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Journal of Agricultural Science and Technology(A) 2012年第3期2卷 363-372页

作者： Francisco Robles-Gonzalez Edgar Diaz Jean Claude Cheve Ricardo Angulo Carlos Gonzfilez Research and Development Department Boehringer Ingelheim Vetmedica S.A. de C. K Guadalajara Jalisco 44940 Mexico Technical Services Boehringer Ingelheim Vetmedica S.A. de C. V. Guadalajara Jalisco 44940 Mexico boehringer Ingelheim vetmedica Inc. St. Joseph Missouri 6450 USA

PCV2 （Porcine circovirus type 2） is considered as the essential infectious agent of PMWS （post weaning multisystemic wasting syndrome） in pigs. Serological studies have shown that the virus is ubiquitous. Currently, there are many reports about the epidemiology and genetic characteristics of this virus around the world, but in Mexico it has not been studied. More than 3,500 samples of serum, rectal swabs, tissues and semen of 34 Mexican porcine farms from 10 important producer regions were analyzed by PCR. Results show that 97% of the farms were positive. Both genotypes, PCV2a and PCV2b were detected. It also found that the most prevalent genotype in Mexico is PCV2b. Regarding to amino acid sequence; three major heterogenic regions were present in the positions 59-91,123-136 and 185-210.

关键词： PCV2 (Porcine circovirus type 2) PMWS PCR pig Mexico.

How to implement the‘one patient,one vote’principle under the framework of estimand

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Statistical Theory and Related Fields 2023年第3期7卷 202-212页

作者： Naitee Ting Department of Biostatistics and Data Sciences Boehringer Ingelheim PharmaceuticalsIncDanburyCTUSA

The scientific foundation of a modern clinical trial is randomization–each patient is randomized to a treatment group,and statistical comparisons are made between treatment *** the study units are individual patients,this‘one patient,one vote’principle needs to be fol-lowed–***’pointofview,eachpatient is equally important,and they need to be treated equally in data *** is critical that statisti-cal analysis should respect design and study design is based on *** from both statistical and medical points of view,data analysis needs to follow this‘one patient,one vote’*** ICH E9(R1),five strategies are recommended to establish‘estimand’.This paper discusses how to implement these strategies using the‘one patient,one vote’principle.

关键词： Estimand LOCF one patient one vote

Protection by Recombinant Newcastle Disease Viruses (NDV) Expressing the Glycoprotein (G) of Avian Metapneumovirus (aMPV) Subtype A or B against Challenge with Virulent NDV and aMPV

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World Journal of Vaccines 2013年第4期3卷 130-139页

作者： Qingzhong Yu Jason P. Roth Haixia Hu Carlos N. Estevez Wei Zhao Laszlo Zsak 1Southeast Poultry Research Laboratory Agricultural Research Services United States Department of Agriculture Athens USA College of Animal Science and Technology Southwest University Chongqing China Southeast Poultry Research Laboratory Agricultural Research Services United States Department of Agriculture Athens USA Southeast Poultry Research Laboratory Agricultural Research Services United States Department of Agriculture Athens USA boehringer-in-gelheim vetmedica St. Joseph USA Southeast Poultry Research Laboratory Agricultural Research Services United States Department of Agriculture Athens USA Merial Ltd. Athens USA

Avian metapneumovirus (aMPV) and Newcastle disease virus (NDV) are threatening avian pathogens that can cause serious respiratory diseases in poultry worldwide. Vaccination, combined with strict biosecurity practices, has been the recommendation for controlling these diseases in the field. In the present study, we generated NDV LaSota vaccine strain-based recombinant viruses expressing the glycoprotein (G) of aMPV, subtype A or B, using reverse genetics technology. These recombinant viruses, rLS/aMPV-A G and rLS/aMPV-B G, were characterized in cell cultures and evaluated in turkeys as bivalent, next-generation vaccines. The results showed that these recombinant vaccine candi-dates were slightly attenuated in vivo, yet maintained similar growth dynamics, cytopathic effects, and virus titers in vitro when compared to the parental LaSota virus. The expression of the aMPV G protein in recombinant virus-infected cells was detected by immunofluorescence. Vaccination of turkeys with rLS/aMPV-A G or rLS/aMPV-B G conferred complete protection against velogenic NDV, CA02 strain challenge and partial protection against homologous patho-genic aMPV challenge. These results suggest that the LaSota recombinant virus is a safe and effective vaccine vector and expression of the G protein alone is not sufficient to provide full protection against aMPV-A or -B infections. Ex-pression of other aMPV-A or -B virus immunogenic protein(s) individually or in conjunction with the G protein may be necessary to induce stronger and more protective immunity against aMPV diseases.

关键词： NDV aMPV-A and -B Glycoprotein Recombinant Virus Bivalent Vaccine Turkeys Protection

Efficacy of a Single Oral Administration of Afoxolaner Alone or in Combination with Milbemycin Oxime against <i>Ixodes hexagonus</i>Ticks in Dogs

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Open Journal of Veterinary Medicine 2019年第4期9卷 45-54页

作者： W. Lebon M. Servonnet D. Larsen P. Dumont F. Beugnet boehringer Ingelheim Animal Health Saint-Vulbas France boehringer Ingelheim Animal Health Lyon France boehringer Ingelheim Animal Health Duluth GA USA

The efficacy of afoxolaner (NexGard? and NexGard Spectra?, boehringer-Ingelheim), administered once orally at the minimum recommended dose, was assessed in dogs experimentally infested with Ixodes hexagonus ticks. The study was a blinded, negative controlled clinical efficacy study using a randomized block design. Twenty-four Beagle dogs, 12 females and 12 males were enrolled. Dogs were randomly allocated either to the negative control group, or to one of the two treated groups. Infestations were performed with 50 adult I. hexagonus ticks on Days-2, 7 and 28. On Day 0, dogs in groups 2 and 3 were treated with NexGard? (afoxolaner) or NexGard Spectra? (afoxolaner + milbemycin oxime), respectively. Tick counts were conducted 48 hours after treatment (Day 2) and 48 hours after each subsequent infestation (Days 9 and 30). In both treated groups, afoxolaner was 100% effective against existing infestations (p ? and NexGard Spectra? respectively. NexGard? and NexGard Spectra? chewable tablets administered once orally at the minimum recommended dose were highly effective against I. hexagonus infestations for the 4 weeks duration of the study.

关键词： Dog Afoxolaner Tick Ixodes hexagonus

An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral

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Protein & Cell 2024年第1期15卷 69-75页

作者： Miao Mei Maria_Antonietta Impagnatiello Jun Jiao Ulrich Reiser Ulrike Tontsch-Grunt Ju Zhang Paul Nicklin Bingke Yu Yu Wang Yuan He Xu Tan Tsinghua-Peking Center for Life Sciences Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureMOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologySchool of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Chinese Institutes for Medical Research Beijing 100069China boehringer Ingelheim RCV GmbH&Co KG ViennaAustria College of Life Sciences and Oceanography Shenzhen UniversityShenzhen 518060China Research Beyond Borders Boehringer IngelheimBiberach an der RissGermany Research Beyond Borders Boehringer IngelheimShanghai 200120China

DearEditor,The coronavirus disease 2019(COVID-19)pandemic caused great global morbidity and mortality concurrent with astronomical socioeconomic damages and *** now,the culpable pathogen,SARS-CoV-2,has infected over 6 hundred million people resulting in more than 6 million deaths worldwide(WHO SARSCoV-2 cases).There is an urgent need for rapid development of effective and affordable therapeutics for COVID-19 patients.

