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Precision measurement of the mass difference between light nuclei and anti-nucle...

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Shashank Tyagi

The basic reliability concepts - parametric ALT plan, failure mechanism and design, acceleration factor, and sample size equation were used in the development of a parametric accelerated life testing method to assess the reliability quantitative test specifications (RQ) of mechanical systems subjected to repetitive stresses. To calculate the acceleration factor of the mechanical system, a generalized life-stress failure model with a new effort concept was derived and recommended. The new sample size equation with the acceleration factor also enabled the parametric ALT to quickly evaluate the expected lifetime. This new parametric ALT should help an engineer uncover the design parameters affecting reliability during the design process of the mechanical system. Consequently, it should help companies improve product reliability and avoid recalls due to the product failures in the field. As the improper design parameters in the design phase are experimentally identified by this new reliability design method and recent patents are addressed, the mechanical system should improve in reliability as measured by the increase in lifetime, LB, and the reduction in failure rate, λ.



Reliability Design of Mechanical Systems Subject to Repetitive Stresses

Bentham Publishers

The Arctic Ocean is warming at two to three times the global rate and is perceived to be a bellwether for ocean acidification. Increased CO2 concentrations are expected to have a fertilization effect on marine autotrophs, and higher temperatures should lead to increased rates of planktonic primary production. Yet, simultaneous assessment of warming and increased CO2 on primary production in the Arctic has not been conducted. Here we test the expectation that CO2-enhanced gross primary production (GPP) may be temperature dependent, using data from several oceanographic cruises and experiments from both spring and summer in the European sector of the Arctic Ocean. Results confirm that CO2 enhances GPP (by a factor of up to ten) over a range of 145–2,099 μatm; however, the greatest effects are observed only at lower temperatures and are constrained by nutrient and light availability to the spring period. The temperature dependence of CO2-enhanced primary production has significant implications for metabolic balance in a warmer, CO2-enriched Arctic Ocean in the future. In particular, it indicates that a twofold increase in primary production during the spring is likely in the Arctic.

Temperature dependence of CO2-enhanced primary production in the European Arctic Ocean

Research Square

The basic reliability concepts - parametric ALT plan, failure mechanism and design, acceleration factor, and sample size equation were used in the development of a parametric accelerated life testing method to assess the reliability quantitative test specifications (RQ) of mechanical systems subjected to repetitive stresses. To calculate the acceleration factor of the mechanical system, a generalized life-stress failure model with a new effort concept was derived and recommended. The new sample size equation with the acceleration factor also enabled the parametric ALT to quickly evaluate the expected lifetime. This new parametric ALT should help an engineer uncover the design parameters affecting reliability during the design process of the mechanical system. Consequently, it should help companies improve product reliability and avoid recalls due to the product failures in the field. As the improper design parameters in the design phase are experimentally identified by this new reliability design method and recent patents are addressed, the mechanical system should improve in reliability as measured by the increase in lifetime, LB, and the reduction in failure rate, λ.

Melanoma is the deadliest skin cancer with ever-increasing incidence. Despite the development in diagnostics and therapies, metastatic melanoma is still associated with significant morbidity and mortality. Oncolytic viruses (OVs) represent a class of novel therapeutic agents for cancer by possessing two closely related properties for tumor reduction: virus-induced lysis of tumor cells and induction of host anti-tumor immune responses. A variety of viruses, either in “natural” or in genetically modified forms, have exhibited a remarkable therapeutic efficacy in regressing melanoma in experimental and/or clinical studies. This review provides a comprehensive summary of the molecular and cellular mechanisms of action of these viruses, which involve manipulating and targeting the abnormalities of melanoma, and can be categorized as enhancing viral tropism, targeting the tumor microenvironment and increasing the innate and adaptive antitumor responses. Additionally, this review describes the “biomarkers” and deregulated pathways of melanoma that are responsible for melanoma initiation, progression and metastasis. Advances in understanding these abnormalities of melanoma have resulted in effective targeted and immuno-therapies, and could potentially be applied for engineering OVs with enhanced oncolytic activity in future.

