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OBJECTIVE: To determine if Pyk2-deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion. SETTING AND SAMPLE: Thirty-six male Pyk2 knockout (KO) and control (WT) mice at 6-weeks of age. MATERIALS AND METHODS: Mice received nickel-titanium spring expanders delivering 0g (no intervention control), 10g or 20g force for 14 days. High-resolution micro-CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry. RESULTS: Pyk2-KO controls (0g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2-KO maxillae also exhibited 12% (10g) and 18% (20g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (−10% at 10g; −22% at 20g) compared with Pyk2-KO maxillae (−11% only at 20g) (p

Objectives To investigate the susceptibility of partially desalivated rats to erosive tooth wear (ETW); the anti-erosive effect of a calcium-supplemented beverage; and the quantification of ETW by microcomputed tomography (micro-CT). Methods The study population consisted of thirty-eight rats, divided into partially desalivated (n = 19) and normal salivary flow (n = 19). They were randomly allocated into three subgroups (n = 6-7): A-diet soda, B-diet soda + calcium, C-water (control). Solutions were provided ad libitum for 28 days, and the rats were euthanized afterwards. Each left hemi-mandible was scanned using micro-CT for enamel volume (three molars) calculation. Visual analysis of photographs of the lingual surface of first molars was performed independently by three blinded examiners. Data were statistically analysed (α = .05). Results Micro-CT revealed no significant differences between partially desalivated or normal groups. Rats consuming A had more enamel loss than those consuming B or C, which did not differ from each other. For visual analysis, desalivation did not affect ETW. Rats consuming C showed the lowest ETW, followed by B and then A, for both partially desalivated and normal rats. Spearman correlation between the two ETW quantification methods was -.65. Conclusions Partial desalivation did not increase ETW. Ca-containing beverage prevented ETW. Micro-CT quantified ETW, although it was not as sensitive as visual analysis.

In semiconductor substrate fabrication process, copper traces are electroplated on prepreg material to play an important role of communicating signals between functional ICs. In recent years, larger size and high I/O number packages such as HFCBGA, 2.5D and 3D IC were developed, finer copper line width and space (L/S) trace substrate design become more and more important. However, the copper trace broken risk under several thermal manufacturing processes and reliability testing also increasing. A temperature cycling test (TCT) is one of the key experimental testing items for package reliability performance evaluation. The accumulated thermal stress will lead to trace broken risk during test, then the discontinue signal cause function failure. For specific application such as Automotive (ATV), function fail is lethal. Thus, consider risk assessment in the primary structure design stage is essential.In this work, a three-dimensional finite element model is used to evaluate structure design and material selection. In generally, the bilinear casting bulk model was used to evaluate copper trace lifetime performance under thermal cycling test condition. However, this bilinear constitutive model is difficult to simulate long-term creep behavior. Therefore, a new experimental technique was developed to measure the copper trace material properties. The mechanical tensile strength of the thin copper foil was tested with a micro-tester to examine the tensile stress–strain relationship. The copper foil is fabricated to be 18 micron thickness which similar to substrate copper trace thickness. Four kinds of tensile speed (1x100 ~ 1x10-3 mm/minute) at four temperature environments (25rC ~ 150°C) were applied and Stress-Strain (S-S) curves were measured by micro force test system. The tensile result of electroplated copper film shows lower Young’s modulus and higher tensile strength than casting bulk copper.The test vehicle of 11.8 x 11.4 mm2 BGA package which has substrate copper trace crack issue after TCT 1000 cycles (-65°C ~ 150°C) was chosen. Besides, the creep behavior of the copper was taken into account in the simulation model to verify the numerical model and copper’s constitutive model. The copper trace broken risk from the simulation was verified against the experimental data. Additional critical data, such as creep strain energy density (CSED) of the copper trace in the organic substrate and the maximum CSED level location in the substrate layer can be predicted. From the result, reduce the package thermal stress can bring lower CSED on trace, and in this study changed the lower Young’s modulus substrate material to control the thermal stress. The experimental and numerical methods presented here can be used as useful performance evaluation tools to support the choice of suitable package geometry and bill of material (BOM) selection.

Purpose Recent case reports suggest that amnion-chorion membranes (ACM) and dense polytetrafluoroethylene membranes (dPTFE) can be left exposed during ridge preservation. The aim of this study was to compare the effectiveness of these membranes in ridge preservation, particularly when they are intentionally left exposed. Materials and methods A split-mouth, single-blind, randomized trial design was used to compare treatments with the two membranes in 22 nonmolar sites on the same arch. Ridge dimensions were recorded clinically and with cone beam computed tomography prior to and 3 months after ridge preservation. Postoperative discomfort was recorded with Visual Analog Scale (VAS) forms. Mixed‑model analysis of variance was used to test significance. Results Clinical and radiographic ridge dimensions were not significantly different between the two treatments. ACM sites had significantly more osteoid and higher bone volume density but significantly less graft particles and bone surface density compared with dPTFE. Mineralized bone area and soft tissue area were not significantly different between the two treatments. ACM sites had significantly lower postoperative VAS scores compared with dPTFE. Conclusion Intentionally exposed ACM is equally effective in ridge preservation compared with dPTFE. Additionally, ACM use may aid in reducing postoperative VAS scores, and potentially result in better quality of bone available for implant placement, as evidenced by improved histomorphometric measures.

