BACKGROUND & AIMS: :Effect of refining element phosphorus (P) on the morphology of the primary silicon in the Al-70 wt.%Si alloy was investigated via the electromagnetic levitation (EML) technique. The morphology and microstructure were analyzed by using high-speed video (HSV) and scanning electron microscopy (SEM). It was found that the morphology of primary silicon transformed from dendrites with several branches to blocky shape, and then to equiaxed grains in Al-70 wt.%Si and Al-70 wt.%Si-1.0 wt.%P alloys with increasing of undercooling. The nucleation number and nucleation rate increased exponentially with the increase of undercooling for both alloys. Finally, the growth velocity of primary silicon was discussed in combination with classical theory.

背景与目标： : 通过电磁悬浮 (EML) 技术研究了精炼元素磷 (P) 对Al-70 wt。% Si合金中初硅形态的影响。使用高速视频 (HSV) 和扫描电子显微镜 (SEM) 分析了形貌和微观结构。发现随着过冷度的增加，初级硅的形态从具有多个分支的枝晶转变为块状，然后在Al-70 wt。% Si和Al-70。% Si-1.0 wt。% P合金中转变为等轴晶粒。两种合金的成核数和成核速率均随过冷度的增加而呈指数增长。最后，结合经典理论讨论了原硅的生长速度。

BACKGROUND & AIMS: :High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3-/- gene knockout mice (Tff3-/-/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3-/- and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3-/--HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3-/- mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.

背景与目标： : 高盐 (HS) 饮食摄入导致对各种生理刺激的血管内皮依赖性反应受损，其中一些是由花生四烯酸 (AA) 代谢产物介导的。转基因Tff3-/-基因敲除小鼠 (Tff3-/C57BL/6N) 的脂质代谢变化可能会影响血管功能和中风的结局。我们旨在研究一周的HS饮食 (4% NaCl) 对Tff3-/-和野生型 (WT/C57BL/6N) 小鼠大脑中动脉短暂闭塞引起的血管功能和中风的影响。在WT-HS小鼠中，颈动脉的血流诱导扩张 (FID) 减少，但在Tff3-/-HS小鼠中不受影响。一氧化氮 (NO) 介导FID。HS饮食不会减少任何产量。相反，在饮食和WT-HS小鼠中，Tff3-/-小鼠中乙酰胆碱诱导的扩张作用均显着降低。HS摄入和Tff3基因耗竭影响血管的结构成分。蛋白质组学分析显示，Tff3基因缺乏对HS饮食诱导的神经元结构蛋白和急性先天免疫反应蛋白表达的变化以及Tff3耗竭有显着影响，但HS饮食并未增加中风量，这与蛋白质组修饰和上调主要参与细胞抗氧化防御的基因有关。总之，Tff3耗竭似乎部分损害了血管功能并恶化了中风的结局，中风受到HS饮食的适度影响。

BACKGROUND & AIMS: :Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations. Therefore, given this still growing and rapidly evolving scenario, the progressive molecular fragmentation may inevitably lead over the time to the disappearance of KIT/PDGFRA WT GIST, destined to be singularly defined by their molecular fingerprint.

背景与目标： : 分子生物学的最新进展比过去彻底改变了KIT/PDGFRA野生型 (WT) 胃肠道间质瘤 (GIST) 的概念。实际上，从被定义为没有KIT或PDGFRA突变的GIST开始，我们现在面临相反的情况，即KIT/PDGFRA WT GIST根据其特定的分子变化被 “肯定” 定义。特别是，如果直到最近KIT/PDGFRA GIST没有KIT，PDGFRA，SDH和RAS信号通路异常被称为四重WT GIST，那么今天GIST的这一小部分也作为一组异质的不同实体出现，具有多种不同的分子改变。因此，鉴于这种仍在增长和快速发展的情况，渐进的分子断裂可能不可避免地导致随着时间的流逝，KIT/PDGFRA WT GIST的消失，注定要由其分子指纹单独定义。

