c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2

T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi- tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene （IEG） c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic （Fos-Tg） mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive （SP） thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.

Effect of basic fibroblast growth factor and danshen on bcl-2 and p53 mRNA expression in the brain of rats exposed to repeated, high, positive acceleration (+Gz)

BACKGROUND： Both animal experiments and clinical studies have shown that basic fibroblast growth factor （bFGF） and danshen （Salvia miltiorrhiza） can exhibit protective effects on ischemia-reperfusion cerebral injury. OBJECTIVE： To test whether bFGF and danshen can protect cerebral injury induced by exposure to repeated, high, positive acceleration （＋Gz） in an animal model and to analyze the possible mechanisms. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was performed at the Research Center for Molecular Biology, Air-force General Hospital of Chinese PLA from April to August 2000. MATERIALS： A total of 20 clean grade, healthy, Sprague Dawley rats of both genders, weighing （200 ± 15） g, were provided by our experimental animal center. Rats were randomly divided into 5 groups： the control group, ＋Gz exposure group, bFGF group, danshen group, and saline group, with 4 animals per group. bFGF （Beijing Bailuyuan Biotechnology Co. Ltd.） and danshen solution （Shanghai Zhongxi Pharmaceutical Co. Ltd.） were used. METHODS： All rats were fixed on a rotary arm of a centrifugal apparatus （2 m in radius） with their heads oriented towards the center of the apparatus. Except for rats in the control group, the value of ＋Gz exposure was ＋14 Gz with an acceleration rate of 1.5 G/s. The peak force lasted for 45 seconds. ＋Gz exposure was performed three times with intervals of 30 minutes. Rats in the control group received the same ＋Gz procedure, but the G value was ＋1 Gz. Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg bFGF or 15 g/kg danshen solution, respectively, at 30 minutes prior to centrifugation and immediately after centrifugation. Rats in saline group were injected with the same volume of saline. Six hours after exposure, rats were decapitated. One hemisphere was preserved in liquid nitrogen for RNA extraction and the other was processed for apoptosis detection. MAIN OUTCOME MEASURES： mRNA levels of bcl-2 and p53 were measured by semi-quantitative reverse-transcription polymerase chain reaction. Apoptotic cell death was detected by terminal deoxynuleotidyl transferase-mediated dUTP nick end labeling. RESULTS： Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated ＋Gz exposures, bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death. CONCLUSION： The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated ＋Gz exposures. Apoptosis is, therefore, one of the molecular mechanisms of brain damage induced by repeated ＋Gz exposures, bFGF and danshen were of the equal potency in preventing brain injury induced by repeated ＋Gz exposures.

Coexistence of positive and negative magnetic entropy changes in CeMn_2(Si_(1-x)Ge_x)_2 compounds

A series of CeMn2（Si1-xGex）2（x = 0.2, 0.4, 0.6, 0.8） compounds are prepared by the arc-melting method. All the samples primarily crystallize in the Th Cr2Si2-type structure. The temperature dependences of zero-field-cooled（ZFC） and FC magnetization measurements show a transition from antiferromagnetic（AFM） state to ferromagnetic（FM） state at room temperature with the increase of the Ge concentration. For x = 0.4, the sample exhibits two kinds of phase transitions with increasing temperature： from AFM to FM and from FM to paramagnetic（PM） at around TN-197 K and T C-300 K,respectively. The corresponding Arrott curves indicate that the AFM–FM transition is of first-order character and the FM–PM transition is of second-order character. Meanwhile, the coexistence of positive and negative magnetic entropy changes can be observed, which are corresponding to the AFM–FM and FM–PM transitions, respectively.

Current status of PI3K-mTOR inhibition in hormone-receptor positive, HER2-negative breast cancer

Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments.The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive/human epidermal growth factor receptor 2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.