Drop test for solder joint reliability is critical for all area arrays and perimeter-leaded surface mount semiconductor devices typically used in handheld electronic products. Joint Electron Device Engineering Council, JEDEC, published a new test standard, JESD22-B111A, to be the revision of the JESD22-B111 for board level drop test in November, 2016. The major differences between JESD22-B111 and JESD22-B111A are PCB size (132×77mm2 to 77×77mm2), PCB layers (8 layers to 10 layers), sample size (15 components/PCB with package size ≦ 15×15 mm2 to 4 components/PCB with package size ≦ 17×17 mm2) and total number of test components (120 components to 48 components). JESD22-B111A also adds the specifications of PCB pad and solder mask opening size for 0.4mm component pitch and 5 lb-in torque value. The component placement on the square board that defined in JESD22-B111A is symmetric so that all of them shall have same stress level during drop test, it is different from the component placement on the rectangular board that defined in JESD22-B111 which results several stress level during drop test. In this paper, board level drop test and simulation followed JESD22-B111 and JESD22-B111A are executed. The simulation result shows conditions follow JESD22-B111A has both smaller normal stress and plastic strain than conditions follow JESD22-B111; drop test experiment result shows JESD22-B111A has longer characteristic life, too. The study of package surface mount placement orientation for rectangular package under JESD22-B111A condition is also executed by simulation, due to it is not defined in the new revised standard. The simulation result shows circumferential oriented component placement has larger plastic strain and radial oriented component placement has larger normal stress, it means the former ease to have solder fracturing failure mode and the latter ease to have intermetallic compound layers fracturing failure mode.

Global measurements of upper tropospheric/lower-stratospheric water vapor and ice particle size distribution in clouds are critically needed to reduce uncertainties in global weather and climate models. To address this need, the conically scanning Tropospheric Water and Cloud ICE (TWICE) millimeter and submillimeter radiometer instrument is being developed. A low-noise, power-efficient command and data handling (C&DH) subsystem has been designed to control TWICE data acquisition and other subsystems. The C&DH prototype board meets functional, noise and size, weight and power (SWaP) requirements for deployment in a 6U-class satellite. Considering the limited power resources available on such platforms, a highly-efficient power regulation board has been designed to minimize power losses and reduce system noise. Furthermore, all of the components have been tested for radiation tolerance in low-Earth orbit.

The problem of pin-constrained electrowetting-ondielectric (EWOD) biochips becomes a serious issue to realize complex bio-chemical operations. Due to limited number of control pins and routing resources, additional Printed Circuit Board (PCB) routing layers may be required which potentially raises the fabrication cost. Previous state-of-the-art work has tried to develop a framework that uses a network-flow-based method for broadcast electrodeaddressing EWOD biochips. Nevertheless, greedily merging of electrical pins in previous works is at high risk of producing unroutable design. Routability should have higher priority than pin reduction. While previous works dedicated their effort on pin reduction, we have addressed our attention on routability of broadcast addressing. Experimental results demonstrate that taking routability into consideration can even have higher pin reduction. Viewed in this light, we present ACER, a routability driven clustering algorithm followed by escape routing using integer linear programming that effectively solves both pin merging and routing in broadcast addressing framework. Our proposed algorithm does not greedily focus on pin-reduction. Instead, routability is taken into consideration through agglomerative clustering. Compared to previous state-of-the-art, our proposed algorithm can further reduce required control pins by an average of 13% and route the design using 68% less wirelength.

In this paper, we present a fast and accurate thermal aware analytical placer. A thermal model is constructed based on a Green function with discrete cosine transform (DCT) to generate full chip temperature profile. Our thermal model is tightly integrated with an analytical placer implemented based on the SimPL framework. A temperature spreading force based on the Gaussian model is proposed to reduce the maximum on-chip temperature and optimize tradeoff between total half-perimeter wirelength and on-chip maximum temperature. The temperature profile generated using our thermal model is verified by the ANSYS ICEPAK and obtains an average deviation within 3.0% with $240\times$ speedup.

Introduction The detailed mechanical and histologic properties of stainless steel miniscrew implants used for temporary orthodontic anchorage have not been assessed. Thus, the purpose of this study was to compare them with identically sized titanium alloy miniscrew implants. Methods Forty-eight stainless steel and 48 titanium alloy miniscrew implants were inserted into the tibias of 12 rabbits. Insertion torque and primary stability were recorded. One hundred grams of tensile force was applied between half of the implants in each group, resulting in 4 subgroups of 24 specimens each. Fluorochrome labeling was administered at weeks 4 and 5. When the rabbits were euthanized at 6 weeks, stability and removal torque were measured in half (ie, 12 specimens) of each of the 4 subgroups. Microdamage burden and bone-to-implant contact ratio were quantified in the other 12 specimens in each subgroup. Mixed model analysis of variance was used for statistical analysis. Results All implants were stable at insertion and after 6 weeks. The only significant difference was the higher (9%) insertion torque for stainless steel. No significant differences were found between stainless steel and titanium alloy miniscrew implants in microdamage burden and bone-to-implant contact regardless of loading status. Conclusions Stainless steel and titanium alloy miniscrew implants provide the same mechanical stability and similar histologic responses, suggesting that both are suitable for immediate orthodontic clinical loads.

