Nano-cutting mechanism of ion implantation-modified SiC: reducing subsurface damage expansion and abrasive wear.

This study utilized ion implantation to modify the material properties of silicon carbide (SiC) to mitigate subsurface damage during SiC machining. The paper analyzed the mechanism of hydrogen ion implantation on the machining performance of SiC at the atomic scale. A molecular dynamics model of nanoscale cutting of an ion-implanted SiC workpiece using a non-rigid regular tetrakaidecahedral diamond abrasive grain was established. The study investigated the effects of ion implantation on crystal structure phase transformation, dislocation nucleation, and defect structure evolution. Results showed ion implantation modification decreased the extension depth of amorphous structures in the subsurface layer, thereby enhancing the surface and subsurface integrity of the SiC workpiece. Additionally, dislocation extension length and volume within the lattice structure were lower in the ion-implanted workpiece compared to non-implanted ones. Phase transformation, compressive pressure, and cutting stress of the lattice in the shear region per unit volume were lower in the ion-implanted workpiece than the non-implanted one. Taking the diamond abrasive grain as the research subject, the mechanism of grain wear under ion implantation was explored. Grain expansion, compression, and atomic volumetric strain wear rate were higher in the non-implanted workpiece versus implanted ones. Under shear extrusion of the SiC workpiece, dangling bonds of atoms in the diamond grain were unstable, resulting in graphitization of the diamond structure at elevated temperatures. This study established a solid theoretical and practical foundation for realizing non-destructive machining at the atomic scale, encompassing both theoretical principles and practical applications.

Combined Strategies Enable Highly Selective Light Olefins and para-Xylene Production on Single Catalyst Bed.

Achieving multiple high-value-added chemical production through novel reaction processes and shape-selective catalytic strategy is the key to realizing efficient low-carbon catalytic processes. In this work, a methanol-toluene coreaction system was developed, and combined control strategies of reaction pathway guidance and shape-selective catalysis were applied for the successful production of light olefins and para-xylene on single HZSM-5 catalyst bed. Cofeeding toluene additionally provides reactive and flowing aromatic hydrocarbon pool species that change the dominant reaction pathway in the complex network of the methanol reaction on HZSM-5 and promote the formation of ethylene. For the first time, the key reaction intermediates methylmethylenecyclodiene are directly captured and identified by experimental and theoretical techniques. This helps to propose the catalytic cycle for the dominant generation of ethylene and, more importantly, enriches the methanol-to-hydrocarbons (MTH) chemistry and hydrocarbon pool mechanism. Furthermore, 0.4HZSM-5@S-1-CLD, an optimized HZSM-5 catalyst modified by the silicalite-1 epitaxial growth followed by silanization approach, realizes highly selective production of light olefins (especially ethylene) and para-xylene, while excellent reactant activity is maintained. This highly efficient coreaction route gives an important leading significance in synthesizing the raw materials for the polyolefin and polyester industries. The establishment of the combined control strategies provides a model for the joint production of multiple target chemicals in complex catalytic processes.

Machinability and Surface Properties of Cryogenic Poly(methyl methacrylate) Machined via Single-Point Diamond Turning.

Poly(methyl methacrylate) (PMMA), with a glass transition temperature (Tg) over 100 °C, shows good mechanical and optical properties and has broad applications after being machined with single-point diamond turning (SPDT) at room temperature. Because of the high Tg, current efforts mostly focus on optimizing machining parameters to improve workpiece precision without considering the modification of material properties. Cryogenic cooling has been proven to be an effective method in assisting ultra-precision machining for certain types of metals, alloys, and polymers, but has never been used for PMMA before. In this work, cryogenic cooling was attempted during the SPDT of PMMA workpieces to improve surface quality. The machinability and surface properties of cryogenically cooled PMMA were investigated based on the mechanical properties at corresponding temperatures. Nanoindentation tests show that, when temperature is changed from 25 °C to 0 °C, the hardness and Young's modulus are increased by 37% and 22%, respectively. At these two temperature points, optimal parameters including spindle speed, feed rate and cut depth were obtained using Taguchi methods to obtain workpieces with high surface quality. The surface quality was evaluated based on the total height of the profile (Pt) and the arithmetic mean deviation (Ra). The measurement results show that the values of Pt and Ra of the workpiece machined at 0 °C are 124 nm and 6 nm, respectively, while the corresponding values of that machined at 25 °C are 291 nm and 11 nm. The test data show that cryogenic machining is useful for improving the form accuracy and reducing the surface roughness of PMMA. Moreover, the relationship between temperature, material properties and machinability weas established with dynamic mechanical analysis (DMA) data and a theoretical model. This can explain the origin of the better surface quality of the cryogenic material. The basis of this is that temperature affects the viscoelasticity of the polymer and the corresponding mechanical properties due to relaxation. Then, the material property changes will affect surface profile formation during machining. The experimental results and theoretical analysis show that cryogenically cooled PMMA has good machinability and improved surface quality when using SPDT compared to that at ambient temperature.

