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The present study was conducted at Sabarmati Ashram Gaushala, Bidaj, Gujarat. A total of 427 donor animals were investigated over a ten-year period to assess the efficiency of Standard protocol of Multiple Ovulation and Embryo Transfer (MOET). Simultaneously a season wise and breed wise study was also conducted. Breeds studied were Gir, HF, HFCB, Jersey, JYCB, Red Sindhi and Sahiwal. Overall average number of embryos, average number of viable embryos, number of pregnancies and conception rate (%) were found to be 7.8, 4.8, 281 and 39.4, respectively. The year-wise number of pregnancies and conception rates varied from 09 to 42, and 24.6% in 2009-10 to the highest 61.3% in 20014-15, respectively. Further, breed-wise results showed average viable embryo in different breeds as 2.8 in Gir, 4.1 in HF, 5.1 in HFCB, 6.3 in Jersey, 5.8 in JYCB, 3.7 in Red Sindhi and 6.6 in Sahiwal, with corresponding conception rates of 67.7. 34.6, 28.8, 53.1, 39.4, 47.1 and 36.4 %, respectively. A trend was observed that the efficiency of MOET programme was less during monsoon (31.2%) as compared to summer and winter (41.5 and 41.4%).

Abdominal seat belt sign (SBS) has historically entailed admission and observation because of the diagnostic limitations of computed tomography (CT) imaging and high rates of hollow viscus injury (HVI). Recent single-institution, observational studies have questioned the utility of this practice.To evaluate whether a negative CT scan can safely predict the absence of HVI in the setting of an abdominal SBS.This prospective, observational cohort study was conducted in 9 level I trauma centers between August 2020 and October 2021 and included adult trauma patients with abdominal SBS.Inclusion in the study required abdominal CT as part of the initial trauma evaluation and before any surgical intervention, if performed. Results of CT scans were considered positive if they revealed any of the following: abdominal wall soft tissue contusion, free fluid, bowel wall thickening, mesenteric stranding, mesenteric hematoma, bowel dilation, pneumatosis, or pneumoperitoneum.Presence of HVI diagnosed at the time of operative intervention.A total of 754 patients with abdominal SBS had an HVI prevalence of 9.2% (n = 69), with only 1 patient with HVI (0.1%) having a negative CT (ie, none of the 8 a priori CT findings). On bivariate analysis comparing patients with and without HVI, there were significant associations between each of the individual CT scan findings and the presence of HVI. The strongest association was found with the presence of free fluid, with a more than 40-fold increase in the likelihood of HVI (odds ratio [OR], 42.68; 95% CI, 20.48-88.94; P .001). The presence of free fluid also served as the most effective binary classifier for presence of HVI (area under the receiver operator characteristic curve [AUC], 0.87; 95% CI, 0.83-0.91). There was also an association between a negative CT scan and the absence of HVI (OR, 41.09; 95% CI, 9.01-727.69; P .001; AUC, 0.68; 95% CI, 0.66-0.70).The prevalence of HVI among patients with an abdominal SBS and negative findings on CT is extremely low, if not zero. The practice of admitting and observing all patients with abdominal SBS should be reconsidered when a high-quality CT scan is negative, which may lead to significant resource and cost savings.

Natalie S. Lui

Background: The process of In Vitro Fertilization (IVF) involves collecting multiple samples of mature eggs that are fertilized with sperms in the IVF laboratory. They are eventually graded, and the most viable embryo out of all the samples is selected for transfer in the mother’s womb for a healthy pregnancy. Currently, the process of grading and selecting the healthiest embryo is performed by visual morphology, and manual records are maintained by embryologists. Objectives: Maintaining manual records makes the process very tedious, time-consuming, and error-prone. The absence of a universal grading leads to high subjectivity and low success rate of pregnancy. To improve the chances of pregnancy, multiple embryos are transferred in the womb elevating the risk of multiple pregnancies. In this paper, we propose a deep learning-based method to perform the automatic grading of the embryos using time series prediction with Long Short Term Memory (LSTM) and Convolutional Neural Network (CNN). Methods: CNN extracts the features of the images of embryos, and a sequence of such features is fed to LSTM for time series prediction, which gives the final grade. Results: Our model gave an ideal accuracy of 100% on training and validation. A comparison of obtained results is made with those obtained from a GRU model as well as other pre-trained models. Conclusion: The automated process is robust and eliminates subjectivity. The days-long hard work can now be replaced with our model, which gives the grading within 8 seconds with a GPU.

