Search results for: Lior Rake
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19

Search results for: Lior Rake

19 Experimental Studies on the Effect of Rake Angle on Turning Ti-6Al-4V with TiAlN Coated Carbides

Authors: Satyanarayana Kosaraju, Venu Gopal Anne, Sateesh Nagari

Abstract:

In this paper, the effect of cutting speed, feedrate and rake angle in tool geometry on cutting forces and temperature generated on the tool tip in turning were investigated. The data used for the investigation derived from experiments conducted on precision lathe according to the full factorial design to observe the effect of each factor level on the process performance. During the tests, depth of cut were kept constant and each test was conducted with a sharp coated tool insert. Ti-6Al-4V was used as the workpiece material. The effects of cutting parameters and tool geometry on cutting forces and tool tip temperature were analyzed. The main cutting force was observed to have a decreasing trend and temperature found to be increasing trend as the rake angle increased.

Keywords: cutting force, tool tip temperature, rake angle, machining

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18 UWB Channel Estimation Using an Efficient Sub-Nyquist Sampling Scheme

Authors: Yaacoub Tina, Youssef Roua, Radoi Emanuel, Burel Gilles

Abstract:

Recently, low-complexity sub-Nyquist sampling schemes based on the Finite Rate of Innovation (FRI) theory have been introduced to sample parametric signals at minimum rates. The multichannel modulating waveforms (MCMW) is such an efficient scheme, where the received signal is mixed with an appropriate set of arbitrary waveforms, integrated and sampled at rates far below the Nyquist rate. In this paper, the MCMW scheme is adapted to the special case of ultra wideband (UWB) channel estimation, characterized by dense multipaths. First, an appropriate structure, which accounts for the bandpass spectrum feature of UWB signals, is defined. Then, a novel approach to decrease the number of processing channels and reduce the complexity of this sampling scheme is presented. Finally, the proposed concepts are validated by simulation results, obtained with real filters, in the framework of a coherent Rake receiver.

Keywords: coherent rake receiver, finite rate of innovation, sub-nyquist sampling, ultra wideband

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17 Maintaining Experimental Consistency in Geomechanical Studies of Methane Hydrate Bearing Soils

Authors: Lior Rake, Shmulik Pinkert

Abstract:

Methane hydrate has been found in significant quantities in soils offshore within continental margins and in permafrost within arctic regions where low temperature and high pressure are present. The mechanical parameters for geotechnical engineering are commonly evaluated in geomechanical laboratories adapted to simulate the environmental conditions of methane hydrate-bearing sediments (MHBS). Due to the complexity and high cost of natural MHBS sampling, most laboratory investigations are conducted on artificially formed samples. MHBS artificial samples can be formed using different hydrate formation methods in the laboratory, where methane gas and water are supplied into the soil pore space under the methane hydrate phase conditions. The most commonly used formation method is the excess gas method which is considered a relatively simple, time-saving, and repeatable testing method. However, there are several differences in the procedures and techniques used to produce the hydrate using the excess gas method. As a result of the difference between the test facilities and the experimental approaches that were carried out in previous studies, different measurement criteria and analyses were proposed for MHBS geomechanics. The lack of uniformity among the various experimental investigations may adversely impact the reliability of integrating different data sets for unified mechanical model development. In this work, we address some fundamental aspects relevant to reliable MHBS geomechanical investigations, such as hydrate homogeneity in the sample, the hydrate formation duration criterion, the hydrate-saturation evaluation method, and the effect of temperature measurement accuracy. Finally, a set of recommendations for repeatable and reliable MHBS formation will be suggested for future standardization of MHBS geomechanical investigation.

