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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

Neurocircuit regeneration by extracellular matrix reprogramming

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Neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian N.Levasseur Kimberly m.Alonge Department of medicinal chemistry University of WashingtonSeattleWAUSA Department of chemistry University of WashingtonSeattleWAUSA Department of medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(Ecm),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's Ecm regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(miyata et al.,2012),cation buffering(moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).considering the diversity of functions,dynamic remodeling of the brain's Ecm indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

关键词： matrix programming

magnetically actuated glaucoma drainage devicefor regulating intraocular pressure afterimplantation

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microsystems & Nanoengineering 2023年第4期9卷 91-105页

作者： Inês c.F.pereira Ralph J.S.van mechelen Hans m.Wyss Leonard Pinchuk Henny J.m.Beckers Jaap m.J.den Toonder microsystems Department of Mechanical EngineeringEindhoven University of Technology5600MB EindhovenThe Netherlands Institute for complex molecular Systems(IcmS) Eindhoven University of Technology5600MB EindhovenThe Netherlands University Eye clinic maastricht Maastricht University Medical Centre+(MUMC+)6202AZ MaastrichtThe Netherlands InnFocus Inc.a Santen CompanyMiamiFlorida 33186USA Ophthalmic Biophysics center Bascom Palmer Eye InstituteUniversity of Miami Miller School of MedicineMiamiFlorida 33136USA

The key risk factor for glaucoma is increased intraocular pressure (IOP). Glaucoma drainage devices implanted in theeye can reduce IOP and thus stop disease progression. However, most devices currently used in clinical practice arepassive and do not allow for postsurgical IOP control, which may result in serious complications such as hypotony (i.e.,excessively low IOP). To enable noninvasive IOP control, we demonstrate a novel, miniature glaucoma implant that willenable the repeated adjustment of the hydrodynamic resistance after implantation. This is achieved by integrating amagnetic microvalve containing a micropencil-shaped plug that is moved using an external magnet, thereby openingor closing fluidic channels. The microplug is made from biocompatible poly(styrene-block-isobutylene-block-styrene)(SIBS) containing iron microparticles. The complete implant consists of an SIBS drainage tube and a housing elementcontaining the microvalve and fabricated with hot embossing using femtosecond laser-machined glass molds. Usingin vitro and ex vivo microfluidic experiments, we demonstrate that when the microvalve is closed, it can providesufficient hydrodynamic resistance to overcome hypotony. Valve function is repeatable and stable over time. Due to itssmall size, our implant is a promising, safe, easy-to-implant, minimally invasive glaucoma surgery device.

关键词： enable implantation overcome

杂原子修饰的碳纳米管对高级氧化过程的催化性能(英文)

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催化学报 2014年第6期35卷 896-905页

作者： Joo Restivo Raquel P.Rocha Adrián m.T.Silva josé J.m.órfo manuel F.R.pereira josé L.Figueiredo Laboratory of catalysis and materials-Associate Laboratory LSRE/Lcm Faculty of Engineering University of Porto Rua Dr.Roberto Frias 4200-465 Porto Portugal

multi-walled carbon nanotubes (cNTs) were submitted to chemical and thermal treatments in order to incorporate different heteroatoms on the surface. O-, S- and N-containing groups were successfully introduced onto the cNTs without significant changes of the textural properties. The cata-lytic activity of these heteroatom-modified cNTs was studied in two liquid phase oxidation processes: catalytic ozonation and catalytic wet air oxidation (cWAO), using oxalic acid and phenol as model compounds. In both cases, the presence of strongly acidic O-containing groups was found to decrease the catalytic activity of the cNTs. On the other hand, the introduction of S species (mainly sulfonic acids) enhanced the removal rate of the model compounds, particularly in the cWAO of phenol. Additional experiments were performed with a radical scavenger and sodium persulfate, in order to clarify the reaction mechanism. Nitrogen functionalities improve the catalytic performance of the original cNTs, regardless of the process or of the pollutant.

