Direct Fabrication of Atomically Defined Pores in MXenes Using Feedback-Driven STEM.

Controlled fabrication of nanopores in 2D materials offer the means to create robust membranes needed for ion transport and nanofiltration. Techniques for creating nanopores have relied upon either plasma etching or direct irradiation; however, aberration-corrected scanning transmission electron microscopy (STEM) offers the advantage of combining a sub-Å sized electron beam for atomic manipulation along with atomic resolution imaging. Here, a method for automated nanopore fabrication is utilized with real-time atomic visualization to enhance the mechanistic understanding of beam-induced transformations. Additionally, an electron beam simulation technique, Electron-Beam Simulator (E-BeamSim) is developed to observe the atomic movements and interactions resulting from electron beam irradiation. Using the MXene Ti3C2Tx, the influence of temperature on nanopore fabrication is explored by tracking atomic transformations and find that at room temperature the electron beam irradiation induces random displacement and results in titanium pileups at the nanopore edge, which is confirmed by E-BeamSim. At elevated temperatures, after removal of the surface functional groups and with the increased mobility of atoms results in atomic transformations that lead to the selective removal of atoms layer by layer. This work can lead to the development of defect engineering techniques within functionalized MXene layers and other 2D materials.

Oxygen Vacancy Injection as a Pathway to Enhancing Electromechanical Response in Ferroelectrics.

Since their discovery in late 1940s, perovskite ferroelectric materials have become one of the central objects of condensed matter physics and materials science due to the broad spectrum of functional behaviors they exhibit, including electro-optical phenomena and strong electromechanical coupling. In such disordered materials, the static properties of defects such as oxygen vacancies are well explored but the dynamic effects are less understood. In this work, the first observation of enhanced electromechanical response in BaTiO3 thin films is reported driven via dynamic local oxygen vacancy control in piezoresponse force microscopy (PFM). A persistence in peizoelectricity past the bulk Curie temperature and an enhanced electromechanical response due to a created internal electric field that further enhances the intrinsic electrostriction are explicitly demonstrated. The findings are supported by a series of temperature dependent band excitation PFM in ultrahigh vacuum and a combination of modeling techniques including finite element modeling, reactive force field, and density functional theory. This study shows the pivotal role that dynamics of vacancies in complex oxides can play in determining functional properties and thus provides a new route toward- achieving enhanced ferroic response with higher functional temperature windows in ferroelectrics and other ferroic materials.

Machine Learning-Assisted Hybrid ReaxFF Simulations.

We have developed a machine learning (ML)-assisted Hybrid ReaxFF simulation method ("Hybrid/Reax"), which alternates reactive and non-reactive molecular dynamics simulations with the assistance of ML models to simulate phenomena that require longer time scales and/or larger systems than are typically accessible to ReaxFF. Hybrid/Reax uses a specialized tracking tool during the reactive simulations to further accelerate chemical reactions. Non-reactive simulations are used to equilibrate the system after the reactive simulation stage. ML models are used between reactive and non-reactive stages to predict non-reactive force field parameters of the system based on the updated bond topology. Hybrid/Reax simulation cycles can be continued until the desired chemical reactions are observed. As a case study, this method was used to study the cross-linking of a polyethylene (PE) matrix analogue (decane) with the cross-linking agent dicumyl peroxide (DCP). We were able to run relatively long simulations [>20 million molecular dynamics (MD) steps] on a small test system (4660 atoms) to simulate cross-linking reactions of PE in the presence of DCP. Starting with 80 PE molecules, more than half of them cross-linked by the end of the Hybrid/Reax cycles on a single Xeon processor in under 48 h. This simulation would take approximately 1 month if run with pure ReaxFF MD on the same machine.

Simulations of the Biodegradation of Citrate-Based Polymers for Artificial Scaffolds Using Accelerated Reactive Molecular Dynamics.

