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2002 International Journal of Reliability, Quality and Safety Engineering (IJRQSE)  
This paper describes how MEADEP, a system level dependability prediction tool, and CASRE, a software reliability growth prediction tool can be used together to predict system reliability (probability of failure in a given time interval), availability (proportion of time service is available), and performability (reward-weighted availability) for a. The system includes COTS hardware, COTS software, radar, and communication gateways. The performability metric also accounts for capacity changes as
more » ... processors in a cluster fail and recover. The Littlewood Verrall and Geometric model is used to predict reliability growth from software test data This prediction is integrated into a system level Markov model that incorporates hardware failures and recoveries, redundancy, coverage failures, and capacity. The results of the combined model can be used to predict the contribution of additional testing upon availability and a variety of other figures of merit that support management decisions.
doi:10.1142/s0218539302000846 fatcat:oisirqokx5bnjplz37i4pjcboq

A Systems Engineering Approach to Exception Handling

Herbert Hecht
2008 Third International Conference on Systems (icons 2008)  
Missing or faulty exception handling has caused a number of spectacular system failures and is a major cause of software failures in extensively tested critical systems. Prior work is reviewed and found lacking in a comprehensive approach at the system level as contrasted with details of exception handling at the programming level. As a path to better understanding of the problem, the needs for exception handling are described as they arise at different times of the development cycle and from
more » ... fferent disciplines. It is seen that a comprehensive solution is difficult but is essential. The details of stating requirements for exception handling are addressed and a methodology for verifying the effectiveness and completeness is described. Further research needs are discussed and the formation of a working group for a best practice or standard on the subject is suggested.
doi:10.1109/icons.2008.77 dblp:conf/icons/Hecht08 fatcat:57owfxcuordwdp7wbpabyunxom

Transient Localized Patterns in Noise-Driven Reaction-Diffusion Systems

Inbal Hecht, David A. Kessler, Herbert Levine
2010 Physical Review Letters  
Noise can induce excitable systems to make transient transitions between quiescent and active states. Here we investigate the possibility that these transitions occur locally in a spatially-extended medium, leading to the occurrence of spatiotemporal patches of activation. We show that this can in fact occur in a parameter range such that there exist (in general unstable) localized solutions of the governing deterministic reaction-diffusion equations. Our work is motivated by a recent
more » ... example showing transiently excited cell membrane regions.
doi:10.1103/physrevlett.104.158301 pmid:20482022 pmcid:PMC2882887 fatcat:wvxujn35aja3llblgam64cd4km

