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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： luís.gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

关键词： Alzheimer diagnosis thereby

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223Ra发射14C核的奇异核衰变

原子核物理评论 1985年第2期 19-21+33页

作者： s.gales 刘国兴法国奥赛核物理研究所

本工作采用强放射源AC 和大立体角磁谱仪研究了Ra 发射C 核的奇异核衰变,经过五天的辐照后使用经过C 束校准的ΔE-E 望远镜在预期的C 的位置观测到一组11个事件,Ra 发射C 相对于发射α粒子的分支比是（5.5±2.0）×10与以前报告的分支比... 详细信息

本工作采用强放射源AC 和大立体角磁谱仪研究了Ra 发射C 核的奇异核衰变,经过五天的辐照后使用经过C 束校准的ΔE-E 望远镜在预期的C 的位置观测到一组11个事件,Ra 发射C 相对于发射α粒子的分支比是（5.5±2.0）×10与以前报告的分支比（8.5±2.5）×10相符合。Becquerel 发现核的放射性衰变已经近一

关键词：立体角 AC 透射曲线核衰变望远镜系统 Ra 磁谱仪分析仪器分支比磁刚度强放射源粒子计数

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冷涡背景下江苏强对流天气特征分析

科技资讯 2024年第16期22卷 216-221页

作者：陆伟徐钦晨泰州市气象局江苏泰州225300 江苏省气象灾害防御技术中心江苏南京210019

冷涡背景下的强对流天气常错报和漏报。为了提高此类强对流天气的预报准确率,利用2013—2022年常规地面和高空观测资料以及地面区域自动站资料,运用统计分析方法,对江苏地区116次冷涡强对流的天气特征进行分析。结果表明:冷涡强对流类... 详细信息

冷涡背景下的强对流天气常错报和漏报。为了提高此类强对流天气的预报准确率,利用2013—2022年常规地面和高空观测资料以及地面区域自动站资料,运用统计分析方法,对江苏地区116次冷涡强对流的天气特征进行分析。结果表明:冷涡强对流类型主要有短时强降水、雷暴大风和混合型,其中,混合型发生频率最高(90%),最大小时雨强主要集中在30~49.9 mm/h和50~79.9 mm/h,雷暴大风风力大多为8~9级(48%),其次是10级以上(36%);对流触发时间呈双峰型分布,主要分布在夜间和午后,最高峰为00—02时;不同类型冷涡下的强对流天气既有共性特征,也存在一定的差异性;短时强降水和雷暴大风比较容易发生在沿淮、淮北地区和沿江、苏南地区这两大区域,冰雹落区则相对比较分散。

关键词：冷涡强对流天气特征短时强降水雷暴大风

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Evaluation of imipenem toxicity in cynomolgus macaques including assessment of biomarkers of renal damage

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中国药理学与毒理学杂志 2013年第3期 492-493页

作者： YU Hong sonya gales ZHENG Wei-jun QIN Qiu-ping Dale THURMAN HU Li-ping QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI Lew KINTER Nigel BARRAss Centre for Drug safety Evaluation and Research Shanghai Institute of Materia Medica AstraZeneca R&D Alderley Park MacclesfieldUK Global safety Assessment AstraZeneca R&D BostonMAUSA