BACKGROUND & AIMS: :So far >180 mutations have been identified within the 153-residue human SOD1 to cause familial amyotrophic lateral sclerosis (FALS), while wild-type (WT) SOD1 was intriguingly implicated in sporadic ALS (SALS). SOD1 mutations lead to ALS by a dominant gain of cytotoxicity but its mechanism still remains elusive. Previously functional studies have revealed that SOD1 mutants became unexpectedly associated with organelle membranes. Indeed we decoded that the ALS-causing truncation mutant L126Z-SOD1 with an elevated toxicity completely loses the ability to fold into the native β-barrel structure but acquire a novel capacity to interact with membranes by forming helices over hydrophobic/amphiphilic segments. Very recently, the abnormal insertion of SOD1 mutants into ER membrane has been functionally characterized to trigger ER stress, an initial event of a cascade of cell-specific damages in ALS pathogenesis. Here we attempted to understand the mechanism for gain of cytotoxicity of the WT SOD1. We obtained atomic-resolution evidence that the nascent WT SOD1 without metalation and disulfide bridge is also highly disordered as L126Z. Most importantly, it owns the same capacity in interacting with membranes by forming very similar helices over the first 125 residues identical to L126Z-SOD1, plus an additional hydrophobic helix over Leu144-Ala152. Our study thus implies that the WT and mutant SOD1 indeed converge on a common mechanism for gain of cytotoxicity by abnormally interacting with membranes. Moreover, any genetic/environmental factors which can delay or impair its maturation might act to transform SOD1 into cytotoxic forms with the acquired capacity to abnormally interact with membranes.

背景与目标： : 到目前为止，已经在153残基人SOD1中发现了180个突变，导致家族性肌萎缩性侧索硬化症 (fars)，而野生型 (WT) SOD1有趣地与散发性ALS (ALS) 有关。SOD1突变通过细胞毒性的优势获得导致ALS，但其机制仍然难以捉摸。先前的功能研究表明，SOD1突变体与细胞器膜意外相关。实际上，我们解码出毒性升高的ALS引起截断突变体L126Z-SOD1完全失去了折叠成天然 β-桶结构的能力，但通过在疏水/两亲链段上形成螺旋而获得了与膜相互作用的新能力。最近，SOD1突变体异常插入ER膜的功能已被表征为触发ER应激，这是ALS发病机理中细胞特异性损伤级联的初始事件。在这里，我们试图了解获得WT sod1细胞毒性的机制。我们获得了原子分辨率的证据，表明没有金属化和二硫键的新生WT SOD1也与L126Z高度无序。最重要的是，通过在与膜相同的前125个残基上形成非常相似的螺旋，加上在Leu144-Ala152上形成额外的疏水螺旋，它具有与L126Z-SOD1相互作用的相同能力。因此，我们的研究表明，WT和突变体SOD1确实通过与膜异常相互作用而收敛于获得细胞毒性的共同机制。此外，任何可能延迟或损害其成熟的遗传/环境因素都可能将SOD1转化为具有与膜异常相互作用的获得性能力的细胞毒性形式。

BACKGROUND & AIMS: BACKGROUND:Mechanical stress is a key pathogenic driver of apoptosis in the tubular epithelium in obstructive nephropathy. Heat shock protein 70 (Hsp70) and Wilms' tumor (WT-1) have been proposed to represent linked downstream effectors of the cytoprotective properties of NO. In the present study, we sought to evaluate whether the cytoprotective effects of L-arginine in neonatal obstructive nephropathy may be associated with NO-dependent increases in WT-1 and Hsp70 expression. METHODS:Neonatal Wistar-Kyoto rats were submitted to complete unilateral ureteral obstruction (UUO) and treated thereafter with vehicle, L-NAME or L-arginine by daily gavage for 14 days to block or augment NO levels, respectively. Normal rat kidney epithelial cells by NRK-52E were exposed to mechanical stress in vitro in the presence or absence of L-NAME, L-arginine, sodium nitroprusside (SNP), L-arginine + SNP or L-arginine/L-NAME. Induction of apoptosis and the mRNA expression of WT-1 and Hsp70 genes were assessed. RESULTS:WT-1 and Hsp70 genes expression decreased in the presence of L-NAME and following UUO coincident with increased tubular apoptosis. L-arginine treatment increased NO levels, reduced apoptosis and restored expression levels of WT-1 and Hsp70 to control levels. L-arginine treatment in vitro reduced basal apoptotic rates and prevented apoptosis in response to mechanical strain, an effect enhanced by SNP co-incubation. L-NAME increased apoptosis and prevented the anti-apoptotic action of L-arginine. CONCLUSIONS:L-arginine treatment in experimental neonatal UUO reduces apoptosis coincident with restoration of WT-1 and Hsp70 expression levels and directly inhibits mechanical strain-induced apoptosis in an NO-dependent manner in vitro. This potentially implicates an NO-Hsp70-WT-1 axis in the cytoprotective effects of L-arginine.