In order to improve the validity and feasibility of the solid model of oral tissue, a new method is provided based on reverse engineering. Biomechanical simulation with FEM is an important technique for orthodontic force analysis and evaluation, as well as treatment design. As the base of FEM simulation, the solid geometrical models of oral tissue including tooth, Periodontal Ligament (PDL) and alveolar bone are difficult to construct through conventional solid modeling methods because the oral models are very complicated in geometry and topology which are generally represented as triangular meshes. But in many cases, solid model is necessary for FEM performing. So how to construct the solid model of oral tissue with good quality and efficiency is a problem should be faced and solved in orthodontic biomechanical simulation. Aiming at this problem, reverse engineering modeling is adopt to transfer triangular meshes to four-sides surface model and together with techniques of medical image processing, three dimensional triangular meshes calculating, surface fitting and solid modeling, the solid geometrical model of oral cavity for FEM analysis is constructed from CT (computerized tomography) images. With a simulation case of rat molar movement test, the whole procedure of solid modeling based on reverse engineering and some main techniques are presented and the validity and feasibility are proved also by the simulation results.

In this article, we propose a flip-flop merging algorithm based on agglomerative clustering. Compared to previous state-of-the-art on flip-flop merging, our proposed algorithm outperforms that of Chang et al. [2010] and Wang et al. [2011] in all aspects, including number of flip-flop reductions, increase in signal wirelength, displacement of flip-flops, and execution time. Our proposed algorithm also has minimal disruption to original placement. In comparison with Jiang et al. [2011], Wang et al. [2011], and Chang et al. [2010], our proposed algorithm has the least displacement when relocating merged flip-flops. While previous works on flip-flop merging focus on the number of flip-flop reduction, we further evaluate the power consumption of clock tree after flip-flop merging. To further minimize clock tree wirelength, we propose a framework that determines a preferable location for relocated merged flip-flops for clock tree synthesis (CTS). Experimental results show that our CTS-driven flip-flop merging can reduce clock tree wirelength by an average of 7.82% with minimum clock network power consumption compared to all of the previous works.

BACKGROUND Growth factors contained in platelet-rich plasma (PRP) have been reported to induce osteoblast differentiation in certain studies, while in others, osteogenesis has not been shown clinically. The aim of the present study was to verify the effect of PRP and its combination with rhBMP-2 as a controlled delivery system during sagittal suture distraction osteogenesis. METHODS Thirty-six-week male New Zealand white rabbits were randomly assigned to sagittal suture distraction osteogenesis groups treated with (1) PRP gel alone; and (2) PRP gel mixed with 10 μg rhBMP-2 (PRP/rhBMP-2), and a control group untreated. A heavy 200-g continuous mechanical force was applied for 33 days using a nickel titanium open spring to distract the suture between 2 miniscrew implants. The suture morphology was evaluated radiographically and histologically after sacrifice. RESULTS The amount of suture separation in the control group and the PRP gel group were statistically greater (P < 0.05) than in the PRP/rhBMP-2 gel group. Compared to the control group, the micro-CT and histologic analysis showed that the local application of PRP gel not only stimulates the new bone formation between the suture gap but accelerates the suture wound healing during distraction without suture fusion. There was a percent of total suture height 15.3 ± 9.5% fusion in PRP/rhBMP-2 gel group and the average thickness of cranium bone in the PRP/rhBMP-2 gel group was statistically greater (P < 0.05) than in the control group and the PRP gel group. CONCLUSIONS In this animal model, both PRP gel and PRP/rhBMP-2 gel are effective in improving new bone formation in suture distraction osteogenesis. PRP gel induces suture bone formation without suture fusion and accelerates the suture wound healing, while the PRP/rhBMP-2 gel group, in which the sutures fused prematurely, showed powerful bone formation ability aided by rhBMP-2. PRP can be alternatively use as a controlled release system for rhBMP-2, but caution should be used before proceeding with the application of high-dose growth factors around the growing craniofacial sutures.

Objective:To establish an association between patient personality traits and potential willingness to undergo various orthodontic treatments.Materials and Methods:One hundred adolescent individuals aged 12–16 years completed an anonymous electronic questionnaire via Survey Monkey. The 24-item questionnaire contained three major sections: patient demographics, a modified Big Five Inventory (BFI)-10 personality index, and a willingness to undergo treatment assessment. Multiple-variable linear regression analyses were used to determine the associations among age, gender, ethnicity, and the five personality traits simultaneously with willingness to undergo treatment. Statistical significance was set at P ≤ .05.Results:Ninety-six of the 100 individuals were included in the statistical analysis. Age, ethnicity, and gender failed to correlate with potential willingness to undergo orthodontic treatment. Several personality dimensions within the modified BFI-10 (agreeableness, conscientiousness, and neuroticism) were significantly associated with willingness to undergo various orthodontic treatments (P ≤ .05). Agreeableness demonstrated positive correlations with five treatment modalities, while both conscientiousness and neuroticism exhibited negative associations with a single treatment modality. Openness and extraversion were the only personality dimensions that failed to associate with any of the treatment modalities. Four of the nine treatment modalities had no association with patient demographics or a patient's personality dimensions.Conclusions:Personality traits are useful in predicting a patient's potential willingness to participate in various orthodontic treatments. The agreeableness dimension provided the most utility in predicting patient willingness. Age, ethnicity, and gender were not significant in predicting patient willingness.

The forces and moments supplied by braces determine the movement of tooth in orthodontic treatment, so clearly quantifying the force value is very important to formulate precise treatment plan. In recent decades, scholars have presented many articles about biomechanical research on orthodontic force. Based on investigations of these papers, techniques on orthodontic force stimulation including oral model (bone, PDL and teeth included) reconstruction and constitute model construction, methods in orthodontic force measurement including physical oral model fabrication and device architectures, and techniques on orthodontic force control such as the use of shape memory alloy and shape memory polymer as the wire material, are reviewed. At the end, the conclusions and future works are given.

