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The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation

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The Journal of Biomedical Research 2013年第4期27卷 249-253页

作者： david K.C.Cooper Hidetaka Hara Mohamed Ezzelarab Rita Bottino Massimo Trucco Carol Phelps david ayares Yifan Dai Thomas E.Starzl Transplantation Institute University of Pittsburgh Medical Center Division of Immunogenetics Children's Hospital of Pittsburgh University of Pittsburgh Revivicor Inc Jiangsu Key Laboratory of Xenotransplantation Nanjing Medical University

There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate＇s adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for 〉 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans- plantation are already in progress. Future developments will involve further genetic manipulations of the organ- source pig, with most of the genes that are likely to be beneficial already identified.

关键词： pig blood transfusion pig genetic-engineered pig islets pig organs xenotransplantation

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Late Ordovician Mass Extinction: Earth, fire and ice

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National Science Review 2024年第1期11卷 51-65页

作者： david A.T.Harper Palaeoecosystems Group Department of Earth SciencesDurham University

The Late Ordovician Mass Extinction was the earliest of the ‘big’ five extinction events and the earliest to affect the trajectory of metazoan life. Two phases have been identified near the start of the Hirnantian period and in the middle. It was a massive taxonomic extinction, a weak phylogenetic extinction and a relatively benign ecological extinction. A rapid cooling, triggering a major ice age that reduced the temperature of surface waters, prompted a drop in sea level of some 100 m and introduced toxic bottom waters onto the shelves. These symptoms of more fundamental planetary processes have been associated with a range of factors with an underlying driver identified as volcanicity. Volcanic eruptions, and other products, may have extended back in time to at least the Sandbian and early Katian, suggesting the extinctions were more protracted and influential than hitherto documented.

关键词： Ordovician LOME paleoecology palaeobiogeography biotas

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One-dimensional monotone nonautonomous dynamical systems

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Science China Mathematics 2024年第2期67卷 281-314页

作者： david Cheban Faculty of Mathematics and Computer Science Laboratory of Fundamental and Applied MathematicsMoldova State UniversityChisinau 2009Moldova

This work is devoted to the study of the dynamics of one-dimensional monotone nonautonomous(cocycle) dynamical systems. A description of the structures of their invariant sets, omega limit sets,Bohr/Levitan almost periodic and almost automorphic motions, global attractors, and pinched and minimalsets is given. An application of our general results is given to scalar differential and difference equations.

关键词： one-dimensional dynamics pinched and minimal sets global attractors monotone nonautonomous cocycle almost periodic solutions scalar differential/difference equations

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Kerogen Kinetic Distributions and Simulations Provide Insights into Petroleum Transformation Fraction (TF) Profiles of Organic-Rich Shales

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Journal of Earth Science 2024年第3期35卷 747-757页

作者： david A.Wood DWA Energy Limited Lincoln LN59JPUnited Kingdom

Two hundred and fifty single first-order Arrhenius reactions are simulated to generate S2 pyrograms at three heating rates 25,15,and 5°C·*** activation energy(E)and pre-exponential factor(A)of the reactions simulated follow a long-established trend of those variable values displayed by shales and *** characteristics of the transformation fraction(TF)profiles(product generation window temperatures)of the simulated single reactions are compared to the TF profiles of recorded shale pyrograms generated by multiple reactions with different E-A values lying near the defined E-A *** similarities and differences are observed between the TF profile values of the two *** similarities support the spread of E-A values involved in shale pyrogram best *** differences are most likely explained by the complexity of the multiple kerogen first-order and second-order reactions contributing to the recorded shale pyrograms versus the simplicity and crispness of the single first-order reactions *** results also justify the validity of using the previously described“variable E-A pyrogram-fitting method”of multi-heating-rate shale pyrograms enabling optimizers to choose multiple reactions from an unlimited range of E-A *** contrast,further doubt is cast on the validity of the constant-A pyrogram-fitting method used by the Easy%Ro technique,in that a distribution of reactions with a single A value is unlikely to represent the complex variety of kerogen macerals observed in shale *** profiles generated by the variable E-A pyrogram-fitting method lie close to the established E-A trend and are likely to provide more realistic TF generation window temperatures than TF profiles generated by the constant-A pyrogram-fitting method.

关键词： transformation fraction profiles simulated S2 pyrograms multiple heating rates kerogen/shale kinetics S2 pyrogram fitting techniques kerogen petroleum research.

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Analysis of ancient mass extinction recoveries in marine environments: generating strategies for managing outcomes of the current mass extinction

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National Science Review 2024年第1期11卷 8-10页

作者： david J.Bottjer Department of Earth Sciences University of Southern California

The defining feature of a mass extinction and its associated recovery is the global amount of extinction that occurred[1]. However, there is finer-scale detail to the story, as seen in the ongoing modern mass extinction(the sixth mass extinction), which exhibits variable effects among marine ecosystems and environments, and hence geographic areas [1].

