High-throughput prescreening of pharmaceuticals using a genome-wide bacterial bioreporter array

Elad, Tal,Seo, Ho Bin,Belkin, Shimshon,Gu, Man Bock Elsevier 2015 Biosensors & bioelectronics Vol.68 No.-

<P><B>Abstract</B></P> <P>We assessed the applicability of multi-strain bacterial bioreporter bioassays to drug screening. To this end, we investigated the reactions of a panel of 15 luminescent recombinant <I>Escherichia coli</I> bacterial bioreporters to a library of 420 pharmaceuticals. The panel included bacterial bioreporters associated with oxidative stress, DNA damage, heat shock, and efflux of excess metals. Eighty nine drugs elicited a response from at least one of the panel members and formed distinctive clusters, some of which contained closely related drugs. In addition, we tested a group of selected nine drugs against a collection of about 2000 different fluorescent transcriptional reporters that covers the great majority of gene promoters in <I>E. coli.</I> The sets of induced genes were in accord with the in vitro toxicity of the tested drugs, as reflected by the response patterns of the 15-member panel, and provided more insights into their toxicity mechanisms. Facilitated by microplates and robotic systems, all assays were conducted in high-throughput. Our results thus suggest that multi-strain assemblages of bacterial bioreporters have the potential for playing a significant role in drug development alongside current in vitro toxicity tests.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We investigated the reactions of bacterial bioreporters to 420 drug library. </LI> <LI> We tested 9 drugs against transcriptional reporters for majority of gene promoters. </LI> <LI> Results suggest that bioreporters have the potential for drug development. </LI> </UL> </P>

Microbial whole‐cell arrays

Elad, Tal,Lee, Jin Hyung,Belkin, Shimshon,Gu, Man Bock Blackwell Publishing Ltd 2008 MICROBIAL BIOTECHNOLOGY -BLACKWELL- Vol.1 No.2

<P><B>Summary</B></P><P>The coming of age of whole‐cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines – the whole‐cell array. In the present review, we highlight the state‐of‐the‐art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high‐performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis and – most importantly – enhanced long‐term maintenance of viability and activity on the fabricated biochips.</P>

IDENTIFYING FUTURE VARIANTS OF FASHION DEMAND: A TREND FORECASTING MODEL FOR MINIMIZING SUPPLY CHAIN COSTS

Michal Koren,Elad Harison,Matan Shnaiderman 글로벌지식마케팅경영학회 2015 Global Fashion Management Conference Vol.2015 No.06

Fashion is primarily based on adoption of trends by consumers in textiles, clothing, footwear, jewelry and art, inter alia. As fashion is based on human preferences, it is characterized by dynamic changes throughout seasons and years, short life cycles, low predictability and high volatility of demand and impulse purchases. In the dynamic environment of apparel markets, fashion firms aim at successfully forecasting both the desirability of new collections and the volumes of each item produced and released to the market under terms of substantial levels of uncertainty. When demand for an item exceeds its supply, the firm is likely to lose additional profits that could have been collected had a sufficient volume of this item been present in the market. Alternatively, if the supply of an item surpassed its demand, it would remain unsold, thereby generating loss equal to its marginal production and distribution costs. The paper proposes a forecasting model that enhances the accuracy of fashion trend forecasting in the context of multiple variants of colour clothing. The model aims at maximizing profits of the firms, while minimizing the forecasting error and reducing the costs that result from excess capacity of production or, alternatively, from loss of potential revenues due to low demand.

