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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.Mcdonald Laxman Pokhrel duy H.Hua Evan C.Titgemeyer barry j.bradfo.d department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

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Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： barry S. Schifrin Brian j. Koos Wayne R. Cohen department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The david Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

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Changes in otolaryngology application requirements and match outcomes:Are we doing any better?

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World journal of Otorhinolaryngology-Head and Neck Surgery 2023年第2期9卷 144-152页

作者： Emma de Ravin Ariel S.Frost Neal R.Godse Amber d.Shaffer Noel jabbour barry M.Schaitkin jason Newman Leila j.Mady department of Otorhinolaryngology-Head and Neck Surgery University of Pennsylvania Health SystemPhiladelphiaPennsylvaniaUSA Head and Neck Institute Cleveland ClinicClevelandOhioUSA division of Pediatric Otolaryngology Children's Hospital of Pittsburgh of UPMCPittsburghPennsylvaniaUSA department of Otolaryngology University of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA department of Otolaryngology-Head and NeckSurgery Medical Universityof South CarolinaCharlestonSouth CarolinaUSA MUSC Hollings Cancer Center CharlestonSouthCarolinaUSA department of Otolaryngology-Head and Neck Surgery Thomas Jefferson UniversityPhiladelphiaPennsylvaniaUSA Cancer Risk and Control Program of Excellence Sidney Kimmel Cancer CenterPhiladelphiaPennsylvaniaUSA

Objectives:Otolaryngology-specific requirements were piloted to minimize applicant and program *** investigated the impact of introducing and then removing these requirements on Match ***:2014-2021 National Resident Matching Program?data were *** primary outcome was the impact of Otolaryngology Resident Talent Assessment(ORTA;prematch 2017,postmatch 2019)and Program-Specific Paragraph(PSP;implemented 2016,optional 2018)on applicant numbers and match *** survey analysis assessed candidate perceptions of PSP/***:Applicant numbers declined significantly during PSP/ORTA(18.9%;p=0.001).With the optional PSP and postmatch ORTA,applicant numbers increased significantly(39.0%;p=0.002).Examined individually,mandatory PSP was associated with a significant decline in applicants(p=0.007),whereas postmatch ORTA was associated with significant increases in applicants(p=0.010).ORTA and PSP negatively impacted the decision to apply to otolaryngology in 59.8%and 51.3%of applicants,***,match rate success improved significantly from 74.8%to 91.2%during PSP/ORTA(p=0.014),followed by a significant decline to 73.1%after PSP was made optional and ORTA moved to postmatch(p=0.002).Conclusions:ORTA and PSP correlated with decreased applicant numbers and increased match rate *** programs seek ways to remove barriers to applying to otolaryngology,the potential consequences of an increasing pool of unmatched candidates must also be considered.

关键词： academic success internship and residency medical students otolaryngology surveys and questionnaires

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Multi-Institutional US Experience of the Occlutech AFR device in Congenital and Acquired Heart disease

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Congenital Heart disease 2022年第1期17卷 107-116页

作者： barry O’Callaghan jenny Zablah joseph Vettukattil daniel Levi Morris Salem Allison Cabalka jason Anderson Makram Ebeid Ryan Alexy Gareth j.Morgan The Heart Institute Children’s Hospital ColoradoAuroraUSA Pediatric Cardiology Helen DeVos Children’s HospitalGrand RapidsUSA Pediatric Cardiology UCLA HealthMattel Children’s HospitalLos AngelesUSA Pediatric Cardiology UCLA Medical CentreLos AngelesUSA Pediatric Cardiology Mayo ClinicRochesterUSA Pediatric Cardiology University of Mississippi Medical CenterJacksonUSA Pediatric Cardiology Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Objectives:To detail the US multi-institutional experience with the Occlutech©(Occlutech International AB,Helsingborg,Sweden)atrial flow regulator(AFR)in children and adults with acquired or congenital heart ***:The creation of a long-term atrial communication is desirable in several cardiovascular disease phenotypes,most notably pulmonary arterial hypertension,disorders of increased left ventricular filling and increased cavopulmonary pressures in patients with a Fontan type ***:Patients were identified for inclusion from the AFR device manufacturer *** was collected using a RedCap database following IRB approval.8 weeks of follow up data was sought for each patient based on available *** was analyzed and summarized using ***:We report the experience of 6 US centers in the implantation of AFR devices in 15 patients,across a wide age range,with different disease phenotypes and a variety of *** was technically successful in all patients and improvement was noted in both clinical and hemodynamic *** were no immediate or intermediate term complications reported.3 patients died remote from *** deaths were not felt to be related to the AFR device or related procedural ***:Compassionate use of the AFR device in children and adults with congenital&acquired heart disease is technically feasible and produces beneficial short term hemodynamic and symptomatic *** uptake of this technique and treatment at specialist centers has the potential to provide significant benefits to a variety of complex patients with currently limited treatment options and indeterminate prognosis.