Flexible thin film thermocouples: From structure, material, fabrication to application.

Flexible thin-film thermocouples (TFTCs) have been garnering interest as temperature sensors due to the advantages of being flexible, ultrathin, and ultralight. Additionally, they have fast response times and enable detection of temperature. These properties have made them suitable for applications such as wearable electronics, healthcare, portable personal devices, and smart detection systems. This review presents the progress in the development of flexible TFTCs. The mechanism, structural design, materials, fabrication methods, and related applications of flexible TFTCs are also elaborated. Finally, future development directions of flexible TFTCs are discussed such as wide-range temperature measurement, multiple sensor integration, and achieving reliable cold-end compensation systems.

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature.

BACKGROUND: Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. CASE SUMMARY: A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. CONCLUSION: PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

Ag Nanoparticle-Thiolated Chitosan Composite Coating Reinforced by Ag-S Covalent Bonds with Excellent Electromagnetic Interference Shielding and Joule Heating Performances.

Conductive composite coatings are an important element in flexible electronics research and are widely used in energy transformation, artificial intelligence, and electronic skins. However, the comparatively low electrical conductivity limits their performance in many specific applications, such as electromagnetic interference (EMI) shielding and Joule heating devices. Therefore, the preparation of ultrahigh-electrical conductivity composite coatings with good flexibility and durability remains a great challenge. Herein, we fabricated multifunctional conductive composite coatings based on thiolated chitosan (TCS) and Ag nanoparticles (AgNPs) by an eco-friendly drop-coating method. The three-dimensional conductive network constructed by thermal sintering imparted the coating with an ultrahigh electrical conductivity of up to 67079.4 S/m. Moreover, the coating reinforced by Ag-S covalent bonding exhibits good stability, including heat resistance, chemical resistance, and mechanical stability. In addition, based on the ultrahigh electrical conductivity, the coating exhibits superior EMI shielding effectiveness and Joule heating capability. With 30 wt % of AgNPs in the coating, the EMI shielding effectiveness of the coating reaches 70.2 dB, far exceeding commercial standards. Additionally, the coating can quickly reach a saturation temperature (Ts) of 195.9 °C at a safe drive voltage of 3 V. These excellent performances demonstrate that the robust and flexible highly conductive composite coatings prepared by this method have attractive potential for EMI shielding and thermal management applications as well as in wearable electronics.

Exploring the nonlinear piezoresistive effect of 4H-SiC and developing MEMS pressure sensors for extreme environments.

Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from -50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from -50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (-0.067% FS/°C) in the range of -50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H2SO4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.

Comparison of L-Shaped and U-Shaped Beams in Bidirectional Piezoelectric Vibration Energy Harvesting.

The traditional single degree of freedom linear piezoelectric vibration energy harvester (PVEH), such as the cantilever type, mainly works and resonates in a single direction and at a single frequency. To adapt broadband and bidirectional ambient vibration, this paper designs and compares two PVEHs of L-shaped beam and U-shaped beam through COMSOL simulation and prototype test. FEA modeling is introduced for accurate structure design with modal analysis, voltage frequency response analysis, and proof mass analysis with multiphysics electromechanical coupling simulation. Two PVEH prototypes with different gravity angles and clamping angles are tested at 0.1 g acceleration to find the optimal angle for maximum output power. The best clamping angle of L-PVEH is 135° with RMS power of 0.3 mW at 7.9 Hz, and that of U-PVEH is 45° with RMS power of 0.4 mW at 5.0 Hz. The proposed U-PVEH shows more advantages in low broadband and bidirectional vibration energy harvesting.

