Application of Teager-Kaiser Energy Operator in the Early Fault Diagnosis of Rolling Bearings.

Rolling bearings are key components that support the rotation of motor shafts, operating with a quite high failure rate among all the motor components. Early bearing fault diagnosis has great significance to the operation security of motors. The main contribution of this paper is to illustrate Gaussian white noise in bearing vibration signals seriously masks the weak fault characteristics in the diagnosis based on the Teager-Kaiser energy operator envelope, and to propose improved TKEO taking both accuracy and calculation speed into account. Improved TKEO can attenuate noise in consideration of computational efficiency while preserving information about the possible fault. The proposed method can be characterized as follows: a series of band-pass filters were set up to extract several component signals from the original vibration signals; then a denoised target signal including fault information was reconstructed by weighted summation of these component signals; finally, the Fourier spectrum of TKEO energy of the resulting target signal was used for bearing fault diagnosis. The improved TKEO was applied to a vibration signal dataset of run-to-failure rolling bearings and compared with two advanced diagnosis methods. The experimental results verify the effectiveness and superiority of the proposed method in early bearing fault detection.

c-Abl inhibition mitigates diet-induced obesity through improving insulin sensitivity of subcutaneous fat in mice.

AIMS/HYPOTHESIS: High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance. METHODS: The expression of c-Abl in different fat tissues from obese humans or mice fed a high-fat diet (HFD) were first analysed by western blotting and quantitative PCR. We employed conditional deletion of the c-Abl gene (also known as Abl1) in adipose tissue using Fabp4-Cre and 6-week-old mice were fed with either a chow diet (CD) or an HFD. Age-matched wild-type mice were treated with the c-Abl inhibitor nilotinib or with vehicle and exposed to either CD or HFD, followed by analysis of body mass, fat mass, glucose and insulin tolerance. Histological staining, ELISA and biochemical analysis were used to clarify details of changes in physiology and molecular signalling. RESULTS: c-Abl was highly expressed in subcutaneous fat from obese humans and HFD-induced obese mice. Conditional knockout of c-Abl in adipose tissue improved insulin sensitivity and mitigated HFD-induced body mass gain, hyperglycaemia and hyperinsulinaemia. Consistently, treatment with nilotinib significantly reduced fat mass and improved insulin sensitivity in HFD-fed mice. Further biochemical analyses suggested that c-Abl inhibition improved whole-body insulin sensitivity by reducing HFD-triggered insulin resistance and increasing adiponectin in subcutaneous fat. CONCLUSIONS/INTERPRETATION: Our findings define a new biological role for c-Abl in the regulation of diet-induced obesity through improving insulin sensitivity of subcutaneous fat. This suggests it may become a novel therapeutic target in the treatment of metabolic disorders.

STK16 regulates actin dynamics to control Golgi organization and cell cycle.

STK16 is a ubiquitously expressed, myristoylated, and palmitoylated serine/threonine protein kinase with underexplored functions. Recently, it was shown to be involved in cell division but the mechanism remains unclear. Here we found that human STK16 localizes to the Golgi complex throughout the cell cycle and plays important roles in Golgi structure regulation. STK16 knockdown or kinase inhibition disrupts actin polymers and causes fragmented Golgi in cells. In vitro assays show that STK16 directly binds to actin and regulates actin dynamics in a concentration- and kinase activity-dependent way. In addition, STK16 knockdown or kinase inhibition not only delays mitotic entry and prolongs mitosis, but also causes prometaphase and cytokinesis arrest. Therefore, we revealed STK16 as a novel actin binding protein that resides in the Golgi, which regulates actin dynamics to control Golgi structure and participate in cell cycle progression.

A Reinvestigation of a Superhard Tetragonal sp³ Carbon Allotrope.

