen, being most recognized. However, few studies have examined the epigenetic regulation of KLKs and its implications to PCa. To assess the biological effect of DNA methylation on KLK6and KLK10expression, we treated PC3 and 22RV1 PCa cells with a demethylating drug, 5-aza-2′deoxycytidine, and observed increased expression of both KLKs, establishing that DNA methylation plays a role in regulating gene expression. Subsequently, we have quantified KLK6and KLK10DNA methylation levels in two independent cohorts of PCa patients operated by radical prostatectomy between 2007–2011 (Cohort I, n = 150) and 1998–2001 (Cohort II, n = 124). In Cohort I, DNA methylation levels of both KLKs were significantly higher in cancerous tissue vs. normal. Further, we evaluated the relationship between DNA methylation and clinicopathological parameters. KLK6 DNA methylation was significantly associated with pathological stage only in Cohort I while KLK10DNA methylation was significantly associated with pathological stage in both cohorts. In Cohort II, low KLK10DNA methylation was associated with biochemical recurrence in univariate and multivariate analyses. A similar trend for KLK6DNA methylation was observed. The results suggest that KLK6and KLK10DNA methylation distinguishes organ confined from locally invasive PCa and may have prognostic value.

The aggregation kinetics have been observed for citrate-reduced 15 nm gold nanoparticles at the native silica and modified silica−water interfaces. At the native, negatively charged silica−water interface, two-phase adsorption is observed: a pseudo-Langmuirian adsorption phase and, after an acid wash to remove the citrate ligand from the adsorbed particles, another pseudo-Langmuirian adsorption phase. A kinetic analysis of these phases shows an average adsorption rate constant of (1.5 ± 0.4) × 106M−1s−1with no measurable desorption. Another acid wash induces a nearly linear aggregation phase with a 4-fold faster nanoparticles deposition rate. SEM imaging of the aggregation-phase surface shows the formation of small nanoparticle clusters of <10 particles. Adsorption on a positively charged, aminated silica surface shows a kinetic trace consistent with aggregations at low surface coverages and has a similar adsorption rate to the aggregation phases on the negatively charged surfaces. SEM imaging reveals clusters of many particles of >10. The refractive index sensitivity of the produced surfaces was measured by varying the analyte refractive index at each phase: the aggregated clusters on the positively charged surface are up to 4 times more sensitive.

Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. In this study, we assessed the combined prognostic utility of IDC/C and CAPRA-S for BCR in three PCa patient cohorts. CAPRA-S+IDC/C improved the predictive accuracy of BCR in all three cohorts (p<0.001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P<0.001, Cohort 2; P<0.001, Cohort 3; P=0.003), intermediate (Cohort 1; P<0.001, Cohort 2; P=0.006, Cohort 3; p=0.03) and high-risk (Cohort 1-3; P<0.001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P<0.001 and Cohort 3; P=0.003) patients. Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.

Addition of fullerene in concentration between 0.065 and 0.75 phr increases Schob elasticity, hardness, and modulus of NR‐based rubber. There is no substantial influence of fullerene on Tg, tan δ, and G‐modulus all evaluated by DMA at twisting within a temperature range −150 to −50°C (glassy state). At temperatures between 0 and 150°C (rubbery state) it is different, namely an increase in modulus and some changes in the slope of segments in G(T) curves were observed. It could be resulted from additional strong physical junctions of the rubber network. This suggests the growth of degradation energies of the branching junctions and related rise in the aging resistance as concentration of fullerene increases. Simultaneously, it could be expected some reduction of tire temperature at service. Because of this, introduction of fullerene could be reasonable for tread rubbers in case of reduction of its price. Permittivity and dielectric loss angle are correlated with fullerene concentration. Compounding technology when fullerene dispersed within carbon black is mixed with raw rubber on available machines could be easily implemented in the industry. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 390–398, 2006

No abstract.

We report new time-resolved measurements relevant to the atmospheric oxidation of C₂H₆, CF₃CF₂H (HFC-125), CF₃CH₃ (HFC-143a) and CF₃CFH₂ (HFC-134a). The radicals R = C₂H₅, CF₃CF₂, CF₃CH₂ and CF₃CFH were produced by photolysis of the corresponding iodides, RI, at 248 nm, using the output from a pulsed excimer laser, in the presence of a large excess of O₂ and with different concentrations of NO present. The loss of NO and the formation of the reaction products, CH₃C(O)H (from C₂H₅ radicals), C(O)F₂ and FNO (from CF₃CF₂), and C(O)F₂ and HFCO (from CF₃CFH) were followed, in real time, via absorption of infrared radiation provided by tuneable diode lasers. Our measurements essentially confirm previous conclusions, based mainly on continuous photolysis experiments, concerning the oxidation mechanisms for these compounds and also how they differ according to whether RO, the ethoxy or substituted ethoxy radical, is formed by mutual reaction of two alkyl peroxy radicals (RO₂ + RO₂) or by reaction of one of these radicals with NO (RO₂ + NO). In addition, we report rate constants for the important atmospheric reactions of ethyl peroxy with NO at 298 K, and of fluorinated ethyl peroxy radicals with NO, for temperatures between 198 and 298 K.

