Determinants of Mortality and Mid-Term Outcomes After Transcarotid Artery Revascularization and Transfemoral Carotid Artery Stenting.

OBJECTIVES: The potential benefit of transcarotid artery revascularization (TCAR) over transfemoral carotid artery stenting (tfCAS) has been studied in the perioperative period with lower rates of stroke and death; however, data on mid-term outcomes are limited. We aimed to evaluate 3-year outcomes after TCAR and tfCAS and determine the primary predictors of 30-day and 1-year mortality following TCAR. METHODS: Data from the Vascular Quality Initiative for patients undergoing TCAR or tfCAS from January 2016 to December 2022 were analyzed. 1:1 propensity score matching using the nearest-neighbor method was used to adjust baseline demographics and clinical characteristics. Kaplan-Meier survival analysis and Cox Proportional Hazard Regression were used to evaluate long-term outcomes. Iterative stepwise multiple logistic regression analysis and Cox Proportional Hazard Regression were used to identify predictors of 30-day and 1-year mortality, respectively, based upon preoperative, intraoperative, and postoperative factors. RESULTS: A total of 70 237 patients were included in analysis (TCAR=58.7%, tfCAS=41.3%). Transcarotid artery revascularization patients were older and had higher rates of comorbid conditions and high-risk medical and anatomic features than tfCAS patients. Propensity score matching yielded 22 322 pairs with no major differences between groups except that TCAR patients were older (71.6 years vs 70.8 years). At 3 years, TCAR was associated with a 24% reduction in hazard of death compared with tfCAS (hazard ratio [HR]=0.76, 95% confidence interval [CI]=0.71-0.82, p<0.001), for both symptomatic and asymptomatic patients. This survival advantage was established in the first 6 months (HR=0.59, 95% CI=0.53-0.62, p<0.001), with no difference in mortality risk from 6 months to 36 months (HR=0.95, 95% CI=0.86-1.05, p=0.31). Transcarotid artery revascularization was also associated with decreased hazard for 3-year stroke (HR=0.81, 95% CI=0.66-0.99, p=0.04) and stroke or death (HR=0.81, 95% CI=0.76-0.87, p<0.001) compared with tfCAS. The top predictors for 30-day and 1-year mortality were postoperative complications. The primary independent predictor was the occurrence of postoperative stroke. CONCLUSIONS: Transcarotid artery revascularization had a sustained mid-term survival advantage associated over tfCAS, with the benefit being established primarily within the first 6 months. Notably, our findings highlight the importance of postoperative stroke as the primary independent predictor for 30-day and 1-year mortal. CLINICAL IMPACT: The ongoing debate over the superiority of TCAR compared to tfCAS and CEA has been limited by a lack of comparative studies examining the impact of pre-operative symptoms on outcomes. Furthermore, data are scarce on mid-term outcomes for TCAR beyond the perioperative period. As a result, it remains uncertain whether the initial benefits of stroke and death reduction observed with TCAR over tfCAS persist beyond one year. Our study addresses these gaps in the literature, offering evidence to enable clinicians to assess the efficacy of TCAR for up to three years. Additionally, our study seeks to identify risk factors for postoperative mortality following TCAR, facilitating optimal patient stratification.

External iliac vein dimensions can change after placement of a more proximal iliac vein stent.

