The complexity of human walking: a knee osteoarthritis study.

This study proposes a framework for deconstructing complex walking patterns to create a simple principal component space before checking whether the projection to this space is suitable for identifying changes from the normality. We focus on knee osteoarthritis, the most common knee joint disease and the second leading cause of disability. Knee osteoarthritis affects over 250 million people worldwide.

Proliferation of dinoflagellates in Kochi estuary, Kerala.

Phytoplankton community structure and dynamics of Kochi estuary (bar mouth) have been studied seasonally. Three seasonal samplings namely pre-monsoon, monsoon and post-monsoon were made, and a wide variation was observed in phytoplankton community with respect to nutrients and other physicochemical parameters. Contrary to other seasons, dinoflagellate cell density increased during pre-monsoon season though species diversity was less pronounced (D > 0.

Targeting the PPM1D phenotype; 2,4-bisarylthiazoles cause highly selective apoptosis in PPM1D amplified cell-lines.

The metal-dependent phosphatase PPM1D (WIP1) is an important oncogene in cancer, with over-expression of the protein being associated with significantly worse clinical outcomes. In this communication we describe the discovery and optimization of novel 2,4-bisarylthiazoles that phenocopy the knockdown of PPM1D, without inhibiting its phosphatase activity. These compounds cause growth inhibition at nanomolar concentrations, induce apoptosis, activate p53 and display impressive cell-line selectivity.

Acquisition of Paleolithic toolmaking abilities involves structural remodeling to inferior frontoparietal regions.

Human ancestors first modified stones into tools 2.6 million years ago, initiating a cascading increase in technological complexity that continues today. A parallel trend of brain expansion during the Paleolithic has motivated over 100 years of theorizing linking stone toolmaking and human brain evolution, but empirical support remains limited.

Axonal noise as a source of synaptic variability.

Post-synaptic potential (PSP) variability is typically attributed to mechanisms inside synapses, yet recent advances in experimental methods and biophysical understanding have led us to reconsider the role of axons as highly reliable transmission channels. We show that in many thin axons of our brain, the action potential (AP) waveform and thus the Ca++ signal controlling vesicle release at synapses will be significantly affected by the inherent variability of ion channel gating. We investigate how and to what extent fluctuations in the AP waveform explain observed PSP variability.

Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter.

Sixty-three Arabic patients (16 males and 47 females) with thyroid toxic and nontoxic goiter who attended the endocrinologist in Nuclear Medicine Hospital and Al Yarmok Nuclear Medicine Department in Baghdad, Iraq were examined for thyroid peroxidase (TPO) gene mutations. A total of ten heterozygous mutations have been identified in the human gene associated with thyroid toxic and nontoxic goiter. These mutations involved transition or transversion of cysteine either by thymine or guanine at the position 1708 of the exon 10 (c.

Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1).

The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology.

Aurora isoform selectivity: design and synthesis of imidazo[4,5-b]pyridine derivatives as highly selective inhibitors of Aurora-A kinase in cells.

Aurora-A differs from Aurora-B/C at three positions in the ATP-binding pocket (L215, T217, and R220). Exploiting these differences, crystal structures of ligand-Aurora protein interactions formed the basis of a design principle for imidazo[4,5-b]pyridine-derived Aurora-A-selective inhibitors. Guided by a computational modeling approach, appropriate C7-imidazo[4,5-b]pyridine derivatization led to the discovery of highly selective inhibitors, such as compound 28c, of Aurora-A over Aurora-B.

The use of reinforcement learning algorithms to meet the challenges of an artificial pancreas.

Blood glucose control, for example, in diabetes mellitus or severe illness, requires strict adherence to a protocol of food, insulin administration and exercise personalized to each patient. An artificial pancreas for automated treatment could boost quality of glucose control and patients' independence. The components required for an artificial pancreas are: i) continuous glucose monitoring (CGM), ii) smart controllers and iii) insulin pumps delivering the optimal amount of insulin.

Scaling-laws of human broadcast communication enable distinction between human, corporate and robot Twitter users.

Human behaviour is highly individual by nature, yet statistical structures are emerging which seem to govern the actions of human beings collectively. Here we search for universal statistical laws dictating the timing of human actions in communication decisions. We focus on the distribution of the time interval between messages in human broadcast communication, as documented in Twitter, and study a collection of over 160,000 tweets for three user categories: personal (controlled by one person), managed (typically PR agency controlled) and bot-controlled (automated system).

The effect of cell size and channel density on neuronal information encoding and energy efficiency.

Identifying the determinants of neuronal energy consumption and their relationship to information coding is critical to understanding neuronal function and evolution. Three of the main determinants are cell size, ion channel density, and stimulus statistics. Here we investigate their impact on neuronal energy consumption and information coding by comparing single-compartment spiking neuron models of different sizes with different densities of stochastic voltage-gated Na(+) and K(+) channels and different statistics of synaptic inputs.

CXCR1/CXCR2 antagonism is effective in pulmonary defense against Klebsiella pneumoniae infection.

Klebsiella pneumoniae-associated pathology is largely mediated by neutrophilic inflammation. In this study, we administered Klebsiella pneumoniae to experimental guinea pig groups and the ELR-CXC chemokine antagonist CXCL8(3-72), ceftazidime, and dexamethasone to different groups, respectively. After 24 h, we assessed the animal's pulmonary inflammatory levels, including gross histopathology, airway neutrophilia, lung myeloperoxidase levels, expressions of CXCL8 and TNF, and airway bacterial loads.

