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Unequal distribution of Innovation Efforts for Neglected Tropical diseases: The Role of Funding Evaluation Criteria

Health（健康） 2024年第5期 490页

作者： Anne M.G.Neevel kenneth d.s.fernald Linda H.M.van de Burgwal

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Health 2024年第5期16卷 490-520页

作者： Anne M. G. Neevel kenneth d. s. fernald Linda H. M. van de Burgwal Athena Institute Faculty of Science Vrije Universiteit Amsterdam Amsterdam Netherlands

Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. Methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, curre

关键词： Neglected Tropical diseases Funding decision Evaluation Criteria Health Research Funding Research Impact

Well-Posedness of stochastic Continuity Equations on Riemannian Manifolds

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Chinese Annals of Mathematics,series B 2024年第1期45卷 81-122页

作者： Luca GALIMBERTI kenneth H.KARLsEN department of Mathematical sciences NTNU Norwegian University of Science and TechnologyN-7491 TrondheimNorway department of mathematics University of OsloP.O.Box 1053BlindernN-0316 OsloNorway

The authors analyze continuity equations with stratonovich stochasticity,■ρ+divh[ρo(u(t,x)+∑_(i=1)^(N)a_(i)(x)w_(i)(t))]=0defined on a smooth closed Riemannian manifold M with metric *** velocity field u is perturbed by Gaussian noise terms Wi(t),:WN(t)driven by smooth spatially dependent vector fields a1(x),...,aN(x)on *** velocity u belongs to L_(t)^(1)W_(x)^(1,2)with divh u bounded in Lf,for p>d+2,where d is the dimension of M(they do not assume div_(h) u∈L_(t,x)^(∞)).For carefully chosen noise vector fields ai(and the number N of them),they show that the initial-value problem is well-posed in the class of weak L^(2) solutions,although the problem can be ill-posed in the deterministic case because of concentration *** proof of this“regularization by noise”result is based on a L^(2) estimate,which is obtained by a duality method,and a weak compactness argument.

关键词： stochastic continuity equation Riemannian manifold Hyperbolic equa-tion Non-smooth velocity field Weak solution Existence Uniqueness

Exciton-polaritons in a 2d hybrid organic-inorganic perovskite microcavity with the presence of optical stark effect

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Chinese Physics B 2024年第3期33卷 551-555页

作者： kenneth Coker 郑楚媛 Joseph Roger Arhin Kwame Opuni-Boachie Obour Agyekum 张伟利 school of Information and Communication Engineering University of Electronic Science and Technology of ChinaChengdu 611731China department of Electrical and Electronic Engineering Ho Technical UniversityHo 00233Ghana Telecommunication Engineering department Kwame Nkrumah University of Science and TechnologyKumasi 00233Ghana

This study investigates the properties of exciton-polaritons in a two-dimensional(2d)hybrid organic-inorganic perovskite microcavity in the presence of optical stark *** both steady and dynamic state analyses,strong coupling between excitons of perovskite and cavity photons is revealed,indicating the formation of polaritons in the perovskite ***,it is found that an external optical stark pulse can induce energy shifts of excitons proportional to the pulse intensity,which modifies the dispersion characteristics of the polaritons.

关键词： exciton-polaritons perovskite microcavity optical stark effect

Tigris, Euphrates, and shatt Al-Arab River system: Historic and Modern Attempts to Manage and Restore Iraq’s Lifeline

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Open Journal of soil science 2024年第1期14卷 28-63页

作者： kenneth Ray Olson david R. speidel College of Agricultural Consumer and Environmental Sciences University of Illinois Urbana USA Us Army Iraq Mosul Iraq Foreign Agricultural service Mahmudiyah Iraq Foreign Agricultural service Washington D.C. USA

In Iraq, the principal rivers are the Tigris, shatt Al-Arab and Euphrates. From their headwater sources in the mountains of eastern Türkiye, these rivers descend through valleys and gorges and flow into the uplands of syria and northern and central alluvial plain of Iraq. The Euphrates and Tigris Rivers confluence to form the shatt Al-Arab river at Al-Qurnah which flows into the Persian Gulf. From sources in the Zagros Mountains other tributaries join the Tigris from the east. The Tigris and Euphrates rivers flow in a southeastern direction through the central plain and discharge into the Mesopotamian Marshes, which include permanent marshes, lakes, and riparian habitat. The rivers and their tributaries drain an area of 879,790 kmsup>2sup> which includes almost the entire area of Iraq as well as land in syria, Türkiye, Kuwait and Iran. The region has historical importance as part of the Fertile Crescent region and where Mesopotamian civilization first emerged. The post war reconstruction efforts in the Yusifiyah township, an important food production region for Baghdad, illustrate the importance of these water resources. In addition, the advent of soil tunnels by Iraqi insurgents within the riverine corridors will make reconstruction of this resource more complex. The primary objectives of this study are to assess lessons learned, manage, and restore the Tigris, Euphrates, and shatt Al-Arab river system lifeline in Iraq.