Targeting melanoma with cancer-killing viruses

PepX is a X-prolyl dipeptidyl aminopeptidase of S15 family that cleaves dipeptides from the N-terminus of polypeptides having a proline or alanine residue at the second position. Involved in bacterial nutrition and in peptide maturation, this serine exopeptidase, counterpart of the mammalian DDP-4, has been proposed to play a role in pathogenicity for Streptococci and to be a promising target against trypanosomes. Searching for specific inhibitors, we undertook docking simulations on the whole surface of PepX from Lactococcus lactis, type example of the S15 family, which revealed a new putative binding site in connection with the active site and involving the C-terminal domain. Accordingly to the results of the computations, we synthesized two peptidomimetics of low molecular weight: the valinephenylpiperazine and the valine-isopropylpiperazine that can accommodate to this putative binding site. Experiments revealed that the valine-phenylpiperazine was an uncompetitive inhibitor whereas the valine-isopropylpiperazine showed to be an activator of the enzyme activity. The valine-phenylpiperazine is interacting with ASN 379, GLU 383, GLU 474, residues in connection with the specificity and active sites, and with the residues from the C-terminal domain LEU 693, GLU 710 and GLN 712. These results point out a role of the C-terminal domain in controlling access to the active site of enzymes of the S15 family, like PepX, the cocaine esterase or the alpha-amino acid ester hydrolase, and could have applications in human health giving new perspectives to struggle against streptococci or trypanosomes by designing inhibitors specific to the S15 family of enzymes.

A New Binding Site Involving the C-terminal Domain to Design Specific Inhibitors of PepX

An asymmetric β‐sheet structure of spider silk is said to induce optical second harmonic generation. In this paper, using an in‐house nonscanning type femtosecond pulse laser second harmonic generation microscope, we characterized the behavior of the β‐sheet of spider silk under an applied external force. The orientation of the β‐sheets was more unidirectional when the silk was extended. One of the origins of the high mechanical strength of the dragline is suggested to be the physical arrangement of its β‐sheets.

Observation of spider silk by femtosecond pulse laser second harmonic generation microscopy

Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-β oligomers (Aβ-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aβ•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its β-secretase cleaving engendering AD-driving Aβ42/Aβ42-os peptides. Aβ•CaSR signalling in NAHAs also drives the release of toxic hyper-phosphorylated Tau proteins in exosomes, and of nitric oxide, and VEGF-A. These several harmful agents comprise the neuron-killing machinery, driving the very slowly spreading AD neurocontagion. VEGF-A over-secretion from Aβ-exposed blood vessel-attached astrocytes induces a functional magnetic resonance imaging- detectable hippocampal neoangiogenesis which indicates approaching AD in amnestic minor cognitive impairment (aMCI) patients. Most important in AD's regard, selective allosteric CaSR antagonists (calcylitics) added to Aβ42/Aβ42-os-exposed NAHAs (or to human neuron cultures) rescue the extracellular shedding of neurotrophic/ neuroprotective sAPPα and suppress all the neurotoxic effects of Aβ•CaSR signalling even when multiple microglial cytokines are also present. Therefore, since the multipotent calcilytics would be reasonably safe and inexpensive drugs for humans, it is worthwhile testing them as AD therapeutics in clinical trials especially in persons in the earliest detectable stages of AD neuropathology progression such as aMCI.

Targeting Human Astrocytes' Calcium-sensing Receptors for Treatment of Alzheimer's Disease

The extreme electro-optical contrast between crystalline and amorphous states in phase-change materials is routinely exploited in optical data storage1 and future applications include universal memories2, flexible displays3, reconfigurable optical circuits4,5, and logic devices6. Optical contrast is believed to arise owing to a change in crystallinity. Here we show that the connection between optical properties and structure can be broken. Using a combination of single-shot femtosecond electron diffraction and optical spectroscopy, we simultaneously follow the lattice dynamics and dielectric function in the phase-change material Ge2Sb2Te5 during an irreversible state transformation. The dielectric function changes by 30% within 100 fs owing to a rapid depletion of electrons from resonantly bonded states. This occurs without perturbing the crystallinity of the lattice, which heats with a 2-ps time constant. The optical changes are an order of magnitude larger than those achievable with silicon and present new routes to manipulate light on an ultrafast timescale without structural changes.

