Analytic Formulas for the Clinical Issues of a UV-Light-Activated Corneal Crosslinking Device

Photo polymerization has been broadly utilized as a part of uses running from synthetic designing to biomedical and biomaterials. It has been utilized forcreation of catheters, amplifiers, surgical veils, medicinal channels, andblood investigation sensors. Photopolymers have additionally been investigated for utilizations in dentistry, drug conveyance, tissue building and cell exemplification frameworks. Bright, unmistakable and infrared lights (360 to 1000 nm) have been utilized as the photo initiators for different photosensitizers.

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Effective Treatment of Currently Intractable Brain Disorders

Many neurological and psychiatric disorders with predominantly cerebral cortical pathology, including most severe strokes, traumatic brain injuries, malignant brain tumors, intractable focal epilepsies and dementias such as Alzheimer’sdisease are currently difficult, if not impossible, to treat. This causes suffering in almost 100 million people worldwide. 

We propose that bioengineered cranial bones with multiple intelligent functions, including sitespecific transmeningeal drug delivery and neurotoxin drainage with EEG feedback, can provide effective treatment of these brain disorders by drug combinations that act on both synapses and genes with concomitant selective drainage of harmful extracellular molecules. After examining and summarizing the rationale andfeasibility of this proposal, we suggest novel methods for extending the functions of the involved components including synergies with existing devices and we highlight relevant preclinical results, discussing medical prospects of this novel neurotherapeutic approach. Finally, we discuss key engineering, scientific, clinical and ethical challenges to introducing bioengineered cranial bones with multiple intelligent functions to the clinic within a decade.

Horizontal Saccadic Eye Movements to Visual and Auditory-Visual Double-Step Stimuli

Tissue tolerable plasma has been used in preclinical and more recently in clinical settings for the debridement of dead tissue and the removal of bacterial biofilms. Cold plasma therapy is an emerging field in medical sciences; it is mainly due to the beneficial effects that lowtemperature plasma has demonstrated anti-inflammatory, ant tumorigenic and anti-microbial effects. The advantage of cold plasma therapy over conventional thermal plasma treatments, arc coagulators and desiccators, is that it allows for more precise application and therefore more controllable effects on the tissue.

Cardiopulmonary Resuscitation as a Graduation Requirement for Biomedical Engineering Students

At the end of a mountain road in Austria during the summer of 2003, I waited for a boat with my family on a dock at a large lake. Suddenly I saw a man fall to the sidewalk. His skin had turned that ashen blue color, andit was clear to me that he was in cardiac arrest. There was a crowd of more than 75 persons just standing and looking at him. I knew what to do when there was no detectable pulse or breathing. 

Cardio-Pulmonary Resuscitation (CPR) chest compressions were started immediately. His skin color returned to nearly normal. After a few minutes, a single bystander came up and said they knew how to do breaths. At that time, recommendations were for intermittent breathing as well as chest compressions. The stricken person made it alive to the EMSvehicle that took nearly 30 minutes to arrive. While I do not know the eventual outcome, I do know he was successfully resuscitated using an Automated External Defibrillator (AED). Furthermore with the quick application of CPR, he likely had a full recovery. Unfortunately, from the crowd response at that time, there were not enough people trained to act in this emergency situation where seconds really count.

The Neural Networks with an Incremental Learning Algorithm

As breast cancer can be very aggressive, only early detection can prevent mortality. The proposed system is to eliminate the unnecessary waiting time aswell as reducing human and technical errors in diagnosing breast cancer. The correct diagnosis of breast cancer is one of the major problems in the medical field. From the literature it has been found that different pattern recognition techniques can help them to improve in this domain. 

This paper uses the neural networks with an incremental learning algorithm as a tool to classify a mass in the breast (benign and malignant) using selection of the most relevant risk factors and decision making of the breast cancer diagnosis To test the proposed algorithm we used the Wisconsin Breast Cancer Database (WBCD). ANN with anincremental learning algorithm performance is tested using classificationaccuracy, sensitivity and specificity analysis, and confusion matrix. The obtained classification accuracy of 99.95%, a very promising result compared with previous algorithms already applied and recent classification techniques applied to the same database.

Stimuli-Responsive Hydrogels Bearing αamino acid Residues

Vinyl hydrogels bearing α-aminoacid residues have been explored as platforms for the treatment of cancer, glaucoma and mood disorder therapies. Ionic/ionizable groups of the L-valine, L-phenylalanine and L-histidine residues are able to modify the swelling properties of the hydrogel on the basis of their thermodynamic characteristics. 

