Self-organization of intrinsically disordered proteins with folded N-termini

Thousands of human proteins lack recognizable tertiary structure in most of their chains. Here we hypothesize that some use their structured N-terminal domains (SNTDs) to organise the remaining protein chain via intramolecular interactions, generating partially structured proteins. This model has several attractive features: as protein chains emerge, SNTDs form spontaneously and serve as nucleation points, creating more compact shapes. This reduces the risk of protein degradation or aggregation. Moreover, an interspersed pattern of SNTD-docked regions and free loops can coordinate assembly of sub-complexes in defined loop-sections and enables novel regulatory mechanisms, for example through posttranslational modifications of docked regions

Maternal Predator Odor Exposure in Mice Programs Adult Offspring Social Behavior and Increases Stress-Induced Behaviors in Semi-Naturalistic and Commonly-Used Laboratory Tasks

Maternal stress has a profound impact on the long-term behavioral phenotype of offspring, including behavioral responses to stressful and social situations. In this study, we examined the effects of maternal exposure to predator odor, an ethologically relevant psychogenic stressor, on stress-induced behaviors in both semi-naturalistic and laboratory-based situations. Adult C57BL/6 mice offspring of dams exposed to predator odor during the last half of pregnancy showed increased anti-predatory behavior, more cautious foraging behavior and, in the elevated plus maze, avoidance of elevated open areas and elevated open areas following restraint stress challenge. These offspring also exhibited alterations in social behavior including reduced free interaction and increased initial investigation despite normal social recognition. These changes in behavior were associated with increased transcript abundance of corticotropin-releasing factor, mineralocorticoid receptor and oxytocin (Oxt) in the periventricular nucleus of the hypothalamus. Taken together, the findings are consistent with a long-term increase in ethologically-relevant behavioral and neural responses to stress in male and female offspring as a function of maternal predator odor exposure

Pfizer

Pfizer was established in 1849 in Brooklyn, New York by cousins Charles Pfizer and Charles Erhart with a loan of $2,500 from Pfizer’s father.2 Today, 167 years later, Pfizer Inc. has international revenues of$49 billion, which makes it the second-largest pharmaceutical manufacturer in the world.3 Despite Pfizer’s success, the company has faced many challenges over the last few decades. The pharmaceutical industry is heavily influenced by legal, political, and technological forces, and all indications are that the industry will continue to experience dramatic changes

Detecting Patches on Road Pavement Images acquired with 3D Laser Sensors using Object Detection and Deep Learning

Regular pavement inspections are key to good road maintenance and road defect corrections. Advanced pavement inspection systems such as LCMS (Laser Crack Measurement System) can automatically detect the presence of different defects using 3D lasers. However, such systems still require manual involvement to complete the detection of pavement defects. This paper proposes an automatic patch detection system using object detection technique. To our knowledge, this is the first time state-of-the-art object detection models Faster RCNN, and SSD MobileNet-V2 have been used to detect patches inside images acquired by LCMS. Results show that the object detection model can successfully detect patches inside LCMS images and suggest that the proposed approach could be integrated into the existing pavement inspection systems. The contribution of this paper are (1) an automatic pavement patch detection models for LCMS images and (2) comparative analysis of RCNN, and SSD MobileNet-V2 models for automatic patch detection

Detecting Patches on Road Pavement Images Acquired with 3D Laser Sensors using Object Detection and Deep Learning

Regular pavement inspections are key to good road maintenance and road defect corrections. Advanced pavement inspection systems such as LCMS (Laser Crack Measurement System) can automatically detect the presence of different defects using 3D lasers. However, such systems still require manual involvement to complete the detection of pavement defects. This work proposes an automatic patch detection system using an object detection technique. Results show that the object detection model can successfully detect patches inside LCMS images and suggest that the proposed approach could be integrated into the existing pavement inspection systems.https://arrow.tudublin.ie/cddpos/1016/thumbnail.jp

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial

OBJECTIVES: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT. RESEARCH DESIGN AND METHODS: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL). RESULTS: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01). CONCLUSIONS: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success. TRIAL REGISTRATION NUMBER: ISRCTN21335883

Comparison of experimental and analytical methods to evaluate thermal bridges in wall systems

Twelve ASTM C0236 guarded hot box experiments have been performed on wall systems containing a variety of thermal bridges. All of the wall systems included steel framing. Six walls also had a concrete block wall system and a concrete slab to simulate a wall/floor intersection. Thermal bridges included in the wall systems included steel studs, steel tracks, steel stud/track joints, fasteners (steel framing system), concrete slab, metal bolts and angle iron, and brick ties (concrete block wall). Two-dimensional finite difference modeling was also employed to characterize the wall systems. The experimental test data was used to tune and ultimately validate the computer simulation model. The average variation between the tested and simulated wall system R-Values was 3.3% and ranged from {minus}3.4 to +7.4%. The model was then used to determine the thermal impact of each individual thermal bridge. Beside the standard complement of temperature sensors that are traditionally used for these laboratory experiments, additional sensors were installed near each thermal bridge to define the area and magnitude of the thermal distortion caused by the thermal bridge. These thermal bridges were analytically simulated and the additional heat flux due to each thermal bridge was computed. This paper summarizes the experimental and analytical analyses used to characterize the wall systems and concentrate on the thermal impact each type of thermal bridge has on the overall performance of the wall systems

The Neurological Ecology of Fear: Insights Neuroscientists and Ecologists Have to Offer one Another

That the fear and stress of life-threatening experiences can leave an indelible trace on the brain is most clearly exemplified by post-traumatic stress disorder (PTSD). Many researchers studying the animal model of PTSD have adopted utilizing exposure to a predator as a life-threatening psychological stressor, to emulate the experience in humans, and the resulting body of literature has demonstrated numerous long-lasting neurological effects paralleling those in PTSD patients. Even though much more extreme, predator-induced fear and stress in animals in the wild was, until the 1990s, not thought to have any lasting effects, whereas recent experiments have demonstrated that the effects on free-living animals are sufficiently long-lasting to even affect reproduction, though the lasting neurological effects remain unexplored. We suggest neuroscientists and ecologists both have much to gain from collaborating in studying the neurological effects of predator-induced fear and stress in animals in the wild. We outline the approaches taken in the lab that appear most readily translatable to the field, and detail the advantages that studying animals in the wild can offer researchers investigating the “predator model of PTSD.

Barrier potential for laser written graphitic wires in diamond

Diamond substrates supporting an internal array of conductive graphitic wires inscribed by a femtosecond pulse laser, are useful for the detection of ionising radiation in a range of applications. Various parameters involved in the laser fabrication process were investigated in this paper to understand their impact on the electrical properties of the wires. The study revealed an effect, whereby the wires exhibit insulating behaviour until a barrier potential is overcome. When high enough voltages are applied, the wires display ohmic behaviour. The magnitude of the barrier potential, which in some cases exceeds 300 V, is shown to be strongly dependent on the laser fabrication parameters. Through process optimisation, the potential barrier may be minimised and effectively removed, coinciding with reduced values of the wire resistance

Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival ofdiagnosis