The Effects of Modifying the Activity of Nitriding Media by Diluting Ammonia with Nitrogen

This paper discusses the issue of the effects of modifying the activity of nitriding media by diluting ammonia with nitrogen and the concomitant variation in the degree of ammonia dissociation on the layer’s growth kinetics and their phase composition. To understand and quantify the effects of the variation in the main parameters that influence the layer growth kinetics, the experimental programming method was used and mathematical models of interactions between influence and kinetics parameters were obtained for two metallic materials: Fe-ARMCO and 34CrAlMo5 nitralloy steel. It was concluded that the nitriding operating temperature and the degree of nitrogen dilution of the ammonia have statistically significant influences on the kinetics of the nitrided layer. In the same context, it was analytically proved and experimentally confirmed that the ammonia degree dissociation from the gaseous ammonia-nitrogen mixture, along with the dilution degree of the medium with nitrogen, significantly influences the nitrogen potential of the gaseous mixture used for nitriding and thus the concentration of nitrogen in balance at the medium thermochemically processed metal product interface.     

通过低能耗绝热脉冲和快速螺旋采样实现的神经系统三维核磁共振光谱成像

目的 提高三维(3D)核磁共振(MR)光谱成像系统的定位精确度和采样速度.材料与方法 本研究所涉及的内容经机构审查委员会(Institutional Review Board)批准并获得患者知情同意.用一台配有32通道头部线圈系统的3T核磁共振成像仪采集体模、5位健康的志愿者以及5位胶质母细胞瘤患者的数据.信号激发手段为定位绝热自旋回波聚焦(LASER),此法采用GOIA-W(16,4)型脉冲信号,脉冲时长3.5ms,带宽20kHz,振幅维度0.81kHz,回讯时间45ms.一组频域信号和两组空间信号由成像系统沿等密度螺旋线隔行扫描获得.在LASER激发步骤之后,传统的相位编码手段(Phase Encoding,PE)给出的每像素lcm3的数据被用作参照标准.在更短时间,同样或者更高空间解析度下,由螺旋采样方法获取的谱图被用于和PE手段获取的谱图进行对比.相关的生化指标水平由分析软件分析谱图获得,并用Bland-Altman方法进行分析.结果 在低空间解析度(每像素1cm3)条件下,螺旋采样获取医用三维核磁共振谱图的速度4倍于传统的椭圆相位编码方法.提高空间解析度至每像素0.39cm3,螺旋采样的速率仍是2倍于每像素1cm3条件下的椭圆相位编码方法.上述提及的螺旋采样成像技术所成的谱图中,信噪比(SNR)均＞5,依此可以判断谱图中生化物质能够被明显地从背景噪声中区分出来.像素点尺寸减小导致的信噪比损失并非线性,因为缩小像素点尺寸需要延长T2阶段.在高空间解析度下,谱图中谱线的宽度由4.8Hz提高至3.5Hz.使用Bland-Ahman方法对螺旋采样和PE的成像结果进行分析,结论为二者之间相互吻合:二者的相似程度为95％(均值分别为0.12和0.18).GIOA-W(16,4)型脉冲信号的使用有效地将化学位移误差降低至2.1％,并把激发过程的不一致度降低至5％,而且可以降低其他干扰抑制技术的需求.结论 上述绝热螺旋采样三维MRI技术可以通过标准的MRI系统实现.该手段能够给予更高的成像质量和更短的成像时间,与现有技术相比能够保障更多的日常核磁共振数据的收集.     

Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial

ABSTRACT: BACKGROUND: The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose-response relationship of everolimus. Results: The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% +/- 98.3%, +22.4% +/- 17.2%, and -15.7% +/- 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time. Conclusions: In this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose-response relationship.     

Combined cardiac-neurosurgical treatment of acute aortic dissection, stroke, and coma

Coma or stroke with secondary brain malperfusion is usually considered a strong contraindication for emergent surgical treatment of acute aortic dissection. Herein, we present the case of a 30-year-old woman who presented with sudden left hemiplegia and level-7 coma on the Glasgow Coma Scale. Transthoracic echocardiography showed type A aortic dissection. Although the patient was unable to communicate, her family approved an emergency Bentall operation. She regained consciousness but developed anisocoria and Glasgow Coma Scale level-4 coma 30 hours after the operation. Computed tomography showed massive cerebral infarction with hernia of the uncus gyri hippocampi. Emergency surgical cerebral decompression was performed. The patient survived; after 1 year, she had full mental acuity and minor left motor sequelae.     