Greater basicity constants of functional groups improve a greater loading of the drug and a longer sustained-release pattern. The pH and the temperature affect the swelling ofthe hydrogel and increase ‘on demand’ the drug availability. A further stimulus based on alternating magnetic fields can be applied on hydrogels containing embedded magnetic nanoparticles used for site-specific controlled drug delivery. 

The diffusion process for the in vitro release of the drug (cisplatin, doxorubicin, pilocarpine, trazodone, citalopram and paroxetine) from the drugloaded hydrogels is mainly controlled by the drug-polymerinteraction, that in the meanwhile preservs it’s bioactivity. The different interaction strength between the drug and the polymer may be a strategy to develop suitable capsules for long-term therapies.

Meta-Analysis of Genomic Data: Between Strengths, Weaknesses and New Perspective

The rapid advances in high-throughput technologies, such as microarrays have revolutionizing theknowledge and understanding of biological systems and genetic signatures of human diseases. This has led to the generation and accumulation of a large amount of genomic data that need to be adequately integrated to obtain more reliable and valid results than those from individual experiments. 

Meta-analysis of microarray data is one of the most common statistical techniques used for combining multiple data sets. Despite its remarkable successes in discovering molecular subtypes, underlying pathways and biomarkers for the pathological process of interest, this method possesses several limitations.

Here, we provided a briefly overview of current meta-analytic approaches together with the basic critical issues in performing meta-analysis of genomic data, with the aim of helpingresearchers to evaluate the quality of existing, published data and obtain more detailed information on what will be the best strategy to adopt to execute a good meta-analysis.

Horizontal Saccadic Eye Movements to Visual and Auditory

Goal-oriented human saccades were recorded under double-step paradigm. The stimuli consisted of either visual or auditory-visual bi-sensory targets. Eye movement data were analyzed based on a 3rd-order linear horizontal saccadic eye movement model, where the inputs to the muscle were agonist and antagonist active-state tensions that were described by pulse-slide-step waveforms with a post inhibitory rebound burst (PIRB) based on a timeoptimal controller. 

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Parameter estimations were calculated using the system identification technique for saccade parameters and neural inputs. Saccade amplitude transition function (ATF) and response latency indicated the saccade programming mechanism. 

The responses were affected by when the second peripheral target was presented. The neural input estimations supported the responsive neuron populations in the superior colliculus under different stimulus conditions, and indicated the double-step visual or auditory-visual stimulus may affect the synchrony of neuron firing. The study described here expanded our previous work and further supported the muscle model as well as the theory of the time-optimal saccade controller under physiological constraints.Read More...

A Bayesian Analysis of Copy Number Variations in Array Comparative Genomic Hybridization Data

Array Comparative Genomic Hybridization (CGH) has been widely used for detecting genomic copy number variations (CNVs). The central goal of array CGH data analysis is to accurately detect homogeneous regions of log intensity ratios which represent relative changes in DNA copy number. Various methods have been proposed in recent years. 

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Most methods, however, do not consider correlations of neighboring probe measurements, and are usually designed for analysis at single sample level rather than detecting common or recurrent CNVs among multiple samples. We propose a Bayesian segment-based approach for efficient analysis of array CGH data. The proposed method is based on simple assumptions but is general enough to accommodate various spatial correlations among probe measurements. 

It also allows for multiple samples with recurrent CNVs, therefore is able to borrow strength across samples. In contrast to another probe-based approach developed in the same Bayesian framework, the segment-based approach parameterizes the mean log intensity ratios in a more appropriate way, which leads to a posterior sampling scheme based on reversible-jump Markov chain Monte Carlo. Want To Read More....

An Ultrasound Based Eye Tracking System

A novel, non-contact ultrasound device is detailed for recording and analyzing 3D fast eye movements (saccades) and smooth pursuit eye movements. Saccades are studied to gain a better understanding of the human oculomotor plant and neuromuscular systems. Abnormal saccades can be indicators of both neurological disorders and mild traumatic brain injury (MTBI). 

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Limitations in existing saccade measurement devices prevent them from being used to measure saccades immediately after a possible MTBI event or easily outside of the clinical environment. The device proposed is portable allowing saccade measurements in the field to immediately assess neurological dysfunction associated with MTBI. 