In this study, we investigate the reactivity and mechanical properties of poly(1,6-hexanediol-co-citric acid) via ReaxFF molecular dynamics simulations. We implement an accelerated scheme within the ReaxFF framework to study the hydrolysis reaction of the polymer which is provided with a sufficient amount of energy known as the restrain energy after a suitable pretransition-state configuration is obtained to overcome the activation energy barrier and the desired product is obtained. The validity of the ReaxFF force field is established by comparing the ReaxFF energy barriers of ester and ether hydrolysis with benchmark DFT values in the literature. We perform chemical and mechanical degradation of polymer chain bundles at 300 K. We find that ester hydrolyzes faster than ether because of the lower activation energy barrier of the reaction. The selectivity of the bond-boost scheme has been demonstrated by lowering the boost parameters of the accelerated simulation, which almost stops the ether hydrolysis. Mechanical degradation of prehydrolyzed and intermittent hydrolyzed polymer bundles is performed along the longitudinal direction at two different strain rates. We find that the tensile modulus of the polymers increases with increase in strain rates, which shows that polymers show a strain-dependent behavior. The tensile modulus of the polyester-ether is higher than polyester but reaches yield stress faster than polyester. This makes polyester more ductile than polyester-ether.

Understanding the influence of defects and surface chemistry on ferroelectric switching: a ReaxFF investigation of BaTiO3.

Ferroelectric materials such as barium titanate (BaTiO3) have a wide range of applications in nano scale electronic devices due to their outstanding properties. In this study, we developed an easily extendable atomistic ReaxFF reactive force field for BaTiO3 that can capture both its field- and temperature-induced ferroelectric hysteresis and corresponding changes due to surface chemistry and bulk defects. Using our force field, we were able to reproduce and explain a number of experimental observations: (1) the existence of a critical thickness of 4.8 nm below which ferroelectricity vanishes in BaTiO3; (2) migration and clustering of oxygen vacancies (OVs) in BaTiO3 and a reduction in the polarization and the Curie temperature due to the OVs; (3) domain wall interaction with the surface chemistry to influence the ferroelectric switching and polarization magnitude. This new computational tool opens up a wide range of possibilities for making predictions for realistic ferroelectric interfaces in energy-conversion, electronic and neuromorphic systems.

In situ atomistic insight into the growth mechanisms of single layer 2D transition metal carbides.

Developing strategies for atomic-scale controlled synthesis of new two-dimensional (2D) functional materials will directly impact their applications. Here, using in situ aberration-corrected scanning transmission electron microscopy, we obtain direct insight into the homoepitaxial Frank-van der Merwe atomic layer growth mechanism of TiC single adlayers synthesized on surfaces of Ti3C2 MXene substrates with the substrate being the source material. Activated by thermal exposure and electron-beam irradiation, hexagonal TiC single adlayers form on defunctionalized surfaces of Ti3C2 MXene at temperatures above 500 °C, generating new 2D materials Ti4C3 and Ti5C4. The growth mechanism for a single TiC adlayer and the energies that govern atom migration and diffusion are elucidated by comprehensive density functional theory and force-bias Monte Carlo/molecular dynamics simulations. This work could lead to the development of bottom-up synthesis methods using substrates terminated with similar hexagonal-metal surfaces, for controllable synthesis of larger-scale and higher quality single-layer transition metal carbides.

Evolution of methane density during melting in nanopores.

Phase properties of gases adsorbed in small nanopores are mainly determined by the pore size and shape as well as the structural heterogeneity of the adsorbate. Here we analyze the evolution of the melting mechanism that occurs in pores <3 nm in size. Melting in slit-shaped graphene pores is compared with melting in SURMOF channel pores with square cross-sections. We show how the melting transformation is related to the adsorption mechanism. We use a graphical representation of the evolution of molecular density as a function of temperature in the nanopores.

Heterogeneous melting of methane confined in nano-pores.

The melting transition of methane adsorbed in nanopores has been studied and compared in two types of structures: carbon slits pores and square shaped channels. We show that the nano-confinement not only modifies the temperatures of phase transformation but also induces strong space heterogeneity of the adsorbate. We emphasize the role of the structural heterogeneity on the mechanism of melting: in nanometric pores, each adsorbed layer exhibits different mechanisms of structural transformation and the notion of a unique transition temperature is not well defined.