The motility-proliferation-metabolism interplay during metastatic invasion

Inbal Hecht, Sari Natan, Assaf Zaritsky, Herbert Levine, Ilan Tsarfaty, Eshel Ben-Jacob
2015 Scientific Reports  
Metastasis is the major cause for cancer patients' death, and despite all the recent advances in cancer research it is still mostly incurable. Understanding the mechanisms that are involved in the migration of the cells in a complex environment is a key step towards successful anti-metastatic treatment. Using experimental data-based modeling, we focus on the fundamentals of metastatic invasion: motility, invasion, proliferation and metabolism, and study how they may be combined to maximize the
more » ... ancer's ability to metastasize. The modeled cells' performance is measured by the number of cells that succeed in migration in a maze, which mimics the extracellular environment. We show that co-existence of different cell clones in the tumor, as often found in experiments, optimizes the invasive ability in a frequently-changing environment. We study the role of metabolism and stimulation by growth factors, and show that metabolism plays a crucial role in the metastatic process and should therefore be targeted for successful treatment. Despite impressive advances in cancer research and therapy, cancer metastasis is still mostly incurable and is responsible for most patient deaths 1 . Metastasis is a multistep cascade that encompasses several stages: collective-to-individual cellular transition, migration, intravasation, extravasation and colonization at distant organs 2,3 . During the first stage of the metastatic process, single cells of the primary tumor detach and migrate through the extracellular matrix (ECM) toward the blood vessels. Then they are carried away by the blood stream to other locations, where they may be able to colonize the tissue and establish new, secondary tumors. The early metastatic process can be visualized using an intra-vital confocal analysis of a mouse abdomen with a primary mammary tumor (Fig. 1a, red) , surrounded by blood vessels (green). Higher magnification demonstrates small groups of cells spreading from the primary tumor toward the blood vessels, and a micrometastasis is also seen as a red lump separate from the primary tumor but close to a blood vessel. Blocking metastasis is the key for defeating cancer. In order to reach the blood (or lymph) system, the metastatic tumor cells must adopt a motility phenotype that allows them to move through a tortuous extracellular matrix [4] . Metastatic carcinoma cells exhibit at least two different phenotypes of motility and invasion -amoeboid and mesenchymal 4,5 . Mesenchymal motility is aided by the secretion of matrix metalloproteinases (MMPs) 6 . An example of MMP production by a tumor is presented in Fig. 1b , taken from a mouse mammary tumor. Matrix repatterning by MMP-based degradation is mostly important for massive cellular migration, which typically occurs after "forerunner cells" create small microtracks in the ECM, thus allowing other cells to follow more easily 7,8 . The primary tumor cells undergo Epithelial to Mesenchymal Transition (EMT) to
doi:10.1038/srep13538 pmid:26337223 pmcid:PMC4642550 fatcat:cuohajgclrhbnlfslmf6ps5xsu

Correlated phenotypic transitions to competence in bacterial colonies

Inbal Hecht, Eshel Ben-Jacob, Herbert Levine
2007 Physical Review E  
Genetic competence is a phenotypic state of a bacterial cell in which it is capable of importing DNA, presumably to hasten its exploration of alternate genes in its quest for survival under stress. Recently, it was proposed that this transition is uncorrelated among different cells in the colony. Motivated by several discovered signaling mechanisms which create colony-level responses, we present a model for the influence of quorum-sensing signals on a colony of B. Subtilis cells during the
more » ... ition to genetic competence. Coupling to the external signal creates an effective inhibitory mechanism, which results in anti-correlation between the cycles of adjacent cells. We show that this scenario is consistent with the specific experimental measurement, which fails to detect some underlying collective signaling mechanisms. Rather, we suggest other parameters that should be used to verify the role of a quorum-sensing signal. We also study the conditions under which phenotypic spatial patterns may emerge.
doi:10.1103/physreve.76.040901 pmid:17994927 fatcat:onvp55zeyvge5jj4ygei5sqtiu

"Self-Assisted" Amoeboid Navigation in Complex Environments

Inbal Hecht, Herbert Levine, Wouter-Jan Rappel, Eshel Ben-Jacob, Christopher V. Rao
2011 PLoS ONE  
Living cells of many types need to move in response to external stimuli in order to accomplish their functional tasks; these tasks range from wound healing to immune response to fertilization. While the directional motion is typically dictated by an external signal, the actual motility is also restricted by physical constraints, such as the presence of other cells and the extracellular matrix. The ability to successfully navigate in the presence of obstacles is not only essential for organisms,
more » ... but might prove relevant in the study of autonomous robotic motion. Methodology/principal findings: We study a computational model of amoeboid chemotactic navigation under differing conditions, from motion in an obstacle-free environment to navigation between obstacles and finally to moving in a maze. We use the maze as a simple stand-in for a motion task with severe constraints, as might be expected in dense extracellular matrix. Whereas agents using simple chemotaxis can successfully navigate around small obstacles, the presence of large barriers can often lead to agent trapping. We further show that employing a simple memory mechanism, namely secretion of a repulsive chemical by the agent, helps the agent escape from such trapping. Conclusions/significance: Our main conclusion is that cells employing simple chemotactic strategies will often be unable to navigate through maze-like geometries, but a simple chemical marker mechanism (which we refer to as "self-assistance") significantly improves success rates. This realization provides important insights into mechanisms that might be employed by real cells migrating in complex environments as well as clues for the design of robotic navigation strategies. The results can be extended to more complicated multi-cellular systems and can be used in the study of mammalian cell migration and cancer metastasis.
doi:10.1371/journal.pone.0021955 pmid:21829602 pmcid:PMC3150345 fatcat:o5v6pxphnzbkzcanfulfqqglh4

