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mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies:A systematic analysis of therapeutic efficacy and study design

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Neuroprotection 2023年第2期1卷 143-159页

作者： alexander m.Scrutton Francesca Ollis Johannes Boltze School of Life Sciences University of WarwickCoventryUK Neurobiology Division MRC Laboratory of Molecular BiologyUniversity of CambridgeCambridgeUK

Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns *** hypothermia(TH)can reduce mortality and,to a limited extent,disability after ***,there is a need for new and effective treatment ***-based treatments using mononuclear cells(mNCs),which can be sourced from umbilical cord blood,are currently being *** promising preclinical results,there is currently no strong indicator for the clinical efficacy of the *** analysis aimed to provide potential explanations for this ***:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and meta-Analysis *** and clinical studies were retrieved from Pubmed,Web of Science,Scopus,and *** using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were *** analyzed overall mNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical ***:There was evidence for mNC therapeutic efficacy in preclinical models of *** methodological quality of preclinical studies was not optimal,and statistical design quality was particularly ***,methodological quality was above the standard in other *** were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher mNC doses being applied in preclinical ***:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical *** is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of mNC treatments in *** preclinical and clinical research is required

关键词： cell therapy hypoxic-ischemic encephalopathy mononuclear cells translational research treatment efficacy

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Control of stem cell fate by engineering their micro and nanoenvironment

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World Journal of Stem Cells 2015年第1期7卷 37-50页

作者： michelle F Griffin Peter E Butler alexander m Seifalian Deepak m Kalaskar UCL Division of Surgery and Interventional Science Centre for Nanotechnology and Regenerative Medicine University College London London NW3 2PF United Kingdom Department of Plastic and Reconstructive Surgery Royal Free Hampstead NHS Trust Hospital London NW3 2PF United Kingdom

Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix(ECm) in vivo have shown to regulate stem cell differentiation. The delivery of ECm components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine.

关键词： Biomaterials Scaffold Stem cells Surfacetopography Tissue engineering

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Formation of a 40 A DC Current Arc During the Opening of Silver Contacts

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Plasma Science and Technology 2014年第5期16卷 471-478页

作者： m'hammed ABBAOUI André LEFORT Erwann CARVOU Damien SALLAIS James Brian alexander mITCHELL Noureddine BEN JEmAA Clermont Université Université d'AuvergneEA 3120LAEPTBP 10448F-63000 Clermont-FerrandFrance Equipe Contacts Electriques IPR(UMR CNRS 6251)Universite de Rennes 135042 Rennes CedexFrance

The erosion of silver contacts due to break arcs with length proportional to time and of variable duration has been measured by weighing the contacts following 5000 openings at a constant current equal to 40 *** experimental results show that,for arc durations shorter than 60 μs,the transfer of metal from the anode to the cathode occurs,but after passing this stage,when the two electrodes are separated by greater distances,each will display *** is the result of the diffusion of material outside the space between the two *** order to interpret these results,we have applied a classical model of the physical phenomena occurring at the root of the *** of the experimental results shows that for an arc duration of less than15 μs,no distinct cathode root is seen to exist,but beyond this,several spots appear gradually on the cathode for arc duration up to 50 μs,after which they merge into a single *** comparison between experiment results and theoretical interpretation is reasonable up to 60 μs.

关键词： arc root cathode spot anode spot erosion contacts current density

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AN EFFICIENT mETHOD FOR mULTIOBJECTIVE OPTImAL CONTROL AND OPTImAL CONTROL SUBJECT TO INTEGRAL CONSTRAINTS

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Journal of Computational mathematics 2010年第4期28卷 517-551页

作者： Ajeet Kumar alexander Vladimirsky Department of Theoretical & Applied mechanics Cornell University Department of mathematics Cornell University

We introduce a new and efficient numerical method for multicriterion optimal control and single criterion optimal control under integral constraints. The approach is based on extending the state space to include information on a ＂budget＂ remaining to satisfy each constraint; the augmented Hamilton-Jacobi-Bellman PDE is then solved numerically. The efficiency of our approach hinges on the causality in that PDE, i.e., the monotonicity of characteristic curves in one of the newly added dimensions. A semi-Lagrangian ＂marching＂ method is used to approximate the discontinuous viscosity solution efficiently. We compare this to a recently introduced ＂weighted sum＂ based algorithm for the same problem [25]. We illustrate our method using examples from flight path planning and robotic navigation in the presence of friendly and adversarial observers.