Development of a synthetic phantom for the selection of optimal scanning parameters in CAD-CT colonography

The aim of this paper is to present the development of a synthetic phantom that can be used for the selection of optimal scanning parameters in computed tomography (CT) colonography. In this paper we attempt to evaluate the influence of the main scanning parameters including slice thickness, reconstruction interval, field of view, table speed and radiation dose on the overall performance of a computer aided detection (CAD)-CTC system. From these parameters the radiation dose received a special attention, as the major problem associated with CTC is the patient exposure to significant levels of ionising radiation. To examine the influence of the scanning parameters we performed 51 CT scans where the spread of scanning parameters was divided into seven different protocols. A large number of experimental tests were performed and the results analysed. The results show that automatic polyp detection is feasible even in cases when the CAD-CTC system was applied to low dose CT data acquired with the following protocol: 13 mAs/rotation with collimation of 1.5 mm x 16 mm, slice thickness of 3.0mm, reconstruction interval of 1.5 mm, table speed of 30 mm per rotation. The CT phantom data acquired using this protocol was analysed by an automated CAD-CTC system and the experimental results indicate that our system identified all clinically significant polyps (i.e. larger than 5 mm).     

Low‐power adiabatic sequences for in vivo localized two‐dimensional chemical shift correlated MR spectroscopy

Novel low‐power adiabatic sequences are demonstrated for in vivo localized two‐dimensional correlated MR spectroscopy, such as correlated spectroscopy and total correlated spectroscopy. The design is based on three new elements for in vivo two‐dimensional MRS: the use of gradient modulated constant adiabaticity GOIA‐W(16,4) pulses for (i) localization (correlated spectroscopy and total correlated spectroscopy) and (ii) mixing (total correlated spectroscopy), and (iii) the use of longitudinal mixing (z‐filter) for magnetization transfer during total correlated spectroscopy. GOIA‐W(16,4) provides accurate signal localization, and more importantly, lowers the SAR for both total correlated spectroscopy mixing and localization. Longitudinal mixing improves considerably (fivefolds) the efficiency of total correlated spectroscopy transfer. These are markedly different from previous 1D editing total correlated spectroscopy sequences using spatially nonselective pulses and transverse mixing. Fully adiabatic (adiabatic mixing with adiabatic localization) and semiadiabatic (adiabatic mixing with nonadiabatic localization) methods for two‐dimensional total correlated spectroscopy are compared. Results are presented for simulations, phantoms, and in vivo two‐dimensional spectra from healthy volunteers and patients with brain tumors obtained on 3T clinical platforms equipped with standard hardware. To the best of our knowledge, this is the first demonstration of in vivo adiabatic two‐dimensional total correlated spectroscopy and fully adiabatic two‐dimensional correlated spectroscopy. It is expected that these methodological developments will advance the in vivo applicability of multi(spectrally)dimensional MRS to reliably identify metabolic biomarkers. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Correlation chemical shift imaging with low-power adiabatic pulses and constant-density spiral trajectories

In this work we introduce the concept of correlation chemical shift imaging (CCSI). Novel CCSI pulse sequences are demonstrated on clinical scanners for two‐dimensional Correlation Spectroscopy (COSY) and Total Correlation Spectroscopy (TOCSY) imaging experiments. To date there has been limited progress reported towards a feasible and robust multivoxel 2D COSY. Localized 2D TOCSY imaging is shown for the first time in this work. Excitation with adiabatic GOIA‐W(16,4) pulses (Gradient Offset Independent Adiabaticity Wurst modulation) provides minimal chemical shift displacement error, reduced lipid contamination from subcutaneous fat, uniform optimal flip angles, and efficient mixing for coupled spins, while enabling short repetition times due to low power requirements. Constant‐density spiral readout trajectories are used to acquire simultaneously two spatial dimensions and f₂ frequency dimension in (k_x,k_y,t₂) space in order to speed up data collection, while f₁ frequency dimension is encoded by consecutive time increments of t₁ in (k_x,k_y,t₁,t₂) space. The efficient spiral sampling of the k‐space enables the acquisition of a single‐slice 2D COSY dataset with an 8 × 8 matrix in 8:32 min on 3 T clinical scanners, which makes it feasible for in vivo studies on human subjects. Here we present the first results obtained on phantoms, human volunteers and patients with brain tumors. The patient data obtained by us represent the first clinical demonstration of a feasible and robust multivoxel 2D COSY. Compared to the 2D J‐resolved method, 2D COSY and TOCSY provide increased spectral dispersion which scales up with increasing main magnetic field strength and may have improved ability to unambiguously identify overlapping metabolites. It is expected that the new developments presented in this work will facilitate in vivo application of 2D chemical shift correlation MRS in basic science and clinical studies. Copyright © 2011 John Wiley & Sons, Ltd.     