THE HERITAGE EFFECT: THE TRANSITION FROM LUXURY TO NEO-LUXURY GOODS IN THE CHINESE MARKET

Yael Pedro,Elad Harison 글로벌지식마케팅경영학회 2017 Global Fashion Management Conference Vol.2017 No.07

The economic growth that East Asian countries (in particular China) experience led to a dramatic increase in the demand for luxury products. The widespread use of them has eliminated to an extent the scarcity effect that distinguishes luxury products from ordinary goods. Yet, these products are largely desired, sought after and distributed with a high price tag, thereupon establishing the new class of neo-luxury products. The current body of knowledge regarding the consumption of luxury products is mostly based on economic and marketing research. There is little reference to the design of luxury goods and even less reference to the effects of design on the perception of luxury goods. Often, marketing research uses terms such as authenticity and aesthetics when defining and describing luxury brands and goods. Nonetheless, “design” is almost completely overlooked in these analyses. Rather, there is an assumption that design is automatically considered an embedded part of luxury creation through words such as “authentic”, “aesthetic” and “heritage.” Nonetheless, looking at the heritage aspects of luxurious products design, one may identify the building blocks that have been present in this market for centuries to create successful brands and products and, during the recent global economic changes, have transform into the new category of mass luxury. This new product category of neo-luxury products should be looked at and analysed as a class of its own, distinct from luxury goods. In this respect, the luxury segment of the Chinese market is particularly interesting, since it had not experienced this genre of consumerism during most of the contemporary history of the western luxury industry post WWII. Thereupon, the new luxury design that addresses this rapidly growing and relatively immature market does it by harnessing the heritage and the conventional framework of luxury and luxury goods in new ways that can referred to as neo-luxury. The role and position of luxury goods are somewhat questioned in today's mass market: Often, in past times, luxury was associated with rarity (or, at least, with singling out an individual user from the masses of consumers of a similar category product). The paper aims at identifying the attributes of the new, rising class of neo-luxury products that distinguish themselves from the “conventional” luxury goods by utilizing qualitative materials and design. In this respect, aspects of heritage play a major role in the strategic design of these products. Further, they assist in establishing, promoting and

고속 동작에 적합한 위상 내삽기 최적화 설계 기술

황혜원(Hye-Won Hwang),Elad Alon,전정훈(Jung-Hoon Chun),권기원(Kee-Won Kwon) 대한전자공학회 2012 電子工學會論文誌-SD (Semiconductor and devices) Vol.49 No.1

본 논문에서는 수학적 해석을 통해 위상 내삽기(Phase Interpolator, PI)를 최적화하는 설계 방법과 인덕터 부하를 이용하여 고속 동작에 적합하도록 개선한 저전력 PI 구조를 제안한다. 정해진 대역폭과 이득을 가지는 PI의 전력이 최소가 되는 설계기준을 공정에 따라 정해지는 상수의 수식으로 제시한다. 또한, 제안된 인덕더 부하를 사용하는 PI구조는 같은 대역폭과 이득에서 소모 전력을 반으로 줄일 수 있다. 0.13㎛ 1.2V CMOS 공정에서 4개의 위상을 가지는 VCO 출력 신호를 이용하여 7-bit PI를 설계한 결과, 인덕터 부하를 사용하고 제안된 설계 기준에 따라 소모 전력을 최적화 하여 12GHz에서 721.2㎼ 소모한다. This paper presents the design optimization technique for a phase interpolator(PI) and suggests the inductor-loaded PI structure for low power consumption suitable for high-speed applications. An analytical study leads to the design criterion composed of the process constants for the minimum power consumption and the proposed inductor-loaded PI reduces the power by half with determined bandwidth and gain of PI. Designed 7-bit PI using 0.13㎛ 1.2V CMOS technology consumes 721.2㎼ in 12GHz with inductor and the suggested optimization technique.

