Role of Post-translational Modifications in Alzheimer's Disease

The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug-discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post-translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in-depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease-relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug-discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD.     

Synthesis,characterization and corrosion protection properties of poly(N-vinyl carbazole-co-glycidyl methacrylate) coatings on low nickel stainless steel

Methacrylate based copolymers are considered as one of the best organic coating materials for anticorrosive application. Poly(N-vinyl carbazole-co-glycidyl methacrylate) have been synthesized by free radical solution polymerization technique from different mole ratios of N-vinyl carbazole (N-Vc) and glycidyl methacrylate (GMA) and characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (¹H NMR and ¹³C NMR). Thermal analyses of the poly(N-Vc-co-GMA) were performed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The number average molecular weight (M_n) of different compositions of the same was determined by gel permeation chromatography (GPC). The corrosion performances of low nickel stainless steel specimens coated with different composition of copolymers were investigated in 1 M H₂SO₄ using potentiodynamic polarization, electrochemical impedance spectroscopic (EIS) method, scanning electron microscopic (SEM) and energy dispersive X-ray analysis (EDAX). Poly(N-Vc-co-GMA) have been provided in order to achieve adherent, low permeability to aggressive ions as well as environmentally favored good anticorrosive coating. Electrochemical corrosion test and surface analysis results clearly showed that poly(N-Vc-co-GMA) coatings served as a stable host matrix on low nickel stainless steel against corrosion. It was also observed that the coatings of poly(N-Vc-co-GMA) with equal mole ratio of N-Vc and GMA exhibited the best corrosion resistance among all combinations.     

Continuum Bed Model for Estuarine Sediments Based on Nonlinear Consolidation Theory

The goal of this note is to examine a continuum theory that describes the evolution of sediment beds when subjected to time-dependent shearing forces resulting from surface water movement. The bed was conceptualized as a medium with continuously varying properties such as shear strength and void ratio. The nonlinear equation describing finite strain consolidation, and the complicated nature of the shearing forces acting on top of the bed, preclude the possibility of analytical solutions. Ramifications of linearizing the governing flow equations were explicitly evaluated for applications in bed modeling. Numerical solutions were obtained for the linear and nonlinear models under transient boundary conditions. Model results indicated that the linear model typically predicts lower void ratios, and consequently underestimates the amounts of sediment eroded from the bed as compared to the nonlinear model.     

Enhancing biometric recognition with spatio-temporal reasoning in smart environments

We discuss smart environments that identify and track their occupants using unobtrusive recognition modalities such as face, gait, and voice. In order to alleviate the inherent limitations of recognition, we propose spatio-temporal reasoning techniques based upon an analysis of the occupant tracks. The key idea underlying our approach is to determine the identity of a person based upon information from a track of events rather than a single event. We abstract a smart environment by a probabilistic state transition system in which each state records a set of individuals who are present in various zones of the smart environment. An event abstracts a recognition step, and the transition function defines the mapping between states upon the occurrence of an event. We express two forms of spatio-temporal reasoning in the form of transition functions: a track-based transition function and an error-correcting transition function. We also define the concepts of ‘precision’ and ‘recall’ to quantify the performance of the smart environment and provide experimental results to clarify the performance improvements from spatio-temporal reasoning. Our conclusion is that the state transition system is an effective abstraction of a smart environment and the application of spatial-temporal reasoning enhances the overall performance of a biometric recognition system.     