Keywords: experimental study, laboratory investigation, excess gas, hydrate formation, standardization, methane hydrate-bearing sediment

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16 A Prediction of Cutting Forces Using Extended Kienzle Force Model Incorporating Tool Flank Wear Progression

Authors: Wu Peng, Anders Liljerehn, Martin Magnevall

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In metal cutting, tool wear gradually changes the micro geometry of the cutting edge. Today there is a significant gap in understanding the impact these geometrical changes have on the cutting forces which governs tool deflection and heat generation in the cutting zone. Accurate models and understanding of the interaction between the work piece and cutting tool leads to improved accuracy in simulation of the cutting process. These simulations are useful in several application areas, e.g., optimization of insert geometry and machine tool monitoring. This study aims to develop an extended Kienzle force model to account for the effect of rake angle variations and tool flank wear have on the cutting forces. In this paper, the starting point sets from cutting force measurements using orthogonal turning tests of pre-machined flanches with well-defined width, using triangular coated inserts to assure orthogonal condition. The cutting forces have been measured by dynamometer with a set of three different rake angles, and wear progression have been monitored during machining by an optical measuring collaborative robot. The method utilizes the measured cutting forces with the inserts flank wear progression to extend the mechanistic cutting forces model with flank wear as an input parameter. The adapted cutting forces model is validated in a turning process with commercial cutting tools. This adapted cutting forces model shows the significant capability of prediction of cutting forces accounting for tools flank wear and different-rake-angle cutting tool inserts. The result of this study suggests that the nonlinear effect of tools flank wear and interaction between the work piece and the cutting tool can be considered by the developed cutting forces model.

Keywords: cutting force, kienzle model, predictive model, tool flank wear

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15 CFD Analysis of an Aft Sweep Wing in Subsonic Flow and Making Analogy with Roskam Methods

Authors: Ehsan Sakhaei, Ali Taherabadi

Abstract:

In this study, an aft sweep wing with specific characteristic feature was analysis with CFD method in Fluent software. In this analysis wings aerodynamic coefficient was calculated in different rake angle and wing lift curve slope to rake angle was achieved. Wing section was selected among NACA airfoils version 6. The sweep angle of wing is 15 degree, aspect ratio 8 and taper ratios 0.4. Designing and modeling this wing was done in CATIA software. This model was meshed in Gambit software and its three dimensional analysis was done in Fluent software. CFD methods used here were based on pressure base algorithm. SIMPLE technique was used for solving Navier-Stokes equation and Spalart-Allmaras model was utilized to simulate three dimensional wing in air. Roskam method is one of the common and most used methods for determining aerodynamics parameters in the field of airplane designing. In this study besides CFD analysis, an advanced aircraft analysis was used for calculating aerodynamic coefficient using Roskam method. The results of CFD were compared with measured data acquired from Roskam method and authenticity of relation was evaluated. The results and comparison showed that in linear region of lift curve there is a minor difference between aerodynamics parameter acquired from CFD to relation present by Roskam.

Keywords: aft sweep wing, CFD method, fluent, Roskam, Spalart-Allmaras model

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14 Efficient Pre-Processing of Single-Cell Assay for Transposase Accessible Chromatin with High-Throughput Sequencing Data

Authors: Fan Gao, Lior Pachter

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The primary tool currently used to pre-process 10X Chromium single-cell ATAC-seq data is Cell Ranger, which can take very long to run on standard datasets. To facilitate rapid pre-processing that enables reproducible workflows, we present a suite of tools called scATAK for pre-processing single-cell ATAC-seq data that is 15 to 18 times faster than Cell Ranger on mouse and human samples. Our tool can also calculate chromatin interaction potential matrices, and generate open chromatin signal and interaction traces for cell groups. We use scATAK tool to explore the chromatin regulatory landscape of a healthy adult human brain and unveil cell-type specific features, and show that it provides a convenient and computational efficient approach for pre-processing single-cell ATAC-seq data.

Keywords: single-cell, ATAC-seq, bioinformatics, open chromatin landscape, chromatin interactome

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13 Experimental and Finite Element Analysis for Mechanics of Soil-Tool Interaction

Authors: A. Armin, R. Fotouhi, W. Szyszkowski

Abstract:

In this paper a 3-D finite element (FE) investigation of soil-blade interaction is described. The effects of blade’s shape and rake angle are examined both numerically and experimentally. The soil is considered as an elastic-plastic granular material with non-associated Drucker-Prager material model. Contact elements with different properties are used to mimic soil-blade sliding and soil-soil cutting phenomena. A separation criterion is presented and a procedure to evaluate the forces acting on the blade is given and discussed in detail. Experimental results were derived from tests using soil bin facility and instruments at the University of Saskatchewan. During motion of the blade, load cells collect data and send them to a computer. The measured forces using load cells had noisy signals which are needed to be filtered. The FE results are compared with experimental results for verification. This technique can be used in blade shape optimization and design of more complicated blade’s shape.

