Early defects in photoreceptor outer segment morphogenesis in zebrafish ift57, ift88 and ift172 Intraflagellar Transport mutants

AbstractIntraflagellar Transport (IFT) refers to a highly conserved process occurring in eukaryotic ciliated structures. In vertebrate photoreceptors, IFT mediates protein trafficking to the outer segments. The IFT particle is a multi-subunit complex and mutations in many individual components causes photoreceptor defects. In zebrafish, mutations in the ift57, ift88, and ift172 genes result in retinal degeneration by 5 days post fertilization (dpf). Although the effects of these mutations on photoreceptor survival have been described, early developmental morphogenesis remains poorly understood. We used transmission electron microscopy and immunohistochemistry to examine these mutants at 60, 72, and 96h post fertilization (hpf) and describe early photoreceptor morphogenesis defects

Network Traffic Behavioral Analytics for Detection of DDoS Attacks

As more organizations and businesses in different sectors are moving to a digital transformation, there is a steady increase in malware, facing data theft or service interruptions caused by cyberattacks on network or application that impact their customer experience. Bot and Distributed Denial of Service (DDoS) attacks consistently challenge every industry relying on the internet. In this paper, we focus on Machine Learning techniques to detect DDoS attack in network communication flows using continuous learning algorithm that learns the normal pattern of network traffic, behavior of the network protocols and identify a compromised network flow. Detection of DDoS attack will help the network administrators to take immediate action and mitigate the impact of such attacks. DDoS attacks are costing enterprises anywhere between $50,000 to$2.3 million per year. We performed experiments with Intrusion Detection Evaluation Dataset (CICIDS2017) available from Canadian Institute for Cybersecurity to detect anomalies in network traffic. We use flow based traffic characteristics to analyze the difference in pattern between normal vs anomaly packet.We evaluate several supervised classification algorithms using metrics like maximum detection accuracy, lowest false negatives prediction, time taken to train and run. We prove that decision tree based Random Forest is the most promising algorithm whereas Dense Neural network performs equally well on certain DDoS types but require more samples to improve the accuracy of low sampled attacks

Molecular Characterisation using 16S rRNA and COI Gene Sequences in Hard Ticks of Gwalior, India

Tick infestation in humans and animals represents a global threat for different tick-borne diseases. In the present study, the ticks from the Gwalior region of India have been mapped to create a database of tick diversity. We explored 773 ticks collected from domestic animals and vegetation in Gwalior. Animals were screened visually, and ticks were collected manually, whereas the flag-drag method was used to collect ticks from the vegetation. The 16S rRNA and cytochrome oxidase I (COI) genes of tick samples were amplified and purified for sequencing and respective phylogenetic trees were constructed. The ticks were morphologically identified using taxonomical keys, revealing the presence of five genera in the region: Hyalomma, Haemaphysalis, Rhipicephalus, Boophilus, and Nosomma. Hyalomma spp. (Hy. annatolicum and Hy. marginatum) were the most abundant accounting for 69.598% of the total sample, followed by Rhipicephalus sanguineus (17.335%), Rhipicephalus microplus (7.115%), Haemaphysalis sp. (5.692%), and Nosomma monstrotum (0.258%). The tick sequences were submitted to the GenBank database. Phylogenetic analysis confirmed the morphological identification at the species level. The combination of molecular and morphological analyses of the ticks supported the result obtained with each method, thus providing more reliable estimates for continued surveillance studies

Extruded and injection moulded virgin PA 6/6 as abrasion resistant material

Polyamide (PA6/6) is often used as a tribological pair in abrasion prevalent applications such as hinges and sliders. PA6/6 is frequently processed by injection moulding and extrusion process. It is known that these processes influence the polymers mechanical behaviour, but their influence on the polymers wear response has not been studied. Hence the present research attempts to study the influence of different manufacturing processes on tribological behaviour for PA6/6. Wear tests were performed on a pin abrading tester (DIN 50322). Abrasion resistance of both extruded and injection moulded PA6/6 were tested at different loads (20 and 35 N). Single-pass (nonoverlapping mode) and multipass testing (overlapping mode) were used to understand the influence of clogging of wear debris. It is evidenced that with increasing load the specific wear rate decreases; moreover, fine abrasives tend to reduce the wear rate. In multipass testing a transfer layer clogged on the counterface that acted as a protective agent and lowers wear rate. Poor mechanical strength of injection moulded polymers is apparently compensated by microstructural response for having a similar wear behaviour between extruded and injection moulded PA 6/6. Hence a proper balance between microstructural and mechanical characteristics is an absolute must in PA 6/6 for better wear performance