Is mediastinoscopy still the gold standard to evaluate mediastinal lymph nodes in patients with non-small cell lung carcinoma?

OBJECTIVES: In this study, we aimed to define the efficacy of F-18 FDG PET/CT for the detection of mediastinal lymph node metastases by comparing the mediastinal findings of F-18 FDG PET/CT with the histopathological results obtained either by mediastinoscopy or thoracotomy in patients with clinically operable non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: This is a prospective, single-institution study of 68 consecutive patients with suspected or pathologically proven, localized, clinically resectable NSCLC (8 females and 60 males; mean age: 60.36 ± 1.01 years, range: 43-78 years). The patients underwent integrated PET/CT scanning at the same PET center. Standard cervical mediastinoscopy and extended mediastinoscopy were performed to sample the lymph nodes. During thoracotomy, complete mediastinal lymph node dissection was routinely performed. RESULTS: Mediastinoscopy gave true positive results in 9 patients and true negative results in 57 patients. There were two false negative results. Mediastinoscopy had a sensitivity of 81.8% (95% CI: 63-82), a specificity of 100% (95% CI: 96-100), a PPV of 100% (95% CI: 77-100), a NPV of 96.6% (95% CI: 93-96), and an accuracy of 97% for the detection of mediastinal lymph node metastases. When PET/CT results were compared with postoperative pathological examination results, PET/CT correctly identified 48 out of 50 patients (96%) who did not have metastatic lymph node involvement. N2/N3 disease was correctly determined by PET/CT in 8 of 11 patients (72.7%) who had positive results on histological analysis. When only N2 and N3 nodal diseases were included in the calculation with the aim of making a comparison with mediastinoscopy (for mediastinal nodes), integrated PET/CT had a sensitivity of 72.7% (95% CI: 51-80), a specificity of 97.7% (95% CI: 92-99), a PPV of 88.9% (95% CI: 62-97), a NPV of 93.3% (95% CI: 88-95) and an accuracy of 92.6% (95% 83-95) for the detection of intrathoracic N2 and N3 nodal metastases. CONCLUSION: Our data shows that due to its high sensitivity and accuracy, mediastinoscopy is still the most reliable method to evaluate mediastinal lymph nodes in patients with NSCLC.

Species diversity of ixodid ticks feeding on humans in Amasya, Turkey: seasonal abundance and presence of Crimean-Congo hemorrhagic fever virus.

Ticks (Acari:Ixodidae) are important pests transmitting tick-borne diseases such as Crimean-Congo hemorrhagic fever (CCHF) to humans. Between 2002 and 2009, numerous CCHF cases were reported in Turkey, including Amasya province. In the current study, species diversity, seasonal abundance of ticks, and presence of CCHF virus (CCHFV) in ticks infesting humans in several districts of Amasya province were determined. In the survey, a total of 2,528 ixodid ticks were collected from humans with tick bite from April to November 2008 and identified to species. Hyalomma marginatum (18.6%), Rhipicephalus bursa (10.3%), Rhipicephalus sanguineus (5.7%), Rhipicephalus (Boophilus) annulatus (2.2%), Dermacentor marginatus (2.5%), Haemaphysalis parva (3.6%), and Ixodes ricinus (1.6%) were the most prevalent species among 26 ixodid tick species infesting humans in Amasya province. Hyalomma franchinii Tonelli & Rondelli, 1932, was a new record for the tick fauna of Turkey. The most abundant species were the members of Hyalomma and Rhipicephalus through summer and declined in fall, whereas relative abundances of Ixodes and Dermacentor ticks were always low on humans in the province. Of 25 Hyalomma tick pools tested, seven pools were CCHFV positive by reverse transcription-polymerase chain reaction. Results indicated diversity of ixodid tick species infesting humans was very high, abundance of ticks changed by season, and ticks infesting humans had potential for transmitting CCHFV.

Apoptosis patterns in eutopic and ectopic endometrium, adhesions and normal-looking peritoneum from women with or without endometriosis.