Keywords: finite element analysis, experimental results, blade force, soil-blade contact modeling

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12 A Survey of the Constraints Associated with the Mechanized Tillage of the Fadama Using Animal Drawn Tillage Implements

Authors: L. G. Abubakar, A. M. El-Okene, M. L. Suleiman, Z. Abubakar

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Fadama tillage in Northern Nigeria and in Zaria in particular, has relied on manual labour and corresponding implements which are associated with drudgery, loss of human energy due to bending and reduced productivity. A survey was conducted to study the present tillage practices and determine the constraints associated with the use of animal traction for mechanized tillage of the Fadama. The study revealed that Fadama farmers (mostly aged between 36 and 60 years) use manual labour with tools like small hoe, big hoe and rake to till during the dry season (October of one year to March of the next year). Most of the Fadama farmers believe that tillage operations like ploughing, harrowing and basin making are very important tillage activities in the preparation of seedbeds for crops like green maize, sugarcane and vegetables, but are constrained to using animal traction for tillage due to beliefs like unsuitability of the workbulls and corresponding implements, Fadama soil being too heavy for the system and the non-attainment of deep tillage required by crops like sugarcane and potato. These were affirmed by local blacksmiths of animal traction implements and agricultural officers of government establishments.

Keywords: snimal traction, Fadama, tillage implements, workbulls

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11 Enhance Engineering Learning Using Cognitive Simulator

Authors: Lior Davidovitch

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Traditional training based on static models and case studies is the backbone of most teaching and training programs of engineering education. However, project management learning is characterized by dynamics models that requires new and enhanced learning method. The results of empirical experiments evaluating the effectiveness and efficiency of using cognitive simulator as a new training technique are reported. The empirical findings are focused on the impact of keeping and reviewing learning history in a dynamic and interactive simulation environment of engineering education. The cognitive simulator for engineering project management learning had two learning history keeping modes: manual (student-controlled), automatic (simulator-controlled) and a version with no history keeping. A group of industrial engineering students performed four simulation-runs divided into three identical simple scenarios and one complicated scenario. The performances of participants running the simulation with the manual history mode were significantly better than users running the simulation with the automatic history mode. Moreover, the effects of using the undo enhanced further the learning process. The findings indicate an enhancement of engineering students’ learning and decision making when they use the record functionality of the history during their engineering training process. Furthermore, the cognitive simulator as educational innovation improves students learning and training. The practical implications of using simulators in the field of engineering education are discussed.

Keywords: cognitive simulator, decision making, engineering learning, project management

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10 A Neural Network System for Predicting the Hardness of Titanium Aluminum Nitrite (TiAlN) Coatings

Authors: Omar M. Elmabrouk

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The cutting tool, in the high-speed machining process, is consistently dealing with high localized stress at the tool tip, tip temperature exceeds 800°C and the chip slides along the rake face. These conditions are affecting the tool wear, the cutting tool performances, the quality of the produced parts and the tool life. Therefore, a thin film coating on the cutting tool should be considered to improve the tool surface properties while maintaining its bulks properties. One of the general coating processes in applying thin film for hard coating purpose is PVD magnetron sputtering. In this paper, the prediction of the effects of PVD magnetron sputtering coating process parameters, sputter power in the range of (4.81-7.19 kW), bias voltage in the range of (50.00-300.00 Volts) and substrate temperature in the range of (281.08-600.00 °C), were studied using artificial neural network (ANN). The results were compared with previously published results using RSM model. It was found that the ANN is more accurate in prediction of tool hardness, and hence, it will not only improve the tool life of the tool but also significantly enhances the efficiency of the machining processes.