The major drawback of using Fluo-4 AM is that it requires an organic anion transporter inhibitor, such as probenecid, to prevent leakage. This can hinder the studies that require extended monitoring time and longer cellular retention. To address the issue, a novel Ca2+ indicator, Calbryte 520 AM, was developed. We compared the performance of Fluo-4 AM and Calbryte 520 AM following prolonged incubation periods after cell loading. Cells loaded with Calbryte 520 AM retained the dye for up to 24 h while exhibiting significant fluorescence brightness and superior Fmax/F0 ratios (Fmax: fluorescence intensity upon stimulation; F0: intensity before stimulation). It demonstrated that the longer retention of Calbryte 520 AM can be exploited to accommodate for the extended time required when monitoring calcium dynamics.

This study examined monthly prevalence of obesity and exercise in active component U.S. military members prior to and during the COVID-19 pandemic. Information about obesity (BMI≥30) and self-reported vigorous exercise (≥150 minutes per week) were collected from Periodic Health Assessment (PHA) data. From 1 January 2018 through 31 July 2021, there was a gradual increase in obesity and an overall decrease in vigorous exercise. Comparing the mean monthly percentage of obesity during the 12-month period prior to the pandemic to the 12 months after its start showed an overall increase in obesity (0.43%); however, no obvious spike in the obesity trend was apparent following the onset of the pandemic. The prevalence of vigorous exercise showed an abrupt decrease following the onset of the COVID-19 pandemic, but this change did not coincide with an abrupt change in the obesity trend. These results suggest that the COVID-19 pandemic had a small effect on the trend of obesity in the active component U.S. military and that obesity prevalence continues to increase.

This study examined the rates of depressive symptoms in active component U.S. service members prior to and during the COVID-19 pandemic and evaluated whether SARS-CoV-2 test results (positive or negative) were associated with self-reported depressive symptoms. Depressive symptoms were measured by the Patient Health Questionnaire-2 (PHQ-2) screening instrument and were defined as positive if the total score was 3 or greater. From 1 January 2019 through 31 July 2021, 2,313,825 PHQ-2s were completed with an increase in the positive rate from 4.0% to 6.5% (absolute % difference, +2.5%; relative % change, +67.1%) from the beginning to the end of the period. While there was a gradual increase of 19.8% in the months prior to the pandemic (1.4%/month average), this increase grew to 40.4% during the pandemic (2.5%/month average). However, no association was found between a positive or negative SARS-CoV-2 test result and the PHQ-2 screening instrument result. These findings suggest that the accelerated increase in depressive symptoms is likely a function of the environment of the COVID-19 pandemic instead of the SARS-CoV-2 infection itself. Further research to better understand specific factors of the pandemic leading to depressive symptoms will improve efficient allocation of military medical resources and safeguard military medical readiness.

OBJECTIVES The oncological efficacy of minimally invasive thymectomy for thymic carcinoma is not well characterized. We compared overall survival and short-term outcomes between open and minimally invasive surgical (video-assisted thoracoscopic and robotic) approaches using the National Cancer Database. METHODS Perioperative outcomes and overall survival of patients who underwent open versus minimally invasive thymectomy for Masaoka stage I–III thymic carcinoma from 2010 to 2015 in the National Cancer Database were evaluated using propensity score-matched analysis and multivariable Cox proportional hazards modelling. Outcomes by surgical approach were assessed using an intent-to-treat analysis. RESULTS Of the 216 thymectomies that were evaluated, 43 (20%) were performed with minimally invasive techniques (22 video-assisted thoracoscopic and 21 robotic). The minimally invasive approach was associated with a shorter median length of stay when compared to the open approach (3 vs 5 days, P < 0.001). In the propensity score-matched analysis of 30 open and 30 minimally invasive thymectomies, the minimally invasive group did not differ significantly in median length of stay (3 vs 4.5 days, P = 0.27), 30-day readmission (P = 0.13), 30-day mortality (P = 0.60), 90-day mortality (P = 0.60), margin positivity (P = 0.39) and 5-year survival (78.6% vs 54.6%, P = 0.15) when compared to the open group. CONCLUSIONS In this national analysis, minimally invasive thymectomy for stage I–III thymic carcinoma was found to have no significant differences in short-term outcomes and overall survival when compared to open thymectomy.