Butadiene rubbers (BRs) differing in isomeric content and cured with different amounts of dicumyl peroxide (DCP) have, according to TMA investigations, regions with two glass transition temperatures (low and high) and different thermal expansion properties. BR network has chemical and cluster type (physical localised) branching junctions. For rubbers of the same isomeric content, shares of such regions depend on concentration of DCP. This fact suggests cis-trans isomerization at curing, which increases the content of a high-temperature region with predominantly chemical branching junctions, because cluster type branching junctions start to relax at T g ″. It is supposed that an essential change in T g , if DCP concentration in the rubber compound is varied, is determined by the different molecular mobility of the chains included in associated structures of cluster junctions of a network of cured rubber. Such mobility also increases if 1,2 (vinyl) isomer is present in the BR chain. The latter is probably distributed uniformly between the chains of both regions. In a low-temperature region it could act as an antiplasticizer, whereas in a high-temperature region as a plasticizer. The molecular weight distribution of the chains between the junctions of a low-temperature region is virtually bimodal for low DCP concentration in rubber compounds. This could result from some zones with different crosslinking degree within the network. It is believed that this region has branching junctions, which are of a low crosslink density of chemical types and a high crosslinking density of cluster type junctions. A wide spectrum of isomeric content in neat and cured BR when a medium content of DCP was used meant that a low-temperature region had unimodal and symmetric MWD between the junctions. In a high-temperature region the exact opposite phenomenon may be observed -- separation of chain segment length giving a bimodal MWD. A possible reason for this is non-uniform distribution of 1,2 (vinyl) isomer within the chains of a high-temperature region. The shift in MWD between the junctions from bimodal to unimodal as DCP content is raised, which was identified using TMA, confirms our H NMR findings. The two splits in the H NMR spectra observed at lower DCP contents could result from regions with different crosslink density, as we have argued in a recently published paper. All these conclusions confirm the applicability of the adopted TMA for testing a complex structure of rubbers.

The yields of CO₂ from the reactions of HOCO radicals with O₂ and with NO have been compared using the technique of time-resolved infrared absorption. In two separate series of experiments, HOCO radicals have been generated by (i) broadband ultraviolet photolysis of acrylic acid (CH₂CHCOOH) and (ii) the reaction, Cl + HCOOH → HCl + HOCO, following pulsed laser photolysis of Cl₂ at 351 nm. In the latter experiments, the observed CO₂ yields were corrected for the loss of Cl atoms by the reactions Cl + NO + He → ClNO + He and Cl + ClNO → Cl₂ + NO. Our measurements on the rate of Cl + NO + He yield a value of the third-order rate constant of (5.1 ± 0.7) × 10−32 cm6 molecule−2 s−1. The results of the main experiments show that the yield of CO₂ from the reaction between NO + HOCO is appreciably less than that from O₂ + HOCO and is dependent on the total pressure in the range 10 to 100 Torr. We interpret this as showing that the reactions HOCO + NO → HNO + CO₂ and HOCO + NO(+M) → HOC(O)NO(+M) occur at similar rates, with the latter reaction being favoured at the higher total pressure.

Static and dynamic mixers set on the Brabender plastograph were used to investigate the grafting of itaconic acid (IA) onto low-density polyethylene (LDPE) by the reactive extrusion. The initiators of free-radical reactions were monoperoxide 2,5-dimethyl-2-hydroxy-5-tert-butylperoxy-3-hexyne and diperoxide 2,5-dimethyl-2,5-di(tert-butyl peroxy)-hexane. The reaction mix contained stabilizers of phenolic type as follows: 2,6-ditert-butyl-4-methyl phenol; ester of 3,5-ditert-butyl-4-hydroxyphenyl-propanoic acid and pentaerythritol; 4-alkoxy-2-hydroxy-benzophenone; and 1,4-dihydroxybenzene. The effect of stabilizers, which follow the radical mechanism on the grafting of IA and on the crosslinking, depends on their solubility in the polymer and the monomer. The stabilizers (e.g., 1,4-dihydroxybenzene) with increased affinity toward the monomer reduce the grafting yield and inhibit crosslinking. At 0.3–0.5 wt % of the stabilizer insoluble in the monomer, the grafting yield can be increased, while inhibiting the LDPE-g-IA crosslinking, irrespective of the peroxide used. Hence, classical stabilizers can initiate grafting reactions at raised concentrations, temperatures, and application of the shearing stresses. They also help to obtain a high-grafting yield and a reduced crosslinking degree. A stabilizer, having a close affinity toward LDPE, influences the LDPE-g-IA structure. The stabilizer content of 0.5 wt % transforms the topological structure of LDPE-g-IA into uniblock. Its molecular weight distribution (MWD) may be narrow (⁻Mn/⁻Mw &lt; 2) or broad (⁻Mn/⁻Mw > 2), depending on the concentration of the initiator used. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 3439–3448, 2001