OBJECTIVE To assess the nephrotoxicity of imipenem and to correlate the pathogenesis of lesions in the kidney with changes in urinary biomarkers of kidney *** study #1,11 monkeys(2-3 /sex /group) were given vehicle or imipenem(180 mg·kg-1,iv infusion once daily for 7 d) and urine was collected on days xxxxx for biomarker *** study #2,24 monkeys(3 /sex /group) were given of vehicle or imipenem(45,90 or 180 mg·kg-1,iv infusion once daily for 7 d).The following endpoints were assessed in both studies: clinical observations,body weight,food consumption,haematology,coagulation,blood chemistry,urine analysis,imipenem concentration /toxicokinetics (TK) and gross and microscopic *** study #1: Imipenem causes minor body weight loss,increased urea and creatinine,and decreased phosphate in *** total protein and bilirubin were observed in the *** effects were progressive and most pronounced at days 7 and *** and relative kidney weights were increased in both *** histopathological findings were present in kidneys of the dosed monkeys,consisting of minimal to moderate tubular necrosis /degeneration /*** biomarkers(α-1 and β-2 microglobulin,clusterin,Tamm-Horsfall protein and vascular endothelial growth factor) increased progressively and significantly from day 2 onward and preceded notable changes in urinalysis or plasma chemistry on day 7 or 8,*** #2: There were similar findings to study #1 in the 180 mg·kg-1 imipenem treatment *** total bilirubin and decreased of phosphate in plasma and an increase of urinary urobilinogen /ketones were observed in a dose related *** to imipenem 〔Cmax and AUC(0-3 h) 〕increased in proportion from 45-90 mg·kg-1 but more than in proportion from 90-180 mg·*** The no observed adverse effect level(NOAEL) for the imipenem induced kidney injury was identified as 90 mg·*** increases of five urinary biomark

关键词： imipenem toxicity biomarkers renal damage

作物生长和土壤条件对英国小麦和大麦产量的影响(综述)

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麦类作物学报 1986年第4期 26-29页

作者： Kenneth gales ,于振文

在过去的40年内,由于改良品种、增施化肥、改进土壤管理和耕作技术,英国的谷物产量增长了两倍,但单产仍低于理论产量之半,田块之间及年际间产量仍有差异.本综述主要讨论了产量与土壤条件、根系生长的关系.

关键词：小麦麦类作物产量大麦土壤条件作物生长英国大不列颠及北爱尔兰联合王国

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闽东沿海台风大风天气分布特征

宁德师范学院学报（自然科学版） 2024年第3期36卷 301-307页

作者：林冰陆璟辉王宇飞李岩福州市预警信息发布中心福建福州350007 福建省福州市气象局福建福州350007

基于2011-2020年中央气象台台风逐小时资料、沿海自动站观测资料,分析闽东沿海台风大风天气分布特征.结果表明:2011-2020年,闽东影响台风共有62个.其中,56个造成闽东沿海大风天气,年均5.6个.闽东沿海台风大风影响时段在6-11月,8月闽东... 详细信息

基于2011-2020年中央气象台台风逐小时资料、沿海自动站观测资料,分析闽东沿海台风大风天气分布特征.结果表明:2011-2020年,闽东影响台风共有62个.其中,56个造成闽东沿海大风天气,年均5.6个.闽东沿海台风大风影响时段在6-11月,8月闽东沿海出现的台风大风天气过程最多,秋季影响台风均能造成闽东沿海大风天气.较其他月份,闽东沿海7月更常出现强烈的台风大风天气,近10年闽东沿海7月的台风大风过程中36%达到了12级及以上,其中18%达到14级及以上,两个等级的强风在7月占比均为各月份中最高,近10年闽东沿海台风大风历史极值也出现在7月.T1、T2、T3型闽东影响台风均造成闽东沿海台风大风天气,92.3%的T4型台风、86.7%的T5型台风也造成闽东沿海大风天气.T1、T2型台风造成的大风最强,阵风最高可达14级及以上,T3、T4、T5型台风大风强度则较弱.不同路径台风各区域极大风存在差异,但大多数情况下,同一纬度,越靠近开阔海面,大风影响程度越严重.台风大风极值多出现在海岛站点,而各地形区域临近开阔海面的站点极大风次之,也都达到较大的等级,临近大陆站点及海湾内部海岛站点风力等级往往最小.

关键词：台风大风台风极端大风分布特征闽东沿海

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Evaluation of cisplatin-induced toxicity in cynomolgus macaques including assessment of potential biomarkers of renal toxicity

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Evaluation of cisplatin-induced toxicity in cynomolgus macaq...