The major drawback of using Fluo-4 AM is that it requires an organic anion transporter inhibitor, such as probenecid, to prevent leakage. This can hinder the studies that require extended monitoring time and longer cellular retention. To address the issue, a novel Ca

Agriculture provides food for human existence, where insects damage the crops. The identification of the insect is a difficult process and subjected to expert opinion. In recent years, researches using deep learning in fields of object detection have been widespread and show accuracy as a result. This study show the comparison of three widely used deep learning meta-architectures (Faster R-CNN, SSD Inception and SSD Mobilenet) as object detection for selected flying insects namely Phyllophaga spp., Helicoverpa armigera and Spodoptera litura. The proposed study is focused on accuracy performance of selected meta-architectures using small dataset of insects. The meta-architecture was tested with same environment for all three architectures and Faster RCNN meta-architecture performs outstanding with an accuracy of 95.33%.

Objectives This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. Background Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. Methods Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. Results Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p Conclusions This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Purpose To examine the association between telomere length and neurodevelopment in children. Methods We examined the relationship between relative telomere length (rTL) and neurodevelopmental outcomes at 9 and 30 months, and 5 years of age in children enrolled in the Seychelles Child Development Study Nutrition Cohort 1 (NC1). Relative telomere length was measured in cord blood and in child blood at age five. Multivariable linear regression examined associations between neurodevelopmental outcomes and rTL adjusting for relevant covariates. Results Mean rTL was 1.18 at birth and 0.71 at age five. Increased cord blood rTL was associated with better scores on two neurodevelopmental tests, the psychomotor developmental index (β = 4.01; 95% confidence interval (CI) = 0.17, 7.85) at age 30 months, and the Woodcock Johnson test of achievement letter-word score (β = 2.88; CI = 1.21–4.56) at age five. The Woodcock Johnson test of achievement letter-word score remained statistically significant after two outliers were excluded (β = 2.83; CI = 0.69, 4.97); the psychomotor developmental index did not (β = 3.62; CI = −1.28, 8.52). None of the neurodevelopmental outcomes at age five were associated with five-year rTL. Conclusion Although increased cord blood rTL was associated with better test scores for a few neurodevelopmental outcomes, this study found little consistent evidence of an association between rTL and neurodevelopment. Future studies with a larger sample size, longer follow-up, and other relevant biological markers (e.g. oxidative stress) are needed to clarify the role of rTL in neurodevelopment and its relevance as a potential surrogate measure for oxidative stress in the field of developmental neurotoxicity.

Lipids are important nutrients that proliferating cells require to maintain energy homeostasis as well as to build plasma membranes for newly synthesized cells. Previously, we identified nutrient-sensing checkpoints that exist in the latter part of the G1 phase of the cell cycle that are dependent upon essential amino acids, Gln, and finally, a checkpoint mediated by mammalian target of rapamycin (mTOR), which integrates signals from both nutrients and growth factors. In this study, we have identified and temporally mapped a lipid-mediated G1 checkpoint. This checkpoint is located after the Gln checkpoint and before the mTOR-mediated cell cycle checkpoint. Intriguingly, clear cell renal cell carcinoma cells (ccRCC) have a dysregulated lipid-mediated checkpoint due in part to defective phosphatase and tensin homologue (PTEN). When deprived of lipids, instead of arresting in G1, these cells continue to cycle and utilize lipid droplets as a source of lipids. Lipid droplets have been known to maintain endoplasmic reticulum homeostasis and prevent cytotoxic endoplasmic reticulum stress in ccRCC. Dysregulation of the lipid-mediated checkpoint forces these cells to utilize lipid droplets, which could potentially lead to therapeutic opportunities that exploit this property of ccRCC.