Keywords: artificial neural network, hardness, prediction, titanium aluminium nitrate coating

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9 Investigating the Influence of Roof Fairing on Aerodynamic Drag of a Bluff Body

Authors: Kushal Kumar Chode

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Increase in demand for fuel saving and demand for faster vehicles with decent fuel economy, researchers around the world started investigating in various passive flow control devices to improve the fuel efficiency of vehicles. In this paper, A roof fairing was investigated for reducing the aerodynamic drag of a bluff body. The bluff body considered for this work is Ahmed model with a rake angle of 25deg was and subjected to flow with a velocity of 40m/s having Reynolds number of 2.68million was analysed using a commercial Computational Fluid Dynamic (CFD) code Star CCM+. It was evident that pressure drag is the main source of drag on an Ahmed body from the initial study. Adding a roof fairing has delayed the flow separation and resulted in delaying wake formation, thus improving the pressure in near weak and reducing the wake region. Adding a roof fairing of height and length equal to 1/7H and 1/3L respectively has shown a drag reduction by 9%. However, an optimised fairing, which was obtained by changing height, length and width by 5% increase, recorded a drag reduction close 12%.

Keywords: Ahmed model, aerodynamic drag, passive flow control, roof fairing, wake formation

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8 Hard Coatings Characterization Based on Chromium Nitrides: Applications for Wood Machining

Authors: B. Chemani, H. Aknouche, A. Zerizer, R. Marchal

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The phenomena occurring during machining are related to the internal friction of the material that deforms and the friction the flake on the rake face of tool. Various researches have been conducted to improve the wear resistance of the tool by thin film deposition. This work aims to present an experimental approach related to wood machining technique to evaluate the wear for the case of ripping Aleppo pine, a species well established in the Mediterranean in general and in Algeria in particular. The study will be done on tungsten carbide cutting tools widely used in woodworking and coated with chrome nitride (CrN) and Chromium Nitride enriched Aluminium (CrAlN) with percentage different of aluminum sputtered through frame magnetron mark Nordiko 3500. The deposition conditions are already optimized by previous studies. The wear tests were performed in the laboratory of ENSAM Cluny (France) on a numerical control ripper of recordi type. This comparative study of the behavior of tools, coated and uncoated, showed that the addition of the aluminum chromium nitride films does not improve the tool ability to resist abrasive wear that is predominant when ripping the Aleppo pine. By against the aluminum addition improves the crystallization of chromium nitride films.

Keywords: Aleppo pine, PVD, coatings, CrAlN, wear

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7 3D Finite Element Analysis for Mechanics of Soil-Tool Interaction

Authors: A. Armin, R. Fotouhi, W. Szyszkowski

Abstract:

This paper is part of a study to develop robots for farming. As such power requirement to operate equipment attach to such robots become an important factor. Soil-tool interaction play major role in power consumption, thus predicting accurately the forces which act on the blade during the farming is prime importance for optimal designing of farm equipment. In this paper a finite element investigation for tillage tools and soil interaction is described by using an inelastic constitutive material law for agriculture application. A 3-dimentional (3D) nonlinear finite element analysis (FEA) is developed to examine behavior of a blade with different rake angles moving in a block of soil, and to estimate the blade force. The soil model considered is an elastic-plastic with non-associated Drucker-Prager material model. Special use of contact elements are employed to consider connection between soil-blade and soil-soil surfaces. The FEA results are compared with experiment ones, which show good agreement in accurately predicting draft forces developed on the blade when it moves through the soil. Also, a very good correlation was obtained between FEA results and analytical results from classical soil mechanics theories for straight blades. These comparisons verified the FEA model developed. For analyzing complicated soil-tool interactions and for optimum design of blades, this method will be useful.

Keywords: finite element analysis, soil-blade contact modeling, blade force, mechanical engineering

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6 Texturing of Tool Insert Using Femtosecond Laser

Authors: Ashfaq Khan, Aftab Khan, Mushtaq Khan, Sarem Sattar, Mohammad A Sheikh, Lin Li

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Chip removal processes are one of key processes of the manufacturing industry where chip removal is conducted by tool inserts of exceptionally hard materials. Tungsten carbide has been extensively used as tool insert for machining processes involving chip removal processes. These hard materials are generally fabricated by single step sintering process as further modification after fabrication in these materials cannot be done easily. Advances in tool surface modification have revealed that advantages such as improved tribological properties and extended tool life can be harnessed from the same tool by texturing the tool rake surface. Moreover, it has been observed that the shape and location of the texture also influences the behavior. Although texturing offers plentiful advantages the challenge lies in the generation of textures on the tool surface. Extremely hard material such as diamond is required to process tungsten carbide. Laser is unique processing tool that does not have a physical contact with the material and thus does not wear. In this research the potential of utilizing laser for texturing of tungsten carbide to develop custom features would be studied. A parametric study of texturing of Tungsten Carbide with a femtosecond laser would be conducted to investigate the process parameters and establish the feasible processing window. The effect of fluence, scan speed and number of repetition would be viewed in detail. Moreover, the mechanism for the generation of features would also be reviewed.