Objective: BoneCeramic can regenerate bone in alveolar defects, but it remains unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate three-dimensional real-time bone responses and micromechanical properties in the grafting sites during orthodontic tooth movement. Methods: Sixty 5-week-old rats were randomly assigned into three groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss), and no graft, respectively, after the extraction of the left maxillary first molar. After 4 weeks, the maxillary left second molar was moved into the extraction for 28 days. Dynamic bone microstructures and root resorption were evaluated using in vivo micro-computed tomography and histology. Stress distribution of tooth roots and biomechanical properties of corresponding bone tissue were examined by finite element methods and nanoindentation. Mixed-model analysis of variance was performed to compare the difference among time points with Bonferroni post hoc tests at the significance level of P < .05. Results: The BoneCeramic group had the least amount of tooth movement and root resorption volume and craters, highest bone volume fraction, trabecular number, mean trabecular thickness, microhardness, and elastic modulus, followed by Bio-Oss and the control group. The highest stress accumulated in the cervical region of the mesial roots. Conclusion: BoneCeramic has better osteoconductive potential and biomechanical properties and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction site.

Global measurements of cloud ice particle size, total ice water content and water vapor content in the upper troposphere are critically needed to improve knowledge of the role of ice clouds in Earth's climate, precipitation and cloud processes. Such observations will enable improvement in cloud and moisture simulations in global climate models as well as precipitation forecasts on a global basis. Measurements at a range of frequencies in the millimeter- and submillimeter-wave frequency range provide sensitivity to ice particle size distribution in the range of tens to hundreds of micrometers. To perform this measurement on a global basis, a new millimeter- and submillimeter-wave instrument is currently under development with suitable mass, power and volume to be deployed on 6U-Class nanosatellites. To achieve miniaturized receivers in this frequency range, InP MMIC technology has been scaled to 25-nm gate length transistors, enabling demonstration of low-noise amplifiers with sufficient gain at frequencies up to 1 THz. This technology is being applied to develop direct-detection submillimeter-wave receivers at 240 GHz, 310 GHz and 670 GHz. InP MMIC technology has also enabled multipliers for local oscillators and subharmonic mixers for temperature and humidity sounding channels near atmospheric absorption lines at 118.75, 183.31 and 380.20 GHz.

Objective: To investigate three-dimensional microarchitecture and micromechanical properties of alveolar bone in the BoneCeramic grafting sites during orthodontic tooth movement. Materials and Methods: Sixty 5-week-old rats were randomly assigned into three groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss), and no graft, respectively, after the extraction of the left maxillary first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures were evaluated using in vivo micro–computed tomography. Micromechanical properties and stress distribution of corresponding tissue were examined by nanoindentation and finite element methods. Mixed-model analysis of variance was performed to compare the difference among time points with Bonferroni post hoc tests at the significance level of P < .05. Results: The BoneCeramic group had the least amount of tooth movement and the highest bone volume fraction, tr...

The forces and moments supplied by braces determine the movement of tooth in orthodontic treatment, so clearly quantifying the force value is very important to formulate precise treatment plan. In recent decades, scholars have presented many articles about biomechanical research on orthodontic force. Based on investigations of these papers, techniques on orthodontic force stimulation including oral model (bone, PDL and teeth included) reconstruction and constitute model construction, methods in orthodontic force measurement including physical oral model fabrication and device architectures, and techniques on orthodontic force control such as the use of shape memory alloy and shape memory polymer as the wire material, are reviewed. At the end, the conclusions and future works are given.

Objective: To quantify the three-dimensional moments and forces produced by pretorqued nickel-titanium (NiTi) rectangular archwires fully engaged in 0.018- and 0.022-inch slots of central incisor and molar edgewise and prescription brackets. Materials and Methods: Ten identical acrylic dental models with retroclined maxillary incisors were fabricated for bonding with various bracket-wire combinations. Edgewise, Roth, and MBT brackets with 0.018- and 0.022-inch slots were bonded in a simulated 2 × 4 clinical scenario. The left central incisor and molar were sectioned and attached to load cells. Correspondingly sized straight and pretorqued NiTi archwires were ligated to the brackets using 0.010-inch ligatures. Each load cell simultaneously measured three force (Fx, Fy, Fz) and three moment (Mx, My, Mz) components. The faciolingual, mesiodistal, and inciso-occluso/apical axes of the teeth corresponded to the x, y, and z axes of the load cells, respectively. Each wire was removed and retested seven times. Three-way analysis of variance (ANOVA) examined the effects of wire type, wire size, and bracket type on the measured orthodontic load systems. Interactions among the three effects were examined and pair-wise comparisons between significant combinations were performed. Results: The force and moment components on each tooth were quantified according to their local coordinate axes. The three-way ANOVA interaction terms were significant for all force and moment measurements (P < .05), except for Fy (P > .05). Conclusion: The pretorqued wire generates a significantly larger incisor facial crown torquing moment in the MBT prescription compared to Roth, edgewise, and the straight NiTi wire.