An ultrasensitive and stretchable strain sensor based on a microcrack structure for motion monitoring.

Flexible strain sensors are promising candidates for intelligent wearable devices. Among previous studies, although crack-based sensors have attracted a lot of attention due to their ultrahigh sensitivity, large strain usually causes fractures in the conductive paths. Because of the unstable crack structure, the tradeoff between sensitivity and workable strain range is still a challenge. As carbon nanotubes (CNTs) and silver nanowires (AgNWs) can form a strong interface with the thermoplastic substrate and strengthen the conductive network by capillary force during water evaporation, CNTs and AgNWs were deposited on electrospun TPU fiber mats via vacuum-assisted filtration in this work. The prestretching treatment constructed a microcrack structure that endowed the sensor with the combined characteristics of a wide working range (0~171% strain), ultrahigh sensitivity (a gauge factor of 691 within 0~102% strain, ~2 × 104 within 102~135% strain, and >11 × 104 within 135~171% strain), a fast response time (~65 ms), small hysteresis, and superior durability (>2000 cycles). Subsequently, the sensing mechanism of the sensor was studied. Distributed microcrack propagation based on the "island-bridge" structure was explained in detail, and its influence on the strain-sensing behavior of the sensor was analyzed. Finally, the sensor was assembled to monitor various vibration signals and human motions, demonstrating its potential applications in the fields of electronic skin and human health monitoring.

[Clinical and genetic analysis of seven Chinese pedigrees affected with multiple endocrine neoplasia type 2A with cutaneous lichen amyloidosis].

OBJECTIVE: To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA). METHODS: Clinical data of 51 members from 7 unrelated pedigrees of MEN2A-CLA were collected. Systemic clinical investigations including biochemical testing, imaging examination, germline RET variant screening and histopathological examination were carried out. RESULTS: RET gene variants were detected in 28 patients with MEN2A (C634G/F/R/S/W and C611Y) including 12 males and 16 females, with the mean age of diagnosis being (41.1 ± 18.3) years old, which were consistent with their clinical manifestations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), hyperparathyroidism (HPTH) and CLA among 28 MEN2A patients were 89.3%, 28.6%, 7.1% and 28.6%, respectively. Comparison of the incidence of MTC/PHEO/HPTH and CLA between C611Y and C634G/F/R/S/W, only PHEO and CLA in C611Y were lower than those in C634G/F/R/S/W (P < 0.05; P < 0.05). Among 8 patients with CLA, the male to female ratio was 2 : 6. The clinical features included pruritus in the interscapular region and presence of dry, thickened, scaly, brown pigment, clustered or desquamate-like plaques. The mean onset age of CLA [(18.4 ± 4.6) years] versus the mean age at diagnosis of CLA or MEN2A were significantly different (P < 0.001; P < 0.001). CONCLUSION: MEN2A-CLA may be the early clinical manifestation of MEN2A and most frequently occurred along with RET-C634 variant. To facilitate the recognition of MEN2A-CLA, to combine family investigation and screening of RET variant are helpful for early diagnosis and standardized treatment, which can improve the long-term outcome of MEN2A-specific tumors.

Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With BAP1-Frame Shift Mutation: Case Report and Literature Review.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are VHL, PBRM1, BAP1, and SETD2, respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of BAP1 in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of BAP1 mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning BAP1 mutation and associated cancers including ccRCC is reviewed.

Highly Selective Carbonylation of CH3 Cl to Acetic Acid Catalyzed by Pyridine-Treated MOR Zeolite.