关键词： Mesopotamian shatt Al-Arab Iraq Tigris Euphrates Baghdad soil Tunnels Yusifiyah

Circulating tumor cells shielded with extracellular vesicle-derived Cd45 evade T cell attack to enable metastasis

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signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang kenneth K.W.To Caimei Cui Min Luo shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu state Key Laboratory of Oncology in south China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China school of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer *** remains elusive how CTCs evade immune surveillance and elimination by immune *** this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived Cd45(termed as Cd45^(+)CTCs)that resisted T cell attack.A higher percentage of Cd45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer ***,Cd45^(+)tumor cells orchestrated an immunosuppressive milieu and Cd45^(+)CTCs exhibited remarkably stronger metastatic potential than Cd45−CTCs in ***,Cd45 expressing on tumor surfaces was shown to form intercellular Cd45-Cd45 homophilic interactions with Cd45 on T cells,thereby preventing Cd45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune ***,these results pointed to an underappreciated capability of EVs-derived Cd45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived Cd45 internalization by CTCs to prevent cancer metastasis.

关键词： Cd45 metastasis prevention

small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi shi Zeping Hu Min Huang Liwu Fu state Key Laboratory of Oncology in south China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China school of Pharmaceutical sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China state Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China school of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

Adding Value to Crop Production systems by Integrating Forage Cover Crop Grazing

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American Journal of Plant sciences 2024年第3期15卷 180-192页

作者： Robert B. Mitchell daren d. Redfearn kenneth P. Vogel Terry J. Klopfenstein Galen Erickson P. stephen Baenziger Bruce E. Anderson Mary E. drewnoski Jay Parsons steven d. Masterson Marty R. schmer Virginia L. Jin UsdA-ARs Wheat Sorghum and Forage Research Unit University of Nebraska-Lincoln Lincoln NE USA department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE USA department of Animal science University of Nebraska-Lincoln Lincoln NE USA department of Agricultural Economics University of Nebraska-Lincoln Lincoln NE USA UsdA-ARs Agroecosystem Management Research Unit University of Nebraska-Lincoln Lincoln NE USA

In addition to their value as cereal grains, wheat (Triticum aestivum L.) and triticale (× Triticosecale Wittmack) are important cool-season annual forages and cover crops. Yearling steer (Bos taurus) performance was compared in the spring following autumn establishment as for age cover crops after soybean [Glycine max (L.) Merr.] grain harvest. Replicated pastures (0.4 ha) were no-till seeded in three consecutive years into soybean stubble in autumn, fertilized, and grazed the following spring near Ithaca, NE, UsA. Each pasture (n = 3) was continuously stocked in spring with four yearling steers (380 ± 38 kg) for 17, 32, and 28 d in 2005, 2006, and 2007, respectively. In 2005, average daily gain (AdG) for steers grazing triticale exceeded the AdG for wheat by 0.31 kghdsup>-1sup>dsup>-1sup>. In 2006, wheat AdG exceeded that for triticale by 0.12 kghdsup>-1sup>dsup>-1sup>. In 2007, steers grazing wheat lost weight, while steers grazing triticale gained 0.20 kghdsup>-1sup>dsup>-1sup>. Based on the 3-year average animal gains valued at $1.32 kgsup>-1sup>, mean net return ($ hasup>-1sup> yrsup>-1sup>) was $62.15 for triticale and $22.55 for wheat. since these grazed cover crops provide ecosystem services in addition to forage, grazing could be viewed as a mechanism for recovering costs and adds additional value to the system. Based on this 3-year grazing trial, triticale was superior to wheat and likely will provide the most stable beef yearling performance across years with variable weather for the western Cornbelt UsA.