OBJECTIVE: We have occasionally observed during vein stenting for proximal iliac vein stenosis, the appearance of a more distal stenosis in the iliac vein that had not been initially observed before placement of the more proximal vein stent. In the present retrospective study, we aimed to document this observation. METHODS: We identified patients in whom changes in the area measurement and linear dimensions of the external iliac vein (EIV) were observed on venography and/or intravascular ultrasound (IVUS) after stent placement for chronic nonthrombotic iliac stenosis in the common iliac vein (CIV). The images of these IVUS scans were subsequently analyzed to determine the cross-sectional area, major axis, and minor axis measurements in the EIV, before and after placement of a proximal CIV stent. RESULTS: A total of 32 limbs with complete and quality IVUS and venography images available that allowed for measurement of the EIV before and after vein stent placement in the CIV were evaluated. The patient cohort was 55% men, with a mean age of 63.8 ± 9.9 years and a mean body mass index of 27.8 ± 7.8 kg/m2. Of the 32 limbs, 18 were left sided and 14 were right sided. Most (n = 12 [60%]) of the limbs had presented with venous-related skin changes (C4 disease). The remainder of the cohort had had active (C6 disease; n = 4 [20%]) or recently healed (C5 disease; n = 1 [5%]) venous ulceration and isolated venous-related edema (C3; n = 3 [15%]). The minimal CIV area before and after CIV stenting was 28.47 ± 23.53 mm2 and 196.34 ± 42.62 mm2, respectively. The minimal mean EIV cross-sectional area before and after CIV stenting was 87.44 ± 38.55 mm2 and 50.69 ± 24.32 mm2, respectively, a statistically significant reduction of 36.75 mm2 (P < .001). The mean EIV major axis and minor axis had both decreased similarly. The minimal mean EIV major axis before and after CIV stenting was 15.22 ± 3.13 mm and 11.13 ± 3.58 mm, respectively (P < .001). The minimal mean EIV minor axis before and after CIV stenting was 7.26 ± 2.40 mm and 5.84 ± 1.42 mm, respectively (P < .001). CONCLUSIONS: The results from the present study have shown that the dimensions of the EIV can change significantly after placement of a proximal CIV stent. Possible explanations include masked stenosis due to distal venous distention resulting from the more proximal stenosis, vascular spasm, and anisotropy. The presence of proximal CIV stenosis can potentially lessen the appearance, or completely mask the presence, of an EIV stenosis. This phenomenon appears unique to venous stenting, and the prevalence is unknown. These findings underscore the importance of completion IVUS and venography after venous stent placement.

Women are Not at Higher Risk for Reintervention or Major Amputation after Lower Extremity Atherectomy for Peripheral Artery Disease.

BACKGROUND: Our objective was to compare short-term and long-term differences in reintervention-free and major amputation-free survival between female and male patients undergoing lower extremity atherectomy for peripheral artery disease. METHODS: We analyzed lower extremity atherectomy procedures performed on 294 patients between January 2014 and September 2019. Reintervention was defined as either open bypass or endovascular procedure to the same region following the index operation. Kaplan-Meier (KM) survival analysis was performed to compare reintervention-free and major amputation-free survival between sexes. Multivariate logistic regression analyses were performed to determine the adjusted odds of reintervention and major amputation based on sex. We conducted subgroup analyses by anatomic region (femoropopliteal vs. tibial), indication (claudication vs. chronic limb-threatening ischemia (CLTI)), and balloon type (drug-coated balloon (DCB) versus plain balloon angioplasty (POBA)) across sexes. RESULTS: Of the 294 patients, 125 (42.5%) were female. Compared to men, women receiving atherectomy were more likely to be Black (28.0% vs. 16.6%; P = 0.018), a nonsmoker (44.8% vs. 21.3%; P < 0.001), and present with CLTI (55.2% vs. 43.2%; P = 0.042). There were no differences in atherectomy region, lesion type, or balloon type between sexes. KM analysis showed similar 4-year reintervention-free survival (68.8% vs. 75.1%; P = 0.88) and major amputation-free survival (97.6% vs. 97.6%; P = 0.41) between sexes. Women and men had similar reintervention-free survival when grouped by femoropopliteal (67.9% vs. 70.8%; P = 0.69) or tibial (76.2% vs. 83.9%; P = 0.68) atherectomy region. Indication (claudication versus CLTI) did not affect reintervention-free survival in either women (64.5% vs. 69.6%; P = 0.28) or men (68.5% vs. 76.7%; P = 0.84). KM curves for DCB versus POBA were also similar between sexes and showed an early benefit in reintervention rate favoring DCB, which dissipated in both women (65.4% vs. 72.7%; P = 0.61) and men (75.5% vs. 78.4%; P = 0.18) by 3 years. CONCLUSIONS: Compared to men, women demonstrate commensurate benefit from atherectomy for lower extremity revascularization. There were no differences seen in long-term reintervention or major amputation between sexes.

Race differences in iliofemoral vein stenting for chronic venous insufficiency.