The selective conversion of methane to high value-added chemicals under mild conditions is of great significance for the commercially viable and sustainable utilization of methane but remains a formidable challenge. Herein, we report a strategy for efficiently converting methane to acetic acid via CH3 Cl as an intermediate. Up to 99.3 % acetic acid and methyl acetate (AA+MA) selectivity was achieved over pyridine-pretreated MOR (MOR-8) under moderate conditions of 523 K and 2.0 MPa. Water, conventionally detrimental to carbonylation reaction over zeolite catalysts, was conducive to the production of AA in the current reaction system. In the 100 h continuous test with the MOR-8 catalyst, the average AA+MA selectivity remained over 98 %. AA was formed by carbonylation of methoxy groups within 8-membered rings of MOR followed by hydrolysis. This strategy provided an approach for highly efficient utilization of methane to oxygenates under mild reaction conditions.

Influences of RF Magnetron Sputtering Power and Gas Flow Rate on a High Conductivity and Low Drift Rate of Tungsten-Rhenium Thin-Film Thermocouples.

Thin-Film Thermocouples (TFTCs) are characterized by their high spatial resolutions, low cost, high efficiency and low interference on the air flow. However, the thermal stability of TFTCs should be further improved for application since their accuracy is influenced by joule heat and temperature time drift. In this paper, 3D molecular dynamics and finite element analysis are used for structural design. The effects of RF magnetron sputtering power and gas flow rate on conductivity and temperature time drift rate (DT) of high thermal stability tungsten-rhenium (95% W/5% Re vs. 74% W/26% Re) TFTCs were analyzed. According to the experimental results, the average Seebeck coefficient reached 31.1 µV/°C at 900 °C temperature difference (hot junction 1040 °C) with a repeatability error at ±1.37% in 33 h. The conductivity is 17.1 S/m, which is approximately 15.2 times larger than the compared tungsten-rhenium sample we presented, and the DT is 0.92 °C/h (1040 °C for 5 h), which is 9.5% of the old type we presented and 4.5% of compared ITO sample. The lumped capacity method test shows that the response time is 11.5 ms at 300 °C. This indicated an important significance in real-time temperature measurement for narrow spaces, such as the aero-engine combustion chamber.

Highly Enhanced Aromatics Selectivity by Coupling of Chloromethane and Carbon Monoxide over H-ZSM-5.

The transformation of methane into high value-added chemicals such as aromatics provides a more desired approach towards sustainable chemistry but remains a critical challenge due to the low selectivity of aromatics and poor stability. Herein, we first report a coupling reaction of CH3 Cl and CO (CCTA) based on methane conversion, which achieves extremely high aromatics selectivity (82.2 %) with the selectivity of BTX up to ca. 60 % over HZSM-5. The promoting effects have been demonstrated on other zeolites especially 10-membered rings (10 MR) zeolites. Multiple characterizations show that 2,3-dimethyl-2-cyclopentene-1-one (DMCPO) is generated from acetyl groups and olefins. Furthermore, isotopic labeling analysis confirms that CO is inserted into the DMCPO and aromatics rings. A new aromatization mechanism is proposed, including the formation of the above intermediates, which conspicuously weakens the hydrogen transfer reaction, leading to a considerable increase of aromatics selectivity and a dramatic drop in alkanes.

Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-Up in Three Families.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. METHODS: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. RESULTS: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and lessaggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. CONCLUSION: Integrated RET screening, serum calcitonin, and plasma metanephrine/ normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

Simultaneous bilateral laparoscopic cortical-sparing adrenalectomy for bilateral pheochromocytomas in multiple endocrine neoplasia type 2.

Purpose: This study aimed to assess the feasibility of synchronous bilateral laparoscopic or open cortical-sparing adrenalectomy (SB-LCSA or SB-OCSA) for bilateral pheochromocytomas (bPHEOs) in multiple endocrine neoplasia type 2 (MEN2). Methods: Altogether, 31 patients (54.8% were women) were diagnosed with MEN2-related bPHEOs, and 29 of them underwent varying specific adrenalectomies. We systematically analyzed and evaluated their clinical profiles, mutation types, tumor histopathological features, and follow-up records. Results: All 31 patients with bPHEOs presented with RET-C634 (90.3%) and RET-M918T (9.7%) mutations, and the median age at initial presentation was 38 years (range, 23-78). bPHEOs were synchronous in 27 patients and metachronous in 4 (12.9%) patients. In total, 29 patients underwent initial cortical-sparing adrenalectomy (CSA) including 23 (79.3%) undergoing synchronous bilateral CSA (18 SB-LCSA and 5 SB-OCSA) and 6 (20.7%) undergoing metachronous CSA. SB-LCSA and synchronous surgery were associated with less bleeding volume and shorter length of hospital stay than SB-OCSA and metachronous surgery (all P's < 0.05). Corticosteroid replacement treatment was necessary for 14 patients (45.2%) after bilateral CSA. During a median follow-up period of 7 years (range, 1.8-23), three of these patients (10.3%) had a recurrent disease that required reoperation. Conclusion: SB-LCSA is feasible for treating synchronous bPHEOs and should be recommended as a prioritized surgical approach.

