Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

Monoclonal antibodies represent an exciting class of therapeutics against respiratory viral infections. Notwithstanding their specificity and affinity, the conventional parenteral administration is suboptimal in delivering antibodies for neutralizing activity in the airways due to the poor distribution of macromolecules to the respiratory tract. Inhaled therapy is a promising approach to overcome this hurdle in a noninvasive manner, while advances in antibody engineering have led to the development of unique antibody formats which exhibit properties desirable for inhalation. In this Opinion, we examine the major challenges surrounding the development of inhaled antibodies, identify knowledge gaps that need to be addressed and provide strategies from a drug delivery perspective to enhance the efficacy and safety of neutralizing antibodies against respiratory viral infections

Two maternal origins of Chinese domestic light-body type goose

China is particularly rich in goose genetic resources. The systemic study of genetic diversity and origin of Chinese indigenous geese will provide important scientific basis for the conservation, utilization of resources and human history. The 521 bp control region (D-loop) of mitochondrial DNA from 13 lightbody type breeds was sequenced. The results showed that in the D-loop region of the 13 gray goose breeds, the content of T, C, A and G nucleotides was 23.8, 29.0, 32.2 and 15.1%, respectively. The average haplotype diversity (Hd) and nucleotide diversity (Pi) of domestic geese were 0.2153 and 0.00046, respectively. The 13 light-body type breeds had bigger nucleotide variance value among populations than the value within populations and all the breeds did not exist population expansion.Shared haplotype analysis and systemic systematic evolution analysis revealed that Chinese lightbody type domestic goose owned two maternal origins. YL goose breed originated from greylag goose (anser anser), and the other 12 light- body type goose breeds originated from swan goose (anser cygnoides)

RDD-Eclat: Approaches to Parallelize Eclat Algorithm on Spark RDD Framework

Initially, a number of frequent itemset mining (FIM) algorithms have been designed on the Hadoop MapReduce, a distributed big data processing framework. But, due to heavy disk I/O, MapReduce is found to be inefficient for such highly iterative algorithms. Therefore, Spark, a more efficient distributed data processing framework, has been developed with in-memory computation and resilient distributed dataset (RDD) features to support the iterative algorithms. On the Spark RDD framework, Apriori and FP-Growth based FIM algorithms have been designed, but Eclat-based algorithm has not been explored yet. In this paper, RDD-Eclat, a parallel Eclat algorithm on the Spark RDD framework is proposed with its five variants. The proposed algorithms are evaluated on the various benchmark datasets, which shows that RDD-Eclat outperforms the Spark-based Apriori by many times. Also, the experimental results show the scalability of the proposed algorithms on increasing the number of cores and size of the dataset.Comment: 16 pages, 6 figures, ICCNCT 201

Role of miR-338-5p as a novel modulator of chemoresistannce in esophageal cancer

Conference Theme: Anticancer Drug Action and Drug Resistance: from Cancer Biology to the ClinicINTRODUCTION: Multimodal treatment incorporating surgical resection and the use of chemotherapeutic drugs is commonly used in the management of esophageal cancer. However, resistance to chemotherapy drugs may contribute to poor treatment outcome and cancer recurrence. Increasing evidence suggests that miRNAs regulate the sensitivity of cancer to chemotherapeutic drugs. 5-Fluorouracil (5-FU) is an antimetabolite agent ...postprin

Alpha-Synuclein in bio fluids and tissues as a potential biomarker for Parkinson’s disease