2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： YU Hong sonya gales ZHENG Wei-jun QIN Qiu-ping Dale THURMAN QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI Lew KINTER Nigel BARRAss Centre for Drug safety Evaduation and Research Shanghai Institute of Materia Medica

OBJECTIVE Cisplatin-induced nephrotoxicity has been characterized previously in animals and humans. Two studies were conducted in cynomolgus macaques to assess the nephrotoxicity of cisplatin and to correlate the pathogenesis of lesions in the kidneys with expression of a panel of potential urinary biomarkers of kidney *** In study #1,6 monkeys(1/sex/group) were given a single *** of cisplatin(1.25,2.5 and 5 mg·kg) and were terminated for necropsy on day 7 *** study #2,36 monkeys(3/sex/group) were given a single iv infusion of vehicle or cisplatin(2.5 mg·kg) and then they were terminated for necropsy on days 2,5,10 or 21,respectively, post - *** following endpoints were assessed in both studies:clinical observations,body weight,food consumption, haematology,coagulation,blood chemistry,urine analysis,cisplatin concentration/toxicokinetics(TK) and gross and microscopic *** of biomarkers for drug-induced kidney injury(DIKI) was confined to study #*** study #1:A single intravenous administration of cisplatin induced occasional vomiting,decreased motor activity, reduced food consumption and minor body weight loss at the highest dose(5 mg·kg).Urea and creatinine were markedly increased,plasma electrolytes showed dose-related alterations and blood and proteins were found in the urine. The high dose animals had reduced urine *** weights were increased following 2.5 and 5 mg·kg and there were progressive renal histopathological *** to cisplatin[C and AUC(04))]increased slightly more than in proportion to the dose of cisplatin across the dose *** #2:One male dosed at 2.5 mg·kg cisplatin was prematurely terminated on day *** other animals survived to their scheduled *** evaluation demonstrated that kidney lesions progressed with *** chemistry results indicated that 7 out of 24 animals treated with cisplatin had moderately to markedly increased urea and

关键词： cisplatin renal toxicity biomarkers

Evaluation of cisplatin-induced toxicity in cynomolgus macaques including assessment of potential biomarkers of renal toxicity

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Evaluation of cisplatin-induced toxicity in cynomolgus macaq...

作者： YU Hong sonya gales ZHENG Wei-jun QIN Qiu-ping Dale THURMAN QIAO Jun-wen REN Jin CHEN Ya-fei Russell BIALECKI Lew KINTER Nigel BARRAss Global safety Assessment Centre for Drug safety Evaduation and Research Shanghai Institute of Materia Medica AstraZeneca R&D Alderley Park

OBJECTIVE Cisplatin-induced nephrotoxicity has been characterized previously in animals and humans. Two studies were conducted in cynomolgus macaques to assess the nephrotoxicity of cisplatin and to correlate the pathogenesis of lesions in the kidneys with expression of a panel of potential urinary biomarkers of kidney *** In study #1,6 monkeys(1/sex/group) were given a single *** of cisplatin(1.25,2.5 and 5 mg·kg~(-1)) and were terminated for necropsy on day 7 *** study #2,36 monkeys(3/sex/group) were given a single iv infusion of vehicle or cisplatin(2.5 mg·kg~(-1)) and then they were terminated for necropsy on days 2,5,10 or 21,respectively, *** following endpoints were assessed in both studies:clinical observations,body weight,food consumption, haematology,coagulation,blood chemistry,urine analysis,cisplatin concentration/toxicokinetics(TK) and gross and microscopic *** of biomarkers for drug-induced kidney injury(DIKI) was confined to study #*** study #1:A single intravenous administration of cisplatin induced occasional vomiting,decreased motor activity, reduced food consumption and minor body weight loss at the highest dose(5 mg·kg~(-1)).Urea and creatinine were markedly increased,plasma electrolytes showed dose-related alterations and blood and proteins were found in the urine. The high dose animals had reduced urine *** weights were increased following 2.5 and 5 mg·kg~(-1) and there were progressive renal histopathological *** to cisplatin〔C_(max) and AUC_((0-24))〕increased slightly more than in proportion to the dose of cisplatin across the dose *** #2:One male dosed at 2.5 mg·kg~(-1) cisplatin was prematurely terminated on day *** other animals survived to their scheduled *** evaluation demonstrated that kidney lesions progressed with *** chemistry results indicated that 7 out of 24 animals treated with cisplatin had moderatel