OBJECTIVE: To test the effect of alcohol on force decay of elastomeric chains in vitro in order to determine if increasing alcohol concentrations results in an increased amount of elastomeric chain force decay. MATERIALS AND METHODS: A prospective laboratory study was completed to test the effect of alcohol exposure on orthodontic elastomeric chain. A total of 450 specimens were divided into five test groups. Two test groups were each exposed to different alcohol concentrations (14% and 26.9%) and the other two test groups were exposed to different commercially available mouth rinses (Cēpacol -14% alcohol and Listerine - 26.9% alcohol) for 60 seconds twice a day. The control group followed all of the same procedures but was only exposed to deionized (DI) water. Force measurements were taken at six time points (initial, 1 day, 7 days, 14 days, 21 days, and 28 days). RESULTS: There were no significant differences among groups at the initial time point (P = .52). Statistically significant effects of time on force decay were seen in all groups. All test groups showed significantly more force decay than the control group. Only a few statistically significant differences were observed when comparing force decay among the test groups. CONCLUSIONS: Alcohol causes an increase in force decay of elastomeric chain over time. A concentration dependence of alcohol on force decay of elastomeric chain was not observed.

Improving routability during both global and detailed routing stage has become a critical problem in modern VLSI design. In this work, we propose a placement framework that offers a complete coverage solution in considering both global and detailed routing congestion. A placement migration strategy is proposed, which improves detailed routing congestion while preserving the placement integrity that is optimized for global routability. Using the benchmarks released from ISPD2014 Contest, practical design rules in advanced node design are considered in our placement framework. Evaluation on routability of our placement framework is conducted using commercial router provided by the 2014 ISPD Contest organizers. Experimental results show that the proposed methodologies can effectively improve placement solutions for both global and detailed router.

Introduction BoneCeramic (Straumann, Basel, Switzerland) can regenerate bone in alveolar defects after tooth extraction, but it is unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate 3-dimensional real-time root resorption and bone responses in grafted sites during orthodontic tooth movement. Methods Sixty 5-week-old rats were randomly assigned to 3 groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss; Geistlich Pharma, Wolhusen, Switzerland), or no graft, after the extraction of the maxillary left first molar. After 4 weeks, the maxillary left second molar was moved into the extraction site for 28 days. Dynamic bone microstructures and root resorption were evaluated using in-vivo microcomputed tomography. Stress distribution and corresponding tissue responses were examined by the finite element method and histology. Mixed model analysis of variance was performed to compare the differences among time points with Bonferroni post-hoc tests at the significance level of P Results The BoneCeramic group had the least amount of tooth movement and root resorption volumes and craters, and the highest bone volume fraction, trabecular number, and mean trabecular thickness, followed by the Bio-Oss and the control groups. The highest stress accumulated in the cervical region of the mesial roots. Conclusions BoneCeramic has better osteoconductive potential and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction sites.

To validate whether applying a well-defined initial three-dimensional (3D) load can create consistently expected tooth movement in patients.Twenty-one patients who needed bilateral canine retraction to close extraction space were selected for this split-mouth clinical trial. After initial alignment and leveling, two canines in each patient were randomly assigned to receive either translation (TR) or controlled tipping (CT) load. The load was delivered by segmental T-loops designed to give specific initial moment/force ratios to the canines in each treatment interval (TI), verified with an orthodontic force tester. Maxillary dental casts were made before canine retraction and after each TI. The casts were digitized with a 3D laser scanner. The digital models were superimposed on the palatal rugae region. The 3D canine displacements and the displacement patterns in terms of TR, CT, and torque were calculated for each TI.The method can reliably detect a TR displacement greater than 0.3 mm and a rotation greater than 1.5°. Ninety-two TIs had displacements that were greater than 0.3 mm and were used for further analysis. Most displacements were oriented within ±45° from the distal direction. The displacement pattern in terms of TR or CT was not uniquely controlled by the initial moment/force ratio.The initial load system is not the only key factor controlling tooth movement. Using a segmental T-loop with a well-controlled load system, large variations in canine displacement can be expected clinically.

Introduction Midpalatal suture expansion could induce osteogenesis to correct maxillary insufficiency; cartilage formation could also be induced, and lower-magnitude forces might generate a preferable response pattern. In this study, we aimed for an enhanced understanding of the cartilage formatting effects of expansion. Methods Thirty 6-week-old male C57BL/6 mice were randomly and evenly assigned to 3 groups; the animals in each group received a sustained suture expansion at 0, 10, and 20 g, respectively. Ten additional mice were fed the same as the baseline controls and received no expansion. After 7 days, the animals were killed; coronal paraffin sections were stained using toluidine blue and safranin-O. The proliferating cell nucleus antigen, the nuclear antigen Ki-67, alkaline phosphatase, and matrix metalloproteinase 13 expressions were visualized with immunohistochemistry. All data were analyzed statistically, and the differences were considered significant at P Results Compared with the control, the cartilage matrix volume was significantly increased by the 20-g expansion, showing increased cartilage matrix and hypertrophic chondrocytes with the highest matrix metalloproteinase 13 expression. The 10-g expansion formed condensed proliferating chondrocyte masses, within which the highest percentages of proliferating cell nucleus antigen and Ki-67 positive cells were present. The 10-g and the 20-g expansions equally intensified the alkaline phosphatase expression. Conclusions The lower expansion (10 g) promoted chondrocyte proliferation and induced a more preferable suture cartilage response pattern compared with the higher expansion (20 g), which just increased the cartilage matrix production.

