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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： Robert Lam joseph K Lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis b virus(HbV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis b surface antigen(HbsAg)loss and suppression of HbV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis b,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HbsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis b virus Treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

TiO_2担载镍催化剂上硝基苯液相加氢(英文)

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催化学报 2012年第8期33卷 1299-1305页

作者： K.joseph Antony RAJ M.G.PRAKASH R.MAHALAKSHMY T.ELANGOVAN b.VISWANATHAN National Centre for Catalysis Research Indian Institute of Technology-Madras Chennai 600036 India PG & Research Department of Chemistry Thiagarajar College Madurai 625009 India

The catalytic hydrogenation of nitrobenzene to aniline employing nickel impregnated on rutile,anatase,and high surface area titania supports has been *** nickel is present in elemental state as fcc phase on the catalyst as evidenced by X-ray diffraction *** Ni crystallite size was found to be greater for Ni/*** temperature-programmed reduction results suggest a greater metal-support interaction for Ni/*** observed order of catalytic activity for the hydrogenation of nitrobenzene is Ni/rutile > Ni/anatase > Ni/TiO2.A conversion of 99% was observed for Ni/rutile at 140 oC and hydrogen pressure of 1.96 ***,aniline is the only product formed which demonstrates the catalytic hydrogenation of nitrobenzene proceeds with atom *** Ni/rutile and Ni/anatase exhibited a better stability than Ni/*** hydrogenation proceeds with the preferential adsorption of hydrogen on nickel present in the catalyst surface,possibly assisted by TiOx species.

关键词： hydrogenation nitrobenzene nickel titania aniline

The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics

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Journal of biosciences and Medicines 2024年第8期12卷 347-356页

作者： Robert b. Raffa joseph V. Pergolizzi Jr. School of Pharmacy (Emeritus) Temple University Philadelphia PA USA College of Pharmacy (Adjunct) University of Arizona Tucson AZ USA NEMA Research Naples FL USA

Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.

关键词： Chaperone Sigma-1 Receptor Energetics Thermodynamics Isothermal Titration Microcalorimetry

Antimicrobial Resistance Patterns and bovine Sub-Clinical Mastitis burden in Low and High Tick Acaricide Resistance Regions of Uganda

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Open Journal of Veterinary Medicine 2022年第8期12卷 71-87页

作者： joseph byaruhanga Yvette Ssebunya Patrick Vudriko Innocent b. Rwego Research Center for Tropical Diseases and Vector Control (RTC) Department of Veterinary Pharmacy Clinics and Comparative Medicine College of Veterinary Medicine Animal Resources and Biosecurity Makerere University Kampala Uganda Division of Veterinary Regulation and Inspection Department of Animal Health Ministry of Agriculture Animal Industry and Fisheries Entebbe Uganda One Health Division Department of Veterinary Population Medicine College of Veterinary Medicine Saint Paul USA Department of biosecurity Ecosystems and Veterinary Public Health College of Veterinary Medicine Animal Resources and Biosecurity (COVAB) Makerere University Kampala Uganda

Mastitis, antimicrobial resistance and acaricide resistance pose significant threats to the development of the dairy industry in sub-Saharan Africa. This study aimed to determine the prevalence of antimicrobial resistance in bacteria isolated from CMT positive cows on farms located in high (HARA) and low (LARA) acaricide resistance challenge regions of Uganda. Among selected herds in both regions, subclinical mastitis (SCM) screening was performed using CMT. CMT positive samples were collected, cultured, bacteria isolated and antibiotic sensitivity tests conducted. Overall, the prevalence of SCM in cows was 71.5% and 27.7% for HARA and LARA respectively. A SCM herd prevalence of 66.3% and 28.2% was recorded for HARA and LARA respectively. Furthermore, 67.5% and 20.8% of the cows in the HARA and LARA groups, respectively, had three out of four udder quarters infected with SCM. Staphylococcus aureus (44.2%) and coagulase-negative Staphylococcus (CNS) (47.6%) were the most prevalent causative agents of SCM isolated from cows from HARA and LARA, respectively. Most isolates from both regions were highly resistant to penicillin (HARA, 84.3%;LARA, 95.6%) and colistin (HARA, 100%;LARA, 97.8%). Tetracycline (77.1%) and oxacillin (76.1%) resistance was high in isolates from HARA and LARA, respectively. Intermediate responses (neither susceptible nor resistant) to antibiotics were more common in isolates from HARA than in those from LARA. With this level of antibiotic resistance, there is a potential risk of failure to control mastitis in dairy cattle using antibiotics, especially in the HARA region, which may possibly jeopardize the growth of the dairy industry in Uganda.

关键词： Antimicrobial Resistance Sub Clinical Mastitis Tick Resistance

The Impacts and Causes of Land Fragmentation on Farm Productivity: Case Review of East African Countries

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Open Journal of Ecology 2024年第5期14卷 455-482页

作者： joseph Mayindo Mayele Jacob b. Kolleh Joel Emmanuel Saburi Department of Agricultural and Resource Economics The University of Tokyo Tokyo Japan Department of Forestry and Wildlife College of Natural Resources and Environmental Studies University of Juba Juba South Sudan Department of Socio-Economic and Applied Statistics Central Agricultural Research Institute (CARI) Suakoko Liberia

This report provides an overall assessment of land fragmentation problems in East Africa. Many parts of East Africa have become highly fragmented, putting development systems and activities in these areas at risk of complete collapse. Land fragmentation occurs when land gets converted for agriculture, industrialization, or urbanization, invaded by non-local plants, or enclosed for individual use and by subdividing farmlands into subsequent smaller units called parcels with varying average farm sizes. Fragmentation results from inappropriate agricultural development processes and ineffective land use planning that fails to recognize how farmland is used, and the importance of its interconnected areas. Insecurity of tenure and resource rights are key factors in making this possible. Land fragmentation is one of the key reasons why the ability of most resources in East Africa becomes scarcer, and those remaining become “privatized” by more powerful community members—keen to maintain their access to them. Such individualistic attitudes are new and disadvantage the poorest even further by affecting the traditional customary safety nets and agricultural outputs. Neither the government nor customary governance systems effectively protect resource access for the poorest. This review summary report identifies the key causes, measures, and implications, government interventions, and the common remedies to land fragmentation problems in the East African Countries of Kenya, Uganda, Rwanda, and Tanzania including neighboring Ethiopia, and the Sudan. The findings indicated from 2005 to 2015, the population kept increasing for all the named countries in East Africa with Rwanda and Uganda having a substantial increase in population density. The study review further explores the trend in the performance of agriculture by average farm sizes within the intervals of five years by highlighting their strong linkages and found that the average farm size has declined drastically, especiall

关键词： Land Fragmentation Land Consolidation Farm Productivity Industrialization Impacts Causes Average Farm Size Population East Africa

The most important questions in cancer research and clinical oncology

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Chinese Journal of Cancer 2017年第2期36卷 1-7页

作者： joseph T. S. Wee Sharon Shuxian Poh Division of Radiation Oncology National Cancer Centre Duke-NUSMedicalSchool

Specific research foci:(1) Mouse models of gamma-herpes virus-68(γHV-68) and polyomavirus(Py V) infections during neonatal versus adult life.(2) For human papilloma virus(HPV)-positive oropharyngeal carcinoma(OPC)—(a) Asking the question: Is oral sex a powerful carcinogen?(b) Examining the evidence for the vertical transmission of HPV infection.(c) Examining the relationship between HPV and Epstein–barr virus(EbV) infections and nasopharyngeal cancer(NPC) in West European, East European, and East Asian countries.(d) Examining the association between HPVpositive OPC and human leukocyte antigen(HLA).(3) For non-smoking East Asian female lung adenocarcinoma—(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts.(b) Examining the association between female lung adenocarcinoma and HPV.(c) Examining the associations of lung adenocarcinoma with immune modulating factors.(4) For triple-negative breast carcinoma(TNbC) in East Asians—(a) Examining the association between TNbC and HPV.(b) Examining the unique epidemiological characteristics of patients with TNbC. A summary "epidemiological" model tying some of these findings together.