47 Pregnancy, birth, postpartum and their influence on bipolar affective disorder

Eva Schmidt, Karen Hecht, Bernd Reininghaus, Daniela Otti, Karin Reisinger, Herbert Juch, Herranhof, Hans-Peter Kapfhammer
2009 Acta Neuropsychiatrica  
doi:10.1017/s0924270800033287 fatcat:qxjurfn7i5h3xhf7ie74dvwnve

Activated Membrane Patches Guide Chemotactic Cell Motility

Inbal Hecht, Monica L. Skoge, Pascale G. Charest, Eshel Ben-Jacob, Richard A. Firtel, William F. Loomis, Herbert Levine, Wouter-Jan Rappel, Philip E. Bourne
2011 PLoS Computational Biology  
Many eukaryotic cells are able to crawl on surfaces and guide their motility based on environmental cues. These cues are interpreted by signaling systems which couple to cell mechanics; indeed membrane protrusions in crawling cells are often accompanied by activated membrane patches, which are localized areas of increased concentration of one or more signaling components. To determine how these patches are related to cell motion, we examine the spatial localization of RasGTP in chemotaxing
more » ... ostelium discoideum cells under conditions where the vertical extent of the cell was restricted. Quantitative analyses of the data reveal a high degree of spatial correlation between patches of activated Ras and membrane protrusions. Based on these findings, we formulate a model for amoeboid cell motion that consists of two coupled modules. The first module utilizes a recently developed two-component reaction diffusion model that generates transient and localized areas of elevated concentration of one of the components along the membrane. The activated patches determine the location of membrane protrusions (and overall cell motion) that are computed in the second module, which also takes into account the cortical tension and the availability of protrusion resources. We show that our model is able to produce realistic amoeboid-like motion and that our numerical results are consistent with experimentally observed pseudopod dynamics. Specifically, we show that the commonly observed splitting of pseudopods can result directly from the dynamics of the signaling patches.
doi:10.1371/journal.pcbi.1002044 pmid:21738453 pmcid:PMC3127810 fatcat:jofjifiyqbfurdfnd2bflc65qm

54 Anxiety as a special concern in pregnancy and the postpartum period

Eva Schmidt, Bernd Reininghaus, Karin Reisinger, Karen Hecht, Daniela Otti, Brigitte Herranhof, Herbert Juch, Hans-Peter Kapfhammer
2009 Acta Neuropsychiatrica  
, Daniela Otti, Brigitte Herranhof, Herbert Juch & Hans-Peter Kapfhammer Psychiatry, Univ.klinik Graz Auenbruggerplatz 31, 8036 Graz, Austria E-mail: Introduction/Objectives  ...  a pretty common symptom and should not be considered as an aggravation. 54 Anxiety as a special concern in pregnancy and the postpartum period Eva Schmidt, Bernd Reininghaus, Karin Reisinger, Karen Hecht  ... 
doi:10.1017/s0924270800033354 fatcat:h5zhk2jgprb7lc7klyqwnbruqy

Determining the scale of the Bicoid morphogen gradient

Inbal Hecht, Wouter-Jan Rappel, Herbert Levine
2009 Proceedings of the National Academy of Sciences of the United States of America͞cgi͞doi͞10.1073͞pnas.0807655106 Hecht et al. ͉͞cgi͞doi͞10.1073͞pnas.0807655106 Hecht et al.  ... 
doi:10.1073/pnas.0807655106 pmid:19190186 pmcid:PMC2644102 fatcat:cozyo35tkbhzlddoxkpvkn3eza