背景与目标：

BACKGROUND & AIMS: :The negative effects of ambient ultraviolet (UVA) on the water environment have been recently highlighted; UVA can create deleterious effects by stimulating stress on pelagic organisms. Little is known about UVA effects on oocyte characteristics of female fish. In the present study we explored the effects of exposure to ecologically relevant levels of simulated UVA radiation on ovaries of two major strains WT (HdrR) and P53 (-/-) of medaka (Oryzias latipes) mature female. Fish were assigned to control and three UVA-exposed groups as (15 min, 30 min, and 60 min/day) for three days and sample selection was 24 h and 14 days after exposure. Histological alterations and oocyte atresia percentage were analyzed in the UVA-exposed fish compared to control. Alteration comprised hyperthrophied follicular cells with increased thickness, breakdown of egg chorion (zona radiata), damage of cortical alveoli, and distorted nucleus and cytoplasm. The atresia percentages significantly increased with higher UVA exposure dose and time for both the wild type and the p53 deficient fish. The wild type displayed significantly higher oocyte atresia percentage than the p53 mutant. These results suggested that UVA exposure provoked histological alterations in both p53 and WT medaka oocytes leading to follicular atresia, which reduce female reproductive ability and larval production. UVA oocyte response showed p53 dependent and independent histological alteration, however, the p53 mutant was less sensitive to UVA than the wild type in medaka fish.

背景与目标： : 最近强调了环境紫外线 (UVA) 对水环境的负面影响; UVA可以通过刺激对中上层生物的压力来产生有害影响。关于UVA对雌鱼卵母细胞特征的影响知之甚少。在本研究中，我们探索了暴露于模拟UVA辐射的生态相关水平对medaka (Oryzias latipes) 成熟雌性的两种主要菌株WT (HdrR) 和P53 (-/-) 的卵巢的影响。鱼被分配到对照组和三个UVA暴露组 (15 min，30 min和60 min/天)，持续三天，样品选择为暴露后24 h和14 d。与对照组相比，分析了暴露于UVA的鱼的组织学改变和卵母细胞闭锁百分比。改变包括厚度增加的高throphied滤泡细胞，绒毛膜破裂 (辐射带)，皮质肺泡受损以及细胞核和细胞质扭曲。野生型和p53缺陷鱼的闭锁百分比随UVA暴露剂量和时间的增加而显着增加。野生型的卵母细胞闭锁率明显高于p53突变体。这些结果表明，UVA暴露会引起p53和WT medaka卵母细胞的组织学改变，从而导致卵泡闭锁，从而降低女性的生殖能力和幼虫的产生。UVA卵母细胞反应显示出p53依赖性和独立的组织学改变，但是，在the鱼中，p53突变体对UVA的敏感性低于野生型。

BACKGROUND & AIMS: :Special high grade zinc and wrought zinc-aluminum (Zn-Al) alloys containing up to 5.5 wt % Al were processed, characterized, and implanted in rats in search of a new family of alloys with possible applications as bioabsorbable endovascular stents. These materials retained roll-induced texture with an anisotropic distribution of the second-phase Al precipitates following hot-rolling, and changes in lattice parameters were observed with respect to Al content. Mechanical properties for the alloys fell roughly in line with strength (190-240 MPa yield strength; 220-300 MPa ultimate tensile strength) and elongation (15-30%) benchmarks, and favorable elastic ranges (0.19-0.27%) were observed. Intergranular corrosion was observed during residence of Zn-Al alloys in the murine aorta, suggesting a different corrosion mechanism than that of pure zinc. This mode of failure needs to be avoided for stent applications because the intergranular corrosion caused cracking and fragmentation of the implants, although the composition of corrosion products was roughly identical between non- and Al-containing materials. In spite of differences in corrosion mechanisms, the cross-sectional reduction of metals in murine aorta was nearly identical at 30-40% and 40-50% after 4.5 and 6 months, respectively, for pure Zn and Zn-Al alloys. Histopathological analysis and evaluation of arterial tissue compatibility around Zn-Al alloys failed to identify areas of necrosis, though both chronic and acute inflammatory indications were present. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 245-258, 2018.