Cholesterol is a critical component of membranes and a precursor for hormones and other signaling molecules. Previously, we showed that unlike astrocytes, glioblastoma cells do not downregulate cholesterol synthesis when plated at high density. In this report, we show that high cell density induces ABCA1 expression in glioblastoma cells, enabling them to get rid of excess cholesterol generated by an activated cholesterol biosynthesis pathway. Because oxysterols are agonists for Liver X Receptors (LXRs), we investigated whether increased cholesterol activates LXRs to maintain cholesterol homeostasis in highly-dense glioblastoma cells. We observed that dense cells had increased oxysterols, which activated LXRβ to upregulate ABCA1. Cells with CRISPR-mediated knockdown of LXRβ, but not ABCA1, had decreased cell cycle progression and cell survival, and decreased feedback repression of the mevalonate pathway in densely-plated glioma cells. LXRβ gene expression poorly correlates with ABCA1 in glioblastoma patients, and expression of each gene correlates with poor patient prognosis in different prognostic subtypes. Finally, gene expression and lipidomics analyses cells revealed that LXRβ regulates the expression of immune response gene sets and lipids known to be involved in immune modulation. Thus, therapeutic targeting of LXRβ in glioblastoma might be effective through diverse mechanisms.

Funding opportunities in science are essential to the research and development ecosystem. Numerous and competitive, the vast majority focus on scientific accomplishment. While the advancement of science remains a top priority, some funding agencies started to reshape their programs to include strict training requirements, from training plans included in proposals to regular evaluations of training progress. At the centre of this change is the recognition of the universities and colleges educational mission through research, and the need for a highly qualified workforce serving industry, science, and research. It is this need for applied research training, expressed by the Canadian aerospace community, that led to the creation of the Canadian Space Agency’s FAST (Flights and Fieldwork for the Advancement of Science and Technology) funding activity in 2011. Among the three main objectives of the 2017 opportunity, two target training the next and current generations of scientists and engineers for space-related areas in Canada by (1) developing and maintaining a critical mass of researchers, and (2) increasing the level of student employability by exposing them to practical experiences. In this paper, we report about the context behind CSA FAST’s creation, the funding opportunity model, and the impact of the funding activity. Concrete results are also shown for the HiCIBaS project, funded by CSA FAST 2015, an ambitious balloon-borne mission with an optical payload for wavefront sensing and exoplanet imaging that was led by 5 graduate students as part of their master’s program, and that culminated with a stratospheric balloon flight in August 2018.

Introduction NHS England announced a new nurse angiographer role with the purpose of reducing hospital waiting lists for elective angiography. Methods Development of a standardised operating procedure for training in Radial Arterial Access (RAA), guidance on how to minimise the risk and recognise complications and post procedural limb management. Obtaining approval at the new procedures committee. Training program 50 consultant supervised nurse led procedures for (RAA), establishing expertise in 100 further procedures, followed by roll out of the program to other nursing staff. Results During training (RAA) cannulation was successful on 1st attempt in 42 out of 50 (success rate allowing for two attempts 84%), with no complications recorded. Successful access by a more experienced operator N = 7, failed (RAA) N = 1. The following 100 were performed independently on unselected patients (success rate 81%; (1st pass 70)), with no complications, need for alternate access routes, N = 1. The following table details the success rate and patient comfort score recorded during 104 procedures performed by a nurse specialist and trainee registrars. Conclusion Nurse-led (RAA) is safe and feasible and has the potential to improve catheter laboratory efficiency, patient satisfaction, standardise procedure training and improve staff retention. Our next steps will be to train more nurses in radial access and progress to nurse led angiography. Conflict of Interest None