关键词：多壁碳纳米管催化性能高级氧化技术杂原子修饰模型化合物含氮基团催化湿式氧化

Transport mechanism in chemically reactive hybrid nanofluid flow containing gyrotactic micro-organisms over a curved oscillatory surface

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 177-192页

作者： m.NAVEED m.ImRAN T.ASGHAR Z.ABBAS Department of mathematics Division of Science and TechnologyUniversity of Education Department of mathematics The Islamia University of Bahawalpur

This paper examines the transport analysis, including both heat transfer and mass transfer, in hybrid nanofluid flow containing gyrotactic microorganisms towards a curved oscillatory surface. The influence of magnetic fields is also inspected in terms of their physical characteristics. To depict the phenomena of transport, modified versions of both Fick's and Fourier's laws are used. Additionally, the characteristics of both heterogeneous and homogeneous chemical reactions are also incorporated. Utilizing a curvilinear coordinate system, the flow problem is formulated as partial differential equations(PDEs)for momentum, concentration, microorganism field, and energy. An analytical solution to the obtained flow equations is achieved utilizing the homotopy analysis method(HAm).The effects of significant flow parameters on the pressure and microorganism fields, velocity, oscillation velocity, concentration, and temperature distributions are shown via graphs. Furthermore, the variations in skin friction, mass transfer rate, heat transfer rate, and local motile number due to different involved parameters are presented in tables and are analyzed in detail. Graphical results indicate that the curves of velocity and temperature fields are enhanced as the values of the solid volume fraction variables *** is also verified that the concentration rate field decreases as the values of the homogeneous reaction strength parameter and the radius of curvature parameter increase, and it increases with the Schmidt number and the heterogeneous reaction strength *** outcomes show a favorable response of the motile number to advanced values of the Peclet number, the Schmidt number, the microorganism difference parameter, and the bio-convective Lewis number.

关键词： Peclet number

Slip-model Performance for Underexpanded micro-scale Rocket Nozzle Flows

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Journal of Thermal Science 2007年第3期16卷 223-230页

作者： joséA.morí■igo joséHermidaQuesada Francisco caballero Requena Dept.of Space Programmes Dept.of

In aerospace micro-Electro mechanical Systems （mEmS）, the characteristic length scale of the flow approaches the molecular mean free path, thus invalidating the continuum description and enforcing the use of particle methods, like the Direct Simulation monte carlo （DSmc）, to deal with the non-equilibrium regions. Within the slip-regime （0.01〈Kn〈-0.1） both approaches, continuum and particle-based, seem to behave well in terms of accuracy. The present study summarizes the implementation and results obtained with a 2nO-order slip boundary condition in a Navier-Stokes solver to address the rarefaction near the nozzle walls. Its assessment and application to a cold-gas micro-scale conical nozzle of 300μm throat diameter, discharging into the low-pressure freestream, constitutes the major aim of the work. The slip-model incorporates the velocity slip with thermal creep and temperature jump, thus permitting to deal with non-isothermal flows as well. Results show that the gas experiences an intense rarefaction in the lip vicinity, pointing to the limits of model validity. Furthermore, a strong mach deceleration is observed, attributed to the rather thick subsonic boundary layer and supersonic bulk heating caused by the viscous dissipation, in contrast with the expansion to occur in large rocket nozzles during underexpanded operation.

关键词： Slip flow mEmS micronozzles

A stable anthraquinone-derivative cathode to develop sodium metal batteries: The role of ammoniates as electrolytes

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Journal of Energy chemistry 2023年第2期77卷 572-580,I0015页

作者： Débora Ruiz-martínez josé m.Orts Roberto Gómez Departament de Química Física i Institut Universitari d’Electroquímica Universitat d’AlacantApartat 99Alicante E-03080Spain

Rechargeable sodium metal batteries constitute a cost-effective option for energy storage although sodium shows some drawbacks in terms of reactivity with organic solvents and dendritic *** we demonstrate that an organic dye,indanthrone blue,behaves as an efficient cathode material for the development of secondary sodium metal batteries when combined with novel inorganic *** electrolytes are ammonia solvates,known as liquid ammoniates,which can be formulated as NaI·3.3NH_(3) and NaBF_(4)·2.5NH_(3).They impart excellent stability to sodium metal,and they favor sodium non-dendritic growth linked to their exceedingly high sodium ion *** advantage is complemented by a high specific *** battery described here can last hundreds of cycles at 10 c while keeping a coulombic efficiency of 99%from the first *** of the high capacity of the cathode and the superior physicochemical properties of the electrolytes,the battery can reach a specific energy value as high as 210 W h kgIB^(-1),and a high specific power of 2.2 kW kgIB^(-1),even at below room temperature(4℃).Importantly,the battery is based on abundant and cost-effective materials,bearing promise for its application in large-scale energy storage.