Background Epidermal growth factor receptor (EGFR) gene mutations identify patients with non-small cell lung cancer (NSCLC) who have a high likelihood of benefiting from treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be technically challenging, resulting in longer turn-around-time, with limited sensitivity for low levels of mutations. This manuscript details the technical performance verification studies and external clinical reproducibility studies of the cobas EGFR Mutation Test, a rapid multiplex real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21. Methods The assay’s limit of detection was determined using 25 formalin-fixed paraffin-embedded tissue (FFPET)-derived and plasmid DNA blends. Assay performance for a panel of 201 specimens was compared against Sanger sequencing with resolution of discordant specimens by quantitative massively parallel pyrosequencing (MPP). Internal and external reproducibility was assessed using specimens tested in duplicate by different operators, using different reagent lots, instruments and at different sites. The effects on the performance of the cobas EGFR test of endogenous substances and nine therapeutic drugs were evaluated in ten FFPET specimens. Other tests included an evaluation of the effects of necrosis, micro-organisms and homologous DNA sequences on assay performance, and the inclusivity of the assay for less frequent mutations. Results A >95% hit rate was obtained in blends with >5% mutant alleles, as determined by MPP analysis, at a total DNA input of 150 ng. The overall percent agreement between Sanger sequencing and the cobas test was 96.7% (negative percent agreement 97.5%; positive percent agreement 95.8%). Assay repeatability was 98% when tested with two operators, instruments, and reagent lots. In the external reproducibility study, the agreement was > 99% across all sites, all operators and all reagent lots for 11/12 tumors tested. Test performance was not compromised by endogenous substances, therapeutic drugs, necrosis up to 85%, and common micro-organisms. All of the assessed less common mutations except one (exon 19 deletion mutation 2236_2248 > AGAC) were detected at a similar DNA input level as that for the corresponding predominant mutation. Conclusion The cobas EGFR Mutation Test is a sensitive, accurate, rapid, and reproducible assay.

Objective: To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. Materials and Methods: A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P < .05. Results: From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Conclusions: Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

Introduction Suture expansion stimulates bone growth to correct craniofacial deficiencies but has a high potential of treatment relapse. The objective of this study was to investigate whether there is a dose-dependent relationship between the recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone formation during suture expansion. Methods Fifty 6-week-old male New Zealand white rabbits were randomly assigned to 5 groups to receive 0 (control), 0.01, 0.025, 0.1, or 0.4 mg/mL of rhBMP-2 delivered by absorbable collagen sponge placed over the interfrontal suture. The suture was expanded for 33 days by 200 g of constant force via a spring anchored with 2 miniscrew implants. Distance of suture expansion, suture volume, and cross-sectional area after expansion were measured using radiographs with bone markers and microcomputed tomography. Suture widths and mineralization appositional rates were calculated based on the widths between bone labels under an epifluorescent microscope. Software (Multilevel Win 2.0; University of Bristol, Bristol, United Kingdom) was used to model distance of suture expansion over time as polynomials to compare group differences. Wilcoxon signed rank tests were performed to compare the suture volume and cross-sectional area, mineral apposition rate, and suture width between groups. The significance level was set at P = 0.05. Results Whereas the sutures were expanded in all groups, sutures were expanded by significantly greater amounts in the control and the 0.01 mg/mL groups without fusing the sutures than in the 0.025, 0.1, and 0.4 mg/mL groups with fusing sutures. Compared with the controls, the 0.01 mg/mL group showed significantly lower suture volumes, cross-sectional areas, and suture widths after expansion. The mineral apposition rate was significantly higher in the 0.01 mg/mL group than in the controls from days 10 to 30. Conclusions The 0.01 mg/mL dose of rhBMP-2 delivered by absorbable collagen sponge can stimulate bone formation at the bony edges of the suture during suture expansion; however, higher concentrations cause suture fusion. With an appropriate concentration, rhBMP-2 might facilitate suture expansion for clinical uses.

Introduction Microdamage reduces bone mechanical properties and thus could contribute to implant failure. The objective of this study was to investigate whether the diameter of mini-implants affects linear microcrack generation and whether this differs between the mandible and the maxilla because of their contrasting cortical thicknesses. Methods Maxillary and mandibular quadrants of 5 dogs were randomly assigned to receive, in situ, no pilot drilling or mini-implant insertion (control), pilot drilling only without mini-implants, or pilot drilling plus a mini-implant of 1 of 3 diameters: 1.4 mm (n = 18), 1.6 mm (n = 18), and 2.0 mm (n = 18). Linear microcracks were assessed on basic fuchsin-stained sections by using epifluorescence microscopy. Results Pilot drilling without mini-implant insertion produced significantly higher linear microcrack burdens in the mandible compared with the maxilla. In the both the mandible and the maxilla, all implants produced higher linear microcrack burdens than did the controls, yet there were no differences between the 3 implant diameters. Conclusions Neither the diameter of the mini-implant nor the site of insertion (mandible vs maxilla) had a significant effect on the amount of linear microdamage adjacent to the implant when the implants were inserted after pilot drilling in situ.