INTRODUCTION: Major disparities in outcomes by race are present throughout vascular surgery, yet little has been published on iliac vein stent outcomes by race. This retrospective study assessed iliac vein stent outcomes by patient race. METHODS: Patients who underwent iliac vein stenting at a single institution for chronic venous insufficiency (CVI) from 2011 to 2021 were reviewed. Demographic, preoperative, perioperative, and postoperative data were collected. Self-reported race groups included Asian, Black, Hispanic, and White. Univariate differences were analyzed using χ2 tests for categorical variables and 1-way ANOVA for continuous variables. Outcomes included change in Venous Clinical Severity Score (VCSS) at interval timepoints relative to a preoperative baseline and reinterventions. Logistic regression models were used to determine the unadjusted and adjusted odds ratio (OR) of any minor and major reintervention. Multivariate regression models controlled for demographic and comorbidity characteristics. RESULTS: A total of 827 patients were included. Asian patients were younger and had a greater proportion of male patients, lower Body mass index (BMI), less smoking history, and fewer comorbidities. White patients were more likely to have a history of deep vein thrombosis (DVT). White patients presented with the most severe CVI symptoms as defined by both Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification and preoperative VCSS composite scores. There were no differences in acute DVT, number of stents deployed, and bilateral versus unilateral stent placement. Black patients had the longest average days of follow-up, followed sequentially by Hispanic, White, and Asian. Black patients had the most reinterventions, while Asian patients had the fewest. Asian patients were less likely to have a major reintervention. No differences in VCSS composite or change in VCSS were observed. CONCLUSIONS: In patients with CVI, Asian patients presented younger and healthier, while White patients presented with the most severe symptoms. No differences were observed in VCSS outcomes, though Black patients had the most reinterventions.

Mechanochemical ablation as an alternative to venous ulcer healing compared with thermal ablation.

OBJECTIVE: We aimed to compare mechanochemical ablation (MOCA) and thermal ablation (radiofrequency ablation and endovenous laser therapy) for venous ulcer healing in patients with clinical class 6 chronic venous insufficiency. METHODS: Electronic medical records were reviewed of patients with venous ulcers who underwent truncal or perforator ablation between February 2012 and November 2015. These records contained history of venous disease and ulcer history, procedures, complications, follow-up, method of wound care, and current status of the ulcer. The patients were grouped according to the method of ablation for comparison. RESULTS: In 66 patients, 82 venous segments were treated, 29 with thermal methods and 53 with MOCA; 16% of patients had prior venous intervention. Before ablation, three patients in the thermal group had a history of deep venous thrombosis compared with seven in the MOCA group. On average, patients treated with MOCA were older (thermal ablation, 57.2 years; MOCA, 67.9 years; P = .0003). Ulcer duration before intervention ranged from 9.2 months for thermal ablation to 11.2 months for MOCA (P = NS). In total, 74% of patients treated with MOCA healed their ulcers compared with 35% of those treated with thermal ablation (P = .01). A healed ulcer was defined as elimination of ulcer depth and superficial skin coverage. The mean time to heal was 4.4 months in the thermal ablation group compared with 2.3 months with MOCA (P = .01). The mean length of follow-up was 12.8 months after thermal ablation and 7.9 months after MOCA (P = .02). Both age (P = .03) and treatment modality (P = .03) independently had an impact on ulcer healing on multiple logistic regression analysis. All but two patients were treated with an Unna boot after venous ablation. Complications included readmission of two patients with nonaccess-related infections, one nonocclusive deep venous thrombosis, and one late death unrelated to the procedure second to pneumonia in the setting of advanced colon cancer. There were three recurrent ulcers at 1 week, 2 months, and 7 months after MOCA that rehealed with Unna boot therapy and continued compression. CONCLUSIONS: MOCA is safe and effective in treating chronic venous ulcers and appears to provide comparable results to methods that rely on thermal ablation. Younger age and use of MOCA favored wound healing. MOCA was an independent predictor of ulcer healing. Randomized studies are necessary to further support our findings.

Activity, Selectivity, and Durability of Ruthenium Nanoparticle Catalysts for Ammonia Synthesis by Reactive Molecular Dynamics Simulation: The Size Effect.

