Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 21

Search results for: Moshe Goldberg

21 Influence of Build Orientation on Machinability of Selective Laser Melted Titanium Alloy-Ti-6Al-4V

Authors: Manikandakumar Shunmugavel, Ashwin Polishetty, Moshe Goldberg, Junior Nomani, Guy Littlefair

Abstract:

Selective laser melting (SLM), a promising additive manufacturing (AM) technology, has a huge potential in the fabrication of Ti-6Al-4V near-net shape components. However, poor surface finish of the components fabricated from this technology requires secondary machining to achieve the desired accuracy and tolerance. Therefore, a systematic understanding of the machinability of SLM fabricated Ti-6Al-4V components is paramount to improve the productivity and product quality. Considering the significance of machining in SLM fabricated Ti-6Al-4V components, this research aim is to study the influence of build orientation on machinability characteristics by performing low speed orthogonal cutting tests. In addition, the machinability of SLM fabricated Ti-6Al-4V is compared with conventionally produced wrought Ti-6Al-4V to understand the influence of SLM technology on machining. This paper is an attempt to provide evidence to the hypothesis associated that build orientation influences cutting forces, chip formation and surface integrity during orthogonal cutting of SLM Ti-6Al-4V samples. Results obtained from the low speed orthogonal cutting tests highlight the practical importance of microstructure and build orientation on machinability of SLM Ti-6Al-4V.

Keywords: additive manufacturing, build orientation, machinability, titanium alloys (Ti-6Al-4V)

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20 On the Role of Cutting Conditions on Surface Roughness in High-Speed Thread Milling of Brass C3600

Authors: Amir Mahyar Khorasani, Ian Gibson, Moshe Goldberg, Mohammad Masoud Movahedi, Guy Littlefair

Abstract:

One of the important factors in manufacturing processes especially machining operations is surface quality. Improving this parameter results in improving fatigue strength, corrosion resistance, creep life and surface friction. The reliability and clearance of removable joints such as thread and nuts are highly related to the surface roughness. In this work, the effect of different cutting parameters such as cutting fluid pressure, feed rate and cutting speed on the surface quality of the crest of thread in the high-speed milling of Brass C3600 have been determined. Two popular neural networks containing MLP and RBF coupling with Taguchi L32 have been used to model surface roughness which was shown to be highly adept for such tasks. The contribution of this work is modelling surface roughness on the crest of the thread by using precise profilometer with nanoscale resolution. Experimental tests have been carried out for validation and approved suitable accuracy of the proposed model. Also analysing the interaction of parameters two by two showed that the most effective cutting parameter on the surface value is feed rate followed by cutting speed and cutting fluid pressure.

Keywords: artificial neural networks, cutting conditions, high-speed machining, surface roughness, thread milling

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19 Study of the Mental Toughness of the Basketball Players

Authors: Jaswinder Singh

Abstract:

The purpose of the study was to compare the mental toughness between male and female basketball players of District shri muktsar sahib Panjab. A sample of fifty male players (N=50) age ranging 18 to 25 years and Fifty female player(N=50) age ranging 18 to 25 years. The Data was collected by using mental toughness questionnaire developed by Goldberg (1998). The t-test was applied to assess the differences male and female basketball players. The level of significance was set at 0.05. Study revealed that there were significant differences male and female basketball players with regard to Rebound Ability, Ability to Handle Pressure, Confidence and Overall Mental Toughness and insignificant differences with regard to Concentration and Motivation.

Keywords: mental toughness, basketball, psychological, competitive

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18 GIS-Based Topographical Network for Minimum “Exertion” Routing

Authors: Katherine Carl Payne, Moshe Dror

Abstract:

The problem of minimum cost routing has been extensively explored in a variety of contexts. While there is a prevalence of routing applications based on least distance, time, and related attributes, exertion-based routing has remained relatively unexplored. In particular, the network structures traditionally used to construct minimum cost paths are not suited to representing exertion or finding paths of least exertion based on road gradient. In this paper, we introduce a topographical network or “topograph” that enables minimum cost routing based on the exertion metric on each arc in a given road network as it is related to changes in road gradient. We describe an algorithm for topograph construction and present the implementation of the topograph on a road network of the state of California with ~22 million nodes.