Keywords: laser, texturing, femtosecond, tungsten carbide

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5 De Novo Design of Functional Metalloproteins for Biocatalytic Reactions

Authors: Ketaki D. Belsare, Nicholas F. Polizzi, Lior Shtayer, William F. DeGrado

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Nature utilizes metalloproteins to perform chemical transformations with activities and selectivities that have long been the inspiration for design principles in synthetic and biological systems. The chemical reactivities of metalloproteins are directly linked to local environment effects produced by the protein matrix around the metal cofactor. A complete understanding of how the protein matrix provides these interactions would allow for the design of functional metalloproteins. The de novo computational design of proteins have been successfully used in design of active sites that bind metals like di-iron, zinc, copper containing cofactors; however, precisely designing active sites that can bind small molecule ligands (e.g., substrates) along with metal cofactors is still a challenge in the field. The de novo computational design of a functional metalloprotein that contains a purposefully designed substrate binding site would allow for precise control of chemical function and reactivity. Our research strategy seeks to elucidate the design features necessary to bind the cofactor protoporphyrin IX (hemin) in close proximity to a substrate binding pocket in a four helix bundle. First- and second-shell interactions are computationally designed to control orientation, electronic structure, and reaction pathway of the cofactor and substrate. The design began with a parameterized helical backbone that positioned a single histidine residue (as an axial ligand) to receive a second-shell H-bond from a Threonine on the neighboring helix. The metallo-cofactor, hemin was then manually placed in the binding site. A structural feature, pi-bulge was introduced to give substrate access to the protoporphyrin IX. These de novo metalloproteins are currently being tested for their activity towards hydroxylation and epoxidation. The de novo designed protein shows hydroxylation of aniline to 4-aminophenol. This study will help provide structural information of utmost importance in understanding de novo computational design variables impacting the functional activities of a protein.

Keywords: metalloproteins, protein design, de novo protein, biocatalysis

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4 Orthogonal Metal Cutting Simulation of Steel AISI 1045 via Smoothed Particle Hydrodynamic Method

Authors: Seyed Hamed Hashemi Sohi, Gerald Jo Denoga

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Machining or metal cutting is one of the most widely used production processes in industry. The quality of the process and the resulting machined product depends on parameters like tool geometry, material, and cutting conditions. However, the relationships of these parameters to the cutting process are often based mostly on empirical knowledge. In this study, computer modeling and simulation using LS-DYNA software and a Smoothed Particle Hydrodynamic (SPH) methodology, was performed on the orthogonal metal cutting process to analyze three-dimensional deformation of AISI 1045 medium carbon steel during machining. The simulation was performed using the following constitutive models: the Power Law model, the Johnson-Cook model, and the Zerilli-Armstrong models (Z-A). The outcomes were compared against the simulated results obtained by Cenk Kiliçaslan using the Finite Element Method (FEM) and the empirical results of Jaspers and Filice. The analysis shows that the SPH method combined with the Zerilli-Armstrong constitutive model is a viable alternative to simulating the metal cutting process. The tangential force was overestimated by 7%, and the normal force was underestimated by 16% when compared with empirical values. The simulation values for flow stress versus strain at various temperatures were also validated against empirical values. The SPH method using the Z-A model has also proven to be robust against issues of time-scaling. Experimental work was also done to investigate the effects of friction, rake angle and tool tip radius on the simulation.