Ease of use and portability allow collection of data at times and places not possible with devices currently available. This increased database of saccades will expand our knowledge of the relationship between saccades and the neurological functioning of the brain. The focus of this paper is the development of a finite element model to establish a starting point for such a design.Read More.....

Identifying DNA Methylation Variation Patterns to Obtain Potential Breast Cancer Biomarker Genes

Patterns of DNA methylation in human cells are crucial in regulating tumor growth and can be indicative of breast cancer susceptibility. In our research, we have pinpointed genes with significant methylation variation in the breast cancer epigenome to be used as potential novel biomarkers for breast cancer susceptibility. 

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Using the statistical software package R, we compare DNA methylation sequencing data from seven normal individuals with eight breast cancer cell lines. This is done by selecting CG sites, or cytosine-guanine pairings, at which normal cell and cancer cell variation patterns fall in different ranges, and by performing upper one-tailed chi-square tests. 

These selected CG sites are mapped to their corresponding genes. Using the ConsensusPath Database software, we generate genetic pathways with our data to study biological relations between our selected genes and tumorigenic cellular mechanisms. Using breast cancer-related genes from the PubMeth and GeneCards databases, we have discovered 26 potential biomarker genes, which are biologically linked to genes known to be associated with breast cancer. Read More...

Visually Guided Horizontal Saccades under the Double-Step Paradigm

Visually goal-oriented saccades were recorded under the double-step paradigm. Data were analyzed to produce parameter estimates using the system identification technique for a 3rd-order linear horizontal saccadic eye movement model. Statistical analysis of a large human saccade data set provided reliable conclusions of the response properties. 

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Saccade amplitude, latency and inter-saccade interval were discussed with time delay, indicating the parallel programming mechanism, which two saccades to different targets could be programmed simultaneously. The results of neural input estimations suggested that the double-step visual targets may affect the synchronous firing of the saccade responsible neurons in the superior colliculus.

Saccades are the fastest eye movements that enable us to rapidly redirect our line of sight from one target to another one. They are conjugate and ballistic, with a typical duration of 30-100 ms and a latency of 100-300 ms when triggered by visual stimuli. The latency is thought to be the time interval during which the CNS determines whether to make a saccade, and, if so, calculates the distance the eyeball is to be moved, transforming retinal errors into transient muscle activity. Read More.....

Linear Quadratic Tracking Control of Smooth Pursuit Eye Movements

Conventional feedback control models of the oculomotor system fail to account for the destabilizing effects of neural transmission delays. To address this shortcoming, a linear quadratic tracking algorithm used to control smoothly pursuing eye movements of various target trajectories is presented. Based on the type of input to the system, it is shown that stability, in the presence of large motor feedback delays, can be maintained by modulating weighting factors intrinsic to the model. 

Conditions, such as the initial orientation of the eye relative to the location of where a target first becomes salient and the possible oscillatory nature that the reference trajectory may present, play important roles in determining the optimal cost to go motor control strategy at the onset of a tracking movement.

Human perception is the process of acquiring, interpreting, selecting and organizing sensory information to effectively interact with the environment. It is argued that the ability to perceive and direct visual attention to an object that warrants more detailed analysis is the most important of the senses. The oculomotor system has evolved to serve this purpose and, consequently, has important communicative value for studying neuromuscular integration.

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Research involving sensorimotor control seeks to answer the fundamental question: How does our brain select inputs to produce a desired intention and manifest it in the form of movement. The difficulty associated with this question becomes more apparent for multi-body, multi-dimensional systems whose equations of motion are nonlinear and coupled. Since the eye is confined to three rotational degrees of freedom, and because the actions of its extraocular muscles are direct, the oculomotor system provides an initial context for gaining insight into more complex strategies of sensorimotor control.Read More......

A Discriminative Feature Space for Detecting and Recognizing Pathologies of the Vertebral Column

Each year it has become more and more difficult for healthcare providers to determine if a patient has a pathology related to the vertebral column. There is great potential to become more efficient and effective in terms of quality of care provided to patients through the use of automated systems. However, in many cases automated systems can allow for misclassification and force providers to have to review more causes than necessary. In this study, we analyzed methods to increase the True Positives and lower the False Positives while comparing them against stateof- the-art techniques in the biomedical community. We found that by applying the studied techniques of a data-driven model, the benefits to healthcare providers are significant and align with the methodologies and techniques utilized in the current research community.