We report a molecular dynamics (MD) simulation employing the reactive force field (ReaxFF), developed from various first-principles calculations in this study, on ammonia (NH3) synthesis from nitrogen (N2) and hydrogen (H2) gases over Ru nanoparticle (NP) catalysts. Using ReaxFF-MD simulations, we predict not only the activities and selectivities but also the durabilities of the nanocatalysts and discuss the size effect and process conditions (temperature and pressure). Among the NPs (diameter = 3, 4, 5, and 10 nm) considered in this study, the 4 nm NPs show the highest activity, in contrast to our intuition that the smallest NP should provide the highest activity, as it has the highest surface area. In addition, the best selectivity is observed with the 10 nm NPs. The activity and selectivity are mainly determined by the hcp, fcc, and top sites on the Ru NP surface, which depend on the NP size. Moreover, the selectivity can be improved more significantly by increasing the H2 pressure than by increasing the N2 pressure. The durability of the NPs can be determined by the mean stress and the stress concentration, and these two factors have a trade-off relationship with the NP size. In other words, as the NP size increases, its mean stress decreases, whereas the stress concentration simultaneously increases. Because of these two effects, the best durability is found with the 5 nm NPs, which is also in contrast to our intuition that larger NPs should show better durability. We expect that ReaxFF-MD simulations, along with first-principles calculations, could be a useful tool in developing novel catalysts and understanding catalytic reactions.

Atomistic Simulation Derived Insight on the Irreversible Structural Changes of Si Electrode during Fast and Slow Delithiation.

Quantifying the irreversible chemical and structural changes of Si during cycling remains challenging. In this study, a continuous reactive molecular dynamics delithiation algorithm, with well-controlled potential gradient and delithiation rate, was developed and used to investigate the "natural" delithiation responses of an aluminum-oxide coated silicon thin-film. Fast delithiation led to the formation of dense Si network near the surface and nanoporosity inside the a-LixSi, resulting in 141% volume dilation and significant amount of Li trapped inside (a-Li1.2Si) at the end of delithiation process. In contrast, slow delithiation allowed the a-LixSi to shrink by near-equilibrium condition, demonstrating no permanent inner pore with nearly Li-free structure (a-Li0.2Si) and minimal volume dilation (44%). However, even without trapped Li, the delithiated a-LixSi still exhibited higher volume (lower density) than the equilibrium structure with the same Li concentration, despite delithiation rate. The origin of this excess volume is the loss of directly bonded Si-Si pairs, which made the subsequent relithiation faster. On the basis of the atomistic modeling and the quantified degradation mechanism, battery operating guidelines, including the delithiation rate and the depth of charge to avoid trapped Li and coating delamination, were suggested to improve the durability Si electrodes.

Comparison of the Effects of Ultrasound-Guided Interfascial Pulsed Radiofrequency and Ultrasound-Guided Interfascial Injection on Myofascial Pain Syndrome of the Gastrocnemius.

OBJECTIVE: To investigate the comparative treatment effects of ultrasound-guided pulsed radiofrequency treatment (UG-PRF) in the gastrocnemius interfascial space and ultrasound-guided interfascial injection (UG-INJ) on myofascial pain syndrome. METHODS: Forty consecutive patients with myofascial pain syndrome of the gastrocnemius were enrolled and were allocated to one of the two groups. Twenty patients were treated by UG-PRF delivered to the gastrocnemius interfascial space (UG-PRF group) and the other 20 patients were treated by interfascial injection (UG-INJ group). The primary outcome measure was the numeric rating score (NRS) for pain on pressing the tender point in the gastrocnemius, and the secondary outcome measure was health-related quality of life as determined by the Short Form-36 questionnaire (SF-36). NRSs were obtained at the first visit, immediately after treatment, and at 2 and 4 weeks post-treatment, and physical component summary scores (PCS) and mental component summary scores (MCS) of the SF-36 questionnaire were measured at the first visit and at 4 weeks post-treatment. RESULTS: Immediately after treatments, mean NRS in the UG-PRF group was significantly higher than that in the UG-INJ group (p<0.0001). However, at 2 and 4 weeks post-treatment, the mean NRS was significantly lower in the UG-PRF group (both p<0.0001). Similarly, at 4 weeks post-treatment, mean PCS and MCS were significantly higher in the UG-PRF group (p<0.0001 and p=0.002, respectively). CONCLUSION: Based on these results, the authors conclude that ultrasound-guided gastrocnemius interfascial PRF provides an attractive treatment for myofascial pain syndrome of the gastrocnemius.