Keywords: metal cutting, smoothed particle hydrodynamics, constitutive models, experimental, cutting forces analyses

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3 Estimation of Source Parameters and Moment Tensor Solution through Waveform Modeling of 2013 Kishtwar Earthquake

Authors: Shveta Puri, Shiv Jyoti Pandey, G. M. Bhat, Neha Raina

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TheJammu and Kashmir region of the Northwest Himalaya had witnessed many devastating earthquakes in the recent past and has remained unexplored for any kind of seismic investigations except scanty records of the earthquakes that occurred in this region in the past. In this study, we have used local seismic data of year 2013 that was recorded by the network of Broadband Seismographs in J&K. During this period, our seismic stations recorded about 207 earthquakes including two moderate events of Mw 5.7 on 1st May, 2013 and Mw 5.1 of 2nd August, 2013.We analyzed the events of Mw 3-4.6 and the main events only (for minimizing the error) for source parameters, b value and sense of movement through waveform modeling for understanding seismotectonic and seismic hazard of the region. It has been observed that most of the events are bounded between 32.9° N – 33.3° N latitude and 75.4° E – 76.1° E longitudes, Moment Magnitude (Mw) ranges from Mw 3 to 5.7, Source radius (r), from 0.21 to 3.5 km, stress drop, from 1.90 bars to 71.1 bars and Corner frequency, from 0.39 – 6.06 Hz. The b-value for this region was found to be 0.83±0 from these events which are lower than the normal value (b=1), indicating the area is under high stress. The travel time inversion and waveform inversion method suggest focal depth up to 10 km probably above the detachment depth of the Himalayan region. Moment tensor solution of the (Mw 5.1, 02:32:47 UTC) main event of 2ndAugust suggested that the source fault is striking at 295° with dip of 33° and rake value of 85°. It was found that these events form intense clustering of small to moderate events within a narrow zone between Panjal Thrust and Kishtwar Window. Moment tensor solution of the main events and their aftershocks indicating thrust type of movement is occurring in this region.

Keywords: b-value, moment tensor, seismotectonics, source parameters

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2 Changing the Biopower Hierarchy between Women’s Bodily Knowledge and the Medical Knowledge about the Body: The Case of Female Ejaculation and #Notpee

Authors: Lior B. Navon

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The objective of this study is to investigate how technology, such as social media, can influence the biopower hierarchy between the medical knowledge about the body and women’s bodily knowledge through the case study of the hashtag 'notpee'. In January 2015, the hashtag #notpee, relating to a feminine physiological phenomenon called female ejaculation (FE) or squirting (SQ) started circulating on twitter. This hashtag, born as a reaction to a medical study claiming that SQ is essentially involuntary emission of urine during sexual activity, sparked an unusual public discourse about FE, a phenomenon that is usually not discussed or referred to in socio-legitimate public spheres. This unusual backlash got the attention of women’s magazines and blogs, as well as more mainstream large and respected outlets such as The Guardian and CNN. Both the tweets on twitter, as well as the media coverage of them, were mainly aimed at rejecting the research’s findings. While not offering an alternative and choosing to define the phenomenon by negation, women argued that the fluid extracted was not pee based on their personal experiences. Based on a critical discourse analysis of 742 tweets with the hashtag 'notpee' between January 2015 and January 2016, and of 15 articles covering the backlash, this study suggests that the #notpee backlash challenged the power balance between the medical knowledge about the feminine body and the feminine bodily knowledge through two different, yet related, forms of resistance to biopower. The first resistance is to the authority over knowledge production — who has the power to produce 'true' statements when it comes to the body? Is it the women who experience the phenomenon, or is it the medical institution? The second resistance to biopower has to do with what we regard as facts or veracity. A critical discourse analysis reveals that while both the scientific field, as well as the women arguing against its findings, use empirical information, they, nevertheless, rely on two dichotomic databases- while the scientific research relies on samples from the 'dead like body', these woman are relying on their lived subjective senses as a source for fact making. Nevertheless, while #notpee is asking to change the power relations between the feminine subjective bodily knowledge and the seemingly objective masculine medical knowledge about the body, it by no means dismisses it. These women are essentially asking the medical institution to take into consideration the subjective body as well as the objective one while acknowledging and accepting the power of the latter over knowledge production.

Keywords: biopower, female ejaculation, new media, bodily knowledge

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1 Broad Host Range Bacteriophage Cocktail for Reduction of Staphylococcus aureus as Potential Therapy for Atopic Dermatitis

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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