关键词： mortality spectrum compound

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化学多样性空间探索与组合药物设计

化学进展 1999年第3期11卷 286-299页

作者：徐峻 boehringer Ingelheim Pharmaceuticals Inc 美国

本文综述组合化学的最新进展，内容涵盖组合化学的基本概念、原理、技术，在药物发现中的应用，以及组合化学和其他科学技术分枝的关系。最后，提出了组合化学工程中亟须研究的一些项目，介绍了开展这些研究所必需的条件。

关键词：组合化学药物设计化学多样性虚拟组织化学库

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Efficacy of Once-Monthly Doses of Oral Afoxolaner and Afoxolaner/Milbemycin Oxime in a Well-Controlled Study for the Treatment of Canine Generalized Demodicosis

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Open Journal of Veterinary Medicine 2018年第12期8卷 250-265页

作者： Steffen Rehbein Christa de Vos Frédéric C. Beugnet Doug S. Carithers Josephus J. Fourie boehringer Ingelheim Kathrinenh of Research Center Rohrdorf Germany Clinvet Universitas Bloemfontein South Africa boehringer Ingelheim Animal Health Lyon France boehringer Ingelheim Animal Health Duluth GA USA

The efficacy of oral treatment with chewable tablets containing afoxolaner 2.27% w/w (NexGard?, Merial, now part of boehringer-Ingelheim) or 1.875% w/w of afoxolaner and 0.375% w/w milbemycin oxime (NexGard Spectra?, Merial, now part of boehringer-Ingelheim) was each assessed in eight dogs diagnosed with generalized demodicosis in this parallel group designed, blinded, randomized, single center negative controlled, efficacy study. Afoxolaner at the therapeutic dose (as close as possible to 2.5 mg/kg) was administered to Group 2 dogs, and afoxolaner (as close as possible to 2.5 mg/kg) with milbemycin oxime at 0.5 mg/kg was administered to Group 3 dogs on Days 0, 28 and 56. All dogs were observed once daily for general health starting on Day -7 until Day 84. All dogs were clinically examined on Days -7, -2, 14, 28, 42, 56, 70 and 84. Dogs were weighed on Days -7, -2, 27, 55, and 84. Live mite counts (based on five scrapings per dog and occasion) and clinical assessments, including photographic documentation, were performed on Days -2, 28, 56 and 84. Three monthly treatments with NexGard or NexGard Spectra against generalized demodicosis in dogs were highly effective resulting in a 99.9% and 100% efficacy against mites, respectively. After treatment with NexGard, only three live mites were recovered in five scrapings in one dog on Day 84. After treatment with NexGard Spectra, no mites were recovered in any scraping on any dogs in this group by Day 84. Both treatments resulted in a marked reduction of skin lesions and >90% hair-regrowth at three months after the initial treatment. Reduction of live mite counts was consistent with reduction in the extent and severity of the skin changes. Although the arithmetic mean mite numbers in the negative control group decreased slightly during the study, infection persisted in 7 of the 8 control dogs until Day 84. Both treatment groups of dogs showed a marked improvement of the associated dermatologic signs with steady improvement

关键词： Demodex canis Demodicosis Treatment Afoxolaner NexGard NexGard Spectra Dog

Comparative Efficacy of Frontline Tri-Act^(■) Spot on(Fipronil/Permethrin)versus Seresto^(■) Collar(Imidacloprid/Flumethrin)against Fleas(Ctenocephalides felis)and Ticks(Rhipicephalus sanguineus)on Dogs with Simulation of Bi-Monthly Rain Exposure

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Open Journal of Veterinary Medicine 2018年第5期8卷 65-74页

作者： Frederic Beugnet Marielle Servonnet Lenaig Halos Wilfried Lebon boehringer-Ingelheim Animal Health LyonFrance

