Verification of bee algorithm based path planning for a 6DOF manipulator using ADAMS

In this article the end effector displacement control for a manipulator robot with 6 rotational joints on a predetermined 3-dimensional trajectory is investigated. Since for any end effector position there are more than a single set of answers, regarding to robot parts orientation, finding a method which gives the designer all existing states will lead to more freedom of action. Hence two different methods were applied to solve robot inverse kinematic issue. In the first method ADAMS software was considered, which is a well-known software in the field of solving inverse kinematic problems, and after that BA algorithm is used as an intelligent method. This method is one of the fastest and most efficient methods among all existing ones for solving non-linear problems. Hence problem of inverse kinematic solution is transformed into an affair of optimization. Comparison of results obtained by both models indicates the reasonable performance of BA because of its capability in providing the answers from all existing states along with the privilege of no need to 3D modeling

An EGFR Targeted PET Imaging Probe for the Detection of Colonic Adenocarcinomas in the Setting of Colitis

Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes. We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models. Cetuximab F(ab′)2 fragments were enzymatically generated, purified, and DOTA-conjugated. Radiolabeling was performed with 67Ga for cell based studies and 64Cu for in vivo imaging. Competitive binding studies were performed on CT26 cells to assess affinity (KD) and receptors per cell (Bmax). In vivo imaging using the EGFR targeted PET probe and 18F FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings. Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged. The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 ± 5% and ≥99% radiochemical purity. The KD was 6.6 ± 0.7 nM and the Bmax for CT26 cells was 3.3 ± 0.1 × 106 receptors/cell. Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both 18F-FDG (3.95 ± 0.13) and the developed 64Cu-DOTA-cetuximab-F(ab′)2 probe (4.42 ± 0.11) in control mice. The TBR for the EGFR targeted probe remained high (3.78 ± 0.06) in the setting of colitis, while for 18F FDG, this was markedly reduced (1.54 ± 0.08). Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo. A clinically translatable PET imaging probe was successfully developed to assess EGFR. The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high-risk patients

Comparison of three primer pairs included: novel primers IS711, universal primers B4 - B5 and 16SrRNA in the diagnosis of human brucellosis in suspected patients in Iran

The genus Brucella is a worldwide distributed intracellular bacteria, which infects animals and human. Currently, this zoonosis has been diagnosed by microbiological and serological laboratory tests. Different PCR protocols with various primer pairs and different target genes have been published for the detection of Brucella, but only a few of these primers have been used in human samples. This study aimed to evaluate and compare the sensitivity and specificity of three primer pairs in the PCR technique, each of which separately amplifies three different regions in the Brucella genome, to determine which are more comfortable for the detecting of Brucella DNA in human clinical samples. 49 clinical serum samples were isolated from suspected patients in different cities in Iran from October 2017 to July 2018. The suspected patients with brucellosis-compatible symptoms were checked. These primers amplified 3 distinctive fragments in BCSP 31 gene (B4/B5), Designed IS711 primers, and a sequence of 16SrRNA of Brucella melitensis. The results showed that the B4/B5 primer pair had the highest sensitivity and specificity for the detection of both positive and negative samples (100%). The designed IS711 primer pair detected 94% of samples, whereas the 16SrRNA primer pair was the least sensitivity, being able to detect only 30.64% of samples. The specificity of 3 techniques was 100%. The B4/B5 primers were able to detect the smallest number of bacteria 0.05 CFU/reaction whereas IS711 was able to detect 2 CFU/reaction and 16SrRNA was able to detect 2×105 CFU/reaction. &nbsp

Fatalities Among Iranian High-altitude Outdoor Enthusiasts: Causes and Mechanisms

Purpose: This study was performed to determine the possible causes and mechanisms of fatalities among Iranian mountaineers during climbing. Methods: By contacting several sources, deceased mountaineers were identified. Data about the causes and mechanism of death was retrospectively obtained using a standard questionnaire for each case. Results: A total of 29 deaths were identified from March 2006 to June 2010. Deceased subjects had a mean age of 39 years (SD: 12.8, Range: 20-67). Falling was the most common accident leading to death of outdoor enthusiasts (n = 14, 48%). Asphyxia (n = 6, 24%) was the most common cause of death among the subjects, followed by heart attack, internal bleeding, cerebral hemorrhage and hypothermia (17%, 17%, 17% and 10%, respectively). Conclusions: Our findings suggest that education of medical service providers of the climbing groups on facing victims in high altitude areas, where they have limited resources, can be particularly helpful. In addition, a national program to educate mountaineers might help to reduce fatalities

The impact of N-myc amplification on median survival in children with neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression

Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients

White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps

Spach Transformer: Spatial and Channel-wise Transformer Based on Local and Global Self-attentions for PET Image Denoising

Position emission tomography (PET) is widely used in clinics and research due to its quantitative merits and high sensitivity, but suffers from low signal-to-noise ratio (SNR). Recently convolutional neural networks (CNNs) have been widely used to improve PET image quality. Though successful and efficient in local feature extraction, CNN cannot capture long-range dependencies well due to its limited receptive field. Global multi-head self-attention (MSA) is a popular approach to capture long-range information. However, the calculation of global MSA for 3D images has high computational costs. In this work, we proposed an efficient spatial and channel-wise encoder-decoder transformer, Spach Transformer, that can leverage spatial and channel information based on local and global MSAs. Experiments based on datasets of different PET tracers, i.e., $^{18}$F-FDG, $^{18}$F-ACBC, $^{18}$F-DCFPyL, and $^{68}$Ga-DOTATATE, were conducted to evaluate the proposed framework. Quantitative results show that the proposed Spach Transformer can achieve better performance than other reference methods.Comment: 10 page

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64$\pm$0.14 and 4.50$\pm$0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88$\pm$0.04 and 0.81$\pm$0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions

A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis

5′AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63–78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63–78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment