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Open-Label, Pilot Study of the Safety and Clinical Effects of Rituximab in Patients with Rheumatoid Arthritis-Associated Interstitial Pneumonia

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Open Journal of Rheumatology and Autoimmune Diseases 2012年第3期2卷 53-58页

作者： Eric L. Matteson tim bongartz Jay H. Ryu Cynthia S. Crowson Thomas E. Hartman Paul F. Dellaripa Department of Health Sciences Research Department of Radiology Mayo Clinic College of Medicine Rochester US Division of Pulmonary and Critical Care Medicine Division of Rheumatology Brigham and Womens Hospital Boston US Division of Rheumatology Milano Italy

Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.

关键词： Rheumatoid Arthritis Interstitial Pneumonitis Rituximab

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Like a G6-nal:transcriptional control of G-protein coupled receptors during oligodendroglial development

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Neural Regeneration Research 2025年第7期20卷 2001-2002页

作者： tim Aberle Michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating *** the central nervous system,this role is taken up by *** are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal *** the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor ***,the timing of myelination and maintenance of the OPC pool both need to be precisely *** transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling *** the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental *** insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).

关键词： gained insulation conduction

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Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets tim Vanmierlo Rudy Schreiber BIOMED Biomedical Research Institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

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Solvable base change and Rankin-Selberg convolutions

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Science China Mathematics 2017年第1期60卷 99-112页

作者： GILLESPIE tim Department of Mathematics St. Ambrose University Davenport IA 52803 USA

Let π and π′ be unitary automorphic cuspidal representations of GL_n(A_E) and GL_m(A_F), and let E and F be solvable Galois extensions of Q of degrees ? and ?′, respectively. Using the fact that the automorphic induction and base change maps exist for E and F, and assuming an invariance condition under the actions of the Galois groups, we attach to the pair(π, π′) a Rankin-Selberg L-function L(s, π×E,Fπ′) for which we prove a prime number theorem. This gives a method for comparing two representations that could be defined over completely different extensions, and the main results give a measure of how many cuspidal components the two representations π and π′ have in common when automorphically induced down to the rational numbers. The proof uses the structure of the Galois group of the composite extension EF and the character groups attached to the fields via class field theory. The second main theorem also gives an indication of when the base change of π up to the composite extension EF remains cuspidal.

关键词： automorphic L-function base change automorphic induction

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Antipredator deception in terrestrial vertebrates

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Current Zoology 2014年第1期60卷 16-25页

作者： tim CARO Department of Wildlife Fish and Conservation Biology and Center of Population Biology University of California Davis CA95616 USA

Abstract Deceptive antipredator defense mechanisms fall into three categories： depriving predators of knowledge of prey＇s presence, providing cues that deceive predators about prey handling, and dishonest signaling. Deceptive defenses in terrestrial vertebrates include aspects of crypsis such as background matching and countershading, visual and acoustic Batesian mimicry, active defenses that make animals seem more difficult to handle such as increase in apparent size and threats, feigning injury and death, distractive behaviours, and aspects of flight. After reviewing these defenses, I attempt a preliminary evaluation of which aspects of antipredator deception are most widespread in amphibians, reptiles, mammals and birds

关键词： Amphibians Birds Defenses Dishonesty Mammals Prey Reptiles

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Male circumcision： towards a World Health Organisation normative practice in resource limited settings

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Asian Journal of Andrology 2010年第5期12卷 628-638页

作者： tim Hargreave Senior Fellow School of Clinical Science Edinburgh University Scotland UK Technical Adviser to the WHO RHR -HRP Africa HIV Prevention Male Circumcision Programme

There is now grade 1 evidence that male circumcision （MC） reduces the risk of a man acquiring HIV. Modelling studies indicate MC could in the next 10 years save up to 2 million lives in those African countries with high HIV prevalence. Several African countries are now scaling up public health MC programmes. The most effective immediate public health MC programmes in Africa will need to target 18-20 years old men. In the longer term there is a need for infant circumcision programmes. In order to implement more widespread MC there is a need to make the surgical procedures as simple as possible so that safe operations can be performed by paramedical staff. The WHO Manual of Male Circumcision under local anaesthetic was written with these objectives in mind. Included in the manual are three adult techniques and four paediatric procedures. The adult procedures are the dorsal slit, the for- ceps guided and the sleeve resection methods. Paediatric methods included are the plastibell technique, the Mogen and Gomco shield method and a standard surgical dorsal slit procedure. Each method is described in a step by step manner with photographic and line drawing illustrations. In addition to the WHO manual of surgical technique a teaching course has been developed and using this course it has been possible in one week to train a circumcision surgeon who has had no or minimal previous surgical experience. Further scaling will require training of circumcision surgeons, monitoring performance, training the trainer workshops as well as advocacy at national, international and government meetings. In addition to proceeding with standardised methods work is in progress to assess novel techniques in adults such as stay on ring devices and policies are being formulated as to how to assess new devices. Also work is in progress to explore efficiencies in surgical processing by task sharing. Proper informed consent and safety remain paramount and great care has to be taken as programmes in

关键词： Africa HIV male circumcision

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Orderly Algorithm to Enumerate Central Groupoids and Their Graphs

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Acta Mathematica Sinica,English Series 2007年第2期23卷 249-264页

作者： tim BOYKETT time’s Up Research Department and Department of Mathematics Johannes-Kepler University

A graph has the unique path property UPPif there is a unique path of length n betweenany ordered pair of *** paper reiterates Royle and MacKay’s technique for constructing orderly *** wishto use this technique to enumerate all UPPgraphs of small orders 3~2 and 4~*** attempt to use thedirect graph formalism and find that the algorithm is *** introduce a generalised problem and derive algebraic and combinatoric structures with appro-priate *** we are able to design an orderly algorithm to determine all UPPgraphs oforder 3~2,which runs fast *** hope to be able to determine the UPPgraphs of order 4~2 in thenear future.