Positive temperature coefficient of resistivity effects of semiconducting (Bi(1/2)Na(1/2)) TiO_3-CaTiO_3-BaTiO_3 ceramics sintered in air atmosphere

Y^3＋-doped （Bi 1/2 Na 1/2） TiO 3-CaTiO 3-BaTiO 3 （BNCBT） positive temperature coefficient of resistivity （PTCR） ceramics sintered in air atmosphere were investigated in this study. （Bi 1/2 Na 1/2） TiO 3 （BNT） component can remarkably increase the onset temperature T c of PTCR ceramics with the expense of the resistivity R 25 increase. CaTiO 3 （9–27 mol%） component can decrease the resistivity, and adjust the effects of BNT phase on the T c point. For the sample containing 3 mol% CaTiO 3 , T c raises from 122 ℃ to 153 ℃ when only 0.6 mol% BNT added, while for the ones with higher CaTiO 3 content （9–27 mol%）, T c is only increased by a rate of 8–9℃/1.0 mol% BNT. The effects of BNT and CaTiO 3 components on R25/Rmin （negative temperature coefficient effect） are also discussed.

NONEXISTENCE AND EXISTENCE OF POSITIVE SOLUTIONS FOR 2nTH-ORDER SINGULAR SUPERLINEAR PROBLEMS WITH STRUM-LIOUVILLE BOUNDARY CONDITIONS

This paper investigates a class of 2nth-order singular superlinear problems with Strum-Liouville boundary conditions. We obtain a necessary and sufficient condition for the existence of C 2 n- 2 [0, 1] positive solutions, and a sufficient condition, a necessary condition for the existence of C 2 n-1 [0, 1] positive solutions. Relations between the positive solutions and the Green’s functions are depicted. The results are used to judge nonexistence or existence of positive solutions for given boundary value problems.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

不同厂家热电池FeS_(2)-CoS_(2)复合正极材料的比较研究

为了加快热电池FeS_(2)-CoS_(2)复合正极材料的优化及应用,采用两种不同厂家生产的CoS_(2)作为导电剂添加到FeS_(2)中,制备出FeS_(2)-CoS_(2)复合正极材料及其单体电池,并对两种CoS_(2)原材料、FeS_(2)-CoS_(2)复合正极材料的微观形貌、粒度分布、X射线衍射分析以及单体电池的放电性能进行了研究。结果表明,广东产的FeS_(2)-CoS_(2)正极材料具有更均匀的微观分布和较少的小粒度粒子,湖南产的FeS_(2)-CoS_(2)正极材料更适合小电流放电应用,而广东产的FeS_(2)-CoS_(2)正极材料更适合于高功率放电。此外,将两种FeS_(2)-CoS_(2)正极材料应用于某型号热电池并进行高低温放电测试,结果表明广东产的FeS_(2)-CoS_(2)正极材料在放电性能上优于湖南产的FeS_(2)-CoS_(2)正极材料。

Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience

BACKGROUND Invasive lobular carcinomas(ILC)form 5%-10%of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2(HER2).AIM To describe the prevalence and prognostic factors of HER2 positive(HER2+)ILC in an Asian population.METHODS A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted.Demographic and clinical data were collected from medical records.We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTS A total of 864 patients were included.Prevalence of HER2 positivity was 10.1%(87 patients).Compared with HER2 negative(HER2-)ILC,HER2+ILC was associated with a higher proportion of estrogen receptor negative(24.4%vs 5.9%,P<0.001),progesterone receptor negative(PR-)(40.2%vs 24%,P=0.002)and grade 3 tumours(Grade 3,29.0%vs 10.2%,P<0.001).Overall survival rate was poorer in patients with HER2+compared to HER2-ILC(56.7%vs 72.9%alive at 10 years;hazard ratio 1.87,95%confidence interval:1.21-2.90,P=0.004).Based on multivariate analysis,negative prognostic factors for overall survival included HER2 positivity,PR negativity,older age,Indian ethnicity and higher tumour stage.CONCLUSION Prevalence of HER2+ILC was 10.1%.HER2+ILC was more likely to have poorer prognostic features such as estrogen receptor negative,PR-and higher tumour grade,and have a poorer survival.