A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study

BACKGROUND: Combined treatment with cisplatin and gemcitabine (CisGem) is the standard of care for patients with advanced biliary tract cancer (ABC). Selumetinib (AZD6244, ARRY-142886) potently and selectively inhibits MEK1/2, an intracellular kinase and has shown activity in ABC. The objective of the ABC-04 trial was to establish the recommended dose of selumetinib in combination with CisGem in patients with ABC. METHODS: Eligible patients were ≥ 18 years, had histologically or cytologically-confirmed unresectable recurrent or metastatic biliary tract, gallbladder or ampullary carcinoma, WHO performance status 0-2, and adequate major organ function. Patients may have had prior surgery, radiotherapy or adjuvant chemotherapy, but no prior CisGem and no prior chemotherapy for locally advanced or metastatic disease. Patients received cisplatin 25 mg/m(2) plus gemcitabine 1000 mg/m(2) intravenously on days 1 and 8 of a 21-day cycle. Selumetinib capsules were taken daily. Patients received up to 8 cycles of CisGem and could receive selumetinib until disease progression. A dose de-escalation scheme was used to determine the recommended dose of selumetinib. The first dose level was 75 mg bd. Patients were recruited in cohorts of 3 and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. RESULTS: Thirteen patients were recruited, of whom 12 were evaluable for DLT (1 did not start treatment). All evaluable patients received the starting dose of selumetinib 75 mg bd and one patient experienced a DLT (cardiac chest pain). The median number of days selumetinib was taken (adjusted for the number of days of dose interruptions) was 171.5 (IQR: 75.5 to 344). Two patients remained on treatment at 14 and 19 months post registration. There were 3 temporary and 1 permanent interruptions of selumetinib in cycle 1. Eight patients were evaluable for objective response (RECIST v1.1): 3 had a partial response and 5 stable disease. The median PFS was 6.4 months (IQR 5.2 to 13.7). Toxicities related to selumetinib were mostly related to oedema and rash, grade 1-2 and manageable. Pharmacokinetic analysis showed that the AUC(0-t), AUC(0-∞) and Cmax of selumetinib increased by 12, 11 and 30 % respectively when it was administered with CisGem, while Cmax for the N-desmethyl metabolite of selumetinib decreased by 40 %. There was no evidence that the time of Cmax for selumetinib or N-desmethyl metabolite of selumetinib were different when selumetinib was administered alone or with CisGem. CONCLUSION: The recommended dose of selumetinib when combined with CisGem was 75 mg bd. Translational studies are underway to identify biomarkers that may predict outcome (ClinicalTrials.gov identifier: NCT01242605 July 6(th) 2010)

A bio-inspired microstructure induced by slow injection moulding of cylindrical block copolymers.

It is well known that block copolymers with cylindrical morphology show alignment with shear, resulting in anisotropic mechanical properties. Here we show that well-ordered bi-directional orientation can be achieved in such materials by slow injection moulding. This results in a microstructure, and anisotropic mechanical properties, similar to many natural tissues, making this method attractive for engineering prosthetic fibrous tissues. An application of particular interest to us is prosthetic polymeric heart valve leaflets, mimicking the shape, microstructure and hence performance of the native valve. Anisotropic layers have been observed for cylinder-forming block copolymers centrally injected into thin circular discs. The skin layers exhibit orientation parallel to the flow direction, whilst the core layer shows perpendicularly oriented domains; the balance of skin to core layers can be controlled by processing parameters such as temperature and injection rate. Heart valve leaflets with a similar layered structure have been prepared by injection moulding. Numerical modelling demonstrates that such complex orientation can be explained and predicted by the balance of shear and extensional flow.This is the author-accepted manuscript. It will be under embargo for 12 months after publication. The final version of this article is published by RSC in Soft Matter and can be found here: http://pubs.rsc.org/en/Content/ArticleLanding/2014/SM/C4SM00884G#!divAbstract

Monsoon prawn fishery by 'Matabala' along the Mangalore coast—a critical study

The article presents a report on a critical study about 'Matabala' also known as 'Disco net' (small version of purse seine net made of nylon), a gear used along the Mangalore coast during monsoon period. It was considered that the net was much more size specific to catch large sized prawns