An analysis of five clear cell papillary cystadenomas of mesosalpinx and broad ligament: four associated with von Hippel-Lindau disease and one aggressive sporadic type

Nogales F F, Goyenaga P, Preda O, Nicolae A, Vieites B, Ruiz‐Marcellan M C, Pedrosa A & Merino M J
(2012) Histopathology  60, 748–757
An analysis of five clear cell papillary cystadenomas of mesosalpinx and broad ligament: four associated with von Hippel‐Lindau disease and one aggressive sporadic type Aims: Clear cell papillary cystadenoma (CCPC) is associated with von Hippel‐Lindau disease (VHLD), but rarely involves mesosalpinx and broad ligament (M/BL). This study provides new data about its behaviour and immunophenotype. Methods and results: We performed an analysis of four benign cases of CCPC of M/BL with either characteristic clinical features or genetic markers [loss of heterozygosity (LOH)] of VHLD in patients ranging from 24 to 36 years and a sporadic case in a 52‐year‐old presenting with peritoneal metastases. All CCPCs were papillary but had solid and tubular areas. Haemorrhage, thrombosis and scarring were constant features and related to an unusual pattern of sub‐epithelial vascularity. All clear or oxyphilic cells co‐expressed cytokeratin 7 (CK7), CAM5.2 and vimentin, with strong apical CD10 and nuclear paired box gene 2 (PAX2) immunoreactivity. Three cases also showed positivity for VHL40, epithelial membrane antigen (EMA), Wilms’ tumour suppressor gene (WT‐1) and cancer antigen 125 (CA125) but only one expressed renal cell carcinoma (RCC) antigen. Vascular plexus overexpressed nuclear and cytoplasmic WT‐1. Conclusion: The VHLD‐associated cases appeared to be benign, but the sporadic case exhibited a low malignant potential. CCPCs show histological and immunophenotypical similarities with the recently reported clear cell papillary RCC, although the previously unreported apical CD10 and nuclear PAX2 expression may be related to their mesonephric origin. CCPC has a distinctive sub‐epithelial vascular pattern that is consistent with its pathogenesis.     

PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins

Prostate androgen regulated (PAR) protein is a 148 amino acid polypeptide ubiquitously expressed in normal cells and overexpressed in many malignancies. Manipulation of PAR mRNA in DU145 and NIH3T3 cells indicated that its expression level is an important determinant of cell in vitro proliferation, clonogenicity in soft agar and in vivo tumorigenicity. In this study, we showed that PAR is a short-lived protein with a peak in G2/M phase. Using immunofluorescent antibodies we showed that PAR moves from centrosomes in prophase and metaphase to spindle midzone in anaphase, and concentrates to midbody in telophase and cytokinesis. During mitosis a fraction of PAR can also be detected in the cytoplasm. PAR pattern of expression and its dynamic localization suggested a functional relationship to chromosomal passenger proteins (CPP). This protein colocalized with Aurora A at centrosomes in metaphase, and with survivin at midbody in telophase and cytokinesis. It also formed complexes with Aurora A, and with survivin, Aurora B and INCENP. In addition, PAR increased Aurora B kinase activity on histone H3. The decreased PAR levels in DU145 cells resulted in defects in centrosome segregation, in failed cytokinesis and chromosome alignment, and in increased number of apoptotic cells, polyploidy and aberrant mitosis. It is known that such defects could lead to genomic instability and tumorigenesis. In this study we also confirm our earlier findings that PAR is overexpressed in many tumors. Due to its involvement in cell cycle and its overexpression in several human cancers PAR could represent an attractive target for therapeutic intervention.