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Human augmentation

Mark Waldron, Stephen David Patterson, Jamie Tallent, Owen Jeffries
BACKGROUND: Taurine is central to many physiological processes, some of which are augmented by exogenous supply and have the potential to facilitate endurance performance; however, its independent effects on performance have not been systematically analysed. OBJECTIVE: To evaluate the effects of isolated oral taurine ingestion on endurance performance and to assess the contribution of (1) the dose and (2) the supplementation period to the ergogenic effect. METHODS: A search was performed using various databases in September 2017...
March 15, 2018: Sports Medicine
Kimberly R Kalli, Matthew S Block, Pashtoon M Kasi, Courtney L Erskine, Timothy J Hobday, Allan Dietz, Douglas Padley, Michael P Gustafson, Barath Shreeder, Danell Puglisi-Knutson, Daniel W Visscher, Toni Kay Mangskau, Glynn Wilson, Keith L Knutson
PURPOSE: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rasa Tamosiuniene, Olga Manouvakhova, Paul Mesange, Toshie Saito, Jin Qian, Mrinmoy Sanyal, Yu-Chun Lin, Linh P Nguyen, Amir Luria, Allen B Tu, Joshua M Sante, Marlene Rabinovitch, Desmond J Fitzgerald, Brian B Graham, Aida Habtezion, Norbert F Voelkel, Laure Aurelian, Mark R Nicolls
<u>Rationale:</u> Pulmonary arterial hypertension (PH) is a life-threatening condition associated with immune dysregulation and abnormal regulatory T cell (Treg) activity, but it is currently unknown whether and how abnormal Treg function differentially affects males and females. <u>Objective:</u> To evaluate whether and how Treg-deficiency differentially affects male and female rats in experimental PH. <u>Methods and Results:</u> Male and female athymic rnu/rnu rats, lacking Tregs, were treated with the vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor SU5416 or chronic hypoxia and evaluated for PH; some animals underwent Treg immune reconstitution (IR) before SU5416 administration...
March 15, 2018: Circulation Research
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Yeon Jung Kim, Rafael Rafael de Molon, Fausto Rioiti Horiguti, Guilherme Piragine Contador, Marco Antonio Coelho, Vinicius Ibiapina Mascarenhas, Ana Paula de Souza Faloni, Joni Augusto Cirelli, Wilson Roberto Sendyk
PURPOSE: The objective of this investigation was to assess vertical bone augmentation using deproteinized bovine bone mineral (DBBM) infused or not with recombinant human bone morphogenetic protein (rhBMP-2) in rabbit tibiae. MATERIALS AND METHODS: A total of 18 female rabbits (New Zealand) received two blocks of DBBM in each tibia. The DBBM blocks were randomly assigned into four experimental groups: DBBM (only the bone graft); DBBM associated with absorbable collagen sponge (ACS); DBBM plus rhBMP-2 (1...
March 15, 2018: International Journal of Oral & Maxillofacial Implants
Mathieu Bonneau, Régis Sabbadin, Fred A Johnson, Bradley Stith
Conversion of wild habitats to human dominated landscape is a major cause of biodiversity loss. An approach to mitigate the impact of habitat loss consists of designating reserves where habitat is preserved and managed. Determining the most valuable areas to preserve in a landscape is called the reserve design problem. There exists several possible formulations of the reserve design problem, depending on the objectives and the constraints. In this article, we considered the dynamic problem of designing a reserve that contains a desired area of several key habitats...
2018: PloS One
Martina Gobec, Tihomir Tomašič, Adela Štimac, Ruža Frkanec, Jurij Trontelj, Marko Anderluh, Irena Mlinaric-Rascan, Žiga Jakopin
Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date...
March 15, 2018: Journal of Medicinal Chemistry
Myungho Lee, Gerd Bruder, Tobias Hollerer, Greg Welch
In this paper, we investigate factors and issues related to human locomotion behavior and proxemics in the presence of a real or virtual human in augmented reality (AR). First, we discuss a unique issue with current-state optical see-through head-mounted displays, namely the mismatch between a small augmented visual field and a large unaugmented periphery, and its potential impact on locomotion behavior in close proximity of virtual content. We discuss a potential simple solution based on restricting the field of view to the central region, and we present the results of a controlled human-subject study...
April 2018: IEEE Transactions on Visualization and Computer Graphics
Hyungil Kim, Joseph L Gabbard, Alexandre Miranda Anon, Teruhisa Misu
This article investigates the effects of visual warning presentation methods on human performance in augmented reality (AR) driving. An experimental user study was conducted in a parking lot where participants drove a test vehicle while braking for any cross traffic with assistance from AR visual warnings presented on a monoscopic and volumetric head-up display (HUD). Results showed that monoscopic displays can be as effective as volumetric displays for human performance in AR braking tasks. The experiment also demonstrated the benefits of conformal graphics, which are tightly integrated into the real world, such as their ability to guide drivers' attention and their positive consequences on driver behavior and performance...
April 2018: IEEE Transactions on Visualization and Computer Graphics
Okan Erat, Werner Alexander Isop, Denis Kalkofen, Dieter Schmalstieg
Drones allow exploring dangerous or impassable areas safely from a distant point of view. However, flight control from an egocentric view in narrow or constrained environments can be challenging. Arguably, an exocentric view would afford a better overview and, thus, more intuitive flight control of the drone. Unfortunately, such an exocentric view is unavailable when exploring indoor environments. This paper investigates the potential of drone-augmented human vision, i.e., of exploring the environment and controlling the drone indirectly from an exocentric viewpoint...
