Mining a cathepsin inhibitor library for new antiparasitic drug leads.

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼ 2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases.

Surface exploration of Amphibalanus amphitrite cyprids on microtextured surfaces.

Microtopography is one of several strategies used by marine organisms to inhibit colonization by fouling organisms. While replicates of natural microtextures discourage settlement, details of larval interactions with the structured surfaces remain scarce. Close-range microscopy was used to quantify the exploration of cyprids of Amphibalanus amphitrite on cylindrical micropillars with heights of 5 and 30 μm and diameters ranging from 5 to 100 μm.

Phylogenetic relationships of the Orang Asli and Iban of Malaysia based on maternal markers.

Malaysia remains as a crossroad of different cultures and peoples, and it has long been recognized that studying its population history can provide crucial insight into the prehistory of Southeast Asia as a whole. The earliest inhabitants were the Orang Asli in Peninsular Malaysia and the indigenous groups in Sabah and Sarawak. Although they were the earliest migrants in this region, these tribes are divided geographically by the South China Sea.

Adaptive tracking of discriminative frequency components in electroencephalograms for a robust brain-computer interface.

In an electroencephalogram (EEG)-based brain-computer interface (BCI), motor imagery has been successfully used as a communication strategy. Motor imagery causes detectable amplitude changes in certain frequency bands of EEGs, which are dubbed event-related desynchronization\synchronization. The frequency components that give effective discrimination between different types of motor imagery are subject specific and identification of these subject-specific discriminative frequency components (DFCs) is important for the accurate classification of motor imagery activities.

Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): analysis of chemoradiation treatment approaches in the United States.

Background: A study was undertaken to examine the patterns of systemic therapy use in conjunction with radiation therapy for patients with locally advanced head and neck squamous cell cancer.

Methods: Between December 1, 2005 and May 11, 2009, 2874 patients with newly diagnosed head and neck squamous cell cancer who were scheduled to receive radiotherapy and/or drug therapy were registered in a prospective national database. The database was specifically analyzed to examine patients who received chemotherapy in conjunction with definitive radiotherapy.

Optimizing the channel selection and classification accuracy in EEG-based BCI.

Multichannel EEG is generally used in brain-computer interfaces (BCIs), whereby performing EEG channel selection 1) improves BCI performance by removing irrelevant or noisy channels and 2) enhances user convenience from the use of lesser channels. This paper proposes a novel sparse common spatial pattern (SCSP) algorithm for EEG channel selection. The proposed SCSP algorithm is formulated as an optimization problem to select the least number of channels within a constraint of classification accuracy.

Molecular dynamics analysis on buckling of defective carbon nanotubes.

Owing to their remarkable mechanical properties, carbon nanotubes have been employed in many diverse areas of applications. However, similar to any of the many man-made materials used today, carbon nanotubes (CNTs) are also susceptible to various kinds of defects. Understanding the effect of defects on the mechanical properties and behavior of CNTs is essential in the design of nanotube-based devices and composites.

Glioma-associated oncogene family zinc finger 1 expression and metastasis in patients with head and neck squamous cell carcinoma treated with radiation therapy (RTOG 9003).

Purpose: Glioma-associated oncogene family zinc finger 1 (GLI1) expression was assessed to determine a potential role of hedgehog (Hh) signaling in head and neck squamous cell carcinoma (HNSCC). Additional proteins known to be modulated by Hh signaling, including beta-catenin (CTNNB1) and epidermal growth factor receptor (EGFR), were also assessed to determine the correlation among these distinct signaling pathways.

Patients And Methods: Nuclear GLI1 and CTNNB1 expression levels were determined in tumors from patients enrolled on Radiation Therapy Oncology Group (RTOG) 9003, a radiation fractionation trial.

DNA repair biomarker profiling of head and neck cancer: Ku80 expression predicts locoregional failure and death following radiotherapy.

Purpose: Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes.

Split Bull's eye shaped aluminum antenna for plasmon-enhanced nanometer scale germanium photodetector.

Bull's eye antennas are capable of efficiently collecting and concentrating optical signals into an ultrasmall area, offering an excellent solution to break the bottleneck between speed and photoresponse in subwavelength photodetectors. Here, we exploit the idea of split bull's eye antenna for a nanometer germanium photodetector operating at a standard communication wavelength of 1310 nm. The nontraditional plasmonic metal aluminum has been implemented in the resonant antenna structure fabricated by standard complementary metal-oxide-semiconductor (CMOS) processing.

Density, viscosity and electrical conductivity of protic alkanolammonium ionic liquids.

Ionic liquids are molten salts with melting temperatures below the boiling point of water, and their qualification for applications in potential industrial processes does depend on their fundamental physical properties such as density, viscosity and electrical conductivity. This study aims to investigate the structure-property relationship of 15 ILs that are primarily composed of alkanolammonium cations and organic acid anions. The influence of both the nature and number of alkanol substituents on the cation and the nature of the anion on the densities, viscosities and electrical conductivities at ambient and elevated temperatures are discussed.

Role of primary care providers in dengue prevention and control in the community.