Cyclic behaviour of infilled steel frames with different beam-to-column connection types

Mohammed A. Sakr,Mohammed M. Eladly,Tarek Khalifa,Saher El-Khoriby 국제구조공학회 2019 Steel and Composite Structures, An International J Vol.30 No.5

Although numerous researchers demonstrated the significant difference in performance between the various beam-to-column connection types, most of the previous studies in the area of infilled steel frames focused on the behaviour of frames with welded connections. Therefore, there is a need for conducting studies on infilled steel frames with other common connection types (extended endplate with and without rib stiffeners, flush endplate and shear connections). In this paper, firstly, a two-dimensional finite-element model simulating the cyclic response of infilled steel frames was presented. The infill-frame interaction, as well as the interactions between connections’ components, were properly modelled. Using the previously-validated model, a parametric study on infilled steel frames with five different beam-to-column connection types, under cyclic loading, was carried out. Several parameters, including infill material, fracture energy of masonry and infill thickness, were investigated. The results showed that the infilled frames with welded connections had the highest initial stiffness and load-carrying capacity. However, the infilled frames with extended endplate connections (without rib stiffeners) showed the greatest energy dissipation capacity and about 96% of the load-carrying capacity of frames with welded connections which indicates that this type of connection could have the best performance among the studied connection types. Finally, a simplified analytical model for estimating the stiffness and strength of infilled steel frames (with different beam-to-column connection types) subjected to lateral cyclic loading, was suggested.

Cosmetic outcomes of simple facial laceration suturing in the pediatric emergency department

Eyal Reiss,Yoav Gronovich,Eyal Heiman,Elad Sela,Giora Weiser 대한소아응급의학회 2024 대한소아응급의학회지 Vol.11 No.2

Purpose: The long-term cosmetic outcomes of simple facial lacerations have not been well addressed, specifically regarding those of suturing by pediatric emergency physicians (PEPs) and plastic surgery (PS) residents. Methods: A retrospective study was performed at the pediatric emergency department of Shaare Zedek Medical Center in Jerusalem, Israel. Cosmetic outcomes of simple facial lacerations sutured within 1 year of the study were reviewed using digital photographs taken by legal guardians of children sutured in the department. The photographs were reviewed and rated blindly using the Stony Brook scar score as measures of cosmetic outcomes by 2 plastic surgeons and 1 PEP, as well as the general numeric score (GNS) rated by the guardians and the 3 doctors. The scores were compared between children sutured by PEPs (PEP group) and those sutured by PS residents (PS group). A sample size of 50 children in each study group was calculated to have enough power to show a difference. Results: Among a total of 108 children who participated in the study (median age, 4.0 years [interquartile range, 3.0-7.0]), 57 and 51 were sutured by PEPs and PS residents, respectively. Guardian-rated median GNS showed no difference between the 2 groups (PEP, 90.0 [70.0-95.0] vs. PS, 90.0 [60.0-90.0]; P = 0.310). In contrast, doctor-rated median GNS was higher in the PEP group (PEP, 75.0 [63.3-86.7] vs. PS, 70.0 [53.3-83.3]; P = 0.046). A Stony Brook scar score of 3 or higher was similarly frequent in both groups (PEP, 87.7% vs. PS, 74.5%; P = 0.173) with a low interrater agreement (Kappa = 0.36). Conclusion: Cosmetic outcomes of simple facial lacerations in the pediatric emergency department were favorable regardless of the specialty or expertise of doctors. The guardians were more satisfied with the outcomes, compared to the doctors.

The Immune Landscape of Cancer

Thorsson, Vé,steinn,Gibbs, David L.,Brown, Scott D.,Wolf, Denise,Bortone, Dante S.,Ou Yang, Tai-Hsien,Porta-Pardo, Eduard,Gao, Galen F.,Plaisier, Christopher L.,Eddy, James A.,Ziv, Elad,Culhane, Elsevier 2018 Immunity Vol.48 No.4

<P><B>Summary</B></P> <P>We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (<I>CTNNB1</I>, <I>NRAS</I>, or <I>IDH1</I>) or higher (<I>BRAF</I>, <I>TP53</I>, or <I>CASP8</I>) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Six identified immune subtypes span cancer tissue types and molecular subtypes </LI> <LI> Immune subtypes differ by somatic aberrations, microenvironment, and survival </LI> <LI> Multiple control modalities of molecular networks affect tumor-immune interactions </LI> <LI> These analyses serve as a resource for exploring immunogenicity across cancer types </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>