背景与目标： : 对含有高达5.5 wt % Al的特殊高级锌和锻造锌铝 (Zn-Al) 合金进行了加工，表征并植入大鼠中，以寻找可能用作生物可吸收血管内支架的新合金家族。这些材料在热轧后保留了辊诱导的织构，并具有第二相Al沉淀物的各向异性分布，并且观察到相对于Al含量的晶格参数变化。合金的机械性能与强度 (190-240 MPa的屈服强度; 220-300 MPa的极限拉伸强度) 和伸长率 (15-30%) 基准大致一致，并且观察到有利的弹性范围 (0.19-0.27%)。Zn-Al合金在鼠主动脉中停留期间观察到晶间腐蚀，表明腐蚀机理与纯锌不同。对于支架应用，需要避免这种失败模式，因为晶间腐蚀会导致植入物破裂和碎裂，尽管在不含铝的材料和含铝的材料之间腐蚀产物的成分大致相同。尽管腐蚀机理存在差异，但对于纯Zn和Zn-Al合金，在4.5个月和6个月后，鼠主动脉中金属的横截面还原在30-40% 和40-50% 几乎相同。尽管存在慢性和急性炎症指征，但组织病理学分析和Zn-Al合金周围动脉组织相容性评估未能确定坏死区域。©2017威利期刊公司J Biomed Mater Res B部分: 应用Biomater，106B: 245-258，2018。

BACKGROUND & AIMS: :In this study, we evaluated the effects of 10 wt% spherical silica filler (SSF) addition on 24-h compressive strength, modulus of elasticity, water uptake, and immediate setting shrinkage of conventional glass-ionomer (Fuji II and Experimental) and resin-modified glass-ionomer (Fuji II LC EM) cements. The glass-ionomer cement powders were modified by being mixed with 10 wt% SSFs with an average particle diameter of 0.3 microm. The materials were mixed to consistencies similar to the flow of Fuji II mixed with a powder-liquid ratio of 2.7:1 (w/w). The 24-h compressive strength, modulus of elasticity, water uptake, and immediate setting shrinkage were observed and the results compared with the original materials mixed with similar flow. The addition of SSF increased the compressive strength value to 1.1 times, while the increase of moduli of elasticity was 1.10 to 1.35 times. In general, the addition of SSF decreased the 24-h water uptake to 80-90% and reduced the immediate setting shrinkage to 70-79% of the original materials. The addition of 10 wt% SSF improved the characteristics of conventional and resin-modified glass-ionomer cement.

背景与目标： : 在这项研究中，我们评估了添加10 wt % 球形二氧化硅填料 (SSF) 对24小时抗压强度，弹性模量，吸水率，以及常规玻璃离聚物 (富士II和实验) 和树脂改性玻璃离聚物 (富士II LC EM) 水泥的立即固化收缩。通过与平均粒径为0.3微米的10 wt % SSFs混合来改性玻璃离聚物水泥粉末。将材料混合至类似于以2.7:1 (w/w) 的粉末-液体比混合的Fuji II的流动。观察了24小时的抗压强度，弹性模量，吸水率和立即凝固收缩率，并将结果与混合有相似流量的原始材料进行了比较。SSF的加入使抗压强度值增加到1.1倍，而弹性模量的增加1.10到1.35倍。通常，添加SSF将24小时的吸水率降低到原始材料的80-90%，并将立即凝结收缩率降低到70-79%。添加10 wt % SSF改善了常规和树脂改性的玻璃离聚物水泥的特性。