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Evaluation of paracetamol toxicity in the cynomolgus monkey

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Evaluation of paracetamol toxicity in the cynomolgus monkey

作者： YU Hong Nigel BARRAss sonya gales Eva LENZ Dan WEsTON lan WILsONB Tony PARRY Helen POWELL Dale THURMAN QIAO Jun-wen QIN Qiu-ping REN Jin Centre for Drug safety Evaluation and Research Shanghai Institute of Materia Medica Global safety Assessment

Paracetamol(acetaminophen,APAP) was administered orally in a rising dose protocol to 2 male and 2 female Cynomolgus monkeys to determine the Maximum Tolerated dose(MTD) for subsequent toxicology *** the subsequent repeat dose study involving 6 monkeys,no dose-limiting toxicity was seen at up to 900 mg·kg~(-1)·d~(-1) APAP for 14 *** analysis showed that plasma exposure rose,albeit less than proportionally,with increasing *** were some fluctuations in clinical chemistry and haematology parameters,but these were not dose-related, and there were no compound-related findings observed *** monkeys at 900 mg·kg~(-1)·d~(-1) had a 5 cm, gas filled segment in their large intestine that was considered *** profiling of the urine showed parent and glucuronidated APAP,but the cysteinyl conjugate which would be anticipated if the monkey has similar metabolism to rats and man was notably *** opens the possibility that metabolism in the cynomolgus monkey differs from that in the other species,and shows that the cynomolgus monkey is a poor model for investigating paracetamol-mediated toxicity in humans.

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Evaluation of imipenem toxicity in cynomolgus macaques including assessment of biomarkers of renal damage

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Evaluation of imipenem toxicity in cynomolgus macaques inclu...

2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

OBJECTIVE To assess the nephrotoxicity of imipenem and to correlate the pathogenesis of lesions in the kidney with changes in urinary biomarkers of kidney *** study #1,11 monkeys(2 -3/sex/group) were given vehicle or imipenem(180 mg·kg,iv infusion once daily for 7 d) and urine was collected on days xxxxx for biomarker *** study #2,24 monkeys(3/sex/group) were given of vehicle or imipenem(45,90 or 180 mg·kg,iv infusion once daily for 7 d).The following endpoints were assessed in both studies:clinical observations,body weight, food consumption,haematology,coagulation,blood chemistry,urine analysis,imipenem concentration/toxicokinetics (TK) and gross and microscopic *** study #1:Imipenem causes minor body weight loss,increased urea and creatinine,and decreased phosphate in *** total protein and bilirubin were observed in the urine. These effects were progressive and most pronounced at days 7 and *** and relative kidney weights were increased in both *** histopathological findings were present in kidneys of the dosed monkeys,consisting of minimal to moderate tubular necrosis/degeneration/*** biomarkers(α-1 andβ-2 microglobulin,clusterin, Tamm-Horsfall protein and vascular endothelial growth factor) increased progressively and significantly from day 2 onward and preceded notable changes in urinalysis or plasma chemistry on day 7 or 8,*** #2:There were similar findings to study #1 in the 180 mg·kg imipenem treatment *** total bilirubin and decreased of phosphate in plasma and an increase of urinary urobilinogen/ketones were observed in a dose related *** to imipenem [C and AUC(0-3h))) increased in proportion from 45 -90 mg-kg but more than in proportion from 90-180 mg·kg. CONClusION The no observed adverse effect level(NOAEL) for the imipenem induced kidney injury was identified as 90 mg·*** increases of five urinary biomarkers of kidney toxicit

关键词： imipenem toxicity biomarkers renal damage