Decaying of Nitrogen Second Positive System by Addition of H₂Gas in Air DB Discharge

Effects of addition of H2 gas in air DB discharge on its optical and electrical characteristics have been studied. Optical emission spectroscopy is used to investigate the effect of hydrogen admixing on the emission intensity of the nitrogen second positive systems (300 - 420 nm) and the relative population density of states. An obvious decaying of the emission intensity of the nitrogen second positive bands with the introduction of H2 has been observed. It has been concluded that quenching of the nitrogen excited state is the responsible reason of this decaying. Mechanisms of excitation and ionization processes of nitrogen molecules in this mixture have been studied. Processes which are responsible for the decaying of the population density of have been reported. Addition of H2 to air improves the electrical characteristics of the DB discharge. An abrupt increasing in the electron density, reached about thirty fold at H2 flow rate of 3 L/min, as a result of increasing the ionization processes has been reported. The breakdown voltage of the discharge decreased from 1.87 kV to about 1.25 kV by the addition of H2 at flow rate of 3 L/min.

Positive Bias Temperature Instability Degradation of Buried InGaAs Channel nMOSFETs with InGaP Barrier Layer and Al2O3 Dielectric

Positive bias temperature instability stress induced interface trap density in a buried InGaAs channel metaloxide-semiconductor field-effect transistor with a InCaP barrier layer and Al2O3 dielectric is investigated. Well behaved split C-V characteristics with small capacitance frequency dispersion are confirmed after the insertion of the InCaP barrier layer. The direct-current Id-Vg measurements show both degradations of positive gate voltage shift and sub-threshold swing in the sub-threshold region, and degradation of positive △Vg in the oncurrent region. The Id-Vg degradation during the positive bias temperature instability tests is mainly contributed by the generation of near interface acceptor traps under stress. Specifically, the stress induced aeceptor traps contain both permanent and recoverable traps. Compared with surface channel InCaAs devices, stress induced recoverable donor traps are negligible in the buried channel ones.

Asymptotic Stability of 2-D Positive Linear Systems with Orthogonal Initial States

这份报纸处理 2-D 的 asymptotic 稳定性有直角的起始的状态的积极线性系统。与 1-D 系统不同，有直角的起始的状态 x 的 2-D 系统的 asymptotic 稳定性(我， 0 )， x ( 0 ， j )( Fornasini-Marchesini ( FM )模型)或 xv (我， 0 )， xh ( 0 ， j )( Roesser 模型)严格地依赖于合适的边界条件。第一，为 2-D 的一个 asymptotic 稳定性标准积极 FM 首先，模型被使起始的状态成为 x 介绍(我， 0 ) ， x (0， j ) 绝对会聚。然后，类似的结果也与任何绝对会聚的起始的状态 xv 为 2-D 被给积极 Roesser 模型(我， 0 ) ， xh (0， j ) 。最后，二个例子被给显示出这些标准的有效性并且由造成指数地会聚的起始的状态表明轨道的集中。

Ki67、P53、VEGF和C-erbB-2在乳腺癌组织中表达的相关性研究及其临床意义

背景与目的:细胞增殖抗原标记物(Ki67)为细胞增殖的一个重要生物学指标。本研究旨在探讨Ki67、P53、VEGF和C-erbB-2在乳腺癌组织中的表达及其与临床病理因素的相关性。方法:用免疫组化方法检测151例乳腺癌组织中Ki67和其他生物学指标的表达,并与临床病理因素进行相关性分析。结果:Ki67在乳腺癌组织中的阳性率为74.8%(113/151)。Ki67表达与乳腺癌临床分期有关(P<0.05),而与患者年龄、肿瘤大小、淋巴结转移状况无显著性相关(P>0.05);Ki67表达与P53、C-erbB-2表达呈正相关(P<0.05),而与VEGF表达无显著性相关;Ki67和VEGF的共表达与肿瘤大小和临床分期有关(P<0.05)。结论:Ki67阳性表达可作为评价乳腺癌发生、发展的生物学指标,联合VEGF检测更有助于乳腺癌临床分期的判断。