Spectrum of Germline RET variants identified by targeted sequencing and associated Multiple Endocrine Neoplasia type 2 susceptibility in China.

BACKGROUND: Germline RET mutations and variants are involved in development of multiple endocrine neoplasia type 2 (MEN2). The present study investigated a spectrum of RET variants, analyzed genotype-phenotype relationships, and evaluated their effect on the MEN2 phenotype in Han Chinese patients. METHODS: Targeted sequencing detected germline RET variants in 697 individuals, including 245 MEN2, 120 sporadic medullary thyroid cancer (MTC), and 15 pheochromocytoma (PHEO) patients and their 493 relatives. In silico analyses and classifications following ACMG-2015 were performed. Demographic, clinical variant types, and endocrine neoplasia molecular diagnosis records were also analyzed. RESULTS: Nineteen different RET mutations (18 point and 1 del/ins mutations) in 214 patients with MEN2A (97.7%) or MEN2B (2.3%) were found, of which exon 11/10 mutations accounted for 79% (169/214). Nineteen compound mutations were found in 31 patients with MEN2A. Twenty-three variants (18 single and 5 double base substitution/compound variants) non-classification were also found. Of these, 17 (3 of pathogenic, 10 of uncertain significance, 2 of likely benign and 2 as benign) were found in 31 patients with MTC/PHEO. The remaining 6 variants (4 of uncertain significance and 2 of likely benign) found in 8 carriers had no evidence of MEN2. The entire cohort showed MEN2A-related PHEO, all occurring in exons 11/10, particularly at C634. Kaplan-Meier curves showed age-dependent penetration rates of MTC and PHEO, and occurrence rates of PHEO in patients with exon 11 mutations were all higher than those within exon 10; these bilateral PHEO were always associated with exon 11 mutations (all P < 0.05). While patient offspring had PHEO, parents with MEN2A had none, the frequency was approximately 10%. Interestingly, at least 6.8% of families were adoptive. Also, 3 non-hotspot RET variants (R114H, T278N, and D489N) appeared with high frequency. Conversely, polymorphism S836S was absent. CONCLUSIONS: These data are largely consistent with current evidence-based recommendations in the clinical practice guidelines. Diversity of RET variants or carriers may involve a different natural disease course. Further large-scale targeted sequencing studies will serve as an accurate and cost-effective approach to investigating MEN2 genotype-phenotype correlations for discovery of rare or unknown variants of RET.

Stress Distribution in Silicon Subjected to Atomic Scale Grinding with a Curved Tool Path.

Molecular dynamics (MD) simulations were applied to study the fundamental mechanism of nanoscale grinding with a modeled tool trajectory of straight lines. Nevertheless, these models ignore curvature changes of actual tool paths, which need optimization to facilitate understanding of the underlying science of the machining processes. In this work, a three-dimensional MD model considering the effect of tool paths was employed to investigate distributions of stresses including hydrostatic stress, von Mises stress, normal and shear stresses during atomic grinding. Simulation results showed that average values of the stresses are greatly influenced by the radius of the tool trajectory and the grinding depth. Besides the averaged stresses, plane stress distribution was also analyzed, which was obtained by intercepting stresses on the internal planes of the workpiece. For the case of a grinding depth of 25 Å and an arc radius 40 Å, snapshots of the stresses on the X-Y, X-Z and Y-Z planes showed internal stress concentration. The results show that phase transformation occurred from α- silicon to ß- silicon in the region with hydrostatic stress over 8 GPa. Moreover, lateral snapshots of the three-dimensional stress distribution are comprehensively discussed. It can be deduced from MD simulations of stress distribution in monocrystalline silicon with the designed new model that a curved tool trajectory leads to asymmetric distribution and concentration of stress during atomic-scale grinding. The analysis of stress distribution with varying curve geometries and cutting depths can aid fundamental mechanism development in nanomanufacturing and provide theoretical support for ultraprecision grinding.