I 4 ¯ -carbon was first proposed by Zhang et al., this paper will report regarding this phase of carbon. The present paper reports the structural and elastic properties of the three-dimensional carbon allotrope I 4 ¯ -carbon using first-principles density functional theory. The related enthalpy, elastic constants, and phonon spectra confirm that the newly-predicted I 4 ¯ -carbon is thermodynamically, mechanically, and dynamically stable. The calculated mechanical properties indicate that I 4 ¯ -carbon has a larger bulk modulus (393 GPa), shear modulus (421 GPa), Young's modulus (931 GPa), and hardness (55.5 GPa), all of which are all slightly larger than those of c-BN. The present results indicate that I 4 ¯ -carbon is a superhard material and an indirect-band-gap semiconductor. Moreover, I 4 ¯ -carbon shows a smaller elastic anisotropy in its linear bulk modulus, shear anisotropic factors, universal anisotropic index, and Young's modulus.

Discovery of N-((1-(4-(3-(3-((6,7-Dimethoxyquinolin-3-yl)oxy)phenyl)ureido)-2-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)propionamide (CHMFL-KIT-8140) as a Highly Potent Type II Inhibitor Capable of Inhibiting the T670I "Gatekeeper" Mutant of cKIT Kinase.

cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited both cKIT wt (IC50 = 33 nM) and cKIT gatekeeper T670I mutant (IC50 = 99 nM). Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM). In the cellular context it strongly inhibited c-KIT mediated signaling pathways and induced apoptosis. In the BaF3-TEL-cKIT-T670I isogenic cell inoculated xenograft mouse model, 35 exhibited dose dependent tumor growth suppression efficacy and 100 mg/kg dosage provided 47.7% tumor growth inhibition (TGI) without obvious toxicity. We believe compound 35 would be a good pharmacological tool for exploration of the cKIT-T670I mutant mediated pathology in GISTs.

Discovery of a Highly Selective STK16 Kinase Inhibitor.

STK16, a serine/threonine protein kinase, is ubiquitously expressed and is conserved among all eukaryotes. STK16 has been implicated to function in a variety of cellular processes such as VEGF and cargo secretion, but the pathways through which these effects are mediated remain to be elucidated. Through screening of our focused library of kinase inhibitors, we discovered a highly selective ATP competitive inhibitor, STK16-IN-1, which exhibits potent inhibitory activity against STK16 kinase (IC50: 0.295 µM) with excellent selectivity across the kinome as assessed using the KinomeScan profiling assay (S score (1) = 0.0). In MCF-7 cells, treatment with STK16-IN-1 results in a reduction in cell number and accumulation of binucleated cells, which can be recapitulated by RNAi knockdown of STK16. Co-treatment of STK16-IN-1 with chemotherapeutics such as cisplatin, doxorubicin, colchicine, and paclitaxel results in a slight potentiation of the antiproliferative effects of the chemotherapeutics. STK16-IN-1 provides a useful tool compound for further elucidating the biological functions of STK16.

Anterolateral intermuscular approach for type A2 intertrochanteric fractures: a cadaveric study.

This cadaveric study was designed to clarify the anatomic basis of using an anterolateral intermuscular approach to repair type A2 intertrochanteric fractures (ITF). The conventional lateral approach to surgery that is used for ITF has several disadvantages that can result in both intraoperative and postoperative complications, especially for type A2 ITF. Previous studies have suggested using minimally-invasive total hip arthroplasty (THA) with an anterolateral approach. The legs of 10 formalin-fixed Asian cadavers were dissected, simulating an anterolateral surgical approach. The distances from the superior gluteal nerve and the lateral femoral circumflex artery branches to the lateral protrusive point of the greater trochanter were measured. The anterolateral intermuscular approach provided excellent exposure of the GT, the lesser trochanter and the femoral neck. The gluteus medius branch of the ascending branch of the lateral femoral circumflex artery (GMB-LFCA) and the most inferior branch of the superior gluteal nerve (MIB-SGN) were found to cross the spatium intermusculare between the gluteus medius and the tensor fasciae latae. The distance from the GMB-LFCA, in the intermuscular plane, to the lateral protrusive point of the GT was (4.04 ± 1.00 cm, range 2.96-6.62 cm); and the distance from the MIB-SGN to the lateral protrusive point of the GT was (5.47 ± 1.61 cm, range 3.68-9.56 cm). The anterolateral intermuscular approach is relatively safe, provides excellent exposure, and causes less soft-tissue damage than the traditional approach, and it represents a promising new method to surgically treat type A2 ITF.