Computer assisted diagnostic system in tumor radiography.

An improved and efficient method is presented in this paper to achieve a better trade-off between noise removal and edge preservation, thereby detecting the tumor region of MRI brain images automatically. Compass operator has been used in the fourth order Partial Differential Equation (PDE) based denoising technique to preserve the anatomically significant information at the edges. A new morphological technique is also introduced for stripping skull region from the brain images, which consequently leading to the process of detecting tumor accurately.

Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia.

Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A K(d) = 7.5 nM, Aurora-B K(d) = 48 nM), FLT3 kinase (K(d) = 6.2 nM), and FLT3 mutants including FLT3-ITD (K(d) = 38 nM) and FLT3(D835Y) (K(d) = 14 nM).

Distribution of potentially pathogenic enteric bacteria in coastal sea waters along the Southern Kerala Coast, India.

This study evaluated the relationship between the traditional indicators of faecal pollution, total coliforms (TC), faecal coliforms (FC) and Faecalstreptococci (FS), and the presence of few potentially pathogenic enteric bacteria, Vibrio cholerae (VC), Vibrio parahaemolyticus (VP), Shigella spp. (SH) and Salmonella spp. (SL) in coastal sea water.

Ultra-low-cost 3D gaze estimation: an intuitive high information throughput compliment to direct brain-machine interfaces.

Eye movements are highly correlated with motor intentions and are often retained by patients with serious motor deficiencies. Despite this, eye tracking is not widely used as control interface for movement in impaired patients due to poor signal interpretation and lack of control flexibility. We propose that tracking the gaze position in 3D rather than 2D provides a considerably richer signal for human machine interfaces by allowing direct interaction with the environment rather than via computer displays.

Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs.

Background: Detailed and systematic understanding of the biological effects of millions of available compounds on living cells is a significant challenge. As most compounds impact multiple targets and pathways, traditional methods for analyzing structure-function relationships are not comprehensive enough. Therefore more advanced integrative models are needed for predicting biological effects elicited by specific chemical features.

Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns.

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD(+) acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD(+) human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro.

Awareness among medical fraternity regarding the role of plastic surgeon.

The field of plastic surgery, while being famous for aesthetic surgery, also includes craniofacial surgery, hand surgery, burn surgery, microsurgery, reconstructive plastic surgery and paediatric plastic surgery. The magnanimous progress in these areas, though a hot topic in conferences, remains cryptic to the layman and also to generalists who are and will remain to be the most important referral source of these patients.[1] Hence, it becomes the duty of plastic surgeons themselves to spread awareness regarding their chosen field of endeavour.

Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma.

Motivation: Genome-wide measurement of transcript levels is an ubiquitous tool in biomedical research. As experimental data continues to be deposited in public databases, it is becoming important to develop search engines that enable the retrieval of relevant studies given a query study. While retrieval systems based on meta-data already exist, data-driven approaches that retrieve studies based on similarities in the expression data itself have a greater potential of uncovering novel biological insights.

The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo.

Aurora kinases regulate key stages of mitosis including centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. Aurora A and B kinase overexpression has also been associated with various human cancers, and as such, they have been extensively studied as novel antimitotic drug targets. Here, we characterize the Aurora kinase inhibitor CCT137690, a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinases with low nanomolar IC(50) values in both biochemical and cellular assays and exhibits antiproliferative activity against a wide range of human solid tumor cell lines.

Risk factors in young patients of acute myocardial infarction.

Background: Ischemic heart disease is a leading cause of death throughout the world. CAD has been recognized among younger age group more frequently in recent years. Very limited data is available regarding the prevalence of various risk factors in our younger patients that is why this study was planed.

Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos- and histology-related changes in lung cancer.

Lung cancer has the highest mortality rate of all of the cancers in the world and asbestos-related lung cancer is one of the leading occupational cancers. The identification of asbestos-related molecular changes has long been a topic of increasing research interest. The aim of this study was to identify novel asbestos-related molecular correlates by integrating miRNA expression profiling with previously obtained profiling data (aCGH and mRNA expression) from the same patient material.

On the method of fitting cardiac output kinetics in severe exercise.

The kinetic responses of oxygen uptake (VO₂) and cardiac output (Q) describe the rate at which these physiological variables approach the required steady state value with work rate transitions. In this issue of the Journal, Adami and colleagues examined the kinetic responses during the transition to severe intensity exercise (metabolic demands exceeding maximal VO₂). Two methods were described for fitting VO₂ kinetics: one was an exponential model that referenced the time course of VO₂ relative to an apparent plateau while the second examined the rate of change with respect to the value predicted to be 120% of maximal VO₂.

The manipulative complexity of Lower Paleolithic stone toolmaking.

Background: Early stone tools provide direct evidence of human cognitive and behavioral evolution that is otherwise unavailable. Proper interpretation of these data requires a robust interpretive framework linking archaeological evidence to specific behavioral and cognitive actions.

Methodology/principal Findings: Here we employ a data glove to record manual joint angles in a modern experimental toolmaker (the 4(th) author) replicating ancient tool forms in order to characterize and compare the manipulative complexity of two major Lower Paleolithic technologies (Oldowan and Acheulean).