OBJECTIVE: To assess the apoptosis rate in eutopic and ectopic endometrial stromal and glandular cells, normal peritoneum and adhesions in women with endometriosis. METHODS: A total number of 97 women with (n:60) and without (n:37) histopathologically confirmed endometriosis who underwent laparoscopy or laparotomy in the early follicular phase of the menstrual cycles for pain and infertility were included in this study. Stage I/II and stage III/IV were categorized as early staged and late-staged endometriosis. The endometrial samples were obtained with a Novack cannula from the corpus of the uterus. Normal-looking peritoneum, peritoneal implants and adhesions were sampled and fixed in formaldehyde for immunohistochemical staining with Bcl-2 and Bax. Tissue samples were fixed in formaldehyde for the assessment of apoptosis via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and M30 cytoDEATH antibody. RESULTS: The intensity of Bax staining of normal-looking peritoneum in early staged endometriosis was higher, compared to women with late-staged and women without endometriosis (P = 0.03). However, degree of Bcl-2 staining did not differ among early and late-staged endometriosis and women without endometriosis (P = 0.1). In terms of Bcl-2 and Bax staining in the stromal and glandular parts of the eutopic endometria, no significant differences were detected among three groups. In cases with early- and late-staged endometriosis the intensity of Bax and Bcl-2 stainings did not differ in both stromal and glandular parts of ectopic endometria. Number of cells with positive apoptotic signals assessed via TUNEL (P = 1.0) and M30 cytoDEATH antibody (P = 0.59) in normal-looking peritoneum did not differ between three groups. In addition, no difference in term of numbers of apoptotic cells obtained from adhesions was observed between three groups (for TUNEL, P = 0.29, for M30, P = 0.19). CONCLUSIONS: Apoptosis patterns did not differ in the eutopic and ectopic endometria as well as adhesions of women with or without endometriosis.

The significance and relationship between mast cells and tumour angiogenesis in non-small cell lung carcinoma.

This study investigated whether microvessel density (MVD) and mast cell infiltration are related to prognosis in non-small cell lung carcinoma (NSCLC), and examined the possible role of mast cells in NSCLC angiogenesis. MVD and mast cell infiltration were analysed retrospectively in tumour specimens from 50 patients with primary NSCLC. Immunohistochemistry with monoclonal antibody anti-CD34 was used to delineate the microvessels and routine Giemsa blue staining was used to assess the number of mast cells. Significant correlations were found between MVD and mast cell infiltration and between MVD and both lymph node metastasis and tumour, node, metastases (TNM) stage. No significant correlations were found with respect to survival for MVD or mast cell infiltration. Multivariate analysis showed that TNM stage and tumour size were independent predictors of survival, suggesting that the TNM staging system remains the most important tool for the estimation of prognosis in NSCLC patients.

Expression of proteins associated with cell-matrix adhesion in proliferative vitreoretinopathy designed by Dispase model.

PURPOSE: During recent years, the interaction of cell surface molecule, extracellular matrix proteins, and cytoskeletal elements has been a topic for research for the purpose of understanding the mechanisms of pathologic conditions. This study aims to evaluate the expression of CD44, as a cell surface adhesion molecule; fibronectin (FN), as an extracellular and a cell surface protein; vinculin and actin/á-smooth muscle actin (alfa-SMA), as cytoskeletal elements; and the interactions of these proteins in the microenvironment of proliferative vitreoretinopathy (PVR). METHODS: This experimental study was designed by the intravitreal Dispase model in rabbits and proteins' expression were evaluated via immunohistochemical staining. RESULTS: As a cell surface protein, CD44 expression was determined in only four eyes focally and weakly, but in a small number of cells. Among the cytoskeletal proteins, vinculin expression was the most extensive and the strongest in intensity in epi- and subretinal membranes. Alpha-SMA expression was mostly present within small foci of cells. Fibronectin expression was determined in some of the eyes only faintly. CONCLUSIONS: Vinculin seems to be involved in PVR pathogenesis. Variability in co-distribution of the expression of vinculin, FN, and alfa-SMA reflects the dynamic interactions evolving between cell and extracellular matrix during the epi- and subretinal membrane formations. The results of this study were determined not to be in support of the assumption that CD44 has a functional role in the pathogenesis of PVR.