乳腺癌组织中C-erbB-2、nm23基因的表达及其预后的关系

目的探讨乳腺癌组织中C-erbB-2基因和nm23基因的表达与预后的关系。方法采用免疫组织化学S-P法检测298例乳腺癌C-erbB-2、nm23基因表达情况并与乳腺癌病理类型、发病年龄、临床分期、腋淋巴结转移情况及5a生存率之间的关系进行分析。结果C-erbB-2基因阳性率36.24%(108/298),nm23基因阳性率为58.05%(173/298);C-erbB-2和nm23基因的表达与肿瘤病理类型、发病年龄、临床分期无明显相关性(P>0.05);C-erbB-2基因表达与腋淋巴结转移呈正相关,与5a生存率呈负相关,nm23基因的表达与腋淋巴结转移呈负相关,与5a生存率呈正相关(P<0.05);C-erbB-2基因表达与nm23基因表达两者之间明显负相关(P<0.05)。结论联合检测乳腺癌组织中C-erbB-2和nm23基因表达可能成为预测、评估乳腺癌患者临床预后的标记物。

青年和绝经后女性乳腺癌c-erbB-2、p53、ER和PR受体表达及意义

目的 探讨青年和绝经后女性乳癌c erbB 2、p53、ER、PR的表达及意义。方法 采用SP法检测青年组 (13 1例 )与绝经组 (13 6例 )乳癌组织中各指标的表达及其与临床分期、腋淋巴结 (ALN )转移、3年无病生存率 (DFS)之间的关系。结果 c erbB 2阳性与临床分期、ALN转移相关 (P <0 .0 5) ,c erbB 2阳性者 3年DFS低于阴性者 (P <0 .0 5)。青年组c erbB 2、p53阳性率高、ER阳性率低 (P <0 .0 1) ,3年DFS低于绝经组 (P <0 .0 5)。结论 c erbB 2表达是乳腺癌预后重要指标 ,青年乳腺癌c erbB 2、p53阳性率高 ,ER阳性率低 ,3年DFS低 。

子宫内膜腺癌C-erbB-2COX-2过度表达的相关性分析

目的:研究C-erbB-2、COX-2在子宫内膜增生性病变和子宫内膜腺癌中的表达特点及其相关性。方法:应用免疫组织化学S-P法检测了20例正常增生期子宫内膜、23例单纯性子宫内膜增生、21例复杂性子宫内膜增生、43例非典型性子宫内膜增生、25例子宫内膜腺癌中C-erbB-2、COX-2的表达。结果:C-erbB-2和COX-2在各实验组中的阳性表达率:单纯性增生组为4.5%和9.1%,复杂性增生组为4.8%和14.3%,低级别非典型增生组为30.0%和25.0%,高级别非典型增生组为60.9%和52.4%,腺癌组为92.0%和91.7%;C-erbB-2、COX-2在各实验组间差异均有显著性(P=0.000)。C-erbB-2与COX-2在各组的表达水平呈显著正相关关系(P<0.01)。结论:C-erbB-2、COX-2可能在子宫内膜癌的发生发展中发挥重要的协同作用,两者联合检测对子宫内膜腺癌及癌前病变的鉴别诊断有较高的诊断价值。