关键词： Optimal control multiobjective optimization Pareto front Vector dynamic programming Hamilton-Jacobi equation Discontinuous viscosity solution Semi-Lagrangian discretization.

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Round spermatid injection into human oocytes:a systematic review and meta-analysis

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Asian Journal of Andrology 2021年第4期23卷 363-369页

作者： Brent m Hanson Taylor P Kohn alexander W Pastuszak Richard T Scott Jr Philip J Cheng James m Hotaling Department of Reproductive Endocrinology and Infertility IVI-Reproductive Medicine Associates of New JerseyBasking RidgeNJ 07920USA Department of Urology The Brady Urological Institute at Johns Hopkins UniversityBaltimoreMD 21287USA Department of Surgery University of Utah Center for Reconstructive Urology and Men's HealthSalt Lake CityUT 84108USA

many azoospermic men do not possess mature spermatozoa at the time of surgical sperm *** study is a systematic review and meta-analysis evaluating outcomes following round spermatid injection(ROSI),a technique which utilizes immature precursors of spermatozoa for *** electronic search was performed to identify relevant articles published through October *** cohort studies in English involving male patients who had round spermatids identified and used for fertilization with human oocytes were *** rate,pregnancy rate,and resultant delivery rate were assessed following ***-analysis outcomes were analyzed using a random-effects *** were extracted from 22 studies involving 1099 couples and 4218 embryo *** fertilization rate after ROSI was 38.7%(95%confidence interval[CI]:31.5%–46.3%),while the pregnancy rate was 3.7%(95%CI:3.2%–4.4%).The resultant delivery rate was low,with 4.3%of embryo transfers resulting in a delivery(95%CI:2.3%–7.7%).The pregnancy rate per couple was 13.4%(95%CI:6.8%–19.1%)and the resultant delivery rate per couple was 8.1%(95%CI:6.1%–14.4%).ROSI has resulted in clinical pregnancies and live births,but success rates are considerably lower than those achieved with mature *** this technique may be a feasible alternative for men with azoospermia who decline other options,couples should be aware that the odds of a successful delivery are greatly diminished and the prognosis is relatively poor.

关键词： azoospermia in vitro fertilization infertility spermatozoa testis

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Increased paracellular permeability of tumor-adjacent areas in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats

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Cancer Biology & medicine 2018年第3期15卷 251-259页

作者： Viktoria V.Bekusova Evgeny L.Falchuk Larisa S.Okorokova Natalia m.Kruglova alexander D.Nozdrachev alexander G.markov Department of Physiology St.Petersburg State University I.P.Pavlov Institute of Physiology Russian Academy of Sciences

Objective: The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending *** bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine(DmH)-induced colon ***: The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical ***: Rats with DmH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however,the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier ***: The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their bar

关键词： Rat 1,2-dimethylhydrazine colorectal cancer Ussing chamber short circuit current transepithelial electrical resistance intestinal permeability

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Erythema nodosum

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World Journal of Pediatrics 2018年第6期14卷 548-554页

作者： alexander K.C.Leung Kin Fon Leong Joseph m.Lam Department of Pediatrics The Alberta Children's HospitalThe University of Calgary#200233-16th Avenue NWCalgaryAB T2M 0H5Canada Pediatric Institute Kuala Lumpur General HospitalKuala LumpurMalaysia Department of Pediatrics and Department of Dermatology and Skin Sciences University of British ColumbiaVancouverBCCanada