Background: Parkinson's disease (PD) is a chronic neurological disorder that impairs normal motor function and has no cure at present. Diagnosis of PD is clinical only; biopsies confirming the presence of the disease can only be done post-mortem. Furthermore, similarities in the manifestation of PD symptoms to other diseases such as Multiple System Atrophy (MSA), make early diagnosis difficult and ambiguous. As a result, there is a high demand for research investigating biomarkers for timely diagnosis of PD. Alpha-synuclein (α-SYN) is a protein found misfolded in the brain and other body tissues of PD patients. Its relevance and association to PD make it a prime biomarker candidate. However, reports in the literature suggest that the structural form and location of α-SYN are key to yield a reliable diagnosis. The aim of this Minireview is to highlight efforts made in studying α-SYN as a biomarker over the past decade. Key Findings: Based on the literature surveyed, α-SYN was indeed the most widely studied candidate biomarker for PD. Cerebrospinal fluid (CSF) and skin were promising sites for assessing α-SYN effectiveness in differentiating PD from MSA. Furthermore, gastro-intestinal α-SYN was suitable for early diagnosis of PD. A combination of total α-SYN and other forms including but not limited to phosphorylated α-SYN were the best predictors of the disease. Conclusion: Misdiagnosis of patients enrolled in clinical trials is a confounding factor for PD drug development. A robust biomarker for PD will help eradicate this problem. Identifying an accurate biomarker for PD will also ensure timely therapeutic intervention to manage symptoms better and improve the quality of life of patients. The promise α-SYN and its phosphorylated form show in different tissues is a step forward in this direction.published_or_final_versio

An FPTAS for Stochastic Unbounded Min-Knapsack Problem

In this paper, we study the stochastic unbounded min-knapsack problem ($\textbf{Min-SUKP}$). The ordinary unbounded min-knapsack problem states that: There are $n$ types of items, and there is an infinite number of items of each type. The items of the same type have the same cost and weight. We want to choose a set of items such that the total weight is at least $W$ and the total cost is minimized. The \prob~generalizes the ordinary unbounded min-knapsack problem to the stochastic setting, where the weight of each item is a random variable following a known distribution and the items of the same type follow the same weight distribution. In \prob, different types of items may have different cost and weight distributions. In this paper, we provide an FPTAS for $\textbf{Min-SUKP}$, i.e., the approximate value our algorithm computes is at most $(1+\epsilon)$ times the optimum, and our algorithm runs in $poly(1/\epsilon,n,\log W)$ time.Comment: 24 page

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Salicylic acid-based organic dyes acting as the photosensitizer for solar cells

A D-π-A metal-free organic dye, featuring salicylic acid as a novel acceptor/anchoring unit, has been designed, synthesized and applied to dye-sensitized solar cell. The detailed photophysical, electrochemical, photovoltaic and sensitizing properties of the organic dye were investigated, in addition to the computational studies of the dye and dye-(TiO2)6 system. A solar cell device using this new organic dye as a sensitizer produced a solar to electric power conversion efficiency (PCE) of 3.49% (J(sc) = 6.69 mAcm-2, V(oc) = 0.74 V and ff = 0.70) under 100 mWcm(-2) simulated AM 1.5 G solar irradiation, demonstrating that the salicylic acid-based organic dye is a suitable alternative to currently used organometallic dye

Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected by wild-type VZV, this could potentiate recombination events of VZV as well

CAS-MINE: Providing personalized services in context-aware applications by means of generalized rules

Context-aware systems acquire and exploit information on the user context to tailor services to a particular user, place, time, and/or event. Hence, they allowservice providers to adapt their services to actual user needs, by offering personalized services depending on the current user context. Service providers are usually interested in profiling users both to increase client satisfaction and to broaden the set of offered services. Novel and efficient techniques are needed to tailor service supply to the user (or the user category) and to the situation inwhich he/she is involved. This paper presents the CAS-Mine framework to efficiently discover relevant relationships between user context data and currently asked services for both user and service profiling. CAS-Mine efficiently extracts generalized association rules, which provide a high-level abstraction of both user habits and service characteristics depending on the context. A lazy (analyst-provided) taxonomy evaluation performed on different attributes (e.g., a geographic hierarchy on spatial coordinates, a classification of provided services) drives the rule generalization process. Extracted rules are classified into groups according to their semantic meaning and ranked by means of quality indices, thus allowing a domain expert to focus on the most relevant patterns. Experiments performed on three context-aware datasets, obtained by logging user requests and context information for three real applications, show the effectiveness and the efficiency of the CAS-Mine framework in mining different valuable types of correlations between user habits, context information, and provided services