Time-domain separation of optical properties from structural transitions in resonantly bonded materials

Feasible sets play an important role in model predictive control (MPC) optimal control problems (OCPs). This paper proposes a multi-parametric programming-based algorithm to compute the feasible set for OCP derived from MPC-based algorithms involving both spectrahedron (represented by linear matrix inequalities) and polyhedral (represented by a set of inequalities) constraints. According to the geometrical meaning of the inner product of vectors, the maximum length of the projection vector from the feasible set to a unit spherical coordinates vector is computed and the optimal solution has been proved to be one of the vertices of the feasible set. After computing the vertices, the convex hull of these vertices is determined which equals the feasible set. The simulation results show that the proposed method is especially efficient for low dimensional feasible set computation and avoids the non-unicity problem of optimizers as well as the memory consumption problem that encountered by projection algorithms.

Polyhedral feasible set computation of MPC-based optimal control problems

HER2 and VEGF are closely related to the progression of several tumors. The inhibitor simultaneously targeting these two proteins will effectively inhibit the progression of tumors. Here, a bispecific antibody, termed as YY0411, targeting both HER2 and VEGF as a potent anticancer therapeutic antibody is reported. YY0411 is the first bispecific antibody constructed in IgG‐Decoy receptor format. It efficiently identifies and combines both HER2 and VEGF protein. YY0411 is believed to be a candidate tumor suppressor as it significantly inhibits the colony formation ability of human cancer cells (Calu‐3, MDA‐MB‐453, and NCI‐N87 cells). The phosphorylation of HER2 and VEGF downstream components are also decreased in these cells with the treatment of YY0411. Similar to other antibodies, YY0411 has the ability to promote the secretion of IFN‐γ by T lymphocytes. In addition, YY0411 significantly inhibits the growth of Calu‐3 cells‐induced xenograft in nude mice. This work demonstrates that YY0411 may be a potential anti‐lung cancer drug.

Construction of a Novel Bispecific Antibody to Enhance Antitumor Activity against Lung Cancer

Background: The research on use of nanofluids for machining applications has gained more attention for over the past two decades. However there is limited review/data, available on the basis of individual nanoparticles performance, when added as an additive to coolant (cutting fluids)/ lubricant used for machining applications. Hence, this article meticulously attempts to come up with an individual nanoparticle wise review, on a wide range of past and present ongoing research and focuses on affirmative aspects of using nanoparticle added coolants/lubricants (nanofluids) used for metal machining.

Method: Investigations by researchers all around the globe reveal that addition of nanoparticles to coolants/lubricants has shown better heat dissipation ability at the machining zone. In the present work an attempt is made by conducting a study of 102 research papers, to come up with a report on individual nanoparticle wise comprehensive review, on the effect of suspending 11 different nanoparticles in various coolants/lubricants used for machining applications. The article is structured in a cogent way, starting with a brief introduction to nanofluids, followed by an individual nanoparticle wise review. Each review section comprises of introduction to the individual nanoparticle, its distinct properties, its method of synthesis and unique advantage upon addition to coolant/lubricant used for various machining related applications.

Results: Addition of nanometer sized particles in suitable proportions to servo cut oil, canola oil, deionized water, coconut oil, vegetable oil, colza oil and soyabean oil used as coolants for machining of different materials like aerospace alloys, steel(of different grades), nickel based alloys etc. have proved to enhance the machining performance. Out of the 11 different nanoparticles, Al2O3, Gr, MoS2, SiO2 and TiO2 find themselves suitable for maximum machining applications. Use of new coolant supply systems like MQL attempt to promote eco-friendly machining with reduced use of coolants and hence the costs associated with machining.

Conclusion: The present review covers most of the important works done by researchers in the area of nanofluids. Effective applications of MQL techniques for machining, call for high thermal conductivity fluids. Hence, from the past two decades the concept of nanofluids has been a revolutionary and appealing area for the researchers. To summarize nanoparticles as additives to coolants/ lubricants combined with Minimum Quantity Lubrication systems could be useful in performing the machining operations with reduction in cost and pollution.

A Review on Nanofluids for Machining

Choir singing is positively associated with well‐being and quality of life, and requires the coordination of physiological systems within and across individuals. Informed by models of interpersonal action coordination, we delineate the network topography of choir singing by analyzing cross‐frequency couplings and within‐frequency couplings (WFCs) of respiratory, cardiac, vocalizing, and motor subsystems. We find that respiratory and cardiac subsystems synchronize with one another during singing and are coupled to oscillatory vocalizing patterns, and to the hand‐movement oscillations of the choir's conductor. The choir's cross‐frequency connections are particularly strong when singing a canon in parts, apparently supporting the interaction and coordination of the different canon entries. In contrast, WFCs are more pronounced when singing the same canon in unison. We conclude that the temporal coordination dynamics of the observed subsystems form part of the functional substrate for choir singing. During singing, the choir functions as a superordinate system, or superorganism, that imposes boundary conditions on the dynamic features of the individual singers.