This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two.Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow.Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography.Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p 0.001). In patients without regional perfusion defects, global stress MBF 1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p 0.001).This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Cholesterol is a critical component of membranes and a precursor for hormones and other signaling molecules. Previously, we showed that unlike astrocytes, glioblastoma cells do not downregulate cholesterol synthesis when plated at high density. In this report, we show that high cell density induces ABCA1 expression in glioblastoma cells, enabling them to get rid of excess cholesterol generated by an activated cholesterol biosynthesis pathway. Because oxysterols are agonists for Liver X Receptors (LXRs), we investigated whether increased cholesterol activates LXRs to maintain cholesterol homeostasis in highly-dense glioblastoma cells. We observed that dense cells had increased oxysterols, which activated LXRβ to upregulate ABCA1. Cells with CRISPR-mediated knockdown of LXRβ, but not ABCA1, had decreased cell cycle progression and cell survival, and decreased feedback repression of the mevalonate pathway in densely-plated glioma cells. LXRβ gene expression poorly correlates with ABCA1 in glioblastoma patients, and expression of each gene correlates with poor patient prognosis in different prognostic subtypes. Finally, gene expression and lipidomics analyses of crLXRβ cells revealed that LXRβ regulates the expression of immune response gene sets and lipids known to be involved in immune modulation. Thus, therapeutic targeting of LXRβ in glioblastoma might be effective through diverse mechanisms.

Glioblastoma is a highly lethal adult brain tumor with no effective treatments. In this review, we discuss the potential to target cholesterol metabolism as a new strategy for treating glioblastomas. Twenty percent of cholesterol in the body is in the brain, yet the brain is unique among organs in that it has no access to dietary cholesterol and must synthesize it de novo. This suggests that therapies targeting cholesterol synthesis in brain tumors might render their effects without compromising cell viability in other organs. We will describe cholesterol synthesis and homeostatic feedback pathways in normal brain and brain tumors, as well as various strategies for targeting these pathways for therapeutic intervention.

In agriculture, Pests are decreasing agricultural productivity. Identifying a pest is a challenging process and subject to expert opinion. Nowadays, lots of work carried out for automatic pest detection. It becomes possible because of emerging Deep Learning’s object detection architectures. This paper shows the multi-class pest detection using Faster R-CNN architecture and compared the performance results of image augmentation with focused on the accuracy performance along with small dataset. We have used Horizontal Flip and 90 Degree Rotation augmentation parameters for solving class imbalance problem. We found that trained pest detection model with augmentation options can perform better with an accuracy of 91.02% using Faster R-CNN architecture.

Magnesium ion (Mg+2) plays an important role in various biological processes. All the commercial indicators available share a common drawback, i.e., they have a higher affinity towards calcium ions (Ca+2) than Mg+2. In this study, we reported a new robust green fluorescent indicator, Mag-520, for detection of Mg+2 in live cells. Our results showed that Mag-520 has 10 fold higher affinity towards Mg+2 than Ca+2, while mag-fluo-4 has less than 0.5 fold affinity to Mg+2 than Ca+2 under the same conditions using flow cytometry and fluorescence microscopy. The results demonstrated that Mag-520 provides a better tool to measure Mg+2 with less interference from Ca+2.

Background: Coronavirus disease-2019 (COVID-19) poses a risk for health care workers necessitating modifications to existing medical pathways In particular, managing patients with suspected COVID-19 represents a risk to the delivery of a primary percutaneous coronary intervention (PPCI) pathway where time-dependent revascularization is key Methods: We sought to evaluate the effect of the COVID-19 pandemic on an established ambulance-triggered PPCI program involving 2 high-volume heart attack centers in London, United Kingdom A systematic analysis was performed in patients with ST-segment elevation myocardial infarction undergoing PPCI comparing the COVID-19 pandemic period March 1, 2020, to April 30, 2020, with a control group from the previous year Results: During the study period, admissions through the PPCI pathway decreased by 34% The time from symptoms onset to first call for help (2020: 11 min vs 2019: 12 min;p = 0 90) and from symptom onset to arrival at PPCI center (2020: 183 min vs 2019: 178 min;p = 0 99) were comparable;however, the time from arrival at PPCI center to revascularization decreased (2020: 44 min vs 2019: 53 min;p = 0 0004) In-hospital mortality during the study period was significantly lower (5% vs 15%;p = 0 04) COVID-19–positive patients (n = 8) had higher rates of cardiogenic shock (25%), intensive care unit admission (50%), and inpatient mortality (38%) [Formula presented] Conclusion: Our data show that the modifications to the existing PPCI pathway were not associated with treatment delay or adverse outcome The reduction in ST-segment elevation myocardial infarction presentations raises concern that patients may not be seeking appropriate medical attention for chest pain Importantly, we demonstrate that PPCI can be delivered safely and efficiently during the COVID-19 pandemic Categories: OTHER: COVID-19

