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MicroRNA-based therapeutics for optic neuropathy:opportunities and challenges

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Neural Regeneration Research 2021年第10期16卷 1996-1997页

作者： Heather K.Mak christopher K.s.Leung Department of Ophthalmology and Visual sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Optic nerve degeneration is a major cause of irreversible blindness worldwide with glaucoma being the most common optic neuropathy,affecting approximately 76 million people worldwide in *** optic nerve comprises axons of retinal ganglion cells(RGCs),the output neurons of the inner *** RGCs and axons from degeneration and regenerating RGC axons to preserve and recover vision in patients with progressive optic neuropathy is an unmet *** embryonic neurons,mature neurons of the mammalian central nervous system fail to regenerate their axons following *** age-related loss of axon regenerative capacity of RGCs over time renders vision loss from optic neuropathy *** failure of injured RGCs to regenerate axons is largely attributed to inhibitory molecules in the extrinsic environment and a change in the intrinsic molecular makeup of aging *** studies have demonstrated that RGCs require specific molecular signals for the stimulation of axon growth even without inhibitory molecules in the extrinsic environment,leading successive efforts to focus on uncovering the intrinsic signaling pathways that control axon extension during RGC development.

关键词： neuropathy degeneration stimulation

Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells

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Neural Regeneration Research 2016年第7期11卷 1033-1042页

作者： George D.Bittner christopher s.spaeth Andrew D.Poon Zachary s.Burgess christopher H.Mc Gill Department of Neuroscience The University of Texas at Austin

The repair（sealing） of plasmalemmal damage,consisting of small holes to complete transections,is critical for cell survival,especially for neurons that rarely regenerate cell *** first describe and evaluate different measures of cell *** measures,including morphological/ultra-structural observations,membrane potential,and input resistance,provide very ambiguous assessments of plasmalemmal *** contrast,measures of ionic current flow and dye barriers can,if appropriately used,provide more accurate *** describe the effects of various substances（calcium,calpains,cytoskeletal proteins,EsCRT proteins,m UNC-13,NsF,PEG） and biochemical pathways（PKA,PKC,PLC,Epac,cytosolic oxidation） on plasmalemmal sealing probability,and suggest that substances,pathways,and cellular events associated with plasmalemmal sealing have undergone a very conservative *** sealing,calcium ion influx mobilizes vesicles and other membranous structures（lysosomes,mitochondria,etc.） in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to ***,we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets,or in a single step involving the fusion of one large wound vesicle with the nearby,undamaged *** describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the ***,we speculate on relationships between plasmalemmal sealing,Wallerian degeneration,and the ability of polyethylene glycol（PEG） to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves.A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develo

关键词： sealing traumatic eukaryotic vesicles axonal membranous closer biochemical vesicular muscular

Therapeutic options for the management of pancreatic cancer

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World Journal of Gastroenterology 2014年第32期20卷 11142-11159页

作者： Maria L Rossi Azeem A Rehman christopher s Gondi Department of Medicine University of Illinois College of MedicinePeoria Peoria IL 61656-1649 United States

since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United states, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.

关键词： Pancreatic cancer Pancreatic cancer stem cells Microenvironment surgical resection Neoadjuvant therapy Adjuvant therapy Chemotherapy Radiation Personalized therapy

Automated Deep Learning Based Cardiovascular Disease Diagnosis Using ECG signals

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Computer systems science & Engineering 2022年第7期42卷 183-199页

作者： s.Karthik M.santhosh M.s.Kavitha A.christopher Paul Department of Computer science&Engineering SNS College of TechnologyCoimbatore641035India Department of Information Technology Karpagam Institute of TechnologyCoimbatore641105India

Automated biomedical signal processing becomes an essential process to determine the indicators of diseased *** the same time,latest develop-ments of artiﬁcial intelligence(AI)techniques have the ability to manage and ana-lyzing massive amounts of biomedical datasets results in clinical decisions and real time *** can be employed for medical imaging;however,the 1D biomedical signal recognition process is still needing to be ***(ECG)is one of the widely used 1-dimensional biomedical sig-nals,which is used to diagnose cardiovascular *** assisted diag-nostic modelsﬁnd it difﬁcult to automatically classify the 1D ECG signals owing to time-varying dynamics and diverse proﬁles of ECG *** resolve these issues,this study designs automated deep learning based 1D biomedical ECG sig-nal recognition for cardiovascular disease diagnosis(DLECG-CVD)*** DLECG-CVD model involves different stages of operations such as pre-proces-sing,feature extraction,hyperparameter tuning,and classiﬁ*** the initial stage,data pre-processing takes place to convert the ECG report to valuable data and transform it into a compatible format for further *** addition,deep belief network(DBN)model is applied to derive a set of feature ***,improved swallow swarm optimization(IssO)algorithm is used for the hyper-parameter tuning of the DBN ***,extreme gradient boosting(XGBoost)classiﬁer is employed to allocate proper class labels to the test ECG *** order to verify the improved diagnostic performance of the DLECG-CVD model,a set of simulations is carried out on the benchmark PTB-XL dataset.A detailed comparative study highlighted the betterment of the DLECG-CVD model interms of accuracy,sensitivity,speciﬁcity,kappa,Mathew correlation coefﬁcient,and Hamming loss.