The objective of the study was to compare the efficacy of one topical insecticide-acaricide (Frontline Tri-Act?) and of one collar (Seresto?) against fleas (Ctenocephalides felis) and ticks (Rhipicephalus sanguineus) on dogs exposed to bi-weekly water showering. Twenty four (24) dogs were enrolled in the study. A first set of 16 dogs were acclimatised to their cages from Day 1 to 7 and a second set of 8 dogs from Day 163 to Day 169. The 24 dogs were randomly allocated to three groups (1 to 3). Dogs assigned to Group 1 were not treated and served as negative controls. Dogs assigned to Group 2 received the Seresto? collar on Day 0 and dogs in Group 3 received Frontline Tri-Act? on Days 170 and 198. The dogs were observed hourly for four hours after treatment administration for possible adverse reactions. Dogs in Groups 1 and 2 underwent water showering on Days 14, 28, 42, 56, 70, 84, 98, 112, 126, 143 and 157. Dogs in all groups underwent water showering on Days 173, 185, 199 and 213. Dogs were infested with approximately 100 (±4) adult, unfed C. felis fleas only on Days 177, 190, 203, and 217, in alternance with infestations with 50 adult unfed R. sanguineus on Days 182, 196, 210, and 224, to assess sustained efficacy. Fleas and ticks were removed and counted on 24 and 48 hours ± 2 hours after each infestation, respectively. Frontline Tri-Act? was >99% effective against C. felis following an initial and a second monthly administration on dogs that were water showered bi-weekly. The Seresto? collar was from 68.3% to 92.9% effective against C. felis Days 178 to 218 after collar administration. Frontline Tri-Act? was effective from 87.8% to 100% against ticks whereas Seresto collar was effective from 82.2% to 94.2% from Day 184 to Day 226.

关键词： Efficacy Dogs Seresto^(■) Frontline Tri-Act^(■) Ctenocephalides felis Rhipicephalus sanguineus

An exo Probe-based Reverse Transcription and Recombinase Polymerase Amplification for Rapid Detection of Feline Calicivirus in Cats

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Biomedical and Environmental Sciences 2024年第3期37卷 325-330页

作者： MU Hong Yun ZHOU Hong Lei JING Zheng LU Wei ZHANG Jian Wei Jiangsu Agri-animal Husbandry Vocational College Taizhou 225300JiangsuChina boehringer Ingelheim Animal Health(Shanghai)Co. LTD.Shanghai 200040China

Feline calicivirus(FCV)was a highly prevalent RNA virus causing upper respiratory tract infections in cats through the mouth and nose around the world,result in the death of cats especially under 1 year old with upper respiratory tract disease(URTD)and virulent systemic disease(FCV-VSD)[1].Infected cats usually presented with mouth ulcers,salivation and ***,both recovered cats and asymptomatic carriers can still carry and spread the FCV virus for extended periods of time,contributing to the potential for *** presented a significant threat to the health and lives of cats,and rare wildlife and took a heavy financial loss on the pet industry,making the prevention and control of the virus ***,rapid identification of FCV in clinical samples was necessary to prevent the spread of FCV and avoid financial loss.

关键词： prevention respiratory Probe

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Gene regulatory network stabilized by pervasive weak repressions: micro RNA functions revealed by the May–Wigner theory

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National Science Review 2019年第6期6卷 1176-1188页

作者： Yuxin Chen Yang Shen Pei Lin Ding Tong Yixin Zhao Stefano Allesina Xu Shen Chung-I Wu School of Life Science Sun Yat-Sen University Target Discovery Research Boehringer Ingelheim Pharma Gmb H & Co KG Department of Biostatistics School of Public Health Yale University Department of Ecology and Evolution University of Chicago

Food web and gene regulatory networks(GRNs) are large biological networks, both of which can be analyzed using the May–Wigner theory. According to the theory, networks as large as mammalian GRNs would require dedicated gene products for stabilization. We propose that micro RNAs(mi RNAs) are those products. More than 30% of genes are repressed by mi RNAs, but most repressions are too weak to have a phenotypic consequence. The theory shows that(i) weak repressions cumulatively enhance the stability of GRNs, and(ii) broad and weak repressions confer greater stability than a few strong ones. Hence, the diffuse actions of mi RNAs in mammalian cells appear to function mainly in stabilizing GRNs. The postulated link between m RNA repression and GRN stability can be seen in a different light in yeast, which do not have mi RNAs. Yeast cells rely on non-specific RNA nucleases to strongly degrade m RNAs for GRN stability. The strategy is suited to GRNs of small and rapidly dividing yeast cells, but not the larger mammalian cells. In conclusion, the May–Wigner theory, supplanting the analysis of small motifs, provides a mathematical solution to GRN stability, thus linking mi RNAs explicitly to ’developmental canalization’.

关键词： micro RNAs network stability canalization May–Wigner theory systems biology RNA crosstalk