The rapid advances in sequencing, genomics and bioinformatics have generated a huge amount of genomic data available at our disposal. However, some proteins, the products of those genes, are expressed in cells or tissues at extremely low levels, making the identification and characterization of proteins the bottle neck for biomedical research field. Approximately, 65% of the human proteome is expressed at less than a few thousand copies. Thus, the availability of protein detection probes and tools becomes a critical element to measure lower abundance protein targets in the cells and tissues to identify clinical significance of the particular target proteins. There are several common signal amplification methods available for detecting low abundance protein targets. However, in some cases, their sensitivities are still not satisfactory. Biotin/avidin amplification system has been predominantly used to enhance detection sensitivity but it is still sometimes not sufficient, leading to extremely challenging to accurately measure the low expressed protein targets. There is urgently unmet need to develop a new signal amplification system with enhanced detection sensitivity. We develop the Power Styramide Signal Amplification (PSA) system that can detect extremely low-abundance targets in cells and tissues. The PSA technique is much more sensitive than the traditionally used biotin/avidin and TSA amplification methods. PSA uses a concept that utilizes the catalytic activity of horseradish peroxide (HRP) for covalent deposition of Styramide in situ. The radicals generated from the Styramide based substrates have much higher reactivity towards the target, thus producing a more robust signal and achieve much higher sensitivity towards lower expressed targets. When this technique was compared to directly conjugated antibody, we saw a significant increase in the signal and improved detection limit by 10-100 folds. Another advantage using Styramide-based substrates is that the need of either primary or secondary antibodies gets significantly reduced. You can get robust signal just by using very little antibodies without sacrificing the quality of the fluorescent images. Overall, this new technology enables us to detect low expressed targets in cells or tissues using lower antibody concentration with high detection limit. Citation Format: Deven Patel, Jixiang Liu, Pengfei Dong, Shu Kan, Haiyan Wu, Qin Zhao, Zhenjun Diwu. An enabling technology to detect low abundance targets in cells and tissues [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6311.

The HiCIBaS (High-Contrast Imaging Balloon System) project aims at launching a balloon borne telescope up to 36km to test high contrast imaging equipment and algorithms. The payload consists of a off the shelf 14-inch telescope with a custom-built Alt-Az mount. This telescope provides lights to two sensors, a pyramidal low order wave front sensor, and a coronagraphic wavefront sensor. Since the payload will reach its cruise altitude at about midnight mission, two target stars have been designated for observations, Capella as the night target, and Polaris as the early morning target. Data will be collected mainly on the magnitude of atmospheric and gondola’s turbulences, the luminosity of the background. The whole system is already built and ready to ship to Timmins for the launch in mid-August 2018.

We present the progress in characterization of a Nuv¨ u Cam ¨ eras CCD Controller for Counting Photons ¯ (CCCP) designed for extreme low light imaging in space environment with the 1024×1024 Teledyne-e2V EMCCD detector (the CCD201-20). The EMCCD controller was designed using space qualified parts before being extensively tested in thermal vacuum. The performance test results include the readout noise, clock-induced charges, dark current, dynamic range and EM gain. We also discuss the CCCP’s integration in the coronagraph of the High-Contrast Imaging Balloon System project: a fine-pointing and optical payload for a future Canadian stratospheric balloon mission. This first space qualified EMCCD controller, named CCCPs, will enhance sensitivity of the future low-light imaging instruments for space applications such as the detection, characterization and imaging of exoplanets, search and monitoring of asteroids and space debris, UV imaging, and satellite tracking.