Over the years there has been an increase in machine learning (ML) techniques, such as Random Forrest (RF), Boosting (ADA), Logistic (GLM), Decision Trees (RPART), Support Vector Machines (SVM), and Artificial Neural Networks (ANN) applied to many medical fields. A significant reason this hasbecome the case is the capacity for human beings to act as diagnostic toolsover time. Stress, fatigue, inefficiencies, and lack of knowledge all become barriers to high- quality outcomes.

There have been studies regarding applications of data mining in different fields, namely: biochemistry, genetics, oncology, neurology and EEG analysis. However, literature suggests that there are few comparisons of machine learning algorithms and techniques in medical and biological areas. Of these ML algorithms, the most common approach to develop nonparametric and nonlinear classifications is based on ANNs.

In general, the numerous methods of machine learning that have been applied can be grouped into two sets: knowledge-driven models and data-driven models. The parameters of the knowledge-driven models are estimated based on the expert knowledge of detecting and recognizing pathologies of the vertebral column. On the other hand, the parameters of data- driven models are estimated based on quantitative measures of associations between evidential features within the data. The classification models used in pathologies of the vertebral column have been SVM.

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ePhenotyping for Abdominal Aortic Aneurysm in the Electronic Medical Records and Genomics (eMERGE) Network

Electronic health records(EHRs) capture a large volume of clinical and physiologic data, and present a valuable resource for research. The “electronic Medical Records and Genomics” (eMERGE) Network was organized by the National Human Genome Research Institute (NHGRI) in 2007 to develop, disseminate, and apply approaches to combine DNA biorepositories with electronic medical record(EMR) systems for large-scale, high-throughput genetic research with the ultimate goal of returning genomic testing results to patients in a clinical care setting. 

To accomplish these goals in the eMERGE Network an important first step is to develop robust algorithms, so called “ePhenotyping” tools, to identify cases and controls directly from the EHR for studies on specific diseases and traits. eMERGE ePhenotypes are developed byone or more primary sites, validated at secondary sites and verified at all other sites that implement them. The results of this rigorous development effort are accurate, robust algorithms that may be used at other sites outside the eMERGE Network.

An abdominal aortic aneurysm (AAA) is a chronic progressively expanding dilatation of the abdominal aorta below the renal arteries and above the iliac artery bifurcation. The Society of Vascular Surgery guidelines define an AAA as a dilatation greater than 3 cm in diameter. Most dilatations expand to exceed the threshold over time and there is an increased risk of rupture with catastrophic consequences when the diameter exceeds 5.5 cm.

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Human-Organoid Models: Accomplishments to Salvage Test-Animals

It takes multi million dollars to develop a new drug as an estimated 1 out of 10,000 chemicals that enter the discovery cycle (Figure 1) ever reaches the market. The rising percentage of late-stage clinical failures (50% in phase 3) is also alarming. The imperative reason for such low success is our inability to represent human tissue in laboratory. Test models like flat surface cell-culture, virtual computational methods and small animals cannot replicate human system; as a consequence the outcome has not been clinically valuable most of the time. Cells accustomed to spatially dynamicmicroenvironment are conventionally studied in isolation; mostly as homogeneous cultures must not be expected to display bona-fide behavior. Engagement of cells with immediate extracellular matrix (ECM) and neighboring cells has been overlooked while evaluating their response to peripheral stimulus; be it in the form of drug or toxin or intrinsic physiological entities like enzymes and hormones. Nevertheless, lack of appropriate ECM milieu has impacted least on in vitro studies related to intracellular molecular-machinery saving us from getting fundamentally wrong.

Non-availability of a flexible 3D system is attributed to be the major obstacle in establishing new standards through organotypic cell culture [3]. Nevertheless, commercial availability of scaffolds like Ultra-Web®, Extracell®, ECM-analog®, BD-Matrigel®, Corning-Matrigel®, Alvetex®, BioVaSc®, Algimatrix® and spheroids of 3D-Biotek® that allow organotypic culture and especially the ones available in conventional plate formats are expected to change the scene.

A dynamic and reciprocal exchange of information between cells and ECM contributes significantly in tissue specific gene expression regulating its morphology and physiology. The hierarchy of ECMmediated signaling in tissue differentiation and physiology is elegantly demonstrated by Bissell et althrough ex vivo modeling of milk secreting mammary glands using Matrigel a tumor derived ECM. We need an efficient cell-interactive scaffold of benign origin, having good shelf-life and stability, for studying cell-ECM dynamics in an experimental micro-environment. Adapting organotype culture could reveal true behavior of cells in real tissue like layout and also elaborate on contextual cell-cell and cell-ECM dynamic relation. Cell- ECM dynamics being at the helm of fundamental understanding of normal vs. abnormal-cell response could thus provide an altogether new meaning to our approach towards therapeutics. Improved comprehension of bi-directional relation of cell with its surrounding milieu has a potential to create a new line of drug design focused on empowering and restoring the natural microenvironment to revert the unhealthy or diseased condition.