关键词： Congenital heart disease pulmonary hypertension left atrial hypertension single ventricle palliation diastolic heart failure

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Restricted nutrient intake does not alter serum-mediated measures of implant response in cell culture

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journal of Animal Science and Biotechnology 2014年第1期5卷 80-87页

作者： Christopher d Reinhardt Tiffany L Lee daniel U Thomson Laman K Mamedova barry j.bradfo.d department of Animal Sciences and Industry 232 Weber Hall Kansas State University department of Clinical Sciences A-111 Mosier Hall Kansas State University

Background： during nutritional stress, reduced intake may reduce the efficacy of anabolic implants. This study was conducted to evaluate basic cellular responses to a growth promotant implant at two intake levels. Methods： Sixteen crossbred steers （293 ± 19.3 kg） were used to evaluate the impact of anabolic implants in either an adequate or a restricted nutritional state. Steers were trained to individual Calan gates, and then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted off presence or absence of an anabolic growth implant （Revalor-XS, 200 mg TBA and 40 mg estradiol; IMPLANT or CONTROL） and a moderate energy, pelleted, starting cattle diet fed at either 2.0 × or 1.0 × maintenance energy （NEM） requirements （HIGH or LOW）. Serum （d O, 14, and 28） was used for application to bovine muscle satellite cells. After treatment with the serum （20% of total media） from the trial cattle, the satellite cells were incubated for 72 h. Protein abundance of myosin heavy chain （MHC）, phosphorylated extracellular signal-related kinase （phospho-ERK）, and phosphorylated mammalian target of rapamycin （phospho-mTOR） were analyzed to determine the effects of implant, intake, and their interaction （applied via the serum）. Results： Intake had no effect on MHC （P = 0.85） but IMPLANT increased （P 〈 0.01） MHC abundance vs. CONTROL. Implant status, intake status, and the interaction had no effect on the abundance of phospho-ERK （P〉0.23）. Implanting increased phospho-mTOR （P 〈 0.01） but there was no effect （P 〉 0.51） of intake or intake x implant. Conclusions： The nearly complete lack of interaction between implant and nutritional status indicates that the signaling molecules measured herein respond to implants and nutritional status independently. Furthermore, results suggest that the muscle hypertrophic effects of anabolic implants may not be mediated by circulating IGF-1.

关键词： Beef cattle Implant Muscle Myosin heavy chain Nutrient restriction Satellite cells

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Robustness Assessment and Adaptive FdI for Car Engine

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International journal of Automation and computing 2008年第2期5卷 109-118页

作者： Mahavir Singh Sangha j.barry Gomm Control Systems Research Group School of EngineeringLiverpool John Moores University

A new on-line fault detection and isolation （FdI） scheme proposed for engines using an adaptive neural network classifier is evaluated for a wide range of operational modes to check the robustness of the scheme in this paper. The neural classifier is adaptive to cope with the significant parameter uncertainty, disturbances, and environment changes. The developed scheme is capable of diagnosing faults in on-line mode and the FdI for the closed-loop system with can be directly implemented in an on-board crankshaft speed feedback is investigated by diagnosis system （hardware）. The robustness of testing it for a wide range of operational modes including robustness against fixed and sinusoidal throttle angle inputs, change in load, change in an engine parameter, and all these changes occurring at the same time. The evaluations are performed using a mean value engine model （MVEM）, which is a widely used benchmark model for engine control system and FdI system design. The simulation results confirm the robustness of the proposed method for various uncertainties and disturbances.

关键词： On-board fault diagnosis automotive engines adaptive neural networks (ANNs) fault classification robustness assessment

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development of a CO_2 Tolerant Fischer-Tropsch Catalyst:from Laboratory to Commercial-Sca1e demonstration in Alaska

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journal of Natural Gas Chemistry 2004年第1期13卷 1-9页

作者： joep j H M Font Freide Tim d Gamlin j Richard Hensman barry Nay Christopher Sharp BP Exploration Operating Company Chertsey RoadSunbury on ThamesMiddlesexTWl6 7LNEnglandDavy Process Technology Lid 20 Eastbourne TerraceLondon W2 6LEEnglandDavy Process Technology Lid 20 Eastbourne TerraceLondon W2 6LEEnglandBP Chemicals LtdChertsey RoadSunbury on ThamesMiddlesexTW16 7LLEnglandBP Chemicals LtdChertsey RoadSunbury on ThamesMiddlesexTW16 7LLEngland

This article describes the development of BP's Fischer-Tropsch catalyst, used for the conversion of carbon monoxide and hydrogen into liquid hydrocarbons. It covers the 18 year period from the early eighties, when laboratory scale preparations and micro-reactors were heavily used, right through to the present day with the commercial scale manufacture and proving of the finished catalyst in BP's new ＄86 million gas to liquids demonstration facility in Nikiski, Alaska. Extensive performance testing and scale-up experiments have been successfully carried out, all proof that a laboratory preparation can indeed be translated into a commercial manufacturing process. In addition, the resulting catalyst does not only meet the process design targets, but also exhibits enhanced stability and is tolerant to carbon dioxide. Above all, a commercial scale, fixed bed Fischer-Tropsch catalyst is now available and ready for licensing. Manufacturing procedures and quality control have all been successfully detailed and transferred to the commercial manufacturer.

