Raja Nassar

Analysis of Surgical Margins With the Molecular Marker eIF4E: A Prognostic Factor in Patients With Head and Neck Cancer

PURPOSE Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study. PATIENTS AND METHODS Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997. RESULTS All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recu rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P =.009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P =. 0001, log-rank test). CONCLUSION In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.

Relative Contribution of Wall Shear Stress and Injury in Experimental Intimal Thickening at PTFE End-to-Side Arterial Anastomoses

BACKGROUND Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

An optimal checkpoint/restart model for a large scale high performance computing system

The increase in the physical size of high performance computing (HPC) platform makes system reliability more challenging. In order to minimize the performance loss (rollback and checkpoint overheads) due to unexpected failures or unnecessary overhead of fault tolerant mechanisms, we present a reliability-aware method for an optimal checkpoint/restart strategy. Our scheme aims at addressing fault tolerance challenge, especially in a large-scale HPC system, by providing optimal checkpoint placement techniques that are derived from the actual system reliability. Unlike existing checkpoint models, which can only handle Poisson failure and a constant checkpoint interval, our model can deal with a varying checkpoint interval and with different failure distributions. In addition, the approach considers optimality for both checkpoint overhead and rollback time. Our validation results suggest a significant improvement over existing techniques.

Focused ion beam milling: Depth control for three-dimensional microfabrication

Ion milling with a focused ion beam (FIB) is a potential method for making micromolds, which will then be the primary elements in the mass production of micro- or mini-objects by embossing or injection molding. The challenge lies in controlling the ion milling to produce cavities with predefined, arbitrary geometric cross-sections. This work involves programming variations as a function of position into the algorithm that generates the dwell times in the pixel address scheme of a FIB. These variations are done according to whether an axis of symmetry or a plane of symmetry determines the final geometry, and the result is 26 new cross-sectional shapes, such as hemispherical pits, parabolic pits, hemispherical domes, etc. The ion milling control programs were used to generate parabolic cross-section trenches, sinusoidal trenches, sinusoidal cross-section rings on an annulus, and hemispherical domes. We observed reasonable agreement between the shapes ion milled in Si(100) and the expected geometry. The dwel...

Reliability-Aware Approach: An Incremental Checkpoint/Restart Model in HPC Environments

For full checkpoint on a large-scale HPC system, huge memory contexts must potentially be transferred through the network and saved in a reliable storage. As such, the time taken to checkpoint becomes a critical issue which directly impacts the total execution time. Therefore, incremental checkpoint as a less intrusive method to reduce the waste time has been gaining significant attentions in the HPC community. In this paper, we built a model that aims to reduce full checkpoint overhead by performing a set of incremental checkpoints between two consecutive full checkpoints. Moreover, a method to find the number of those incremental checkpoints is given. Furthermore, most of the comparison results between the incremental checkpoint model and the full checkpoint model (Liu et al., 2007) on the same failure data set show that the total waste time in the incremental checkpoint model is significantly smaller than the waste time in the full checkpoint model.

Expression of eIF4E During Head and Neck Tumorigenesis: Possible Role in Angiogenesis†‡

Objective: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation. 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF‐2) by selectively enhancing their translation. 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins. Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions. Molecular events underlie the histological changes that herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis.

A compact finite-difference scheme for solving a one-dimensional heat transport equation at the microscale: 431

Heat transport at the microscale is of vital importance in microtechnology applications. The heat transport equation is different from the traditional heat diffusion equation since a second-order derivative of temperature with respect to time and a third-order mixed derivative of temperature with respect to space and time are introduced. In this study, we develop a high-order compact finite-difference scheme for the heat transport equation at the microscale. It is shown by the discrete Fourier analysis method that the scheme is unconditionally stable. Numerical results show that the solution is accurate.

Microfabrication techniques using focused ion beams and emergent applications

The application of focused ion beam (FIB) machining in several technologies aimed at microstructure fabrication is presented. These emergent applications include the production of micromilling tools for machining of metals and the production of microsurgical tools. An example of the use of microsurgical manipulators in a circulatory system measurement is presented. The steps needed to transform the laboratory fabrication of these tools and manipulators into a routine FIB production process are discussed. The ion milling of three-dimensional cavities by the exact solution of a mathematical model of the FIB deflection is demonstrated. A good agreement between the model calculation and the ion beam control has been obtained for parabolic and cosine cross-section features with planes of symmetry.

Depth control of focused ion-beam milling from a numerical model of the sputter process

A mathematical model of focused ion-beam milling is used to generate dwell times for the vector scanned pixel address scheme of a focused ion-beam deflection system. The model incorporates the absolute sputter yield of the solid as a function of the angle of incidence, and the relationship between the ion-beam current distribution and the pixel size of the deflection pattern. The object of this work is to be able to call for an arbitrary geometric shape to be ion milled and then have the numerical model compute the pixel dwell times for the deflection system such that the final cavity is sputtered. Experimental verification of the procedure was accomplished with parabolic troughs, hemispherical troughs, and cosine troughs. The term “trough” means a plane of symmetry in the ion-milled cavity. These same geometric shapes were also ion milled using a rotational axis of symmetry, yielding sinusoidal ring patterns, parabolic dishes, and hemispherical dishes. The absolute maximum depth for each of the cavities ...

Focused ion beam technology applied to microstructure fabrication

Focused ion beams (FIBs) have found a place in several research thrusts for the manufacture of mini or micro mechanical objects. This article reports the use of FIB in three distinct applications in microfabrication: prototype structures, micron-sized machine tools and microsurgical manipulators, and ion milling of three dimensional features. Examples of each of these applications are given with the FIB component identified as the enabling or critical component in the technology. The possibility of using FIB milling as part of a production method for micron-sized machine tools is discussed, and the mass production consequences of molds fabricated by three dimensional ion beam milling is also considered. The mathematical procedure and programming steps needed to accurately control FIB three dimensional milling are outlined.Focused ion beams (FIBs) have found a place in several research thrusts for the manufacture of mini or micro mechanical objects. This article reports the use of FIB in three distinct applications in microfabrication: prototype structures, micron-sized machine tools and microsurgical manipulators, and ion milling of three dimensional features. Examples of each of these applications are given with the FIB component identified as the enabling or critical component in the technology. The possibility of using FIB milling as part of a production method for micron-sized machine tools is discussed, and the mass production consequences of molds fabricated by three dimensional ion beam milling is also considered. The mathematical procedure and programming steps needed to accurately control FIB three dimensional milling are outlined.