Dengue fever is a major public health threat in Malaysia, especially in the highly urbanized states of Selangor and the Federal Territory of Kuala Lumpur. It is believed that many seek treatment at the primary care clinics and are not admitted. This study aims at establishing the fact that primary care practitioners, as the first point of patient contacts, play a crucial role in advising patients suspected of having dengue to take early preventive measures to break the chain of dengue transmission.

An image-based assay for high throughput screening of Giardia lamblia.

Giardia lamblia is a protozoan parasite that causes widespread gastrointestinal illness. Drugs to treat giardiasis are limited, but efforts to discover new anti-giardial compounds are constrained by the lack of a facile system for cell culture and inhibitor testing. We achieved robust and reproducible growth of G.

Optimum spatio-spectral filtering network for brain-computer interface.

This paper proposes a feature extraction method for motor imagery brain-computer interface (BCI) using electroencephalogram. We consider the primary neurophysiologic phenomenon of motor imagery, termed event-related desynchronization, and formulate the learning task for feature extraction as maximizing the mutual information between the spatio-spectral filtering parameters and the class labels. After introducing a nonparametric estimate of mutual information, a gradient-based learning algorithm is devised to efficiently optimize the spatial filters in conjunction with a band-pass filter.

Hyperfractionated or accelerated radiotherapy for head and neck cancer.

Background: Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear.

Objectives: The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival.

Search Strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials.

Combination of anti-IGF-1R antibody A12 and ionizing radiation in upper respiratory tract cancers.

Purpose: The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers.

Methods And Materials: Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays.

Online performance evaluation of motor imagery BCI with augmented-reality virtual hand feedback.

The online performance of a motor imagery-based Brain-Computer Interface (MI-BCI) influences its effectiveness and usability in real-world clinical applications such as the restoration of motor control. The online performance depends on factors such as the different feedback techniques and motivation of the subject. This paper investigates the online performance of the MI-BCI with an augmented-reality (AR) 3D virtual hand feedback.

Clinical study of neurorehabilitation in stroke using EEG-based motor imagery brain-computer interface with robotic feedback.

This clinical study investigates the ability of hemiparetic stroke patients in operating EEG-based motor imagery brain-computer interface (MI-BCI). It also assesses the efficacy in motor improvements on the stroke-affected upper limb using EEG-based MI-BCI with robotic feedback neurorehabilitation compared to robotic rehabilitation that delivers movement therapy. 54 hemiparetic stroke patients with mean age of 51.

Blasted cell line names.

Background: While trying to integrate multiple data sets collected by different researchers, we noticed that the sample names were frequently entered inconsistently. Most of the variations appeared to involve punctuation, white space, or their absence, at the juncture between alphabetic and numeric portions of the cell line name.

Results: Reasoning that the variant names could be described in terms of mutations or deletions of character strings, we implemented a simple version of the Needleman-Wunsch global sequence alignment algorithm and applied it to the cell line names.

Larynx preservation clinical trial design: summary of key recommendations of a consensus panel.

An international consensus panel was convened to develop guidelines for the conduct of phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. According to their recommendations, future trial populations should include patients with T2 or T3 laryngeal or hypopharyngeal squamous cell carcinoma not considered for partial laryngectomy and should exclude those with laryngeal dysfunction or aged >70 years. Baseline and post-treatment functional assessments should include speech and swallowing evaluations.

Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma.

Purpose: Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-and-neck squamous cell carcinoma (HNSCC).

Methods And Materials: EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial.

Early impact of aortic wrapping on patients undergoing aortic valve replacement with mild to moderate ascending aorta dilatation.

Background: The management of mild to moderate dilatation of the ascending aorta of less than 5 cm is controversial, particularly when concomitant surgical correction of aortic valve is required. We investigate the impact of a simple method of aorta reduction using Dacron graft wrapping during aortic valve replacement on the rest of the aorta.

Methods: We studied 14 patients who had ascending aorta dilatation of 4-5 cm before undergoing aortic wrapping during their aortic valve replacement and compared with their post-operative imaging within a month.

Candidate dosimetric predictors of long-term swallowing dysfunction after oropharyngeal intensity-modulated radiotherapy.

Purpose: To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia.

Methods And Materials: Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans.

Discovery of novel benzoxaborole-based potent antitrypanosomal agents.

We report the discovery of benzoxaborole antitrypanosomal agents and their structure-activity relationships on central linkage groups and different substitution patterns in the sulfur-linked series. The compounds showed in vitro growth inhibition IC50 values as low as 0.02 μg/mL and in vivo efficacy in acute murine infection models against Tryapnosoma brucei.

Testicular microlithiasis predicts concurrent testicular germ cell tumors and intratubular germ cell neoplasia of unclassified type in adults: a meta-analysis and systematic review.

Background: There is an increasing body of literature associating testicular microlithiasis (TM), a common finding on testicular ultrasound, with testicular germ cell tumor (TGCT) and intratubular germ cell neoplasia of unclassified type (ITGCNU). Determining these associations is pertinent both clinically and biologically. To the authors' knowledge, no previous systematic review or meta-analysis has been performed.