Using thermomechanical analysis, the molecular weight distribution and relaxation transitions were investigated in commercial PA6 and in this polymer after passage through an extruder with a static mixer. A diblock or triblock amorphous structure and a crystalline portion in the studied PA6 were found. These amorphous structures differ in the glass transition temperatures by 80–180°C. There was a principal difference in the topological and molecular structures of PA6 depending on the processing conditions—number of cycles and shear rates. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2361–2368, 2001

Diblock amorphous topological structure of a filled vulcanizate network made of natural rubber (NR) and Emulsion Butadiene Rubber (EBR) was found. These blocks differ in the transition temperatures about 200°C. Dual transitions of such rubbers have been assigned as a motion of the mixed soft block [low glass transition temperature (Tg )] in the glassy state and the motion in elements of a network around physical and chemical crosslinking sites in a rigid block (high Tg ), respectively. Compaction of the topological structure of a high-temperature block during curing (manifested by the growth of Tg ) was noticed. The molecular weight distribution of the chains between the junctions of the network and shares of these amorphous blocks in the structure of the rubber network vs curing time were calculated using the methodology shown. Introduction of Perkalink 900 at constant quantity of sulfur changes a structure of the junctions in the tested rubber network from mixed (10–15% of chemical bonds, and remaining are cluster type and topological junctions) into practically all chemical bonds. Optimal curing time evaluated by the thermomechanical analysis, at which molecular structures formed in both blocks reflect the equilibrium state of adsorption layers of two rubbers introduced into the compound, is close to that evaluated by the vulcametric tests. The location of the molecular weight distribution curve in both blocks one against another depends on rubber formulation. Also, a fact that crosslinks are gathered, as was predicted by Vilgis and Heinrich calculations, was confirmed experimentally. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 732–742, 2000

A rubber compound containing butadiene rubber (BR), natural rubber (NR), and carbon black was investigated by thermomechanical analysis (TMA). A difference in dynamics of the formation of molecular and topological structures of a vulcanizate were found to be dependent on the mixing technology and curing time. Separation of the topological structure of cured rubber into two blocks with differing transition temperatures was visible after 20 min of vulcanization, when a share of a low-temperature block is minimal and &Mmacr;n(n) reaches a stable value of about 2400. A low-temperature block had a predominant concentration of covalent branching junctions, independent of the mixing procedures, whereas the high-temperature block had covalent and topological junctions in concentrations that were dependent on the mixing method. For curing times longer than 20 min, the characteristic changes in values of &Mmacr;n(n) are dependent on the procedure of rubber compound mixing. After additional homogenization of compounds and vulcanization, the rubbers are characterized by a diblock structure with the same qualitative structure of the branching junctions as for nonhomogenized ones. In some cases, the homogenization increases the relative concentration of the covalent junctions in the high-temperature block. When a preblend of BR and carbon black was prepared first, and then mixed with NR, this technology makes rubber compounds less sensitive to additional homogenization during further processing. A mechanism of creation and transformation of rubber–carbon black junctions during compounding and vulcanization of rubber compounds with two raw rubbers that differed in adsorption ability was proposed. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 660–669, 2000

Rubber compounds containing natural rubber (NR) filled with carbon black were investigated with the help of the thermomechanical method according to the procedure described in a previous article (Jurkowska et al. J Appl Polym Sci, in press). It was stated that NR filled with carbon black has two amorphous blocks differing in the transition temperatures and one pseudo-crystalline structure. A ratio of these morphology structures changes during mixing with carbon black depending on the carbon black content and mixing time. A crystalline structure has two or three temperatures characterizing the beginning of melting and the beginning of flow. This evidences its complex architecture. Vulcanized rubber of NR mixed with butadiene rubber (BR) in a ratio of 70/30, filled with carbon black, has two-block amorphous structure without a pseudo-crystalline structure. A dynamics of forming molecular and topological structures of vulcanizates depends on carbon black content. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3305–3315, 1999

