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Melanoma:Molecular genetics,metastasis,targeted therapies,immunotherapies,and therapeutic resistance

Genes & Diseases 2022年第6期9卷 1608-1623页

作者： William Wagstaff Rimel N.Mwamba Karina Grullon Mikhayla Armstrong Piao Zhao Bryce hendren-Santiago Kevin h.Qin alexander J.Li Daniel A.hu Andrew Youssef Russell R.Reid hue h.Luu Le Shen Tong-Chuan he Rex C.haydon The Pritzker School of Medicine and the Medical Scientist Training ProgramThe University of Chicago Medical CenterChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Orthopaedic Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

Cutaneous melanoma is a common cancer and cases have steadily increased since the mid *** some patients,early diagnosis and surgical removal of melanomas is lifesaving,while other patients typically turn to molecular targeted therapies and immunotherapies as treatment *** sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF,NRAS,and TERT genes,some of which can be therapeutically *** initially effective,many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory *** represent an alternative to molecular targeted ***,inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long *** the protocol for combination therapies develop,so will our scientific understanding of the many pathways at play in the progression of *** future direction of the field may be to find a molecule that connects all of the ***,noncoding RNAs have been shown to play important roles in melanoma development and *** noncoding RNAs may help us to understand how resistance e both primary and acquired e develops;ultimately allow us to harness the true potential of current *** review will cover the basic structure of the skin,the mutations and pathways responsible for transforming melanocytes into melanomas,the process by which melanomas metastasize,targeted therapeutics,and the potential that noncoding RNAs have as a prognostic and treatment tool.

关键词： BRAF inhibitors Checkpoint inhibitors Drug resistance Immunotherapy Melanoma Melanoma metastasis Skin cancer Targeted therapy Therapeutic resistance

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Effects of Broussonetia papyrifera invasion and land use on vegetation characteristics in a tropical forest of Ghana

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Journal of Forestry Research 2019年第4期30卷 1363-1373页

作者： David M.Adigbli alexander K.Anning James K.Adomako Benedicta Y.Fosu-Mensah Institute for Environment and Sanitation Studies University of GhanaLegonAccraGhana Department of Theoretical and Applied Biology Kwame Nkrumah University of Science and TechnologyKumasiGhana Department of Botany University of GhanaLegonAccraGhana

The purpose of this study was to evaluate the effects of Broussonetia papyrifera(paper mulberry)invasion and land use on the floristic composition of a dry semideciduous forest in ***-five plots(25 m×25 m each),distributed among three land uses-selectively logged(SL);abandoned farmlands(AF);and an undisturbed reference(RF)-were *** showed lower tree species richness(S),diversity(h’),evenness(S)and basal area(BA)in the SL(46,0.78,0.32 and 269.12 m2 ha-1,respectively)and AF(40,0.53,0.45,and 131.16 m^2 ha^-1)sites compared to the RF site(79,2.66,0.87,963.72 m^2 ha^-1).Similar patterns were found at the shrub layer,but no differences were observed at the herb ***-metric multidimensional scaling ordination revealed distinct species composition among the land *** two disturbed habitats,SL and AF,were associated with increased *** invasion particularly in the overstory,with importance value index and mean relative density of 45 and 65.03%,and 42 and 53.29%,***,the species was only sparsely represented in the RF *** density of *** correlated negatively with h’,S,E,BA,and native tree density and *** findings highlight the strong link between human land use(i.e.,logging and slash-andburn farming),invasion,and vegetation characteristics,and suggest the need to limit these disturbances to conserve biodiversity within tropical forest ecosystems.