Keywords: topograph, RPE, routing, GIS

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17 Fuel Properties of Distilled Tire Pyrolytic Oil and Its Blends with Biodiesel and Commercial Diesel Fuel

Authors: Moshe Mello, Hilary Rutto, Tumisang Seodigeng

Abstract:

Tires are extremely challenging to recycle due to the available chemically cross-linked polymer which constitutes their nature and therefore, they are neither fusible nor soluble and consequently, cannot be remoulded into other shapes without serious degradation. Pyrolysis of tires produces four valuable products namely; char, steel, tire pyrolytic oil (TPO) and non-condensable gases. TPO has been reported to have similar properties to commercial diesel fuel (CDF). In this study, distillation of TPO was carried out in a batch distillation column and biodiesel was produced from waste cooking oil. FTIR analysis proved that TPO can be used as a fuel due to the available compounds detected and GC analysis displayed 94% biodiesel concentration from waste cooking oil. Different blends of TPO/biodiesel, TPO/CDF and biodiesel/CDF were prepared at different ratios. Fuel properties such as viscosity, density, flash point, and calorific value were studied. Viscosity and density models were also studied to measure the quality of different blends.

Keywords: biodiesel, distillation, pyrolysis, tire

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16 Verifying Environmental Performance through Inventory and Assessment: Case Study of the Los Alamos National Laboratory Waste Compliance and Tracking System

Authors: Oral S. Saulters, Shanon D. Goldberg, Wendy A. Staples, Ellena I. Martinez, Lorie M. Sanchez, Diego E. Archuleta, Deborah L. Williams, Scot D. Johnson

Abstract:

To address an important set of unverified field conditions, the Los Alamos National Laboratory Waste Compliance and Tracking System (WCATS) Wall-to-Wall Team performed an unprecedented and advanced inventory. This reconciliation involved confirmation analysis for approximately 5850 hazardous, low-level, mixed low-level, and transuranic waste containers located in more than 200 staging and storage areas across 33 technical areas. The interdisciplinary team scoped, planned, and developed the multidimensional assessments. Through coordination with cross-functional site hosts, they were able to verify and validate data while resolving discrepancies identified in WCATS. The results were extraordinary with an updated inventory, tailored outreach, more cohesive communications, and timely closed-loop feedback.

Keywords: circular economy, environmental performance data, social-ecological-technological systems, waste management

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15 Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin

Authors: Attapon Kamlangdee, Brock Kingstad-Bakke, Tavis K. Anderson, Tony L. Goldberg, Jorge E. Osorio

Abstract:

A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection post vaccination. Both neutralizing antibodies and antigen-specific CD4+and CD8+ T cells were still detected at 5 months post vaccination, suggesting that MVA-H5M provides long-lasting immunity.

Keywords: modified vaccinia Ankara, MVA, H5N1, hemagglutinin, influenza vaccine

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14 Adsorptive Desulfurization of Tire Pyrolytic Oil Using Cu(I)–Y Zeolite via π-Complexation

Authors: Moshe Mello, Hilary Rutto, Tumisang Seodigeng

Abstract:

The accelerating requirement to reach 0% sulfur content in liquid fuels demands researchers to seek efficient alternative technologies to challenge the predicament. In this current study, the adsorption capabilities of modified Cu(I)-Y zeolite were tested for removal of organosulfur compounds (OSC) present in TPO. The π-complexation-based adsorbent was obtained by ion exchanging Y-zeolite with Cu+ cation using liquid phase ion exchange (LPIE). Preparation of the adsorbent involved firstly ion-exchange between Na-Y zeolite with a Cu(NO3)2 aqueous solution of 0.5M for 48 hours followed by reduction of Cu2+ to Cu+. Batch studies for TPO in comparison with model diesel comprising of sulfur compounds such as thiophene (TH), benzothiophene (BTH), dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophe (4,6-DMDBT) showed that modified Cu(I)-Y zeolite is an effective adsorbent for removal of OSC in liquid fuels. The effect of multiple operating conditions such as adsorbent dosage, reaction time and temperature were studied to optimize the process. For model diesel fuel, the selectivity for adsorption of sulfur compounds followed the order 4,6-DMDBT> DBT> BTH> TH. Interpretation of the results was justified using the molecular orbital theory and calculations. Langmuir and Freundlich isotherms were used to predict adsorption of the reaction mixture. The Cu(I)-Y zeolite is fully regeneratable and this is achieved by a simple procedure of blowing the adsorbent with air at 350 °C, followed by reactivation at 450 °C in a rich helium surrounding.