关键词： HPV The most important questions in cancer research and clinical oncology

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Impacts of late Quaternary environmental change on the long-tailed ground squirrel(Urocitellus undulatus)in Mongolia

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Zoological Research 2018年第5期39卷 364-372页

作者： bryan S.McLean batsaikhan Nyamsuren ANDrey Tchabovsky joseph A.Cook University of Florida Florida Museum of Natural History Department of biology School of Arts and Sciences National University of Mongolia Laboratory of Population Ecology A.N. Severtsov Institute of Ecology and Evolution University of New Mexico Department of Biology and Museum of Southwestern Biology

Impacts of Quaternary environmental changes on mammal faunas of central Asia remain poorly understood due to a lack of comprehensive phylogeographic sampling for most *** help address this knowledge gap,we conducted the most extensive molecular analysis to date of the long-tailed ground squirrel （Urocitellus undulatus Pallas 1778） in Mongolia,a country that comprises the southern core of this species＇ *** on material from recent collaborative field expeditions,we genotyped 128 individuals at two mitochondrial genes （cytochrome b and cytochrome oxidase Ⅰ;1797 bp total）.Phylogenetic inference supports the existence of two deeply divergent infraspecific lineages （corresponding to subspecies *** and ***）,a result in agreement with previous molecular investigations but discordant with patterns of range-wide craniometric and external phenotypic *** the widespread western eversmanni lineage,we recovered geographically-associated clades from the：（a） Khangai,（b） Mongolian Altai,and （c） Govi Altai mountain *** structure in *** is consistent with an isolation-by-distance model;however,genetic distances are significantly lower than among subspecies,and intra-clade relationships are largely *** latter patterns,as well as the relatively higher nucleotide polymorphism of populations from the Great Lakes Depression of northwestern Mongolia,suggest a history of range shifts into these lowland areas in response to Pleistocene glaciation and environmental change,followed by upslope movements and mitochondrial lineage sorting with Holocene *** study illuminates possible historical mechanisms responsible for *** genetic structure and contributes to a framework for ongoing exploration of mammalian response to past and present climate change in central Asia.

关键词： Central Asia Gobi Desert Great LakesDepression Mongolia Phylogeography

Colorless-to-colorful switching of electrochromic MXene by reversible ion insertion

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Nano Research 2022年第4期15卷 3587-3593页

作者： Jianxia Jiang Leiqiang Qin joseph Halim Per O.Å.Persson Lintao Hou Johanna Rosen Guangzhou Key Laboratory of Vacuum Coating Technologies and New Energy Materials Physics DepartmentJinan UniversityGuangzhou 510632China Department of Physics Chemistry and Biology(IFM)Linköping UniversityLinköping SE-58183Sweden

Electrochromic(EC)materials that change color with voltage have been widely studied for use in dynamic ***,colorless-to-colorful switching with high contrast ratio is generically unattainable,especially for colorless-to-black electrochromic materials with an ultrahigh contrast ratio over the entire visible *** this work,we developed Nb_(1.33)C MXene-based dynamic windows with colorless-to-black switching of up to 75%reversible change in transmittance from 300 to 1,500 *** exploring the electrochromic effects of different electrolytes through in situ optical changes and electrochemical quartz crystal microbalance(EQCM),it is found that electrochromic behavior is greatly influenced by the extent of reversible Li^(+)insertion/deinsertion between the two-dimensional Nb_(1.33)C MXene *** addition,a colorless-to-black EC device based on Nb_(1.33)C with an overall integrated contrast ratio over 80%was successfully constructed by a solution-processable spin coating *** work enables a simple route to fabricate MXene-based high-performance electrochromic smart windows,which is important for further expanding the application of MXenes to optoelectronic and photonic applications.