关键词： Biomedical signals 1-dimensional signal electrocardiogram artiﬁcial intelligence deep learning cardiovascular disease decision making

Wing, tail, and vocal contributions to the complex acoustic signals of courting Calliope hummingbirds

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Current Zoology 2011年第2期57卷 187-196页

作者： christopher James CLARK Peabody Museum of Natural History Yale University PO Box 208106 New Haven CT 06511 USA Museum of Vertebrate Zoology University of California- Berkeley Berkeley CA USA

Multi-component signals contain multiple signal parts expressed in the same physical modality. One way to identify individual components is if they are produced by different physical mechanisms. Here, I studied the mechanisms generating acoustic signals in the courtship displays of the Calliope hummingbird stellula calliope. Display dives consisted of three synchronized sound elements, a high-frequency tone （hfl）, a low frequency tone （lft）, and atonal sound pulses （asp）, which were then followed by a frequency-modulated fall. Manipulating any of the rectrices （tail-feathers） of wild males impaired production of the lft and asp but not the hfl or fall, which are apparently vocal. I tested the sound production capabilities of the rectrices in a wind tunnel. single rectrices could generate the lft but not the asp, whereas multiple rectrices tested together produced sounds sitlfilar to the asp when they fluttered and collided with their neighbors percussively, representing a previously unknown mechanism of sound production. During the shuttle display, a trill is generated by the wings during pulses in which the wingbeat frequency is elevated to 95 Hz, 40% higher than the typical hovering wingbeat frequency. The Calliope hummingbird courtship displays include sounds produced by three independent mechanisms, and thus include a minimum of three acoustic signal components. These acoustic mechanisms have different constraints and thus potentially contain different messages. Producing multiple acoustic signals via multiple mechanisms may be a way to escape the constraints present in any single mechanism .

关键词： Calliope Hummingbird Courtship Multicomponent signal sonation Wind Tunnel

sARs-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance:Implications for Antibody Therapy and Vaccinations against COVID-19

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Research 2024年第3期2023卷 1-15页

作者： Xiaoying Ma Jady Liang Guangheng Zhu Preeti Bhoria Aron A.shoara Daniel T.MacKeigan christopher J.Khoury sladjana slavkovicl Lisha Lin Danielle Karakas Ziyan Chen Viktor Prifti Zhenze Liu Chuanbin shen Yuchong Li Cheng Zhang Jiayu Dou Zack Rousseau Jiamin Zhang Tiffany Ni Xi Lei Pingguo Chen Xiaoyu Wu Hamed shaykhalishahi samira Mubareka Kim AConnelly Haibo Zhang Ori Rotstein Heyu Ni Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Department of Laboratory Medicine Keenan Research Centre for Biomedical Science of St.Michael’s HospitalTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Department of Physiology University of TorontoTorontoONCanada CCOA Therapeutics Inc. TorontoONCanada Canadian Blood services Centre for Innovation TorontoONCanada The state Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Laboratory Medicine The Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Advanced Pharmaceutics&Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoONCanada Department of Medical Microbiology and Infectious Disease Sunnybrook Health Science CentreToronto ONCanada Department of Medicine University of TorontoTorontoONCanada Division of Cardiology.st.Michael's Hospital TorontoONCanada Department of Anesthesiology and Pain Medicine and Division of Critical Care Medicine University of TorontoTorontoONCanada interdepartmental Division of Critical Care Medicine University of TorontoTorontoONCanada Department of surgery University of Toronto TorontoONCanada.

The COVID-19 pandemic caused by sARs-CoV-2 virus is an ongoing global health *** cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately *** infection and vaccination utilize the spike protein receptor-binding domain(RBD)of *** found that intravenous injection of recombinant RBD caused significant platelet clearance in *** investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa *** RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−***,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and sARs-CoV-2 infection and replication in Vero E6 *** data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and *** newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of sARs-CoV-2 virus antigen but also importantly for therapy against COVID-19.

关键词： Antibody diagnosis vaccine

social media as passive geo-participation in transportation planning-how effective are topic modeling&sentiment analysis in comparison with citizen surveys?