mTOR – the mammalian/mechanistic target of rapamycin – has been implicated as a key signaling node for promoting survival of cancer cells. However, clinical trials that have targeted mTOR with rapamycin or rapamycin analogs have had minimal impact. In spite of the high specificity of rapamycin for mTOR, the doses needed to suppress key mTOR substrates have proved toxic. We report here that rapamycin when combined with AICAR – a compound that activates AMP-activated protein kinase makes rapamycin cytotoxic rather than cytostatic at doses that are tolerated clinically. AICAR by itself is able to suppress mTOR complex 1 (mTORC1), but also stimulates a feedback activation of mTORC2, which activates the survival kinase Akt. However, AICAR also suppresses production of phosphatidic acid (PA), which interacts with mTOR in a manner that is competitive with rapamycin. The reduced level of PA sensitizes mTORC2 to rapamycin at tolerable nano-molar doses leading reduced Akt phosphorylation and apoptosis. This study reveals how the use of AICAR enhances the efficacy of rapamycin such that rapamycin at low nano-molar doses can suppress mTORC2 and induce apoptosis in human cancer cells at doses that are clinically tolerable.

The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of G1 cell cycle progression. Two key substrates of mTORC1 are ribosomal subunit S6 kinase (S6K) and eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4E-BP1). We reported previously that simultaneous knockdown of S6K and eIF4E causes a transforming growth factor-β (TGF-β)-dependent G1 cell cycle arrest in MDA-MB-231 human breast cancer cells. Rapamycin inhibits the phosphorylation of S6K at nano-molar concentrations in MDA-MB-231 cells; however, micro-molar concentrations of rapamycin are required to inhibit phosphorylation of 4E-BP1 – the phosphorylation of which, liberates eIF4E to initiate translation. Micro-molar doses of rapamycin are required for complete G1 cell cycle arrest – indicating that 4E-BP1 is a critical target of mTOR for promoting cell cycle progression. Data are provided demonstrating that G1 cell cycle arrest induced by rapamycin is due to up-regulation of TGF-β signaling and down-regulation of Rb phosphorylation via phosphorylation of the mTORC1 substrates S6K and 4E-BP1 respectively. These findings enhance the current understanding of the cytostatic effects of mTORC1 suppression with therapeutic implications.

AIMS We aimed to examine the prevalence, clinical outcomes and procedural characteristics of percutaneous coronary intervention (PCI) complicated by coronary artery perforation (CAP) in a contemporary patient population. METHODS AND RESULTS Procedural records of 39,115 patients undergoing PCI between 2005 and 2016 were reviewed. CAP affected 149 cases (0.37%). The prevalence of CAP increased from 0.31% in 2005 to 0.45% in 2016 (p=0.03), reflecting an increase in more complex PCI (from 14% in 2005 to 21% in 2016; p

Background. Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)–infected children of low-middleincome countries (LMIC). Methods. An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. Results. Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26–33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5–22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4–17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudineefavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. Conclusions. Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

The frequent traffic jams at major junctions call for an efficient traffic management system in place. The resulting wastage of time and increase in pollution levels can be eliminated on a city-wide scale by these systems. In this paper we present an overview of image processing and analysis tools used in these applications and we relate these tools with complete systems developed for specific traffic applications. More specifically, we categorize processing methods based on their input data as feature-driven, area-driven, or model-based and the domain of processing as spatial or temporal frames.The image sequences from a camera are analyzed using various edge detection and object counting methods to obtain the most efficient technique. Subsequently, the number of vehicles at the intersection is evaluated and traffic is efficiently managed. The paper also proposes to implement a real-time emergency vehicle detection system. In case an emergency vehicle is detected, the lane is given priority over all the others.