Suture compression is a widely used approach to inhibit maxillary growth; however, biological responses in sutures to compressive force are still unclear. The objective of this pilot study was to investigate the matrix metalloproteinase (MMP) expression and osteoclast activities during the midpalatal suture compression.56 six-week old male C57BL/6 mice were randomly assigned to the control and compression groups. The mice in the compression and control groups received helix springs bonded to the maxillary molars delivering initial compressive forces of 0.20 and 0N (no activation), respectively. On Days 1, 4, 7 and 14, animals were sacrificed and scanned using micro-computed tomography to quantify suture width and bone mineral density. Serial histological sections were stained with HE, TRAP, and immunohistochemistry to observe changes in bone resorption, osteoclast activities, and MMP-1, 8, and 13 expressions. Bone volume/total volume (Bv/Tv) ratio, osteoclast count, osteoclast covering area, and MMP expression intensity were measured. The Mann-Whitney and the Kruskal-Wallis tests with Bonferroni post-hoc corrections were performed to compare differences between groups and between time points in the same group at significant level of P0.05.Compared to the control, suture width in the compression group was significantly reduced on Day 1, but continuously widened with reduced bone mineral density afterwards. With MMP-1 and -13 evidently intensified expressions, osteoclast number and activities significantly increased, leading to reduced Bv/Tv ratio and progressive bone resorption from Days 4 to 14.Suture compression elevated the MMP-1 and 13 expressions, activated osteoclasts, reduced bone density, and induced bone resorption adjacent to the suture. It suggests that suture compression can be used for bone volume reduction.

In this paper, we propose a fast and accurate thermal aware analytical placer. Thermal model is constructed based on Green function with enhanced DCT to generate full chip temperature profile. Unlike other previous thermal aware placers, our thermal model is tightly integrated with a flat force directed placement. A thermal spreading force based on 2D Gaussian model is proposed to reduce maximum on-chip temperature with dynamic hot region size control, optimizing between total half-perimeter wirelength (HPWL) and on-chip temperature distribution. Our thermal model is evaluated by the most recent commercial tool and has an average deviation of 6.5% with 242× speed up. Our placer can reach the same quality compared to Capo and APlace2 with 2–3× speed up. Experiments are tested using ISPD 2005 benchmark with up to 2 million gate design. The results are further evaluated using GSRC Bookshelf Evaluator for total HPWL, and using ICEPAK for temperature distribution. To the best of our knowledge, this is the first thermal-aware placer using analytical thermal model and experimented on large scale design. It takes 6.5 hours to complete entire 2005 ISPD benchmark using our thermal aware placer.

While both intermittent and continuous forces are commonly used to expand sutures, it remains unclear which force is most effective. Using nickel-titanium (NiTi) open coil springs (50 g) and 3 mm long miniscrew implants (MSIs) for skeletal anchorage, intermittent and continuous forces were used to expand the midsagittal sutures in 18 New Zealand white juvenile male rabbits, 11 weeks of age, for 29 days. In the intermittent group, expansion forces of 50 g were delivered for 5 days (on) and paused for 1 day (off); the on/off cycles were repeated five times. Expansion forces of 50 g were delivered for 29 consecutive days in the continuous group. Longitudinal biometric and histomorphometric analyses were performed to evaluate sutural separation and bone formation using implanted tantalum bone markers and fluorescent bone labelling, respectively. Multilevel modelling procedures were undertaken to compare the groups and time intervals. Continuous forces produced significantly greater overall sutural separation (1.3 mm) than intermittent forces (0.8 mm). Although they were delivered over a period of time 86 per cent as long, intermittent forces produced only 61 per cent of the sutural separation of continuous forces. Between days 7 and 17, continuous forces resulted in significantly greater mineral apposition and bone formation rates than intermittent forces. Intermittent forces produced approximately 59 per cent as much mineral apposition and 61 per cent as much bone formation as continuous forces. Due to greater sutural separation and bone formation, continuous forces provide a more effective approach for separating sutures than intermittent forces.

Introduction The purpose of this study was to establish the causal relationships between expansion force magnitudes, sutural separation, and sutural bone formation. Methods Thirty-seven 6-week-old rabbits were randomly assigned to 4 force groups (0, 50, 100, or 200 g). Constant forces were delivered for 42 days by nickel-titanium open-coil springs to miniscrew implants (MSIs) placed in the frontal bone on both sides of the midsagittal suture. Inter-MSI and bone marker widths were measured biweekly to quantify sutural separation and MSI movements. Sutural bone formation was quantified based on the incorporation of fluorescent bone labels administered at days 18, 28, and 38. Results Nine of 74 MSIs failed between days 0 and 14, including 4 in the controls and 5 in the 50-g group. A decelerating curvilinear pattern of sutural separation was evident in the 50-g, 100-g, 200-g groups. Bone markers showed that sutural widths increased by 0.6, 3.2, 5.1, and 6.2 mm in the control, 50-g, 100-g, and 200-g groups, respectively. Except for the 200-g group, significantly greater amounts of bone formation were observed between days 18 and 28 than between days 28 and 38. Sutural bone formation also increased with increasing forces up to 100 g; there was no difference between the 100-g and the 200-g groups. Sutural separation explained 71% and 53% of the variations in bone formation between days 18 and 28 and days 28 and 38, respectively. Conclusions Within the limits of this study, sutural bone formation is directly related to the amount of sutural separation, which is in turn related to the amount of force applied. The results suggest that there is a level of induced sutural separation that provides the greatest amount of bone formation.