BACKGROUND & AIMS: :Here we investigate activation of the p53 pathway by inhibition of transcription. Comparison of cells with either mutant p53 or wt p53 indicated that inhibition of p53- dependent transcription is necessary and sufficient for wt p53 accumulation. In addition to Mdm-2, p21 is required for effective p53 degradation. Transient inhibition of transcription resulted in initial downregulation of p21 and Mdm-2 leading to accumulation of wt p53. This was followed by induction of p21 and Mdm-2, normalization of p53 levels, and p21-dependent growth arrest. Although simultaneous induction of p53 and p21 could be detected by immunoblot, levels of p53 and p21 were discordant in individual cells. By inducing p21 and Mdm-2, p53 discriminates between transient and sustained inhibition of transcription. Transient inhibition results in p21-dependent growth, while sustained inhibition of transcription leads to p53-facilitated cell death. One can envision p53 as a physiological sensor of transcriptional integrity. Transient inhibition of p53- stimulated transcription by numerous stimuli including nucleotide depletion, hypoxia, UV light may be an prevalent mechanism of activation of wt p53 and its downstream pathways.

背景与目标： : 在这里，我们研究通过抑制转录激活p53途径。与突变型p53或wt p53的细胞比较表明，抑制p53依赖性转录对于wt p53的积累是必要且足够的。除Mdm-2外，p21是有效的p53降解所必需的。转录的瞬时抑制导致p21和Mdm-2的初始下调，导致wt p53的积累。随后是p21和Mdm-2的诱导，p53水平的正常化以及p21-dependent的生长停滞。尽管可以通过免疫印迹检测到p53和p21的同时诱导，但单个细胞中p53和p21的水平不一致。通过诱导p21和Mdm-2，p53区分转录的瞬时和持续抑制。瞬时抑制导致p21-dependent生长，而持续抑制转录导致p53-facilitated细胞死亡。人们可以设想p53作为转录完整性的生理传感器。许多刺激 (包括核苷酸耗竭，缺氧，紫外线) 对p53刺激的转录的瞬时抑制可能是wt p53及其下游途径激活的普遍机制。

BACKGROUND & AIMS: INTRODUCTION:Preoperative chemotherapy is recommended for children with Wilms tumour with intravascular extension. Extended chemotherapy may improve resectability, but increase tumour adherence to vascular endothelium, precluding complete resection. To evaluate the optimal length of preoperative treatment, we report a two-part review comprising systematic review of the literature and investigation of patients treated in the International Society of Paediatric Oncology (SIOP) WT 2001 trial. METHODS:Studies were identified using Medline and Embase databases from 1996 to present. English language titles reporting management of intravascular Wilms tumour were analysed. Patients with Wilms tumour and thrombus were identified from the SIOP WT 2001 trial. Overall survival (OS) and event-free survival (EFS), tumour regression, completeness of resection and cavectomy were investigated. RESULTS:The search retrieved 43 articles documenting 498 children. Note that 72% of the patients received neoadjuvant chemotherapy: 101 received standard course (4-6 weeks, standard course neoadjuvant chemotherapy [StC]) and 62 extended course (> 6 weeks, extended course neoadjuvant chemotherapy [EC]). There was no significant difference between the groups in terms of thrombus regression or completeness of resection. EFS was greater in the StC group (78 vs 54%; P = .04). Of 4511 patients registered in the SIOP WT 2001 trial, 166 had thrombus. Note that 97% of the patients received neoadjuvant chemotherapy: 63 StC and 67 EC. There was no significant difference between the groups with regard to tumour regression, complete resection, or cavectomy. Survival was significantly higher in those receiving StC than EC (OS: 95% vs 82%, P = .025; EFS: 88% vs 72%, P = .047). CONCLUSION:There is no evidence that prolonged courses of neoadjuvant chemotherapy beyond the recommended protocols confer any additional benefit in treating intravascular extension of Wilms tumour.

背景与目标：

BACKGROUND & AIMS: :Aromatic substrates tyrosol (p-hydroxyphenylethanol) and 2,6-dihydroxynaphthalene (2,6-DHN) were converted into chromane derivatives by means of chemoenzymatic reactions catalyzed by the aromatic prenyltransferase of bacterial origin NovQ, using dimethylallyl bromide as allylic substrate instead of the natural isoprenyl pyrophosphate substrate. Stereoselective prenylation occurred in o-position with respect to the phenol hydroxyl in both compounds. Prenylated derivatives were readily converted into chromane products via a selective 6-endo-trig cyclization involving the oxygen atom from the phenol moiety and the double bond of the prenyl substituent, a process catalyzed by FeCl(3). These findings set up the basis of a most convenient two-step, one-pot process which allows for easy recovery of the chromane products in high yields. The chromane derivatives thus obtained were tested for cytotoxicity and pro-apoptotic activity using LoVo WT cells, a line of human colon adenocarcinoma.