Anatomic study of individualized and improved pedicle screw implantation in the lower cervical spine.

The objective of this study was to explore a safe, reliable, and effective method for pedicle screw implantation in the lower cervical spine. Recently, a number of studies have shown that cervical pedicle screw fixation is better than roadside steel plate after cervical screw internal fixation within the scope of its indications. However, the difficulty of the former surgery technology is relatively higher and it is much easier to cause many complications. Therefore, domestic and foreign scholars have been positively exploring safer, easier operations and cheaper methods of pedicle screw implantation in the lower cervical spine. The lower cervical spine areas (C3-C7) of 7 adult cadavers were carried out with computed tomography (CT) scans of 1-mm slices. The entry point, angle, and length of the screws were determined by the measurement of CT images in a picture archiving and communication system. The pedicle screws were implanted with the technique of improved Abumi pedicle screw placement in the lab. The accuracy of the screws was evaluated by the Andrew CT classification criteria of pedicle screw position and gross observation after the experiment. A total of 66 screws were implanted in the lower cervical spine, and 90.9% of the screws inserted were found to be in an optimal position. The method of individualized and improved pedicle screw implantation in the lower cervical spine is relatively safe and reliable, which can be considered to be used in the clinic.

Enhanced suicide gene therapy by chimeric tumor-specific promoter based on HSF1 transcriptional regulation.

Two tandem cassettes, one containing the telomerase reverse transcriptase gene (hTERT) promoter upstream of a constitutively activated form of heat shock transcription factor 1 (cHSF1) and followed by the other containing the heat shock protein 70B (hsp70B) promoter (HSE) upstream of the cytosine deaminase (CD) gene, could greatly enhance the efficiency of CD gene therapy while retaining tumor specificity in vitro and in vivo. This hTERT-cHSF1/HSE promoter could restrict gene expression in tumor cells and was about 1.5-3-fold more potent than the cytomegalovirus (CMV) promoter. hTERT-cHSF1/HSE-CD transfection led to tumor cells more sensitive to 5-fluorocytosine compared with hTERT-CD and its toxicity was comparable to that of CMV-CD. Besides enhancement of promoter activity, cHSF1 overexpression itself could enhance the bystander effect of CD gene therapy that could be reversed by anti-Fas antibody. This system also led to activation of stress-related genes such as hsp70 in tumor cells, which in the presence of cell killing by the cytotoxic gene is a highly immunostimulatory event. Furthermore, a more potent anti-tumor effect of hTERT-cHSF1/HSE-CD was observed in nude mice inoculated with Bcap37 cells. No obvious activity of the hTERT-cHSF1/HSE promoter was observed in normal tissues after intravenous administration. These results indicate that the hTERT-cHSF1/HSE promoter is highly tumor-specific and strong with potential application in targeted gene therapy, and therefore may be useful for construction of vectors for systemic therapy.

Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma.

BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling and cellular assays to develop a potent, selective, and irreversible BTK kinase inhibitor, QL47, which covalently modifies Cys481. QL47 inhibits BTK kinase activity with an IC50 of 7 nM, inhibits autophosphorylation of BTK on Tyr223 in cells with an EC50 of 475 nM, and inhibits phosphorylation of a downstream effector PLCγ2 (Tyr759) with an EC50 of 318 nM. In Ramos cells QL47 induces a G1 cell cycle arrest that is associated with pronounced degradation of BTK protein. QL47 inhibits the proliferation of B-cell lymphoma cancer cell lines at submicromolar concentrations.