April 2018: IEEE Transactions on Visualization and Computer Graphics
Hua Ye, Xuyu Chai, Xiaoyu Wang, Qi Zheng, Dingcheng Zheng, Feng Wu, Cheng Zheng, Ping Chen
The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2-positive NCI-N87 cell lines (Tzb-refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb-refractory cells...
April 2018: Oncology Letters
Neeraja Purandare, Mallika Somayajulu, Maik Hüttemann, Lawrence I Grossman, Siddhesh Aras
Coiled-coil-helix-coiled-coil-helix domain-containing 10 (CHCHD10) and CHCHD2 (MNRR1) are homologous proteins with 58% sequence identity and belong to the twin CX9C family of proteins that mediate cellular stress responses. Despite the identification of several neurodegeneration-associated mutations in the CHCHD10 gene, few studies have assessed its physiological role. Here, we investigated CHCHD10's function as a regulator of oxidative phosphorylation in the mitochondria and the nucleus. We show that CHCHD10 co-purifies with cytochrome c oxidase (COX) and up-regulates COX activity by serving as a scaffolding protein required for MNRR1 phosphorylation, mediated by ARG (ABL proto-oncogene 2, non-receptor tyrosine kinase [ABL2])...
March 14, 2018: Journal of Biological Chemistry
Peng Jin, Seung-Hyun Shin, Yang-Sook Chun, Hyun-Woo Shin, Yong Jae Shin, Yeri Lee, Donggeon Kim, Do-Hyun Nam, Jong-Wan Park
During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells...
March 14, 2018: Oncogene
Adam J Pelzek, Bo Shopsin, Emily E Radke, Kayan Tam, Beatrix M Ueberheide, David Fenyö, Stuart M Brown, Qianhao Li, Ada Rubin, Yi Fulmer, William K Chiang, David N Hernandez, Hanane El Bannoudi, William E Sause, Alexis Sommerfield, Isaac P Thomsen, Andy O Miller, Victor J Torres, Gregg J Silverman
Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S...
March 13, 2018: MBio
Ying-Chun Shih, Chao-Ling Chen, Yan Zhang, Rebecca L Mellor, Evelyn M Kanter, Yun Fang, Hua-Chi Wang, Chen-Ting Hung, Jing-Yi Nong, Hui-Ju Chen, Tzu-Han Lee, Yi-Shuan Tseng, Chiung-Nien Chen, Chau-Chung Wu, Shuei-Liong Lin, Kathryn A Yamada, Jeanne M Nerbonne, Kai-Chien Yang
<u>Rationale:</u> Cardiac fibrosis plays a critical role in the pathogenesis of heart failure (HF). Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting co-expression gene network analysis on RNA sequencing data from failing human heart, we identified thioredoxin domain containing 5 (TXNDC5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum (ER) protein, as a potential novel mediator of cardiac fibrosis and we completed experiments to test this hypothesis directly...
March 13, 2018: Circulation Research
Fiona M Z van den Heiligenberg, Tanya Orlov, Scott N Macdonald, Eugene P Duff, David Henderson Slater, Christian F Beckmann, Heidi Johansen-Berg, Jody C Culham, Tamar R Makin
The human brain contains multiple hand-selective areas, in both the sensorimotor and visual systems. Could our brain repurpose neural resources, originally developed for supporting hand function, to represent and control artificial limbs? We studied individuals with congenital or acquired hand-loss (hereafter one-handers) using functional MRI. We show that the more one-handers use an artificial limb (prosthesis) in their everyday life, the stronger visual hand-selective areas in the lateral occipitotemporal cortex respond to prosthesis images...
March 9, 2018: Brain: a Journal of Neurology
Huiyi H Chang, Jih-Chao Yeh, Ronaldo M Ichiyama, Larissa V Rodriguez, Leif A Havton
Spinal cord epidural stimulation (SCS) represents a form of neuromodulation for the management of spasticity and pain. This technology has recently emerged as a new approach for potentially augmenting locomotion and voiding function in humans and rodents after spinal cord injury. However, the effect of SCS on micturition has not been studied extensively. Here, SCS was first applied as a direct stimulus onto individual segmental levels of the lumbar spinal cord in rats to map evoked external urethral sphincter (EUS) electromyography activity and SCS-induced voiding contractions...
March 9, 2018: Experimental Neurology
Caroline E Cameron
Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a prevalent disease in low- and middle-income countries, and has re-emerged in key populations, including men who have sex with men, in high-income nations. The rising number of cases shows syphilis elimination will require augmentation of public health screening and treatment campaigns with syphilis vaccine development and implementation initiatives. Optimal vaccine candidates, deciphered from careful consideration of the pathogenic mechanisms employed by T...
March 9, 2018: Sexually Transmitted Diseases
Michael Fenton, David Lynch, David Fagan, Stepan Kucera, Holger Claussen, Michael O'Neill
Evolutionary Computation is used to automatically evolve small cell schedulers on a realistic simulation of a 4G-LTE heterogeneous cellular network. Evolved schedulers are then further augmented by human design to improve robustness. Extensive analysis of evolved solutions and their performance across a wide range of metrics reveals evolution has uncovered a new human-competitive scheduling technique which generalises well across cells of varying sizes. Furthermore, evolved methods are shown to conform to accepted scheduling frameworks without the evolutionary process being explicitly told the form of the desired solution...
March 12, 2018: Evolutionary Computation
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