The Effect of Age on Post-EVAR Outcomes.

BACKGROUND: This study aims to investigate the relationship of increased age on post-endovascular aneurysm repair (EVAR) outcomes. METHODS: A total of 1,380 of 1,853 consecutive patients who underwent EVAR between 1992 and 2012 met our inclusion criteria and were reviewed. Five hundred of the 1,380 patients had computed tomography angiography data to characterize anatomic differences. Age <70 years and ≥70 years were compared. RESULTS: Older patients had higher Glasgow Aneurysm Scores (85.8 ± 8.2 vs. 70.9 ± 8.5, P < 0.0001), indicating higher preoperative risk in patients ≥70 years of age. Patients ≥70 years had increased tortuosity indices, angulation, and iliac calcification. Older patients required higher transfusion volumes (101.1 ± 266.8 vs. 57.6 ± 202.6 mL, P = 0.018). Overall comorbidities, blood loss, and procedure times were similar between groups. The older cohort had higher major and minor perioperative complication rates (10.7% vs. 7.0%, P = 0.007), with a trend toward more major perioperative complications (7.5% vs. 4.8%, P = 0.077). AAA-related perioperative mortality, all-cause perioperative mortality, and intraoperative complication rates were similar between the 2 cohorts. Patients <70 years were more likely to be discharged on postoperative day 1 (76.1% vs. 67.6%, P < 0.0001). Older patients were more likely to develop endoleaks (21.9% vs. 12.8%, P < 0.0001) and required more reinterventions (7.2% vs. 4.7%, P = 0.003). Freedom from AAA-related mortality was similar between the 2 groups (P = nonsignificant); however, patients <70 years had improved overall survival (P < 0.001). CONCLUSIONS: Older age is associated with more complex aneurysm morphology. These features likely resulted in more endoleaks, reinterventions, and complications observed in patients ≥70 years following EVAR.

Atomic Insight into the Lithium Storage and Diffusion Mechanism of SiO2/Al2O3 Electrodes of Lithium Ion Batteries: ReaxFF Reactive Force Field Modeling.

Atomically deposited layers of SiO2 and Al2O3 have been recognized as promising coating materials to buffer the volumetric expansion and capacity retention upon the chemo-mechanical cycling of the nanostructured silicon- (Si-) based electrodes. Furthermore, silica (SiO2) is known as a promising candidate for the anode of next-generation lithium ion batteries (LIBs) due to its superior specific charge capacity and low discharge potential similar to Si anodes. In order to describe Li-transport in mixed silica/alumina/silicon systems we developed a ReaxFF potential for Li-Si-O-Al interactions. Using this potential, a series of hybrid grand canonical Monte Carlo (GCMC) and molecular dynamic (MD) simulations were carried out to probe the lithiation behavior of silica structures. The Li transport through both crystalline and amorphous silica was evaluated using the newly optimized force field. The anisotropic diffusivity of Li in crystalline silica cases is demonstrated. The ReaxFF diffusion study also verifies the transferability of the new force field from crystalline to amorphous phases. Our simulation results indicates the capability of the developed force field to examine the energetics and kinetics of lithiation as well as Li transportation within the crystalline/amorphous silica and alumina phases and provide a fundamental understanding on the lithiation reactions involved in the Si electrodes covered by silica/alumina coating layers.

Injury of the Corticospinal Tract in Patients with Mild Traumatic Brain Injury: A Diffusion Tensor Tractography Study.