Optimal design of SiC piezoresistive pressure sensor considering material anisotropy.

Material properties of SiC determine the application potential of corresponding sensors in a high temperature and harsh environment. However, few reports are available to describe basic design principles of SiC sensors. In this paper, aiming at improving the sensitivity of the sensor, the structural design of a full-SiC piezoresistive pressure sensor is studied from the aspects of diaphragm structure, material, piezoresistor arrangement, and dimension. The differences between the isotropy theoretical calculation and the anisotropy simulation are analyzed. Furthermore, in order to conform to the anisotropic intrinsic properties of the SiC material, a fitting curve between the diaphragm stress and the corresponding design parameter a/h is obtained by using a quadratic function. Through comparison, a square diaphragm can obtain more stress than a circular diaphragm; however, it is not suitable for SiC pressure sensors due to the process difficulties in anisotropic etching. Both experiment and simulation results show that higher output sensitivity can be obtained when the four piezoresistors are distributed along the radial direction of the diaphragm. With the control variable method, we found that when the area of the edge piezoresistors is increased by 10 times, output sensitivity will decline by 23.66%. Instead, the size of the two piezoresistors at the center shows a minor impact. Therefore, the size of edge piezoresistors has a significant effect on output sensitivity, which is worth paying attention to and should be minimized. Sensor prototypes were fabricated with optimal design, and preliminary experimental results show that zero output is only slightly affected by temperature due to the good thermal stability of SiC materials.

RET S409Y Germline Mutation and Associated Medullary Thyroid Carcinoma.

Background: Inherited medullary thyroid carcinoma (MTC) is primarily caused by RET mutations that are commonly localized in exons 5, 8, 10, 11, and 13-16. In this study, we report pedigrees for individuals with MTC that harbor a germline S409Y variant within exon 6 of the RET proto-oncogene. Methods: Targeted sequencing was used to diagnose four apparently sporadic MTC index cases carrying the germline RET S409Y (c.1226 C>A) variant. Subsequently, 27 relatives of these individuals underwent clinical and genetic assessments and/or thyroid surgery. Furthermore, in silico analyses and in vitro assays were performed to predict or verify the potential oncogenic activity of the S409Y variant. Results: Overall, 15 of 31 participants were found to carry the RET S409Y variant. Of these, 6 presented with isolated MTC (mean age 50.2 years; range 41-75 years), of which 3 presented with neck lymph node metastases and 2 presented with distant liver or lung metastases. Among the remaining 9 carriers, 3 (mean age 56 years; range 41-76 years) had elevated serum calcium-stimulated calcitonin (sCtn) or concurrent marginally elevated serum calcitonin (Ctn) levels, whereas the other 6 (mean age 37.5 years; range 14-52 years) exhibited typical Ctn/sCtn levels (p < 0.05). None of the 15 carriers in these 4 families presented clinical evidence of pheochromocytoma, hyperparathyroidism, or Hirschsprung's disease. In silico analyses revealed that S409Y was a "possibly damaging" mutation that could affect the RET protein inter-domain interface. An in vitro assay revealed that the phosphorylation level of RET tyrosine 905 was relatively higher in the RET S409Y mutant than in wild-type (WT) RET. Moreover, transfection of HEK 293 cells with S409Y enhanced the phosphorylation activity of AKT, ERK pathways, and it increased cell proliferation compared with WT RET, but to a lesser degree than that for the RET C618Y and C634Y mutations. Conclusions: This study demonstrates that the novel germline RET S409Y variant is likely pathogenic and is associated with lower penetrance of MTC than that for the C618Y and C634Y mutations. Individuals with S409Y should be managed using a personalized approach, and additionally, "at-risk" family members should be evaluated. Additional studies are needed to elucidate the correlation between the S409Y mutation and multiple endocrine neoplasia type 2-specific tumors.