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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

Simulation of Impurity Diffusion in a Strained Nanowire Using Off-Lattice KMC

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Communications in Computational Physics 2007年第1期2卷 164-176页

作者： Weidong Guo tim P.Schulze Weinan e Department of Mathematics University of TennesseeKnoxvilleTN 37996-1300USA Department of Mathematics and Program in Applied and Computational Mathematics Princeton UniversityPrincetonNJ 08544-1000USA.

Kinetic Monte Carlo(KMC)is a stochastic model used to simulate crystal ***,most KMC models rely on a pre-defined lattice that neglects dislocations,lattice mismatch and strain *** this paper,we investigate the use of a 3D off-lattice KMC *** test this method by investigating impurity diffusion in a strained FCC *** faster than a molecular dynamics simulation,the most general implementation of off-lattice KMC is much slower than a lattice-based *** improved procedure is achieved for weakly strained systems by precomputing approximate saddle point locations based on unstrained lattice *** this way,one gives up some of the flexibility of the general method to restore some of the computational speed of lattice-based *** addition to providing an alternative approach to nano-materials simulation,this type of simulation will be useful for testing and calibrating methods that seek to parameterize the variation in the transition rates for lattice-based KMC using continuum modeling.

关键词： Off-lattice KMC nanowire strain rate impurity diffusion.

The Flemish Performance-based Research Funding System: A Unique Variant of the Norwegian Model

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Journal of Data and Information Science 2018年第4期3卷 45-60页

作者： tim C.e.engels Raf Guns Centre for R&D Monitoring (eCOOM) Faculty of Social Science University of Antwerp

The BOF-key is the performance-based research funding system that is used in Flanders, Belgium. In this paper we describe the historical background of the system, its current design and organization, as well as its effects on the Flemish higher education landscape. The BOFkey in its current form relies on three bibliometric parameters: publications in Web of Science, citations in Web of Science, and publications in a comprehensive regional database for SSH publications. Taken together, the BOF-key forms a unique variant of the Norwegian model: while the system to a large extent relies on a commercial database, it avoids the problem of inadequate coverage of the SSH. Because the bibliometric parameters of the BOF-key are reused in other funding allocation schemes, their overall importance to the Flemish universities is substantial.

关键词： Performance-based research funding systems Flanders(Belgium) Norwegian model Web of Science VABB-SHW

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

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

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

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

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

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