Synchronous osteoclastoma and anaplastic astrocytoma: A case report.

Multiple primary neoplasms are defined as multiple occurrences of malignant neoplasms of differing histological origin in the same individual. The present study describes the case of a 46-year-old male who suffered from two synchronous primary malignant neoplasms, an osteoclastoma of the left femoral trochanter and an anaplastic astrocytoma of the the Sylvian fissure area in the brain. At the 6-month follow-up, the patient presented no problems following the aggressive treatment, including surgical resection, radiation therapy and chemotherapy. To the best of our knowledge, this is the first study in the medical literature of such a presentation.

[New anterolateral approach of distal femur for treatment of distal femoral fractures].

OBJECTIVE: To assess the effectiveness of the new anterolateral approach of the distal femur for the treatment of distal femoral fractures. METHODS: Between July 2007 and December 2009, 58 patients with distal femoral fractures were treated by new anterolateral approach of the distal femur in 28 patients (new approach group) and by conventional approach in 30 patients (conventional approach group). There was no significant difference in gender, age, cause of injury, affected side, type of fracture, disease duration, complication, or preoperative intervention (P > 0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, hospitalization days, and Hospital for Special Surgery (HSS) score of knee were recorded. RESULTS: Operation was successfully completed in all patients of 2 groups, and healing of incision by first intention was obtained; no vascular and nerves injuries occurred. The operation time and intraoperative fluoroscopy frequency of new approach group were significantly less than those of conventional approach group (P < 0.05). But the intraoperative blood loss and the hospitalization days showed no significant difference between 2 groups (P > 0.05). All patients were followed up 12-36 months (mean, 19.8 months). Bone union was shown on X-ray films; the fracture healing time was (12.62 +/- 2.34) weeks in the new approach group and was (13.78 +/- 1.94) weeks in the conventional approach group, showing no significant difference (t=2.78, P=0.10). The knee HSS score at last follow-up was 94.4 +/- 4.2 in the new approach group, and was 89.2 +/- 6.0 in the conventional approach group, showing significant difference between 2 groups (t=3.85, P=0.00). CONCLUSION: New anterolateral approach of the distal femur for distal femoral fractures has the advantages of exposure plenitude, minimal tissue trauma, and early function rehabilitation training so as to enhance the function recovery of knee joint.

[Effectivenes of anterolateral C-shaped approach in treatment of intertrochanteric fracture of femur in elderly patient].

OBJECTIVE: To study the effectiveness of anterolateral C-shaped approach in the treatment of intertrochanteric fracture of the femur in elderly patient by comparing with traditional anterolateral approach. METHODS: Between April 2010 and November 2011, 66 patients with intertrochanteric fracture of the femur were analyzed retrospectively. Of 66 patients, 37 underwent improved anterolateral C-shaped approach combined with fixation of dynamic hip screw (DHS) (improved group), and 29 underwent traditional anterolateral approach combined with fixation of DHS (conventional group). There was no significant difference in gender, age, injury cause, side, disease duration, fracture type, and complication between 2 groups (P > 0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and hospitalization time were recorded; and X-ray films were taken to observe the fracture healing. The hip function was evaluated according to self-established criterion. RESULTS: The operation was successfully completed in all patients, and primary healing of incision was achieved. All patients were followed up 12-24 months (mean, 17.8 months). Bone union was achieved in both groups; the fracture healing time was 3-6 months (mean, 4.8 months). No loosening or breaking of internal fixation was observed during follow-up period. The operation time and postoperative drainage volume of improved group were significantly less than those of conventional group (P < 0.05); no significant difference was found in intraoperative blood loss and hospitalization days between 2 groups (P > 0.05). According to self-established criterion, improved group was significantly better than conventional group in recovery of hip joint motion and function at 6 and 12 months after operation (P < 0.05). CONCLUSION: Anterolateral C-shaped approach combined with DHS could minimize muscle injury and scar formation, which is beneficial to surgical exposure and early postoperative rehabilitation.