Keywords: adsorption, desulfurization, TPO, zeolite

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13 A Comparative Study of Mental Toughness among Players of Team and Individual Sports

Authors: P. B. Thumar

Abstract:

Today’s athletes face acute and unique challenges as the competition standards are higher and tougher. There are certain moments during a competition that appear to carry great psychological significance when the momentum starts to shift in one direction or another. These situations require athletes to remain completely focused and calm in facing the difficult circumstances. The purpose of the study was to compare the Mental Toughness level among the players of the team and individual sports. Purposive sampling was done in which subjects for the present study were the male students of The M. S. University of Baroda, Vadodara studying various courses in the academic year 2014-15. Thus, a total number of 120 boys were identified and included in the study from which 60 boys had participated in individual sports and 60 in team sports. ‘The Mental Toughness Questionnaire’ prepared by Dr. Alan Goldberg was used to determine mental toughness level of the players of the team and individual sports. The scores arrived from 60 individual players and 60 team players were compared by applying the t-test. Significant difference was found on overall Mental Toughness and in subcomponents there was significant difference in ability to handle pressure, concentration and confidence whereas there was no significant difference in reboundability and motivation among team and individual sports players. This could be largely due the nature of both sports. Team players of MSU found to be having more overall mental toughness, and team players are able to handle pressure more than individual players, can concentrate more and are also more confident while playing in the team. Team preparation and training prior to competition could have increased the level of ability to handle pressure, concentration and confidence of team players.

Keywords: mental toughness, reboundability, confidence, team sports, individual sports

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12 Role of ABC Transporters in Non-Target Site Herbicide Resistance in Black Grass (Alopecurus myosuroides)

Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

Abstract:

Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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11 Determination of the Runoff Coefficient in Urban Regions, an Example from Haifa, Israel

Authors: Ayal Siegel, Moshe Inbar, Amatzya Peled

Abstract:

This study examined the characteristic runoff coefficient in different urban areas. The main area studied is located in the city of Haifa, northern Israel. Haifa spreads out eastward from the Mediterranean seacoast to the top of the Carmel Mountain range with an elevation of 300 m. above sea level. For this research project, four watersheds were chosen, each characterizing a different part of the city; 1) Upper Hadar, a spacious suburb on the upper mountain side; 2) Qiryat Eliezer, a crowded suburb on a level plane of the watershed; 3) Technion, a large technical research university which is located halfway between the top of the mountain range and the coast line. 4) Keret, a remote suburb, on the southwestern outskirts of Haifa. In all of the watersheds found suitable, instruments were installed to continuously measure the water level flowing in the channels. Three rainfall gauges scattered in the study area complete the hydrological requirements for this research project. The runoff coefficient C in peak discharge events was determined by the Rational Formula. The main research finding is the significant relationship between the intensity of rainfall, and the impervious area which is connected to the drainage system of the watershed. For less intense rainfall, the full potential of the connected impervious area will not be exploited. As a result, the runoff coefficient value decreases as do the peak discharge rate and the runoff yield from the storm event. The research results will enable application to other areas by means of hydrological model to be be set up on GIS software that will make it possible to estimate the runoff coefficient of any given city watershed.

Keywords: runoff coefficient, rational method, time of concentration, connected impervious area.

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10 Safeners, Tools for Artificial Manipulation of Herbicide Selectivity: A Zea mays Case Study

Authors: Sara Franco Ortega, Alina Goldberg Cavalleri, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

Abstract:

Safeners are agrochemicals that enhance the selective chemical control of wild grasses by increasing the ability of the crop to metabolise the herbicide. Although these compounds are widely used, their mode of action is not well understood. It is known that safeners enhance the metabolism of herbicides, by up-regulating the associated detoxification system we have termed the xenome. The xenome proteins involved in herbicide metabolism have been previously divided into four different phases, with cytochrome P450s (CYPs) playing a key role in phase I metabolism by catalysing hydroxylation and dealkylation reactions. Subsequently, glutathione S-transferases (GSTs) and UDP-glucosyltransferases lead to the formation of Phase II conjugates prior to their transport into the vacuole by ABCs transporters (Phase III). Maize (Zea mays), was been treated with different safeners to explore the selective induction of xenome proteins, with a special interest in the regulation of the CYP superfamily. Transcriptome analysis enabled the identification of key safener-inducible CYPs that were then functionally assessed to determine their role in herbicide detoxification. In order to do that, CYP’s were codon optimised, synthesised and inserted into the yeast expression vector pYES3 using in-fusion cloning. CYP’s expressed as recombinant proteins in a strain of yeast engineered to contain the P450 co-enzyme (cytochrome P450 reductase) from Arabidopsis. Microsomes were extracted and treated with herbicides of different chemical classes in the presence of the cofactor NADPH. The reaction products were then analysed by LCMS to identify any herbicide metabolites. The results of these studies will be presented with the key CYPs identified in maize used as the starting point to find orthologs in other crops and weeds to better understand their roles in herbicide selectivity and safening.

Keywords: CYPs, herbicide detoxification, LCMS, RNA-Seq, safeners

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9 Identifying Patterns of Seeking and Providing Help Online among Adolescents in Israel

Authors: Gali Pesin, Yuliya Lipshits-Braziler, Sima Amram-Vaknin, Moshe Tatar

Abstract:

The present study introduces four different patterns of seeking and providing help online among adolescents: (I) ‘Transceivers’ - adolescents who both seek as well as provide help online; (II) ‘Receivers’ - adolescents who seek help online, yet don’t provide it; (III) ‘Transmitters’ - adolescents who provide help online, yet don’t seek it; and (IV) ‘Idles’ - adolescents who refrain from seeking and providing help online. The study examined differences in seeking and providing help online between possible combinations of the four patterns, as well as gender differences within each pattern. Data was collected from 528 adolescents in Israel (59% were girls). Findings revealed that Transceivers are the largest group (45%) in this study, with higher representation of girls (65%). These adolescents seek help mainly around social difficulties, and they turn to peers who are both known and unknown to them. In addition, their preferred way to seek and provide help is through social network sites. Moreover, they often accept and give others emotional support. Receivers are the smallest group (5%) in this study. They turn to both known and unknown professionals more often than to friends and family. In addition, they seek help mostly around health and nutrition issues, and they usually receive instrumental support. For Receivers, the most important factor for seeking help online is anonymity, and the least important factor is familiarity with the help giver. Transmitters represent 16% of the adolescents in this study, with a greater representation of boys (52%). Their main reason to refrain from seeking help online is self-reliance. Nevertheless, these adolescents provide help to others online, mainly to those known to them through posting or responding to posts on social network sites. Idles represent 34% of the adolescents in this study. They refrain from seeking help online mainly due to their preference to seek help face to face, and due to their lack of trust in the internet or those using it. Idles and Transmitters are willing to seek help online mostly from friends and family. In addition, they are willing seek help online mainly regarding questions concerning military or civil service. They consider the most important facilitators for seeking help online as confidentiality and reliability. The present study’s main contribution is exploring the role of providing online help in understanding the adolescent behavior of seeking help online. In addition, the results of the present study have practical implications for the work of mental health providers, such as counseling psychologists and online mental health support.

Keywords: adolescents, counseling, online help-seeking, online help-providing

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8 A Method for Clinical Concept Extraction from Medical Text

Authors: Moshe Wasserblat, Jonathan Mamou, Oren Pereg

Abstract:

Natural Language Processing (NLP) has made a major leap in the last few years, in practical integration into medical solutions; for example, extracting clinical concepts from medical texts such as medical condition, medication, treatment, and symptoms. However, training and deploying those models in real environments still demands a large amount of annotated data and NLP/Machine Learning (ML) expertise, which makes this process costly and time-consuming. We present a practical and efficient method for clinical concept extraction that does not require costly labeled data nor ML expertise. The method includes three steps: Step 1- the user injects a large in-domain text corpus (e.g., PubMed). Then, the system builds a contextual model containing vector representations of concepts in the corpus, in an unsupervised manner (e.g., Phrase2Vec). Step 2- the user provides a seed set of terms representing a specific medical concept (e.g., for the concept of the symptoms, the user may provide: ‘dry mouth,’ ‘itchy skin,’ and ‘blurred vision’). Then, the system matches the seed set against the contextual model and extracts the most semantically similar terms (e.g., additional symptoms). The result is a complete set of terms related to the medical concept. Step 3 –in production, there is a need to extract medical concepts from the unseen medical text. The system extracts key-phrases from the new text, then matches them against the complete set of terms from step 2, and the most semantically similar will be annotated with the same medical concept category. As an example, the seed symptom concepts would result in the following annotation: “The patient complaints on fatigue [symptom], dry skin [symptom], and Weight loss [symptom], which can be an early sign for Diabetes.” Our evaluations show promising results for extracting concepts from medical corpora. The method allows medical analysts to easily and efficiently build taxonomies (in step 2) representing their domain-specific concepts, and automatically annotate a large number of texts (in step 3) for classification/summarization of medical reports.

Keywords: clinical concepts, concept expansion, medical records annotation, medical records summarization

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7 Desulphurization of Waste Tire Pyrolytic Oil (TPO) Using Photodegradation and Adsorption Techniques

Authors: Moshe Mello, Hilary Rutto, Tumisang Seodigeng

Abstract:

The nature of tires makes them extremely challenging to recycle due to the available chemically cross-linked polymer and, therefore, they are neither fusible nor soluble and, consequently, cannot be remolded into other shapes without serious degradation. Open dumping of tires pollutes the soil, contaminates underground water and provides ideal breeding grounds for disease carrying vermins. The thermal decomposition of tires by pyrolysis produce char, gases and oil. The composition of oils derived from waste tires has common properties to commercial diesel fuel. The problem associated with the light oil derived from pyrolysis of waste tires is that it has a high sulfur content (> 1.0 wt.%) and therefore emits harmful sulfur oxide (SOx) gases to the atmosphere when combusted in diesel engines. Desulphurization of TPO is necessary due to the increasing stringent environmental regulations worldwide. Hydrodesulphurization (HDS) is the commonly practiced technique for the removal of sulfur species in liquid hydrocarbons. However, the HDS technique fails in the presence of complex sulfur species such as Dibenzothiopene (DBT) present in TPO. This study aims to investigate the viability of photodegradation (Photocatalytic oxidative desulphurization) and adsorptive desulphurization technologies for efficient removal of complex and non-complex sulfur species in TPO. This study focuses on optimizing the cleaning (removal of impurities and asphaltenes) process by varying process parameters; temperature, stirring speed, acid/oil ratio and time. The treated TPO will then be sent for vacuum distillation to attain the desired diesel like fuel. The effect of temperature, pressure and time will be determined for vacuum distillation of both raw TPO and the acid treated oil for comparison purposes. Polycyclic sulfides present in the distilled (diesel like) light oil will be oxidized dominantly to the corresponding sulfoxides and sulfone via a photo-catalyzed system using TiO2 as a catalyst and hydrogen peroxide as an oxidizing agent and finally acetonitrile will be used as an extraction solvent. Adsorptive desulphurization will be used to adsorb traces of sulfurous compounds which remained during photocatalytic desulphurization step. This desulphurization convoy is expected to give high desulphurization efficiency with reasonable oil recovery.

Keywords: adsorption, asphaltenes, photocatalytic oxidation, pyrolysis

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6 Relatively High Heart-Rate Variability Predicts Greater Survival Chances in Patients with Covid-19

Authors: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

Abstract:

Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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5 Electrohydrodynamic Patterning for Surface Enhanced Raman Scattering for Point-of-Care Diagnostics

Authors: J. J. Rickard, A. Belli, P. Goldberg Oppenheimer

Abstract:

Medical diagnostics, environmental monitoring, homeland security and forensics increasingly demand specific and field-deployable analytical technologies for quick point-of-care diagnostics. Although technological advancements have made optical methods well-suited for miniaturization, a highly-sensitive detection technique for minute sample volumes is required. Raman spectroscopy is a well-known analytical tool, but has very weak signals and hence is unsuitable for trace level analysis. Enhancement via localized optical fields (surface plasmons resonances) on nanoscale metallic materials generates huge signals in surface-enhanced Raman scattering (SERS), enabling single molecule detection. This enhancement can be tuned by manipulation of the surface roughness and architecture at the sub-micron level. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for SERS-based sensing devices. While most SERS substrates are manufactured by conventional lithographic methods, the development of a cost-effective approach to create nanostructured surfaces is a much sought-after goal in the SERS community. Here, a method is established to create controlled, self-organized, hierarchical nanostructures using electrohydrodynamic (HEHD) instabilities. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements. HEHD pattern formation enables the fabrication of multiscale 3D structured arrays as SERS-active platforms. Importantly, each of the HEHD-patterned individual structural units yield a considerable SERS enhancement. This enables each single unit to function as an isolated sensor. Each of the formed structures can be effectively tuned and tailored to provide high SERS enhancement, while arising from different HEHD morphologies. The HEHD fabrication of sub-micrometer architectures is straightforward and robust, providing an elegant route for high-throughput biological and chemical sensing. The superior detection properties and the ability to fabricate SERS substrates on the miniaturized scale, will facilitate the development of advanced and novel opto-fluidic devices, such as portable detection systems, and will offer numerous applications in biomedical diagnostics, forensics, ecological warfare and homeland security.

Keywords: hierarchical electrohydrodynamic patterning, medical diagnostics, point-of care devices, SERS

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4 Work-Family Conflict and Family and Job Resources among Women: The Role of Negotiation

Authors: Noa Nelson, Meitar Moshe, Dana Cohen

Abstract:

Work-family conflict (WFC) is a significant source of stress for contemporary employees, with research indicating its heightened severity for women. The conservation of resources theory argues that individuals experience stress when their resources fall short of demands, and attempt to reach balance by obtaining resources. Presumably then, to achieve work-family balance women would need to negotiate for resources such as spouse support, employer support and work flexibility. The current research tested the hypotheses that competent negotiation at home and at work associated with increased family and job resources and with decreased WFC, as well as with higher work, marital and life satisfaction. In the first study, 113 employed mothers, married or cohabiting, reported to what extent they conducted satisfactory negotiation with spouse over division of housework, and their actual housework load compared to spouse. They answered a WFC questionnaire, measuring how much work interferes with family (WIF) and how much family interferes with work (FIW), and finally, measurements of satisfaction. In the second study, 94 employed mothers, married or cohabiting reported to what extent they conducted satisfactory negotiation with their boss over balancing work demands with family needs. They reported the levels of three job resources: flexibility, control and family-friendly organizational culture. Finally, they answered the same WFC and satisfaction measurements from study 1. Statistical analyses –t-tests, correlations, and hierarchical linear regressions- showed that in both studies, women reported higher WIF than FIW. Negotiations associated with increased resources: support from spouse, work flexibility and control and a family-friendly culture; negotiation with spouse associated also with satisfaction measurements. However, negotiations or resources (except family-friendly culture) did not associate with reduced conflict. The studies demonstrate the role of negotiation in obtaining family and job resources. Causation cannot be determined, but the fact is that employed mothers who enjoyed more support (at both home and work), flexibility and control, were more likely to keep active interactions to increase them. This finding has theoretical and practical implications, especially in view of research on female avoidance of negotiation. It is intriguing that negotiations and resources generally did not associate with reduced WFC. This finding might reflect the severity of the conflict, especially of work interfering with family, which characterizes many contemporary jobs. It might also suggest that employed mothers have high expectations from themselves, and even under supportive circumstances, experience the challenge of balancing two significant and demanding roles. The research contributes to the fields of negotiation, gender, and work-life balance. It calls for further studies, to test its model in additional populations and validate the role employees have in actively negotiating for the balance that they need. It also calls for further research to understand the contributions of job and family resources to reducing work-family conflict, and the circumstances under which they contribute.

Keywords: sork-family conflict, work-life balance, negotiation, gender, job resources, family resources

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3 Carbon Nanotubes (CNTs) as Multiplex Surface Enhanced Raman Scattering Sensing Platforms

Authors: Pola Goldberg Oppenheimer, Stephan Hofmann, Sumeet Mahajan

Abstract:

Owing to its fingerprint molecular specificity and high sensitivity, surface-enhanced Raman scattering (SERS) is an established analytical tool for chemical and biological sensing capable of single-molecule detection. A strong Raman signal can be generated from SERS-active platforms given the analyte is within the enhanced plasmon field generated near a noble-metal nanostructured substrate. The key requirement for generating strong plasmon resonances to provide this electromagnetic enhancement is an appropriate metal surface roughness. Controlling nanoscale features for generating these regions of high electromagnetic enhancement, the so-called SERS ‘hot-spots’, is still a challenge. Significant advances have been made in SERS research, with wide-ranging techniques to generate substrates with tunable size and shape of the nanoscale roughness features. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for miniaturised sensing devices. Carbon nanotubes (CNTs) have been concurrently, a topic of extensive research however, their applications for plasmonics has been only recently beginning to gain interest. CNTs can provide low-cost, large-active-area patternable substrates which, coupled with appropriate functionalization capable to provide advanced SERS-platforms. Herein, advanced methods to generate CNT-based SERS active detection platforms will be discussed. First, a novel electrohydrodynamic (EHD) lithographic technique will be introduced for patterning CNT-polymer composites, providing a straightforward, single-step approach for generating high-fidelity sub-micron-sized nanocomposite structures within which anisotropic CNTs are vertically aligned. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements with each of the EHD-CNTs individual structural units functioning as an isolated sensor. Further, gold-functionalized VACNTFs are fabricated as SERS micro-platforms. The dependence on the VACNTs’ diameters and density play an important role in the Raman signal strength, thus highlighting the importance of structural parameters, previously overlooked in designing and fabricating optimized CNTs-based SERS nanoprobes. VACNTs forests patterned into predesigned pillar structures are further utilized for multiplex detection of bio-analytes. Since CNTs exhibit electrical conductivity and unique adsorption properties, these are further harnessed in the development of novel chemical and bio-sensing platforms.

Keywords: carbon nanotubes (CNTs), EHD patterning, SERS, vertically aligned carbon nanotube forests (VACNTF)

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2 High-Resolution Facial Electromyography in Freely Behaving Humans

Authors: Lilah Inzelberg, David Rand, Stanislav Steinberg, Moshe David Pur, Yael Hanein

Abstract:

Human facial expressions carry important psychological and neurological information. Facial expressions involve the co-activation of diverse muscles. They depend strongly on personal affective interpretation and on social context and vary between spontaneous and voluntary activations. Smiling, as a special case, is among the most complex facial emotional expressions, involving no fewer than 7 different unilateral muscles. Despite their ubiquitous nature, smiles remain an elusive and debated topic. Smiles are associated with happiness and greeting on one hand and anger or disgust-masking on the other. Accordingly, while high-resolution recording of muscle activation patterns, in a non-interfering setting, offers exciting opportunities, it remains an unmet challenge, as contemporary surface facial electromyography (EMG) methodologies are cumbersome, restricted to the laboratory settings, and are limited in time and resolution. Here we present a wearable and non-invasive method for objective mapping of facial muscle activation and demonstrate its application in a natural setting. The technology is based on a recently developed dry and soft electrode array, specially designed for surface facial EMG technique. Eighteen healthy volunteers (31.58 ± 3.41 years, 13 females), participated in the study. Surface EMG arrays were adhered to participant left and right cheeks. Participants were instructed to imitate three facial expressions: closing the eyes, wrinkling the nose and smiling voluntary and to watch a funny video while their EMG signal is recorded. We focused on muscles associated with 'enjoyment', 'social' and 'masked' smiles; three categories with distinct social meanings. We developed a customized independent component analysis algorithm to construct the desired facial musculature mapping. First, identification of the Orbicularis oculi and the Levator labii superioris muscles was demonstrated from voluntary expressions. Second, recordings of voluntary and spontaneous smiles were used to locate the Zygomaticus major muscle activated in Duchenne and non-Duchenne smiles. Finally, recording with a wireless device in an unmodified natural work setting revealed expressions of neutral, positive and negative emotions in face-to-face interaction. The algorithm outlined here identifies the activation sources in a subject-specific manner, insensitive to electrode placement and anatomical diversity. Our high-resolution and cross-talk free mapping performances, along with excellent user convenience, open new opportunities for affective processing and objective evaluation of facial expressivity, objective psychological and neurological assessment as well as gaming, virtual reality, bio-feedback and brain-machine interface applications.

Keywords: affective expressions, affective processing, facial EMG, high-resolution electromyography, independent component analysis, wireless electrodes

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1 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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