Background Erythema nodosum can be associated with a number of systemic diseases. There is, however, a paucity of information in the pediatric literature on this condition. The purpose of this article is to familiarize pediatricians with the evaluation, diagnosis, and treatment of erythema nodosum. Data sources A Pubmed search was completed in Clinical Queries using the key terms 'erythema nodosum'. Results Clinically, erythema nodosum presents with a sudden onset of painful, erythematous, subcutaneous nodules mainly localized to the pretibial areas. Lesions are usually bilateral and symmetrical, ranging from 1 to 5 cm in diameter. Erythema nodosum may be associated with a variety of conditions such as infection, medications, sarcoidosis, pregnancy, inflamma-tory bowel disease, vaccination, autoimmune disease, malignancy, and miscellaneous causes. The condition is idiopathic in approximately 50% of cases. The diagnosis is mainly clinical with biopsy reserved for atypical cases. To evaluate for the underlying cause, some basic laboratory screening studies are worthwhile in most cases and include a complete blood cell count, erythrocyte sedimentation rate and/or C-reactive protein, throat swab culture, antistreptococcal O titers, and a chest radiograph. Other tests should be individualized, guided by the history and physical examination results. most cases of ery-thema nodosum are self-limited and require no treatment. Bed rest and leg elevation are generally recommended to reduce the discomfort. Nonsteroidal anti-inflammatory drugs are the first-line treatment for pain management. Conclusions As erythema nodosum is often a cutaneous manifestation of a systemic disease, a thorough search should be performed to reveal the underlying cause.

关键词： Drug-induced Group A β-hemolytic streptococcal infection Sarcoidosis Subcutaneous pretibial nodules Tuberculosis Yersinia infection

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On Identitiesand m-Neutral Sequencesof n-Ary Groups

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Communications in mathematics and Statistics 2016年第4期4卷 495-508页

作者： alexander m.Gal’mak Viktoria A.Kovaleva Department of Technology Mogilev State University of Food Technologies212027 MogilevBelarus Department of mathematics Francisk Skorina Gomel State University246019 GomelBelarus

In this paper,we study such polyadic analog of an identity of a group asm-neutral *** particular,we prove that all Post's equivalence classes of thefree covering group of any n-ary group[where n=k(m-1)+1 and k≥1]definedby m-neutral sequences form the(k+1)-ary group,which is isomorphic to the n-arysubgroup of all identities of the n-ary group in the case when m=2.

关键词： n-Ary group Identity m-Neutral sequence

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Syntheses,Crystal Structures and Luminescent Properties of Lead(Ⅱ) and Cadmium(Ⅱ) Coordination Polymers Constructed from Biphenyl-2,5,3′-tricarboxylate

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Chinese Journal of Structural Chemistry 2014年第6期33卷 888-896页

作者：高竹青李红晋 m.Kirillov alexander 顾金忠 School of Chemical and Biological Engineering Taiyuan University of Science and Technology Centro de Química Estrutural Complexo I Instituto Superior TécnicoThe University of Lisbon College of Chemistry and Chemical Engineering Lanzhou University

Two coordination polymers, namely [Pb（Hbtc）（phen）]n（1） and {[Cd3（btc）2（H2O）4]·2H2O}n（2, H3btc = biphenyl-2,5,3＇-tricarboxylic acid, phen = 1,10-phenanthroline）, were assembled. Single-crystal X-ray diffraction studies show that compound 1 possesses a zigzag chain 1D coordination network, which is further extended into a 3D supramolecular architecture via O–H···O hydrogen bonds and π-π packing interactions. Compound 2 features a 3D open framework based on a tricadmium（II） subunit, generating a trinodal 4,4,6-connected net with the 4,4,6T24 topology defined by the point symbol of（44·62）3（46·69）2. Thermal stability and luminescent properties of both compounds were studied and discussed.

关键词： coordination polymer crystal structrue luminescent properties

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USING DURABILITY TO ENHANCE CONCRETE SUSTAINABILITY

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Journal of Green Building 2009年第3期4卷 52-60页

作者： J.R.mackechnie m.G.alexander Department of Civil Engineering University of CanterburyChristchurchNew Zealand Department of Civil Engineering University of Cape TownCape TownSouth Africa

INTRODUCTION The sustainability of concrete buildings and infrastructure must be considered both in terms of its benefi ts to society and the environmental impact associated with its use in *** of Portland cement(PC),in particular,is energy intensive and generates a signifi cant amount of carbon *** is,however,only a relatively small component of concrete and overall the material is resource effi cient and has moderate embodied energy and carbon dioxide footprint.

关键词： concrete dioxide construction.

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