Prognostic significance of fascin expression in endometrioid carcinoma.

PURPOSE OF INVESTIGATION: Actin bundling protein fascin has been previously associated with tumor progression in human cancers. We evaluated whether fascin also plays a role in endometrioid carcinomas. METHODS: Cases of 28 proliferative and hyperplastic endometrium and 43 endometrioid carcinomas were examined by immunohistochemistry using antihuman fascin antibody. RESULTS: Weak fascin expression in glandular epithelium was observed in 39% of non-neoplastic samples and various degrees of fascin expression were observed in 74% of neoplastic samples. The number of positively stained samples and intensity of epithelial staining were significantly higher in endometrioid carcinoma compared to the non-neoplastic group (p < 0.001). The number of positively stained samples and total fascin scores of stroma were significantly higher in proliferative and hyperplastic endometrium biopsies compared to the endometrioid carcinoma (p < 0.001). Higher grade endometrioid carcinoma cases had significantly increased total epithelial fascin scores (.042, p < 0.05). There was also a significant difference between tumor grade and patient survival (.040, p < 0.05). There was a significant correlation between microvessel count and disease-free survival (r = .412, p = .006). In the proliferative and hyperplastic endometrial biopsies microvessels stained homogeneously in all cases (28/28), but in the endometrioid carcinoma group eight out of 43 cases showed heterogeneous fascin staining of microvessels. The difference was significant (.019, p < 0.05). CONCLUSIONS: Our study supported the dynamic role of actin bundling protein fascin in generating and maintaining endometrial neoplasms. It also showed that in the development of neoplasia, stromal fascin expression decreases but epithelial fascin expression up-regulates.

Computed tomography findings of primary serous papillary carcinoma of the peritoneum in women.

With the aim to describe preoperative computed tomography (CT) findings, the clinical, histopathological, and CT findings of the 12 consecutive patients with a confirmed diagnosis of primary peritoneal serous papillary carcinoma (PPSPC) were retrospectively evaluated. Of the 12 patients with a mean age of 57.5 +/- 10.3 years, ten (83.3%) were postmenopausal. Serum Ca-125 levels were elevated in all patients. Ten (83.3%) had Stage III and two (16.7%) patients had Stage IV disease and none of the excised ovaries had deep parenchymal involvement. The most common CT findings were the omental (n = 11), mesenterial (n = 11) and parietal peritoneal involvements (n = 10), and variable amount of ascites (n = 10). Pelvic peritoneal involvement in four (33.3%) patients was so extensive that it resembled a mass in the Douglas pouch. Thickening of the wall of gastrointestinal viscera (n = 9), lymphadenopathy (n = 5) and pleural effusion (n = 5) were the other CT findings and calcification was seen in only three (25.0%) patients. Although, none of them was characteristic, CT features of diffuse peritoneal, omental and mesenterial involvement especially in middle-aged or elderly postmenopausal women with normal-size ovaries in the absence of an identifiable primary site in conjunction with elevated level of serum CA-125 should suggest the possibility of PPSPC.

Bcl-2 expression in preinvasive and invasive cervical lesions.

PURPOSE: To determine the correlation between bcl-2 expression and clinicopathological findings in cervical intraepithelial neoplasias (CIN I, II, III) and invasive cervical lesions, and its effect on overall survival rate. METHODS: Fifty specimens derived from 22 preinvasive and invasive cervical cancer cases up to surgical stage IIb (21 squamous cervical carcinoma and 7 adenocarcinoma cases) were preserved in paraffin blocks from primary surgery and constituted the study group. Tissues were processed and stained by immunohistochemical methods to assess the degree of bcl-2 expression. RESULTS: Positive bcl-2 expression was detected in 54% (13/21) of invasive lesions, while negative in 46% of cases. In CIN's, overall bcl-2 positivity was detected in 68% of cases. Bcl-2 expression was highly relevant between low grade (CIN I) and high grade (CIN II-III) lesions (p < 0.05). As regards degree of tissue staining for bcl-2 in CIN III cases, a statistically relevant difference was detected in comparison with low-grade preinvasive lesions (p < 0.05). In invasive cervical cancer cases, patients with bcl-2 positivity had a longer survival rate. By using the Cox regression model, univariate analysis did not show any specific prognostic factor to be important for survival rate, whereas, on multivariate analysis, histopathologic subtypes (p = 0.0390) and stage of tumor (p = 0.0451) had a statistically significant impact on overall survival rate. CONCLUSIONS: Bcl-2 expression, especially in preinvasive lesions, may play a role in the apoptotic process and be regarded as a marker for disease progression. In invasive cervical carcinomas, bcl-2 expression has not been shown to be effective in overall survival rates.