Background The occurrence of mandibular defects caused by tumors has been continuously increasing in China in recent years. Conversely, results of the repair of mandibular defects affect the recovery of oral function and patient appearance, and the requirements for accuracy and high surgical quality must be more stringent. Digital techniques — including model reconstruction based on medical images, computer-aided design, and additive manufacturing — have been widely used in modern medicine to improve the accuracy and quality of diagnosis and surgery. However, some special software platforms and services from international companies are not always available for most of researchers and surgeons because they are expensive and time-consuming. Methods Here, a new technical solution for guided surgery for the repair of mandibular defects is proposed, based on general popular tools in medical image processing, 3D (3 dimension) model reconstruction, digital design, and fabrication via 3D printing. First, CT (computerized tomography) images are processed to reconstruct the 3D model of the mandible and fibular bone. The defect area is then replaced by healthy contralateral bone to create the repair model. With the repair model as reference, the graft shape and cutline are designed on fibular bone, as is the guide for cutting and shaping. The physical model, fabricated via 3D printing, including surgical guide, the original model, and the repair model, can be used to preform a titanium locking plate, as well as to design and verify the surgical plan and guide. In clinics, surgeons can operate with the help of the surgical guide and preformed plate to realize the predesigned surgical plan. Results With sufficient communication between engineers and surgeons, an optimal surgical plan can be designed via some common software platforms but needs to be translated to the clinic. Based on customized models and tools, including three surgical guides, preformed titanium plate for fixation, and physical models of the mandible, grafts for defect repair can be cut from fibular bone, shaped with high accuracy during surgery, and fixed with a well-fitting preformed locking plate, so that the predesigned plan can be performed in the clinic and the oral function and appearance of the patient are recovered. This method requires 20% less operating time compared with conventional surgery, and the advantages in cost and convenience are significant compared with those of existing commercial services in China. Conclusions This comparison between two groups of cases illustrates that, with the proposed method, the accuracy of mandibular defect repair surgery is increased significantly and is less time-consuming, and patients are satisfied with both the recovery of oral function and their appearance. Until now, more than 15 cases have been treated with the proposed methods, so their feasibility and validity have been verified.

Introduction The goal of this study was to evaluate whether human recombinant bone morphogenetic protein-2 (rhBMP-2) enhances sutural bone formation or causes premature sutural fusion. Methods Thirty 6-week-old rabbits underwent midsagittal sutural expansion. The animals were randomly assigned to receive 0 (control), 0.1 mg per milliliter, or 0.4 mg per milliliter of rhBMP-2, delivered by an absorbable collagen sponge placed over the suture. A 100-g constant force was delivered for 33 days by using a nickel-titanium spring to expand the suture between 2 miniscrew implants anchored in the frontal bone. At days 10, 20, and 30, sutural separation was evaluated and modeled over time as polynomials by using multilevel statistical procedures. Bone formation and sutural gaps were analyzed histomorphometrically between days 10 and 20 and days 20 and 30. Results The control group showed significantly greater overall sutural bone formation than did the 2 rhBMP-2 groups. Over time, bone formation decreased significantly in all groups. Between days 10 and 20, the 0.4 mg per milliliter group produced significantly more (58%) bone than did the 0.1 mg per milliliter group; there were no significant differences in bone formation between the 2 experimental groups between days 20 and 30. Both 0.1 and 0.4 mg per milliliter of rhBMP-2 in the absorbable collagen sponge caused premature fusion by forming a bony bridge connecting the ectocranial aspect of the sutural margins. Premature fusion significantly reduced sutural separation between 10 and 30 days (to 56% and 62% of control values for the 0.1 and 0.4 mg per milliliter groups, respectively). There were no significant differences in sutural separation between the 0.1 and 0.4 mg per milliliter groups. Conclusions Compared with the 0.1 mg per milliliter group, 0.4 mg per milliliter of rhBMP-2 accelerated sutural bone formation between days 10 and 20. After 10 to 20 days, rhBMP-2 in the absorbable collagen sponge caused premature sutural fusion, despite the constant expansion forces.

Introduction The goal of this study was to evaluate whether human recombinant bone morphogenetic protein-2 (rhBMP-2) enhances sutural bone formation or causes premature sutural fusion. Methods Thirty 6-week-old rabbits underwent midsagittal sutural expansion. The animals were randomly assigned to receive 0 (control), 0.1 mg per milliliter, or 0.4 mg per milliliter of rhBMP-2, delivered by an absorbable collagen sponge placed over the suture. A 100-g constant force was delivered for 33 days by using a nickel-titanium spring to expand the suture between 2 miniscrew implants anchored in the frontal bone. At days 10, 20, and 30, sutural separation was evaluated and modeled over time as polynomials by using multilevel statistical procedures. Bone formation and sutural gaps were analyzed histomorphometrically between days 10 and 20 and days 20 and 30. Results The control group showed significantly greater overall sutural bone formation than did the 2 rhBMP-2 groups. Over time, bone formation decreased significantly in all groups. Between days 10 and 20, the 0.4 mg per milliliter group produced significantly more (58%) bone than did the 0.1 mg per milliliter group; there were no significant differences in bone formation between the 2 experimental groups between days 20 and 30. Both 0.1 and 0.4 mg per milliliter of rhBMP-2 in the absorbable collagen sponge caused premature fusion by forming a bony bridge connecting the ectocranial aspect of the sutural margins. Premature fusion significantly reduced sutural separation between 10 and 30 days (to 56% and 62% of control values for the 0.1 and 0.4 mg per milliliter groups, respectively). There were no significant differences in sutural separation between the 0.1 and 0.4 mg per milliliter groups. Conclusions Compared with the 0.1 mg per milliliter group, 0.4 mg per milliliter of rhBMP-2 accelerated sutural bone formation between days 10 and 20. After 10 to 20 days, rhBMP-2 in the absorbable collagen sponge caused premature sutural fusion, despite the constant expansion forces.