关键词： Sodium metal batteries Anthraquinone-based cathode Vat dye Indanthrone blue Inorganic electrolytes Liquid ammoniates

multiple primary colorectal cancer: Individual or familial predisposition?

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 434-444页

作者： josé A Pajares josé Perea Department of Gastreoenterology Gregorio Maranon University Hospital Department of Surgery 12 de Octubre University Hospital

colorectal carcinoma(cRc) is one of the most frequent cancers. Along the surface of the large bowel, several foci of cRc may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary cRc(mPcRc):When more than one tumour is diagnosed at the same time, it is known as synchronous cRc(ScRc), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous cRc(mcRc). multiple issues can promote the development of mPcRc, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in mPcRc. An increased risk for mPcRc has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial cRcs should also be considered as risk factors for mPcRc. Environmental factors can promote damage to colon mucosae that enable the concurrence of mPcRc. Epigenetics are thought to play a major role in the carcinogenesis of sporadic mPcRc. The methylation state of the DNA depends on multiple environmental factors(e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the mPcRc rate. certain clinical features may also suggest individual predisposition for mPcRc. Different etiopathogenic factors are suspected to be involved in ScRc and mcRc, and different familial vs individual factors may be implicated. mcRc seems to follow a familial pattern, whereas individual factors are more important in ScRc. Further studies must be carried out to know the molecular basis of risks for mPcRc in order to modify, if necessary, its clinical management, especially from a preventive point of view.

关键词： multiple primary colorectal cancer Synchronous colorectal cancer metachronous colorectal cancer chromosomal instability microsatellite instability cpG island methylator phenotype

Improving cover and management factor (c-factor) estimation using remote sensing approaches for tropical regions

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International Soil and Water conservation Research 2019年第4期7卷 325-334页

作者： André Almagro Thais caregnatto Thomé carina Barbosa colman Rodrigo Bahia pereira josé marcato Junior Dulce Buchala Bicca Rodrigues Paulo Tarso Sanches Oliveira Federal University of mato Grosso do Sul CxP 549 Campo Grande MS 79070-900 Brazil

The Revised Universal Soil Loss Equation (RUSLE)'s cover and management factor (c-factor) is one of the most difficult factors to obtain,mainly because long-term monitoring soil erosion plots under natural rainfall are ***,remote sensing approaches have been used as an alternative for obtaining this ***,there is a lack of studies comparing values of this factor computed from remote sensing approaches with measured *** this study,we compare two widely used remote sensing approaches (crA and cVK) to estimate the c-factor based on the Normalized Difference Vegetation Index (NDVI) with the literature (cLIT) and field experimental data..We also investigated the influence of c-factor methods on the prediction of soil loss and sediment yield (SY) using measured data in the Guariroba basin,central-West *** obtained mean c-factor values of 0.032,0.023 and 0.137 for cLIT,crA and cVK,*** found an average annual soil loss of 2.20 tha-1 yr-1,2.02 t ha-1 yr-1 and 10.07 tha-1 yr-1 and SY values of 6875 tyr-1,6468 tyr-1 and 33,435 t yr1,for cLIT,crA and cVK *** results indicated a significant improvement in soil loss and SY estimations by using the crA approach developed for tropical regions,with a bias of 13% to the measured SY (5709tyr-1).We conclude that the crA method present the most suitable alternative to compute soil loss and SY in tropical ***,this approach allows large-scale evaluation and temporal monitoring,therefore enhancing multi spatial and temporal assessment of soil erosion processes.

关键词： Soil erosion RUSLE NDVI Landsat 8 Land use/land cover