The significance of local cellular immune response of women 50 years of age and younger with endometrial carcinoma.

OBJECTIVE: Local cellular immune response and traditional histopathologic parameters in endometrial carcinoma patients 50 years old and younger were compared with those of patients older than 50 years of age. MATERIALS AND METHODS: We retrospectively compared the clinicopathologic factors and outcomes of 24 younger and 82 older women who were operated on for endometrioid type endometrial carcinoma at our institution. RESULTS: No significant difference was determined in survival with respect to age and menopausal status in patients with endometrial carcinoma. Younger and older age groups had a similar distribution of most pathologic features including myometrial invasion, cervical involvement, lymph node metastasis, vascular invasion, perivascular lymphocytic infiltrates and tumor infiltrating lymphocytes. While older women had higher-grade tumors, younger women had more frequent ovarian metastasis. Tumor infilrating lymphocytes were seen more frequently in the postmenopausal group than those of the premenopausal group. CONCLUSION: The distribution of local cellular immune response, most histopathologic parameters and survival were the same for younger and older women.

Calciphylaxis in a patient with rheumatoid arthritis without renal failure and hyperparathyroidism: the possible role of long-term steroid use and protein S deficiency.

Calciphylaxis is a rare and life-threatening condition of progressive cutaneous necrosis secondary to small and medium-sized vessel calcification that is seen almost exclusively in patients with end-stage renal disease and hyperparathyroidism. We report a case of calciphylaxis that may very well be due to a long-term steroid use in a rheumatoid arthritis patient who had neither end-stage renal disease nor hyperparathyroidism. We also discuss the possible role of protein S deficiency as a contributing factor.

Intrathyroidal water-clear cell parathyroid adenoma: a case report.

Adenomas of the parathyroid gland, the majority of which contain mixed cell populations, are the most frequent cause of primary hyperparathyroidism. Parathyroid adenomas composed exclusively of water-clear cells are exceptionally rare. Until now, only 2 cases have been reported in English literature. We report a water-clear cell adenoma of the parathyroid gland in an intrathyroidal position, which has not been described previously according to our knowledge.

Cerebral blood flow alterations in progressive communicating hydrocephalus: transcranial Doppler ultrasonography assessment in an experimental model.

OBJECT: In many cases communicating hydrocephalus is the result of impairments in cerebrospinal fluid absorption in the arachnoid villi at the cranial convexity. Reported methods of creating experimental hydrocephalus have not sought to produce an arachnoidal adhesion in the cranial convexity. In this study the authors investigate alterations in cerebral blood flow (CBF) in experimental communicating hydrocephalus induced by the injection of kaolin into the subarachnoid space at the convexity in neonatal rats. METHODS: In neonatal rats, kaolin was injected into the subarachnoid space at the cranial convexity. Assessment of CBF alterations was performed using transcranial Doppler ultrasonography preinjection and at 10 days, 4 weeks, and 8 weeks postinjection. Light microscopy examination was also performed at 4 weeks and 8 weeks postinjection. Conspicuous lateral ventricle enlargements of different dimensions were observed in kaolin-injected rats at 4 to 8 weeks postinjection. The third and fourth ventricles were dilated to a lesser extent. Resistance to CBF and increased mean CBF velocity were apparent 8 weeks after kaolin injection. Further, destruction and even loss of ependymal layers were more prominent at the chronic stage. CONCLUSIONS: The present model may be considered a progressive communicating hydrocephalus because of marked changes in blood flow dynamics and destruction of the ependymal layer at the chronic stage.