关键词： MXenes electrochromic materials colorless-to-black switching high contrast ratio reversible Li^(+)insertion

Assessment of ERA5 and ERA-Interim in Reproducing Mean and Extreme Climates over West Africa

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Advances in Atmospheric Sciences 2023年第4期40卷 570-586页

作者： Imoleayo Ezekiel GbODE Toju Esther bAbALOLA Gulilat Tefera DIRO joseph Daniel INTSIFUL Department of Meteorology and Climate Science Federal University of Technology AkureP.M.B.704 Ilesa-Owo ExpresswayAkureOndo State 340420Nigeria Department of Water Resources Management and Agro-Meteorology Federal University Oye-Ekiti371104Nigeria Canadian Network for Regional Climate and Weather Processes University of Quebec at Montreal201 President-Kennedy AvenueMontrealQC H2X 3Y7Canada Division of Mitigation and Adaptation Green Climate FundIncheon 22004South Korea

In situ data in West Africa are scarce,and reanalysis datasets could be an alternative source to alleviate the problem of data ***,because of uncertainties in numerical prediction models and assimilation methods,among other things,existing reanalysis datasets can perform with various degrees of quality and ***,a proper assessment of their shortcomings and strengths should be performed prior to their *** this study,we examine the performance of ERA5 and ERA-interim(ERAI)products in representing the mean and extreme climates over West Africa for the period 1981-2018 using observations from CRU and *** major conclusion is that ERA5 showed a considerable decrease in precipitation and temperature biases and an improved representation of inter-annual variability in much of western ***,the annual cycle is better captured by ERA5 in three of the region’s climatic zones;specifically,precipitation is well-reproduced in the Savannah and Guinea Coast,and temperature in the *** terms of extremes,the ERA5 performance is ***,both reanalyses underestimate the intensity and frequency of heavy precipitations and overestimate the number of wet days,as the numerical models used in reanalyses tend to produce drizzle more *** ERA5 performs better than ERAI,both datasets are less successful in capturing the observed long-term *** ERA5 has achieved considerable progress compared to its predecessor,improved datasets with better resolution and accuracy continue to be needed in sectors like agriculture and water resources to enable climate impact assessment.

关键词： West Africa ERAI ERA5 reanalysis precipitation temperature extremes

Directing the Metabolism of Drugs Away from CYP450: The Use of Oxetane Rings

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Pharmacology & Pharmacy 2019年第11期10卷 465-473页

作者： Robert b. Raffa joseph V. Pergolizzi Jr. Neumentum Inc. Palo Alto CA USA Enalare LLC Naples FL USA College of Pharmacy University of Arizona Tucson AZ USA Temple University School of Pharmacy Philadelphia PA USA NEMA Research Inc. Naples FL USA.

Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or over-the-counter (OTC). With the consumption of multiple medications, drug-drug interactions (DDIs) are a concern. The site of drug-drug interactions is often at the level of drug metabolism. If a drug inhibits (or enhances) the metabolism of another, the blood level (therapeutic effect) can be decreased below the required level, or adverse effects can increase. because most currently used drugs are metabolized via cytochrome P450-catalyzed pathways, drug discovers seek drugs that are metabolized by alternate pathways. Medicinal chemists have come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized via CYP450. The same modification gives other desirable physical properties to the molecule. Although there are no guarantees that there will be fewer DDIs or an absence of other unexpected problems, the strategy could pave the way for new drugs that are safer and easier to use with concomitant medications.

关键词： Drug Metabolism CYP450 Drug-Drug Interaction Oxetane Analgesic Drug Discovery