胃粘膜癌变过程中幽门螺杆菌感染与p53,c-erbB-2基因表达的研究

目的探讨胃粘膜癌变过程中幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ，Ｈｐ）感染与ｐ５３，ｃｅｒｂＢ２基因表达的关系．方法浅表性胃炎１６例，肠上皮化生２２例，异型增生１４例，早期胃癌１８例及进展期胃癌４０例作为研究对象．用ＷａｒｔｈｉｎＳｔａｒｙ银染色法检测Ｈｐ，用免疫组化Ｓｐ法检测ｐ５３和ｃｅｒｂＢ２的基因表达产物．结果Ｈｐ，ｐ５３，ｃｅｒｂＢ２在浅表性胃炎的检出率各为５００％，００％，００％；在肠上皮化生的检出率各为５９１％，２２７％，１３６％；在异型增生的检出率各为８５７％，６４３％，２８６％；在早期胃癌的检出率各为１６７％，３３３％，１１１％；在进展期胃癌的检出率各为５０％，５２５％，５５０％；在癌旁粘膜的Ｈｐ检出率为８６７％；在癌前病变中，Ｈｐ阳性组的ｐ５３，ｃｅｒｂＢ２表达率均高于Ｈｐ阴性组．结论Ｈｐ感染参与了胃癌前病变的发生与发展；Ｈｐ感染可引起野生型ｐ５３基因失活和ｃｅｒｂＢ２基因激活，从而导致胃粘膜的癌变．

survivin在乳腺癌中的表达及其与Ki-67和c-erbB-2表达的关系

目的观察凋亡抑制蛋白survivin在乳腺癌组织中的表达,及其与c-erbB-2、Ki-67增殖指数的相关性及临床病理意义。方法应用免疫组织化学SP法检测survivin在正常乳腺组织(20例)和乳腺癌组织(96例)中的表达以及Ki-67、c-erbB-2在乳腺癌组织中的表达。结果 survivin阳性表达乳腺癌的Ki-67增殖指数(35.32±21.28)%明显高于survivin阴性者(20.42±11.34)%,survivin表达与肿瘤细胞增殖呈正相关(P<0.01);survivin在乳腺癌组织中的阳性表达率为70.83%(68/96),正常乳腺组织未见survivin表达;survivin蛋白的表达与c-erbB-2的表达呈正相关(P<0.01);sur-vivin蛋白的表达与临床分期、淋巴结转移和5年生存率有关(P<0.05),与年龄、是否绝经、肿瘤大小和组织学分级均无关。结论 survivin不仅参与凋亡的调控,还促进了细胞增殖,在乳腺癌发生、发展中起重要作用,过度表达提示预后不良。

胃癌组织p53、c-erbB-2、p21和nm23基因表达及其与预后的关系

目的:探讨胃癌组织p53、cerbB2、p21和nm23联合基因产物表达检测对胃癌诊断、治疗及预后判断的价值。方法:应用免疫组化技术对123例手术切除胃癌组织标本中p53、cerbB2、p21和nm23基因产物表达进行测定。结果:高分化胃癌组p53表达阳性率38.0%(27/71),cerbB2为59.2%(42/71),p21为39.4%(28/711),nm23为71.8%(51/71),低分化胃癌组4种基因表达阳性率分别为46.2%(24/52)、36.5%(19/52)、69.2%(24/52)和34.6%(18/52);在非胃癌组织(胃、十二指肠溃疡、胃息肉、重度不典型增生胃炎胃镜标本)未见cerbB2、p21、nm23基因表达。p53、cerbB2、p21的表达与胃癌的分化程度、肿瘤浸润深度、肿瘤转移程度呈正相关(r=0.53,r=0.67,r=0.48,P<0.05);nm23的表达与胃癌的分化程度、肿瘤浸润深度、肿瘤转移程度呈负相关(r=-0.36,P<0.05)。结论:胃癌组织p53、cerbB2、p21、nm23基因表达检测在胃良恶性肿瘤鉴别、非手术临床分期的判断及指导临床治疗等方面具有一定价值,多基因表达检测对胃癌预后判断明显优于单基因表达检测。