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In silico Study of Bacillus brevis Xylanase

The most important building block of hemicelluloses is xylan. It is broken down into xylose oligomer residues by Xylanase - an enzyme, produced by most organisms, to utilize xylose as primary source of carbon. The Xylanase produced are classified into families, viz 5, 8, 10, 11 and 43 - of Glycoside Hydrolases (GH). Xylanase from family GH 11 are monospecific, they consist solely of Xylanase activity, exclusively active on D-xylose containing substrates.They are inactive on aryl cellobiosides. The fungal Xylanase are produced in higher concentrations, as compared to bacterial Xylanase, but have limited use in pulp bleaching, as they affect the viscosity and strength of the product. In the present study, we have worked upon the Xylanase of Bacillus brevis, which is fulfilling all the required quality needed to be a commercial Xylanase, and thus is used by many industries. The enzyme, when studied after modelling, provided similar structural configuration with high stability. When compared with other bacterial and fungal Xylanase structures, it provided better potential to ‘activity enhancement’ and ‘in silico handling’.

Hemicellulose is one of the most important polysaccharide found in the cell wall of the woody plants. It is made up of various building blocks, which are heteropolysaccharides found along with cellulose constituting about 20-30% of the wood dry weight. It is the second most abundant polysaccharide after cellulose. Xylan is built fromhomopolymeric backbone chain of 1, 4-linked β-D-xylopyranose units, including short chains of O-acetyl, α-L-arabinofuranosyl and D-glucuronyl or O-methyl-D-glucuronyl residues. Complete degradation of xylan requires a concerted and synergistic function of several enzymes - including endo-beta-1, 4-D-Xylanase (EC 3.2.1.8). Xylanase break down the xylan into oligoxylose residues, which are utilized by microbes as primary source of carbon.

Different types of Xylanase have been grouped under the category of Glycoside Hydrolases (GH), which are further classified into various families. These families are classified on the basis of similarities in their amino acid sequences and hydrophobic cluster analysis. Xylanase are classified into many families like 5, 8, 10, 11 and 43 of Glycoside Hydrolases. Xylanase are also classified into two groups, based on their molecular weight and pI. One group has low molecular weight <30 kDa and basic pI, while the other group has higher molecular weight >30 kDa and acidic pI. Xylanase from family 10 (GH10) and family 11 (GH11) of Glycoside Hydrolases are the major and beststudied Xylanase.

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A Revolutionary Method of Treatment

A tumor without a supporting network of blood vessel formation is like a car without wheels-it’s not going anywhere!

That was until suddenly, in early March, 2003, when Providence unexpectedly whisked me away from my home in Burbank, CA and guided me directly to the one person, who was to change my life forever so that I would be free of any new or recurring tumors of any variety, have a quality life and even have it extended several years! He is Mr. Nick Kostovic, a pioneer and visionary in energetic medicine, and his health clinic, the Bio Technological Health Center, Inc., in San Pedro, California is where he not only killed my malignant brain tumors, but where this brilliant, caring therapist is helping heal my malignant brain tumors, but where this brilliant, caring therapist is helping heal many other patients by eradicating othertreacherous lifethreatening diseases such as diabetes, cancer, Lou Gehrigs Disease (ALS), Parkinson’s, MS, strokes and more. 

There I found the most knowledgeable, unusual, gifted, medical healer I’ve ever met in all my years of involvement with traditional medicine. This is not to say Western medicine hasn’t helped me in many life threatening crises, it has. What I am saying is that those doctors were not able to heal me as completely as this man has.

A deeply spiritual man once said that “The ultimate, unique sense of an event, and this very truth of the event, will communicate itself only and always when the subject experiencing the event gives himself up to it, all the while trying to understand it. An event revealsitself to those who actively experience it; it reveals itself only in a genuineexperience that rises to the level of the event…” These were the experiences I was to share with Nick Kostovic, a man of great humility and vast knowledge. He inspired me to “rise to the event” by trusting him and God.