Motor weakness is an important sequela after traumatic brain injury (TBI). Although the majority of cases of TBI are classified as mild TBI, little is known about motor weakness in mild TBI. In this study, we attempted to investigate injury of the corticospinal tract (CST), an important neural tract for motor function, in patients with mild TBI, using diffusion tensor tractography (DTT). There were 53 patients with mild TBI and 36 control subjects who were recruited. The patients were assigned to two groups according to the presence of abnormality of the right (dominant) hand function in terms of fine motor activity and grip strength: group A-abnormal hand function, group B-normal hand function. The left CST was reconstructed, and DTT parameters (fractional anisotropy [FA] and fiber number) and configuration were estimated. There were 35 (66%) patients who had an abnormal function of the right hand. The values of FA and fiber number of patient group A were significantly lower than those of patient group B and the control group (p < 0.001). On configurational analysis of DTT for the left CST in patient group A, 80% showed partial tearing at the subcortical white matter and 20% showed narrowing. We found that in terms of DTT parameters and configuration, a significant portion of patients with mild TBI showed injury of the CST. These results suggest that DTT could provide useful information in detecting injury of the CST, and evaluation of the CST using DTT would be necessary for patients who complain of hand weakness after mild TBI.

Self-generated concentration and modulus gradient coating design to protect Si nano-wire electrodes during lithiation.

Surface coatings as artificial solid electrolyte interphases have been actively pursued as an effective way to improve the cycle efficiency of nanostructured Si electrodes for high energy density lithium ion batteries, where the mechanical stability of the surface coatings on Si is as critical as Si itself. However, the chemical composition and mechanical property change of coating materials during the lithiation and delithiation process imposed a grand challenge to design coating/Si nanostructure as an integrated electrode system. In our work, we first developed reactive force field (ReaxFF) parameters for Li-Si-Al-O materials to simulate the lithiation process of Si-core/Al2O3-shell and Si-core/SiO2-shell nanostructures. With reactive dynamics simulations, we were able to simultaneously track and correlate the lithiation rate, compositional change, mechanical property evolution, stress distributions, and fracture. A new mechanics model based on these varying properties was developed to determine how to stabilize the coating with a critical size ratio. Furthermore, we discovered that the self-accelerating Li diffusion in Al2O3 coating forms a well-defined Li concentration gradient, leading to an elastic modulus gradient, which effectively avoids local stress concentration and mitigates crack propagation. Based on these results, we propose a modulus gradient coating, softer outside, harder inside, as the most efficient coating to protect the Si electrode surface and improve its current efficiency.

The impact of sex on angioplasty and primary stenting for femoropopliteal occlusive disease: results of the DURABILITY II trial.

BACKGROUND: This study investigates the impact of sex on angioplasty and primary stenting for the treatment of claudicants with femoropopliteal occlusive disease (FPOD). METHODS: Two hundred eighty-seven patients enrolled in the Safety and Effectiveness Study of EverFlex Stent to Treat Symptomatic Femoral-popliteal Atherosclerosis (DURABILITY II) trial (a prospective, nonrandomized, core laboratory audited, and independently adjudicated investigational device exemption trial) were stratified by sex (190 men and 97 women) and reviewed. RESULTS: Women presented with FPOD at an older age than men (71.3 ± 11.2 vs. 65.9 ± 9.9 years; P < 0.001). Men were more likely to be hyperlipidemic (89.5% vs. 79.4%; P = 0.030). No other statistically significant differences were observed with regard to periprocedural comorbidities and demographics. Clinically, women presented more often with severe claudication (64.9% vs. 51.1%; P = 0.033) as compared with men that had more moderate claudication (44.2% vs. 29.9%; P = 0.022). The incidence of rest pain and tissue loss was low and did not vary between sexes. Angiographically, women had smaller reference vessels (4.4 ± 0.8 mm vs. 5.0 ± 0.9 mm; P < 0.001). Longer lesions (91.6 ± 46.8 mm vs. 87.8 ± 43.9 mm) and higher primary (79.0% vs. 76.5%), primary-assisted (90.6% vs. 85.1%), and secondary patency (90.6% vs. 85.7%) rates in women did not achieve statistical significance (P = NS). Mean percent stenosis and occlusion rates were similar between groups, but men were more likely to have severe calcification (47.9% vs. 34.0%; P = 0.020). Inter-Society Consensus for the Management of Peripheral Arterial Disease II classifications were similar between groups. The target lesion revascularization, major adverse event, and mortality rates were similar between groups. At baseline, the absolute claudication distance was 0.29 miles for men, while women only reached 0.14 miles (P < 0.0001). Walking improvement questionnaire scores were also compared; women had significantly lower scores at baseline and at 1 year. CONCLUSIONS: Despite presenting with FPOD at a later age, with more severe claudication, a shorter absolute claudication distance, and smaller vessels than men, women achieved equal patency rates using angioplasty and primary stenting with similar target lesion revascularization, major adverse event, and mortality rates. Despite these findings, women subjectively have worse symptoms at baseline and at 1 year.