关键词： carbon dioxide Fisher-Tropsch development syngas commercial catalyst

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COVId-19 has triggered a new century of vaccination and infection control for the benefit of all mankind

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Precision Clinical Medicine 2021年第2期4卷 77-79页

作者： barry j.Marshall Helicobacter pylori Research Laboratory School of Biomedical SciencesMarshall Centre for Infectious Disease Research and TrainingUniversity of Western AustraliaNedlands 6009Australia

Modern safe vaccinations were pioneered in 1796 by Edward jenner in England,when he noticed that milkmaids had beautiful complexions,clear of the blemishes from smallpox *** was attributed to their exposure to‘cowpox... 详细信息

关键词： vaccination infection attributed

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Control of the carrier-envelope phases of a synchronously pumped femtosecond optical parametric oscillator and its applications

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Chinese Science Bulletin 2008年第5期53卷 642-651页

作者： SUN jingHua barry j S Gale derryck T Reid Ultrafast Optics Group School of Engineering and Physical Sciences Heriot-Watt University Edinburgh EH14 4AS UK Laboratory of Optical Physics Institute of Physics Chinese Academy of Sciences Beijing 100080 China

The intrinsic synchronization, multi-color outputs and related carrier-envelope phases (CEP) among pulses bring advantages to synchronously pumped femtosecond optical parametric oscillators and the pumping sources for broadband frequency comb generation and ultrashort waveform coherent syn-thesis. In this paper, we discuss our latest research results in this field, which cover the following as-pects: the phase relationship and energy conservation law in an OPO and related experimental verifi-cation; control of the pumping Ti:sapphire femtosecond laser's CEP by self-referencing technology, and its repetition-rate locking by piezoelectric transducer (PZT); CEP locking of the pulses from the OPO by beating the non-phase-matched visible outputs against pump supercontinuum to obtain a driving signal for a fast PZT on the OPO end mirror; the generation of a broadband frequency comb spanning from 400 nm to 2.4 μm with 1.2 kHz bandwidth; and the realization of coherent interference between phase controlled pump pulses and signal second harmonic pulses.

关键词：光学参数振荡器载波包络相同步控制超短光脉冲

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Predicting an Athlete’s Physiological and Haematological Response to Live High-Train High Altitude Training Using a Hypoxic Sensitivity Test

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journal of Science in Sport and Exercise 2022年第4期4卷 371-385页

作者： Gareth Turner Kate L.Spilsbury david j.Green barry W.Fudge jamie S.M.Pringle Alan j.Richardson Neil S.Maxwell Environmental Extreme Laboratory University of BrightonEastbourneUK English Institute of Sport Bisham AbbeyUK Queensland Academy of Sport BrisbaneAustralia English Institute of Sport LoughboroughUK Aspire Academy DohaQatar University of Birmingham BirminghamUK

Purpose Elite endurance runners frequently utilise live high-train high(LHTH)altitude training to improve endurance per-formance at sea level(SL).Individual variability in response to the hypoxic exposure have resulted in contradictory *** the present case study,changes in total haemoglobin mass(tHbmass)and physiological capacity,in response to 4-weeks of LHTH were *** tested if a hypoxic sensitivity test(HST)could predict altitude-induced adaptations to *** Fifteen elite athletes were selected to complete 4-weeks of LHTH(~2400 m).Athletes visited the laboratory for preliminary testing(PRE),to determine lactate threshold(LT),lactate turn point(LTP),maximal oxygen uptake VO_(2max)and *** LHTH,athletes completed daily physiological measures[arterial oxygen saturation(SpO2)and body mass]and subjective wellbeing *** was repeated,for those who completed the full camp,post-LHTH(POST).Additionally,athletes completed the HST prior to *** A difference(Pd from PRE to POST in average tHbmass(1.8%±3.4%),VO_(2max)(2.7%±3.4%),LT(6.1%±4.6%)and LTP(5.4%±3.8%),after 4-weeks *** revealed a decrease in oxygen saturation at rest(ΔSp_(r))and higher hypoxic ventilatory response at rest(HVRr)predicted individual changes *** hypoxic cardiac response at rest(HCRr)and higher HVRr predicted individual changes VO_(2max).Conclusion Four weeks of LHTH at~2400 m increased tHbmass and enhanced physiological capacity in elite endurance *** was no observed relationship between these changes and baseline characteristics,pre-LHTH serum ferritin levels,or reported incidents of musculoskeletal injury or *** HST did however,estimate changes in tHbmass and VO_(2max).HST prior to LHTH could allow coaches and practitioners to better inform the acclimatisation strategies and train-ing load application of endurance runners at altitude.

关键词： Altitude training Runners Endurance Haemoglobin mass Performance Hypoxic sensitivity

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