Using thermomechanical spectroscopy, the molecular-weight distribution and relaxation transitions have been investigated in commercial LDPE and grafted by itaconic acid (LDPE-g-IA). This grafting in the molten LDPE was done by reactive extrusion with varied content of reactants in the blend under alternating of a shearing rate applied onto the melt. The dependence of structural relaxation changes in LDPE is shown upon the depth of the mechanochemical transformations and the competing reactions at IA grafting, and also on the chemical crosslinking of the macromolecules. The reason for MWD bimodality for LDPE-g-IA obtained in dynamic mixing is the raised homogenization degree of the reactive blend and the higher grafted product yield compared with static mixers. The mixer type substantially affects the structure of the LDPE-g-IA amorphous phase. The data obtained reflect chemical transformations of LDPE molecules in IA's presence without an initiator of radical reactions (DCP). Most probable is the IA initiation of molecular crosslinking reactions. There could also occur IA thermodegradation and oligomerization. LDPE and IA or products of acid chemical transformations do not agree thermodynamically (the calculated solubility parameters are 16.1 (MJ/m³)^0.5 for polyethylene and 26.4 (MJ/m³)^0.5 for IA). From the above procedure it can be supposed that nongrafted IA (or its oligomers) exerts an antiplastifying effect on LDPE and LDPE-g-IA. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1771–1779, 1999

A thermomechanical method was applied to study the topological and molecular structure of SKD butadiene rubber masticated and mixed with carbon black. Triblock structure (two amorphous blocks and one a pseudocrystalline structure) of a studied raw rubber and rubber compound networks were found. A ratio of these morphology structures changes during mastication. After mastication, a low-temperature block has two glass transition temperatures that shows its more complex structure than that in raw rubber. This shows deep transformations taking place during the mastication process. Despite applying high shear forces and heating during mixing with carbon black in a filled BR compound, we present three structures characteristic for BR. However, introduction of carbon black changes the topological structure of polybutadiene. A part of both amorphous blocks grows. A part of a crystalline structure lowers from 88% after 2.5 min of mixing to 54% after 20 min of compounding. The molecular weight distribution of the chains between the junctions of the network and parts of low-temperature and high-temperature amorphous blocks, and pseudocrystalline structures in architecture of the rubber network were also calculated. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 729–737, 1999

A novel method was applied to study the topological and molecular structures of multicomponent rubber. This method is based on the thermomechanical analysis of a solid polymer. A diblock amorphous structure was found for the studied rubber network. These blocks differ a great deal in their glass transition temperature. The methodology of how to calculate the crosslink density in each block, the molecular weight distribution of the chains between the junctions of the network, and the shares of low-temperature (soft) and high-temperature (hard) blocks in a structure of the rubber network were also shown. Based on these data it is possible to calculate the number-average and weight-average molecular weight and the polydispersity coefficients of the chains between the junctions of the network. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 490–501, 1999

Rotationally resolved infrared spectra of the ν1 and ν3 N−H stretching vibrations of the Ar−NH2⁺ radical ionic complex have been observed by means of photodissociation spectroscopy. The analysis of the rotational structure shows that the complex has a ³Σ^- ground electronic state with a linear or quasi-linear proton-bound structure Ar−H−N−H⁺ characterized by an intermolecular center of mass separation of 3.085 Å. The origins of the ν1 and ν3 bands were determined as 2803.65(2) and 3287.36(2) cm^-1, and the frequency of the intermolecular stretch vibration, νs, as 170.4(6) cm^-1. Ab initio calculations performed at the UMP2 level of theory confirm that the quasi-linearity and the diradical character of NH2⁺ in its electronic ground state are not changed upon Ar complexation. The calculated properties of the intermolecular bond of the complex (De = 1773 cm^-1, RAr-H ~ 2.01 Å, νs ~ 185 cm^-1) and the predicted complexation induced frequency shifts for ν1 and ν3 are in good agreement with the experimental results.

Infrared (IR) photodissociation spectra of mass selected Arn−HN2⁺ complexes (n = 1−13) have been recorded in the 4 μm spectral range in a tandem mass spectrometer. The dominant features are assigned to the ν1 + mνs (m = 1, 2) combination bands, where ν1 corresponds to the intramolecular N−H stretch mode and νs to the intermolecular stretching vibration of the first (proton-bound) Ar ligand. Systematic size-dependent complexation-induced frequency shifts and fragmentation branching ratios enabled the development of a consistent model for the cluster growth. The Ar−HN2⁺ dimer has a linear proton-bound structure and further Ar ligands fill two equatorial solvation rings around the linear dimer core, each of them containing up to five Ar atoms. The attachment of the 12th argon atom at the nitrogen end of HN2⁺ leads to the completion of the first solvation shell with an icosahedral structure. Weaker bands in the IR photodissociation spectra are attributed to less stable isomers. Comparison with previous studies of the related Arn−HOSi⁺ and Arn−HCO⁺ complexes reveals several similarities in the cluster growth. However, due to different charge distributions and anisotropies of the repulsive walls of the ionic cores, subtle differences occur in the order of shell filling as well as the occurrence and stability of isomeric structures. These differences are rationalized by two-dimensional intermolecular potential energy surfaces calculated at the MP2/aug-cc-pVTZ^# level of theory.