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Gastroesophageal reflux following peroral endoscopic myotomy for achalasia:Bumps in the road to success

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World Journal of Gastroenterology 2024年第29期30卷 3461-3464页

作者： david Itskoviz Stephen david Howard Malnick Kaplan Medical Center Institute of Gastroenterology and HepatologyHebrew University Medical School of JerusalemRehovot 76100Israel Kaplan Medical Center Department of Internal Medicine CHebrew University Medical School of JerusalemRehovot 76100Israel

Achalasia can significantly impair the quality of *** clinical presentation typically includes dysphagia to both solids and liquids,chest pain,and *** can be delayed in patients with atypical presentations,and they might receive a wrong diagnosis,such as gastroesophageal reflux disease(GERD),owing to overlapping symptoms of both *** the cause of achalasia is poorly understood,its impact on the motility of the esophagus and gastroesophageal junction is well *** treatment modalities have been utilized,with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon ***,peroral endoscopic myotomy(POEM)has gained popularity as an effective treatment for achalasia,despite a relatively high incidence of GERD occurring after treatment compared to other *** magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related *** longterm sequelae of post-POEM GERD are yet to be determined,but it appears to have a benign course and is usually manageable with clinically available *** risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

关键词： Achalasia Per-oral endoscopic myotomy Gastroesophageal reflux Pneumatic dilatation Heller myotomy Proton pump inhibitor Acidic fermentation

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Discovery of strong bulk Dzyaloshinskii-Moriya interaction in composition-uniform centrosymmetric magnetic single layers

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Science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 174-180页

作者： Lijun Zhu david Lujan Xiaoqin Li State Key Laboratory of Superlattices and Microstructures Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China College of Materials Science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 100049China Department of Physics Center for Complex Quantum SystemsUniversity of Texas at AustinAustin 78712USA

Dzyaloshinskii-Moriya interaction(DMI)is the key ingredient of chiral spintronic phenomena and the emerging technologies based on such phenomena.A nonzero DMI usually occurs at magnetic interfaces or within non-centrosymmetric single ***,we report the observation of a strong unexpected DMI within a centrosymmetric polycrystalline ferromagnet that has neither a crystal inversion symmetry breaking nor a composition *** DMI is a bulk effect,increases with the thickness of the magnetic layer,and is insensitive to the symmetry of the interfaces or the neighboring *** observe a total DMI strength that is a factor of>2 greater than the highest interfacial DMI in the *** DMI most likely arises from the strong spin-orbit coupling,strong orbital hybrization,and a“hidden”long-range asymmetry in the *** discovery of the strong unconventional bulk DMI in centrosymmetric,composition-uniform magnetic single layers provides fundamental building blocks for the emerging field of spintronics and will stimulate the exploitation of unconventional spin-orbit phenomena in a wide range of materials.

关键词： Brillouin light scattering Dzyaloshinskii-Moriya interaction spin wave

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Evaluation of hand infections in the emergency department using point-of-care ultrasound

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World Journal of Emergency Medicine 2024年第4期15卷 283-288页

作者： david Ahmad Haidar david Mintz Brandon M Wubben Omar Rizvi Srikar Adhikari Department of Emergency Medicine Michigan MedicineAnn Arbor 48109-1382USA University of Arizona College of Medicine Tucson 85724USA Department of Emergency Medicine University of IowaIowa City 52242-1009USA Department of Surgery University of Arizona College of MedicineTucson 85724USA Department of Emergency Medicine University of Arizona College of MedicineTucson 85724USA

BACKGROUND:We aimed to evaluate the utility of point-of-care ultrasound(POCUS)in the assessment of hand infections that present to the emergency department(ED)and its impact on medical decision making and patient ***:We conducted a retrospective review of patients who presented to two urban academic EDs with clinical presentations concerning for skin and soft tissue infections(SSTI)of the hand between December 2015 and December *** trained POCUS fellowship physicians reviewed an ED POCUS database for POCUS examinations of the *** then reviewed patients’electronic health records(EHR)for demographic characteristics,history,physical examination findings,ED course,additional imaging studies,consultations,impact of POCUS on patient care and final ***:We included a total of 50 cases(28 male,22 female)in the final *** most common presenting symptoms and exam findings were pain(100%),swelling(90%),and erythema(74%).The most common sonographic findings were edema(76%),soft tissue swelling(78%),and fluid surrounding the tendon(57%).POCUS was used in medical decision making 68%of the time(n=34),with the use of POCUS leading to changes in management 38%of the time(n=19).POCUS use led to early antibiotic use(11/19),early consultation(10/19),and led to the performance of a required procedure(8/19).The POCUS diagnosis was consistent with the discharge diagnosis of flexor tenosynovitis 8/12 times,abscess 12/16 times,and cellulitis 14/20 ***:POCUS is beneficial for evaluating of hand infections that present to the ED and can be used as an important part of medical decision making to expedite patient care.

关键词： Ultrasound Point-of-care ultrasound Cellulitis Abscess Flexor tenosynovitis

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Ubiquitination-mediated regulation of receptorlike kinases in symbiosis and immunity

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Molecular Plant 2024年第9期17卷 1335-1337页

作者： david Landry and Benoit Lefebvre Laboratory of Plant-Microbe-Environment Interactions(LIPME) Universite de ToulouseINRAECNRS31326Castanet-TolosanFrance

Receptor-like kinases(RLKs)are plasma membrane(PM)proteins that monitor the extracellular environment and regulate various processes such as biotic *** motif(LysM)RLKs are a specific class of RLKs involved in the recognition of chitin-derived molecules produced by microorganisms(Buendia et al.,2018).Notably,the LysM-RLK heterocomplex LjNFR1/LjNFR5 recognizes lipochitooligosaccharides(LCOs,also called Nod factors)leading to root nodule symbiosis(RNS)in Lotus japonicus,whereas the heterocomplexes AtLYK5/AtCERK1 and OsCEBIP/OsCERK1 recognize chitooligosaccharides(COs)leading to defense responses in Arabidopsis thaliana and rice,respectively(Buendia et al.,2018).These receptors function as *** ligand binding activates the intracellular kinase activity of LjNFR1,AtCERK1,and OsCERK1,which mediate phosphorylation-dependent signaling cascades.

关键词： extracellular immunity kinases

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The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin david M.Lubman Department of Surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer *** play an important role in medicine and are involved in various human disease conditions including ***-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and *** N-glycosylation significantly impacts cancer processes and targeted therapies in ***,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and *** review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and ***,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are *** and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been ***,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

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