背景与目标： : 通过细菌来源NovQ的芳族异戊二烯基转移酶催化的化学酶反应，将酪醇 (对羟基苯乙醇) 和2,6-二羟基萘 (2,6-dhn) 转化为铬烷衍生物，使用二甲基烯丙基溴作为烯丙基底物代替天然异戊二烯基焦磷酸底物。在两种化合物中，相对于苯酚羟基，立体选择性异戊烯化发生在o位。异戊二烯化的衍生物很容易通过选择性的6-内-trig环化反应转化为色胺产物，该环化反应涉及苯酚部分的氧原子和异戊二烯基取代基的双键，该过程由FeCl(3) 催化。这些发现为最方便的两步一锅法奠定了基础，该法可以轻松地以高收率回收色度产品。使用LoVo WT细胞 (人结肠腺癌的细胞系) 测试了由此获得的色马衍生物的细胞毒性和促凋亡活性。

BACKGROUND & AIMS: Twenty-four hamster-sheep hybrid cell lines representing eleven ovine synteny groups were used to make syntenic assignments for seven loci ALDOB (aldolase B, fructose biophosphate); AMH (anti-Müllerian hormone); CYP19 [cytochrome P450 aromatase, subfamily XIX (aromatization of androgens)]; WT (Wilms' tumour gene); SOX2 (SRY-related HMG-box gene 2); FSHB (follicle-stimulating hormone, beta polypeptide); and SRY (sex region of Y chromosome). These loci were assigned to synteny groups U11(chr2) (ALDOB); U19 (AMH); U3(chr7) (CYP19); and to chromosome 15 (WT) and 1 (SOX2). SRY defines the hybrids containing the Y chromosome.

背景与目标： 代表11个绵羊合成组的24个仓鼠-绵羊杂交细胞系用于七个基因座ALDOB (醛缩酶B，果糖生物磷酸盐); AMH (抗苗勒氏激素); CYP19 [细胞色素P450芳香化酶，亚家族XIX (雄激素的芳香化)]; WT (Wilms' 肿瘤基因); SOX2 (SRY相关HMG-box基因2); FSHB (促卵泡激素，β 多肽); 和SRY (Y染色体的性别区域)。这些基因座被分配到同位组U11(chr2) (ALDOB); U19 (AMH); U3(chr7) (CYP19); 以及15号染色体 (WT) 和1号染色体 (SOX2)。SRY定义了包含Y染色体的杂种。

BACKGROUND & AIMS: WT 1, an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). This antigen is strongly expressed on thymic T blasts, and on peripheral T cells activated by phytohaemagglutinin, whereas cortical thymocytes and peripheral T cells are moderately positive for WT 1. In contrast, B lymphocytes, myeloid and erythroid cells, including the progenitor cells of these lineages, and terminal deoxynucleotidyl transferase positive cells in the bone marrow, are all WT 1 negative. Binding of WT 1 to T cells is blocked by a previously described antibody (3A1) suggesting that both antibodies bind to the same antigen present on human T cells. WT 1, however, is also reactive with T lymphocytes from rhesus monkeys whereas 3A1 is not. Therefore, the biological effects of WT 1 could be studied in a monkey model. In a skin allograft model, WT 1 was immunosuppressive and induced a marked prolongation of graft survival.

背景与目标： IgG2a亚类单克隆抗体WT 1识别人T谱系特异性抗原 (mol. wt 40,000)。该抗原在胸腺T细胞和被植物血凝素激活的外周T细胞上强烈表达，而皮质胸腺细胞和外周T细胞对WT 1呈中等阳性。相反，B淋巴细胞，髓样和红系细胞 (包括这些谱系的祖细胞) 以及骨髓中的末端脱氧核苷酸转移酶阳性细胞均为WT 1阴性。WT 1与T细胞的结合被先前描述的抗体 (3A1) 阻断，这表明两种抗体与存在于人T细胞上的相同抗原结合。但是，WT 1也与恒河猴的T淋巴细胞反应，而3A1则没有。因此，可以在猴子模型中研究WT 1的生物学效应。在同种异体皮肤移植模型中，WT 1具有免疫抑制作用，并显着延长了移植物的存活时间。