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Geo-spatial Information science 2020年第4期23卷 275-292页

作者： Oliver Lock christopher Pettit City Futures Research Centre Faculty of Built EnvironmentUniversity of New South Wales(UNSW)SydneyAustralia Expanded Perception and Interaction Centre(Epicentre) Faculty of Art&DesignUniversity of New South Wales(UNSW)SydneyAustralia

We live in an era of rapid urbanization as many cities are experiencing an unprecedented rate of population growth and *** transport is playing an increasingly important role in urban mobility with a need to move people and goods efficiently around the *** such pressures on existing public transportation systems,this paper investigates the opportunities to use social media to more effectively engage with citizens and customers using such *** research forms a case study of the use of passively collected forms of big data in cities-focusing on sydney,***,it examines social media data(Tweets)related to public transport ***,it joins this to longitudinal big data-delay information continuously broadcast by the network over a year,thus forming hundreds of millions of data ***,tones,and sentiment are modeled using machine learning and Natural Language Processing(NLP)*** resulting data,and models,are compared to opinions derived from a citizen survey among *** validity of such data and models versus the intentions of users,in the context of systems that monitor and improve transport performance,are *** such,key recommendations for developing smart Cities were formed in an applied research context based on these data and techniques.

关键词： social media smart cities public participation urban sensing transport planning natural language processing machine learning big data

Assessment of scapulohumeral rhythm for scapular plane shoulder elevation using a modified digital inclinometer

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World Journal of Orthopedics 2012年第6期3卷 87-94页

作者： Jason s scibek christopher R Carcia Department of Athletic Training School of Health Sciences Duquesne UniversityJohn G Rangos Sr.Pittsburgh PA 15282 United States Department of Physical Therapy School of Health Sciences Duquesne UniversityJohn G Rangos Sr.Pittsburgh PA 15282 United States

AIM: To develop a better understanding of scapulohumeral rhythm during scapular plane shoulder ***: Thirteen healthy, college-aged subjects participated in this study. subjects were free from any upper extremity, neck or back pathology. A modified digital inclinometer was utilized to measure scapular upward rotation of the subject's dominant shoulder. Upward rotation was measured statically as subjects performed clinically relevant amounts of shoulder elevation in the scapular plane. Testing order was randomized by arm position. scapular upward rotation was assessed over the entire arc of motion and over a series of increments. The percent contributions to shoulder elevation for the scapula and glenohumeral joint were calculated. scapulohumeral rhythm was assessed and represented the ratio of glenohumeral motion to scapulothoracic motion(glenohumeral elevation: scapular upward rotation). A one-way ANOVA wasused to compare scapular upward rotation between elevation ***: scapulohumeral rhythm for the entire arc of shoulder elevation was equal to a ratio of 2.34 :1 and ranged from 40.01:1 to 0.90:1 when assessed across the different increments of humeral elevation. Total scapular motion increased over the arc of shoulder elevation. The scapula contributed 2.53% of total motion for the first 30 degrees of shoulder elevation, between 20.87% and 37.53% for 30o-90 o of shoulder elevation, and 52.73% for 90o-120 o of shoulder elevation. statistically significant differences in scapular upward rotation were identified across the shoulder elevation increments [F(3,48) = 12.63, P = 0.0001].CONCLUsION: Clinically, we must recognize the usefulness of the inclinometer in documenting the variable nature of scapulohumeral rhythm in healthy and injured shoulders.

关键词： Biomechanics Kinematics scapula shoulder

Pillar design and coal burst experience in Utah Book Cliffs longwall operations

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International Journal of Mining science and Technology 2021年第1期31卷 33-41页

作者： christopher Mark Michael Gauna Mine safety and Health Administration Technical support PittsburghPA 15236USA

Longwall mining has existed in Utah for more than half a *** of this mining occurred at depths of cover that significantly exceed those encountered by most other Us longwall *** cover causes high ground stress,which can combine with geology to create a coal burst *** every longwall mine operating within the Utah’s Book Cliffs coalfield has been affected by coal *** design has been a key component in the burst control strategies employed by mines in the Book ***,most longwall mines employed double-use two-entry yield pillar ***-use signifies that the gate system serves first as the headgate,and then later serves as the tailgate for the adjacent *** the 1996 burst fatality at the Aberdeen Mine,the inter-panel barrier design was *** this layout,a wide barrier pillar protects each longwall panel from the previously mined panel,and each gate system is used just *** paper documents the deep cover longwall mining conducted with each type of pillar design,together with the associated coal burst *** of the six longwall mining complexes in the Book Cliffs having a coal burst history is described on a panel-by-panel *** analysis shows that where the mining depth exceeded 450 m,each design has been employed for about 38000 total m of longwall panel *** double-use yield pillar design has been used primarily at depths less than 600 m,however,while the inter-panel barrier design has been used mainly at depths exceeding 600 *** its greater depth of use,the inter-panel barrier gate design has been associated with about one-third as much face region burst activity as the double-use yield pillar design.

关键词： Longwall Ground control Coal burst Pillar design Yield pillar