关键词： Afram headwaters Forest Reserve Broussonetia papyrifera Forest community characteristics human-caused disturbances Plant invasion

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Assessment of hindlimb motor recovery affer severe thoracic spinal cord injury in rats: classification of CatWalk XT■ gait analysis parameters

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Neural Regeneration Research 2023年第5期18卷 1084-1089页

作者： Guoli Zheng hao Zhang Mohamed Tail hao Wang Johannes Walter Thomas Skutella Andreas Unterberg Klaus Zweckberger alexander Younsi Department of Neurosurgery University Hospital HeidelbergHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyUniversity of HeidelbergHeidelbergGermany

Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT■gait analysis. To determine the potential bias from weight changes, corrected hindlimb(h) values(divided by the unaffected forelimb(F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT■parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwar.s. Of note, corrected values(h/F) of CatWalk XT■parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT■parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT■gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT■parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency.

关键词： Basso Beattie and Bresnahan rating scale behavioral assessment CatWalk XT■gait analysis contusive and compressive injury hindlimb motor function histological changes spinal cord injury spontaneous recovery thoracic weight

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Surface-enhanced Raman scattering on dielectric microspheres with whispering gallery mode resonance

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Photonics Research 2018年第5期6卷 346-356页

作者： STEVEN h.hUANG XUEFENG JIANG Bo PENG COREY JANISCh alexander COCKING SAhIN KAYA OZDEMIR ZhIWEN LIU LAN YANG Department of Electrical and Systems Engineering Washington University in St.LouisSt.LouisMissouri 63130USA Department of Electrical Engineering Pennsylvania State UniversityUniversity ParkPennsylvania 16802USA

Conventionally, metallic nanostructures are used for surface-enhanced Raman spectroscopy(SERS), but recently there has been increasing interest in the enhancement of Raman scattering from dielectric substrates due to their improved stability and biocompatibility compared with metallic substrates. here, we report the observation of enhanced Raman scattering from rhodamine 6 G molecules coated on silica microspheres. We excite the whispering gallery modes(WGMs) supported in the microspheres with a tapered fiber coupler for efficient WGM excitation, and the Raman enhancement can be attributed to the WGM mechanism. Strong resonance enhancement in pump laser intensity and modified Raman emission from the Purcell effect in the microsphere resonator are observed from the experiment and compared with theoretical results. A total Raman enhancement factor of 1.4 × 10~4 is observed, with contribution mostly from the enhancement in pump laser intensity. Our results show that, with an efficient pumping scheme, dielectric microspheres are a viable alternative to metallic SERS substrates.

关键词： Surface-enhanced Raman scattering dielectric microspheres with whispering gallery mode resonance

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haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第33期22卷 7518-7535页

作者： Niteen Tapuria Sameer Junnarkar Mahmoud Abu-amara Barry Fuller alexander M Seifalian Brian R Davidson Department of hPB Surgery and Liver transplantation Royal Free Hospital

AIM To investigate the hepatic microcirculatory changes due to haemoxygenase(hO),effect of hO inhibition on remote ischemic preconditioning(RIPC) and modulation of *** Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,hO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P hO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P hO induction) reproduced the effects of RIPC in hepatic IR. PDTC restored RBC velocity(300.88 ± 22.109 μm/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(hO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P hil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P he effects of RIPC. Zn PP(hO inhibition) increased venular(589.04 ± 144.36) and sinusoida

关键词： Reperfusion injury CINC Microcirculation Ischaemic preconditioning Remote preconditioning haemoxygenase

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First Record of a Tylosaurine Mosasaur from the Latest Cretaceous Phosphates of Morocco

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Open Journal of Geology 2022年第11期12卷 883-906页

作者： Trevor h. Rempert Brennan P. Martens alexander P. M. Vinkeles Melchers Department of Physiology and Biophysics Case Western Reserve University Cleveland USA Department of Biological Sciences University of Alberta Edmonton Canada The Vancouver Paleontological Society Richmond Canada