Background Coronary artery calcium (CAC) imaging by unenhanced computed X-ray tomography (CT) is recommended as an initial diagnostic test for patients with stable chest pain symptoms but a low likelihood (10–29%) of underlying obstructive coronary artery disease (CAD) after clinical assessment. The recommendation has not previously been tested prospectively in a rapid access chest pain clinic (RACPC). Methods We recruited 300 consecutive patients presenting with stable chest pain to the RACPC of three hospitals. All patients underwent CAC imaging, followed by invasive coronary angiography (ICA) in patients with CAC ≥1000Agatston units (Au) and CT coronary angiography (CTCA) in those with CAC 400 Au have a high prevalence of obstructive CAD and further investigation with ICA or functional imaging may be warranted rather than CTCA. These findings support NICE guidance for the investigation of stable chest pain. ClinicalTrials. gov Identifier NCT01464203

The conjugations of biopolymers are critical tasks in life science field. A traditional method is to use SMCC, but SMCC-modified protein is unstable and easy to cause self-crosslink if the protein contains thiol group. Another known method is based on S-HyNic and Sulfo-S-4FB chemistry, but catalyst is required and the procedure is tedious and long. We developed a Buccutite method to crosslink antibodies to biopolymers (e.g. enzymes and ligonucleotides) or nano particles (such as Qdots and latex beads). This new technique is based on a pair of crosslinkers: Buccutite FOL and MTA. One protein is labeled with MTA, and the other is pre-activated with FOL; when two parts are mixed, the conjugation occurs promptly without any catalyst required. The Buccutite method was validated with the conjugation of antibody with HRP or phycobiliproteins (PE, APC or their tandems). ELISA assays showed the Buccutite antibody-HRP has the same sensitivity as traditional antibody-HRP conjugate. Flow cytometry result also showed the Buccutite conjugates performed as well as the ones prepared with traditional SMCC method when evaluated with human lymphocytes CD antibodies conjugates. Pre-activated proteins (e.g., PE-FOL) were stable for 12 months without any decreasing in performance. Buccutite conjugation was very efficient: there was less than ~10% of the free antibody left, while there was still more than 40% free antibody remaining for the traditional SMCC method. In conclusion, Buccutite method has demonstrated a way to prepare conjugate at high efficiency in short reaction time and mild reaction conditions with the same performance. It is a superior and effective alternative to the existing methods for crosslinking biopolymers to their targets.

BACKGROUND: Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitro fertilization treatment. AIM: The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population. MATERIALS AND METHODS: It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology. RESULTS: Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%). CONCLUSION: Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer.

During G1-phase of the cell cycle, normal cells respond first to growth factors that indicate that it is appropriate to divide and then later in G1 to the presence of nutrients that indicate sufficient raw material to generate two daughter cells. Dividing cells rely on the "conditionally essential" amino acid glutamine (Q) as an anaplerotic carbon source for TCA cycle intermediates and as a nitrogen source for nucleotide biosynthesis. We previously reported that while non-transformed cells arrest in the latter portion of G1 upon Q deprivation, mutant KRas-driven cancer cells bypass the G1 checkpoint, and instead, arrest in S-phase. In this study, we report that the arrest of KRas-driven cancer cells in S-phase upon Q deprivation is due to the lack of deoxynucleotides needed for DNA synthesis. The lack of deoxynucleotides causes replicative stress leading to activation of the ataxia telangiectasia and Rad3-related protein (ATR)-mediated DNA damage pathway, which arrests cells in S-phase. The key metabolite generated from Q utilization was aspartate, which is generated from a transaminase reaction whereby Q-derived glutamate is converted to α-ketoglutarate with the concomitant conversion of oxaloacetate to aspartate. Aspartate is a critical metabolite for both purine and pyrimidine nucleotide biosynthesis. This study identifies the molecular basis for the S-phase arrest caused by Q deprivation in KRas-driven cancer cells that arrest in S-phase in response to Q deprivation. Given that arresting cells in S-phase sensitizes cells to apoptotic insult, this study suggests novel therapeutic approaches to KRas-driven cancers.

This seminal article, published over forty years ago, first outlines the history and diversity of funerary and commemorative architecture in South Asia. It then reproduces a chapter from a medieval...