Simulation of titanium metal/titanium dioxide etching with chlorine and hydrogen chloride gases using the ReaxFF reactive force field.

In this study, a new ReaxFF reactive force field has been developed to describe reactions in Ti/O/Cl/H materials. This force field was applied to etching simulations for titanium metal and titanium dioxide with chlorine and hydrogen chloride gases. The ReaxFF force field parameters are fitted against a quantum mechanical (QM) training set containing structures and energies related to bond dissociations, angle and dihedral distortions, and reactions between titanium and chlorine gases as well as heats of formation of TiClx crystals. These newly developed Ti-Cl force field parameters were combined with a recently developed Ti-O-H force field. ReaxFF accurately reproduces the QM training set for structures and energetics of small clusters and TiClx crystals. In the etching simulations, titanium and titanium dioxide slab models with chlorine and hydrogen chloride gases were used in molecular dynamics simulations. The etching ratio between HCl and Cl2 are compared to experimental results, and satisfactory results are obtained, indicating that this ReaxFF extension provides a useful tool for studying the atomistic-scale details of the etching process.

Development of a ReaxFF reactive force field for titanium dioxide/water systems.

A new ReaxFF reactive force field has been developed to describe reactions in the Ti-O-H system. The ReaxFF force field parameters have been fitted to a quantum mechanical (QM) training set containing structures and energies related to bond dissociation energies, angle and dihedral distortions, and reactions between water and titanium dioxide, as well as experimental crystal structures, heats of formation, and bulk modulus data. Model configurations for the training set were based on DFT calculations on molecular clusters and periodic systems (both bulk crystals and surfaces). ReaxFF reproduces accurately the QM training set for structures and energetics of small clusters. ReaxFF also describes the relative energetics for rutile, brookite, and anatase. The results of ReaxFF match reasonably well with those of QM for water binding energies, surface energies, and H2O dissociation energy barriers. To validate this ReaxFF description, we have compared its performance against DFT/MD simulations for 1 and 3 monolayers of water interacting with a rutile (110) surface. We found agreement within a 10% error between the DFT/MD and ReaxFF water dissociation levels for both coverages.

BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling.

The mouse prostate gland develops by branching morphogenesis from the urogenital epithelium and mesenchyme. Androgens and developmental factors, including FGF10 and SHH, promote prostate growth (Berman, D.M., Desai, N., Wang, X., Karhadkar, S.S., Reynon, M., Abate-Shen, C., Beachy, P.A., Shen, M.M., 2004. Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev. Biol. 267, 387-398; Donjacour, A.A., Thomson, A.A., Cunha, G.R., 2003. FGF-10 plays an essential role in the growth of the fetal prostate. Dev. Biol. 261, 39-54), while BMP4 signaling from the mesenchyme has been shown to suppresses prostate branching (Lamm, M.L., Podlasek, C.A., Barnett, D.H., Lee, J., Clemens, J.Q., Hebner, C.M., Bushman, W., 2001. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev. Biol. 232, 301-314). Here, we show that Bone Morphogenetic Protein 7 (BMP7) restricts branching of the prostate epithelium. BMP7 is expressed in the periurethral urogenital mesenchyme prior to formation of the prostate buds and, subsequently, in the prostate epithelium. We show that BMP7(lacZ/lacZ) null prostates show a two-fold increase in prostate branching, while recombinant BMP7 inhibits prostate morphogenesis in organ culture in a concentration-dependent manner. We further explore the mechanisms by which the developmental signals may be interpreted in the urogenital epithelium to regulate branching morphogenesis. We show that Notch1 activity is associated with the formation of the prostate buds, and that Notch1 signaling is derepressed in BMP7 null urogenital epithelium. Based on our studies, we propose a model that BMP7 inhibits branching morphogenesis in the prostate and limits the number of domains with high Notch1/Hes1 activity.