The latest Cretaceous Phosphates of Morocco preserve the highest biodiversity of mosasaurid squamates anywhere in the world. Intensive sampling over the past century has uncovered at least ten genera and thirteen species from the mosasaur subgroups halisauromorpha, Plioplatecarpinae, and Mosasaurinae. Notably missing from the assemblage are members of the macropredatory Tylosaurinae. The Tylosaurinae were globally rare in the Maastrichtian and their apparent absence has been previously explained by either collecting bias, ecological preference for deeper waters, or habitat restriction to higher paleolatitudes. here, we describe a new tylosaurine mosasaurid, hainosaurus boubker sp. nov., based on several partial skulls and isolated teeth originating from the Couche III layer of the Sidi Chennane Phosphate quarry near Oued Zem, Morocco. It is unique amongst tylosaurine mosasaurids in possessing blade-like teeth that are laterally compressed, encircled by enamel facets, and differentiated along the dental margin. The discovery of this new taxon in the Maastrichtian of Morocco is remarkable as it represents both the youngest species of Tylosaurinae and the first occurrence in North Africa.

关键词： Cretaceous Mosasaur Morocco Africa Tylosaurinae

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Developing a low-cost milliliter-scale chemostat array for precise control of cellular growth

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Frontiers of Electrical and Electronic Engineering in China 2018年第2期6卷 129-141页

作者： David Skelding Samuel F M hart Thejas Vidyasagar alexander E Pozhitkov Wenying Shou Division of Basic Sciences Fred Hutchinson Cancer Research Center Seattle WA 98109 USA University of Washington Seattle WA 98195-3770 USA

Background： Multiplexed milliliter-scale chemostats are useful for measuring cell physiology under various degrees of nutrient limitation and for carrying out evolution experiments. In each chemostat, fresh medium containing a growth rate-limiting metabolite is pumped into the culturing chamber at a constant rate, while culture effluent exits at an equal rate. Although such devices have been developed by various labs, key parameters the accuracy, precision, and operational range of flow rate -- are not explicitly characterized. Methods： here we re-purpose a published multiplexed culturing device to develop a multiplexed milliliter-scale chemostat. Flow rates for eight chambers can be independently controlled to a wide range, corresponding to population doubling times of 3-13 h, without the use of expensive feedback systems. Results： Flow rates are precise, with the maximal coefficient of variation among eight chambers being less than 3%. Flow rates are accurate, with average flow rates being only slightly below targets,i.e., 3%-6% for 13-h and 0.6%- 1.0% for 3-h doubling times. This deficit is largely due to evaporation and should be correctable. We experimentally demonstrate that our device allows accurate and precise quantification of population phenotypes. Conclusions： We achieve precise control of cellular growth in a low-cost milliliter-scale chemostat array, and show that the achieved precision reduces the error when measuring biological processes.

关键词： chemostats microbes evolution physiology multiplex

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Optimal Extraction of Groundwater in Gaza Coastal Aquifer

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Journal of Water Resource and Protection 2009年第4期1卷 249-259页

作者： Khalid QAhMAN Abdelkader LARABI Driss OUAZAR Ahmed NAJI alexander.h.-D. ChENG 不详

Two multi-objective management models are applied on a local area selected from the regional Gaza coastal aquifer. The objectives and constraints of these management scenarios include maximizing the total volume of water pumped, minimizing the salt concentration of the pumped water, and controlling the drawdown limits. The physical model is based on the CODESA-3D density-dependent advective-dispersive solute transport model. Genetic algorithm is used as the optimization tool. The models are tested on a part of the aquifer ( ) with 9 existing pumping wells located at various depths. The results of the optimization show that the optimization/simulation approach can give better decision if there is enough information to feed to the model. It confirms that the use of the concept of safe yield alone is not enough for sustainable develop-ment of the coastal aquifer. It shows that the optimum pumping rate is in the range of 26%–34% of the total natural replenishment. The application shows that the proposed technique is a powerful tool for solving this type of management problems.

关键词： Seawater Intrusion Genetic Algorithm Pumping Optimization Density-dependent Miscible Transport

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Mainline

Mainline

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作者： L.G.alexander R.h.Kingsbury

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Mainline

Mainline

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作者： L.G.alexander R.h.Kingsbury

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