BACKGROUND & AIMS: :The effect of long period stacking ordered (LPSO) phase and γ' precipitates on the ageing behavior and mechanical properties of the extruded Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr (wt.%) alloy was investigated. The results show that more β' phases precipitate during ageing treatment in the LPSO phase containing alloy so that the LPSO phase containing alloy exhibits a higher age-hardening response than the γ' precipitates containing alloy. The precipitation strengthening induced by β' precipitates is the greatest contributor to the strength of the peak-aged LPSO-containing alloys. Higher strength is achieved in γ' precipitates containing alloy due to the more effective strengthening induced by dense nanoscale γ' precipitates than LPSO phases as well as the higher volume fraction of coarse unrecrystallized grains with strong basal texture. The extruded alloy containing γ' precipitates after T5 peak-ageing treatment shows ultra-high tensile yield strength of 462 MPa, high ultimate tensile strength of 520 MPa, and superior elongation to failure of 10.6%.

背景与目标： : 研究了长周期堆积有序 (LPSO) 相和 γ' 沉淀物对挤压Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr (wt。%) 合金的时效行为和机械性能的影响。结果表明，在时效处理过程中，含LPSO相的合金中会析出更多的 β' 相，因此，含LPSO相的合金比含 γ' 的合金表现出更高的时效硬化响应。Β' 沉淀引起的沉淀增强是峰值时效含LPSO合金强度的最大贡献者。由于致密的纳米级 γ' 沉淀物比LPSO相更有效地增强，以及具有较强基础织构的粗未再结晶晶粒的较高体积分数，因此在含 γ' 沉淀物的合金中实现了更高的强度。经T5峰时效处理后的含 γ' 析出物的挤压合金具有462  MPa的超高拉伸屈服强度，520  MPa的高极限拉伸强度和优异的10.6% 破坏伸长率。

BACKGROUND & AIMS: :Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

背景与目标： : 在国际儿科肿瘤学会 (SIOP) 肾肿瘤研究小组的试验中，囊胚型Wilms肿瘤 (bt-wt) 已被确定为肾切除术前化疗后评估的WT中的高风险组织学亚组。因此，在SIOPWT2001中，加强了对BT-WT的术后化疗，以提高生存率。将所有单侧BT-WT患者的生存分析 (SIOPWT2001) (n = 238) 与历史BT-WT对照 (SIOP93-01) (n = 113) 进行了比较。研究了351/4061 (8.6%) 单侧非转移性BT-WT患者 (SIOP93-01/SIOPWT2001)。诊断时的中位年龄为43个月 (四分位距离 (IQR) 24-68个月)，阶段: I (n = 140，40%)，II (n = 106，30%)，III (n = 105，30%)。与其他WT患者相比，bt-wts分期更高，术前化疗后显示出更大的体积减少，并且在中位年龄较大的情况下被诊断出。SIOP93-01和siopwt2001之间的患者特征没有显着差异。单因素分析显示5年无事件生存率 (EFS) 为80% (95% 置信区间 (CI): 75-86%) (SIOPWT2001)，而SIOP93-01为67% (95% CI: 59-76%; p = 0.006)，88% 总生存率 (OS) 为95% CI: 83-93%) (SIOPWT2001) 与SIOP93-01中的84% (95% CI: 77-91%; p = 0.4) 相比。95% 的复发是远处转移 (SIOP93-01/SIOPWT2001)。治疗方案，诊断年龄，肿瘤分期 (III与I/II) 和体积 (手术时) 是EFS的预后变量 (单和多变量Cox回归分析)。OS的独立预后指标是诊断时的年龄，肿瘤分期和体积 (手术时)。强化治疗的最显着生存益处是在I期观察到的 (SIOPWT2001中的EFS 96% (OS 100%)，SIOP93-01中的71% (OS 90%))。Bt-wt从更密集的化疗中获益，这反映在复发风险降低上。然而，通过添加阿霉素，仅在I期bt-wts中观察到更强化的化疗改善OS的益处。