关键词： orderly algorithms paths in directed graphs enumeration

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Impact of Background Dynamic and Thermodynamic States on Distinctive Annual Cycle of Near-Equatorial Tropical Cyclogenesis over the Western North Pacific

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Journal of Meteorological Research 2020年第4期34卷 822-835页

作者： Liyuan DENG tim LI Key Laboratory of Meteorological Disaster Ministry of Education/Joint International Research Laboratory of Climate and Environmental Change/Collaborative Innovation Center on Forecast and Evaluation of Meteorological DisastersNanjing University of Information Science&TechnologyNanjing 210044China International Pacific Research Center and Department of Atmospheric Sciences School of Ocean and Earth Science and TechnologyUniversity of HawaiiHonoluluHI 96822USA

In a sharp contrast to tropical cyclone(TC) genesis over the main development region of the western North Pacific(WNP), near-equatorial(0°-5°N) TCs exhibit a distinctive annual cycle, peaking in boreal winter and being inactive in boreal summer. The relative roles of dynamic and thermodynamic background states on near-equatorial TCs formation were investigated based on the observational diagnosis of the genesis potential index(GPI) and high-resolution model simulations. It is found that the background vorticity makes a major contribution to the distinctive annual cycle, while mean temperature and specific humidity fields are not critical. Numerical simulations further indicate that seasonal mean cyclonic vorticity in boreal winter has three effects on TC genesis near the equator. First, the environmental cyclonic vorticity interacts with TC vortex to promote a mid-level outflow, which strengthens boundary layer friction induced ascending motion and thus condensational heating. Second, it produces an equivalent Coriolis effect(via enhanced absolute vorticity), which strengthens positive feedback between primary and secondary circulation. Third, it helps to merge small-scale vortical hot towers(VHTs) into a mesoscale core through vorticity segregation process. However, background vorticity in boreal summer has an opposite effect on TC development near the equator.

关键词： near-equatorial tropical cyclone(TC) equivalent Coriolis effect vorticity segregation

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An Empirical Model of Tropical Cyclone Intensity Forecast in the Western North Pacific

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Journal of Meteorological Research 2022年第5期36卷 691-702页

作者： Chen MA tim LI Jiangsu Meteorological Observatory Jiangsu Meteorological BureauNanjing 210019China Key Laboratory of Meteorological Disaster Ministry of Education(KLME)/Joint International Research Laboratory of Climate and Environmental Change(ILCEC)/Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD)NanjingUniversityof Information Science&TechnologyNanjing210044China International Pacific Research Center and Department of Atmospheric Sciences School of Ocean and Earth Science and TechnologyUniversityofHawaiiHI96822USA Key Laboratory of Transportation Meteorology China Meteorological AdministrationNanjing 210019China

The relative impact of environmental parameters on tropical cyclone(TC) intensification rate(IR) was investigated through a box difference index(BDI) method, using TC best track data from Joint Typhoon Warning Center and environmental fields from the NCEP final analysis data over the western North Pacific(WNP) during 2000–*** are total 6307 TC samples with a 6-h interval, of which about 14% belong to rapid intensification(RI) category. The analysis shows that RI occurs more frequently with higher environmental sea surface temperature, higher oceanic heat content, and lower upper-tropospheric temperature. A moderate easterly shear is more favorable for TC intensification. TC intensification happens mostly equatorward of 20°N while TC weakening happens mostly when TCs are located in the northwest of the basin. Mid-tropospheric relative humidity and vertical velocity are good indicators separating the intensification and non-intensification groups. A statistical model for TC intensity prediction was constructed based on six environmental predictors, with or without initial TC intensity. Both models are skillful based on Brier skill score(BSS) relative to climatology and in comparison with other statistical models, for both a training period(2000–2018) and an independent forecast period(2019–2020).

关键词： tropical cyclone rapid intensification prediction model

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Increasing Trend of Summertime Synoptic Wave Train Activity over the Western North Pacific since 1950

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Journal of Meteorological Research 2020年第5期34卷 1013-1024页

作者： Xinyi ZHOU tim LI Key Laboratory of Meteorological Disaster Ministry of Education(KLME)/Joint International Research Laboratory of Climate and Environmental Change(ILCEC)/Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD)Nanjing University of Information Science&TechnologyNanjing 210044China International Pacific Research Center and Department of Atmospheric Sciences School of Ocean and Earth Science and TechnologyUniversity of HawaiiHonoluluHI 96822USA

The change of summertime synoptic-scale wave train(SWT) activity over the western North Pacific(WNP) since1950 was investigated based on the NCEP–NCAR reanalysis data. It is found that the intensity of SWT has a rising trend, while its structure and phase propagation characteristics remain unchanged. Environmental factors responsible for the rising trend are investigated. By separating the whole period into three warming phases(P1: 1950–1958, P2:1978–1986, and P3: 2006–2014), we found that even though the vertical velocity shows a rising trend, the background low-level vorticity over the monsoon trough region increases from P1 to P2 but decreases from P2 to P3, and so is the low-level barotropic energy conversion(CK). Thus, just the environmental dynamic factor could not explain the continuous rising SWT trend. On the other hand, thermodynamic factor, such as the sea surface temperature(SST), moisture, and atmospheric instability, shows a clear step-by-step increasing trend. A non-dimensional synoptic activity index(SAI) that combines the dynamic and thermodynamic factors is then proposed. This index well captures the observed long-term trend of the SWT intensity.

关键词： global warming synoptic wave train barotropic energy conversion(CK) atmospheric instability parameter synoptic activity index(SAI)

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