Complex networks emerging during choir singing

Intracranial aneurysms are present in 1-5% of population and can be described as “ticking time bombs” that can go off at any time and cause serious harms including permanent disability and death. There are two routinely practiced treatment options for this disease; endovascular coiling and surgical clipping. In recent years other promising methods, such as stent-assisted coiling, flow diverting devices and Onyx embolic agent, have also been developed and tested. The studies reviewed here suggest endovascular coiling to be the most commonly chosen treatment method and that there are reservations on using the newly developed techniques, despite studies suggesting their safety and effectiveness. Therefore, it is now becoming clear that a competent management system, in which treatment methods are chosen to best fit the characterisation of the patient and the aneurysm, should be developed in order to effectively diagnose and treat intracranial aneurysms. One way to develop such a system could be through the advancements of nanotechnology and smart materials. Neurosurgery, like many other areas of the medical field, is moving towards adopting the exciting and rapidly developing technologies based on nanomaterials as the nano-approach to detect and treat intracranial aneurysms could offer surgical opportunities that were more invasive or out of rich at the microneurosurgery level.

  Intracranial Aneurysms; In Need of Early Diagnostic and Treatment Using Bio- and Nanotechnology

Allelopathy plays crucial roles in invasive plant viability and agricultural production systems. However, there is no well‐established hands‐on learning activity to teach the concept of allelopathy. Nor is there an activity which allows students to gain knowledge about glucosinolates and their corresponding enzyme, myrosinase, which are present in almost all Brassica crops. Lettuce germination was counted by the students from three different treatments including water treated with Parafilm sealing, horseradish treated with Parafilm sealing, and horseradish treated without Parafilm sealing. Additionally, lettuce root length was measured by students using ImageJ software from each treatment using pictures captured by students' smartphones. Students took an identical quiz as a pre‐laboratory and a post‐laboratory assignment. Their average scores on the pre‐laboratory and post‐laboratory quizzes were 3.14 and 6.56 out of 10, respectively, indicating the lab activity significantly improved students' understanding of allelopathy and glucosinolate‐myrosinase system. In addition, students (n = 76) completed a survey post‐laboratory to assess their self‐efficacy. This simple and cost‐effective laboratory activity improved students' knowledge and skill development as it made learning more inviting, meaningful, and fun. © 2019 International Union of Biochemistry and Molecular Biology, 1–8, 2019.

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et. al

Reliability Design of Mechanical Systems Subject to Repetitive Stresses

Seong-Woo Woo et. al

Temperature dependence of CO2-enhanced primary production in the European Arctic Ocean

J. M. Holding et. al

Reliability Design of Mechanical Systems Subject to Repetitive Stresses

Seong-Woo Woo et. al

Targeting melanoma with cancer-killing viruses

Tiantian Zhang et. al

A New Binding Site Involving the C-terminal Domain to Design Specific Inhibitors of PepX

Joseph Andre et. al

Observation of spider silk by femtosecond pulse laser second harmonic generation microscopy

Yue Zhao et. al

Targeting Human Astrocytes' Calcium-sensing Receptors for Treatment of Alzheimer's Disease

Anna Chiarini et. al

Time-domain separation of optical properties from structural transitions in resonantly bonded materials

Lutz Waldecker et. al

Polyhedral feasible set computation of MPC-based optimal control problems

Lantao Xie et. al

Construction of a Novel Bispecific Antibody to Enhance Antitumor Activity against Lung Cancer

Wei Yin et. al

A Review on Nanofluids for Machining

Harshit Bhalachandra Kulkarni et. al

Complex networks emerging during choir singing

Viktor Müller et. al

Intracranial Aneurysms; In Need of Early Diagnostic and Treatment Using Bio- and Nanotechnology

Shima Salmasi et. al

Demonstration of allelopathy of horseradish root extract on lettuce seed

Tyler Simpson et. al

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