关键词： Cover crops soybean Triticale Wheat

Evolution of Mount Cameroon volcanism: Geochemistry, mineral chemistry and radiogenic isotopes(Pb, sr, Nd)

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Geoscience Frontiers 2020年第6期11卷 2157-2168页

作者： Emmanuel Wenjeh Wembenyui kenneth d.Collerson Jian-xin Zhao school of Earth and Environmental sciences The University of QueenslandSt.Lucia CampusQLD4072BrisbaneAustralia Institute for Geological and Mining Research(IRGM)//Hydrological Research Centre Cameroon Ministry of Scientific Research and InnovationNkolbissonYaoundeCameroon

Mount Cameroon volcano has erupted several times in the 20 th Century with documented eruptions in 1909,1922,1954,1959,1982,1999 and *** of historic volcanism is represented by several older lava flows and lahar deposits around the flanks of the *** study aims to assess the evolution of Mount Cameroon volcanism through its eruptive history via interpretation of mineralogical,whole rock geochemical and Pb,sr,Nd isotope data generated from historic and recent lava *** this study,samples were collected from the 1959,1982,1999 and 2000 eruptions and from several historic eruption sites with unknown eruption *** of major and trace element data demonstrates that Mount Cameroon is geotectonically associated with within-plate Ocean Island Basalt *** than 90%of the studied historic lavas(n=29)classify as tephrites and basanites whereas the modern lavas(n=38)are predominantly trachybasalts,demonstrating evolution from primitive to evolved lavas over time typically in response to fractional ***,the lavas are porphyritic with main mineral phases being olivine,clinopyroxene,plagioclase feldspars and Fe-Ti-Cr *** 1982 lavas are predominantly aphyric and dominated by lath-shaped flow-aligned plagioclase in the *** chemistry shows variable forsterite compositions from *** vary from diopside through augite to titanaugite with chemical composition ranges from Wo45En32Fs7 to *** feldspars vary from labradorite(An567 O)to bytownite(An80-87).For the Fe-Ti-Cr oxides,calculated ulvospinel component shows a wide variation from ***-normative classification on the di-Ol-Hy-Qz-Ne system shows that all Mount Cameroon lavas are nepheline-normative(Ne ranges from4.20 wt.%to 11.45 wt.%).Radiogenic isotope data demonstrate that Mount Cameroon lavas are HIMU(or high μ=238U/204Pb),characterized by 206Pb/204Pb=20.19-20.46,207Pb/204Pb=15.63-15.69,208Pb/204

关键词： Mount Cameroon HIMU Petrogenesis Geochemical evolution Radiogenic isotopes Mineral chemistry

Biparental behavior in the burying beetle Nicrophorus orbicollis： a role for dopamine？

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Current Zoology 2016年第3期62卷 285-291页

作者： s. Carmen PANAITOF Jazmine d. W. YAEGER Jarod P. sPEER kenneth J. RENNER department of Biology UniversiW of Nebraska at Keamey Kearney NE 68849 USA department of Biology University of South Dakota Vermillion SD 57069 USA

Burying beetles Nicrophorus orbicollis exhibit facultative biparental care of young. To reproduce, a male-female burying beetle pair bury and prepare a small vertebrate carcass as food for its altricial young. during a breeding bout, male and female behavior changes synchronously at appropriate times and is coordinated to provide effective care for offspring. Although the ecologicaJ and evolutionary factors that shape this remarkable reproductive plasticity are well characterized, the neuromodulation of parental behavior is poorly understood. Juvenile hormone levels rise dramat- ically at the time beetle parents accept and feed larvae, remain highly elevated during the stages of most active care and fall abruptly when care is terminated. However, hormonal fluctuations alone cannot account for this elaborate control of reproduction. The biogenic amines octopamine （OA）, dopamine （dA）, and serotonin （5-HT） mediate a diversity of insect reproductive and social behav- iors. In this study, we measured whole brain monoamine levels in individual male and female bury- ing beetles and compared OA, dA, and 5-HT profiles between breeding （parental） and nonbreed- ing, unmated beetles. Remarkably, after 24 h of care, when parental feeding rates begin to peak, dA brain levels increase in breeding beetles when compared to nonbreeding controls. In contrast, brain OA and 5-HT levels did not change significantly. These results provide the first evidence for a potential role of dA in the modulation of burying beetle parental behavior.

关键词： dopamine Nicrophorus neuromodulation octopamine parental care serotonin.