Results of transition zone biopsy in black and white men with suspected prostate cancer

OBJECTIVES: To determine whether biopsy-detectable transition zone tumors are more common in black than in white men with suspected Stage T1c and T2 prostate cancer. METHODS: We performed a prospective study of transition zone prostate biopsy (TZ biopsy) in 1 78 black and 261 white men who had not undergone previous prostate biopsy and in 61 black and 65 white men who had undergone one benign sextant peripheral zone prostate biopsy (PZ biopsy). RESULTS: The mean age of the 239 black and 326 white study patients was 68.6+/-7.4 and 67.2+/-7.2 years, respectively (P = 0.02), the mean prostate-specific antigen (PSA) was 8.4+/-7.4 and 6.4+/-5.4 ng/mL, respectively (P = 0.003), and the mean PSA density was 0.20+/-0.23 and 0.16+/-0.16 ng/mL/mL, respectively (P = 0.006). Overall, cancer was diagnosed by TZ biopsy only in 7 black men (3%) and in no white men (0%) (P = 0.003). However, cancer detection with a TZ biopsy only was not significantly different in the black and white men when controlled for age, PSA, or PSA density (P>0.90). A TZ biopsy only detected cancer in 1% of patients who had not undergone prior PZ biopsy and in 2% of patients who had undergone prior PZ biopsy. Of the seven cancers detected with TZ biopsy, six (86%) had a Gleason score of 2 to 6. CONCLUSIONS: Prostate cancer detection with a TZ biopsy only is not common and when controlled for confounding variables is the same in black and white men. The preferential use of TZ biopsies in black men is not warranted, and the low diagnostic yield argues against routine use of the biopsy technique in men of either race.     

Chaincode contour processing for handwritten word recognition

Contour representations of binary images of handwritten words afford considerable reduction in storage requirements while providing lossless representation. On the other hand, the one-dimensional nature of contours presents interesting challenges for processing images for handwritten word recognition. Our experiments indicate that significant gains are to be realized in both speed and recognition accuracy by using a contour representation in handwriting applications     

Challenges and Opportunities in Many-Core Computing

In this paper, we present some of the challenges and opportunities in software development based on the current hardware trends and the impact of massive parallelism on both the software and hardware industry. We indicate some of the approaches that can enable software development to effectively exploit the many-core architectures. Some of these include encapsulating domain-specific knowledge in reusable components, such as libraries, integrating concurrency with languages, and supporting explicit declarations to help compilers and operating system schedulers. Tighter interaction between software and underlying hardware is required to build scalable and portable applications with predictable performance and higher power-efficiency. Overall, many-core computing provides us opportunities to enable new application scenarios that support enhanced functionality and a richer experience for the user on commodity hardware.     

Steroid content in endometrial tissue

Recent studies indicate beneficial effects of androgen depletion in male mice, before trauma-hemorrhage on cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Nonetheless, it remains unknown whether androgen receptor blockade following the insult has any salutary effects. To study this, male C3H/HeN mice were either sham-operated or subjected to soft-tissue trauma (i.e., 2.5 cm midline laparotomy) followed by hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) and then adequately resuscitated (shed blood and lactated Ringer's). Immediately after the completion of resuscitation, as well as 24 and 48 h thereafter, the animals received either vehicle, 10 mg/kg body weight (BW) flutamide or 25 mg/kg BW flutamide subcutaneously. At 72 h after resuscitation, all animals were killed. The spleens and peritoneal macrophages (M phi) were then harvested and cultures established to determine IL-2 and IL-3 release, splenocyte proliferative capacity, as well as splenic and peritoneal M phi IL-1 release. Moreover, plasma testosterone and corticosterone levels were measured. Our results indicate that trauma-hemorrhage resulted in significant depression of splenocyte and M phi functions in vehicle-treated and animals receiving 10 mg/kg BW flutamide. Treatment with 25 mg/kg BW flutamide following trauma-hemorrhage, however, resulted in levels of cytokine release which were comparable with those found in sham-operated animals. No significant alterations in plasma corticosterone and testosterone levels were observed in any of the experimental groups. These findings indicate that short-term therapy of males with the androgen receptor blocker, flutamide at 25 mg/kg BW, following trauma-hemorrhage has protective effects on immune functions. This protective effect is dose dependent, since 10 mg/kg BW flutamide did not produce significant salutary effects. Thus, flutamide represents a novel and safe agent for improving the depressed functions in male trauma patients suffering severe blood loss.