An Approach for Adaptive Fault Tolerance in Object-Oriented Open Distributed Systems

Eltefaat Shokri, Herbert Hecht, Patrick Crane, Jerry Dussault, K. H. (Kane) Kim
1998 International journal of software engineering and knowledge engineering  
Effective fault-management in emerging complex distributed applications requires the ability to dynamically adapt resource allocation and fault tolerance policies in response to possible changes in environment, application requirements, and available resources. This paper presents an architecture framework of an Adaptive Fault Tolerance Management (AFTM) middleware using a CORBAcompliant object request broker resting on the Solaris open system platform. The paper also discusses approaches which
more » ... have been tested through an AFTM prototyping effort.
doi:10.1142/s0218194098000182 fatcat:ghsl3ckxpzayxk52vij7lz7jpu

Randomised clinical trial of snus versus medicinal nicotine among smokers interested in product switching

Dorothy K Hatsukami, Herbert Severson, Amanda Anderson, Rachael Isaksson Vogel, Joni Jensen, Berry Broadbent, Sharon E Murphy, Steven Carmella, Stephen S Hecht
2015 Tobacco Control  
doi:10.1136/tobaccocontrol-2014-052080 pmid:25991608 pmcid:PMC4785094 fatcat:t4cfzwutofbc5pkh47gqc7p4si

Nucleotide metabolism. VII. The incorporation of radioactivity from orotic acid-6-C14 into ribonucleic acid in cell-free systems from rat liver

1957 Journal of Biological Chemistry  
HERBERT, V. R. POTTER, AND I,. I. HECHT 663 again after Step 6 to obtain an accurate estimate of RNA in the plated sample.  ...  The preparation of the latter columns, the placement of the samples on the column, and the elution procedure for the separation of the acid-soluble nucleotides were those employed by Herbert et al.  ... 
pmid:13416269 fatcat:hfclufeetfcjzokqlt6msjutpu

How Do Brain Areas Communicate During the Processing of Noxious Stimuli? An Analysis of Laser-Evoked Event-Related Potentials Using the Granger Causality Index

Thomas Weiss, Wolfram Hesse, Mihaela Ungureanu, Holger Hecht, Lutz Leistritz, Herbert Witte, Wolfgang H. R. Miltner
2008 Journal of Neurophysiology  
Hecht, D. Spohn, and W.H.R. Miltner, unpublished observations) , with the possibility of distinguishing subparts (e.g., Schweinhardt et al. 2006) .  ... 
doi:10.1152/jn.00912.2007 pmid:18337366 fatcat:oawsqxdzijfppeyymdlyy4n3s4

Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial

Robert Orenstein, Erik R. Dubberke, Sahil Khanna, Christine H. Lee, David Yoho, Stuart Johnson, Gail Hecht, Herbert L. DuPont, Dale N. Gerding, Ken F. Blount, Sarah Mische, Adam Harvey
2022 BMC Infectious Diseases  
Background Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660—a standardized microbiota-based investigational live biotherapeutic—and a closely-matched historical control cohort. Methods This prospective, multicenter, open-label Phase 2 study enrolled patients
more » ... o had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8 weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment. Results In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p < 0.0001; Chi-square test). Post-hoc analysis indicated that 91% (88/97) of evaluable RBX2660 responders remained CDI occurrence-free to 24 months after treatment demonstrating durability. RBX2660 was well-tolerated with mostly mild to moderate adverse events. The composition and diversity of RBX2660 responders' fecal microbiome significantly changed from before to after treatment to become more similar to RBX2660, and these changes were durable to 24 months after treatment. Conclusions In this Phase 2 trial, RBX2660 was safe and effective for reducing rCDI recurrence as compared to a historical control group. Microbiome changes are consistent with restorative changes implicated in resisting C. difficile recurrence. Clinical Trials Registration NCT02589847 (10/28/2015)
doi:10.1186/s12879-022-07256-y pmid:35279084 pmcid:PMC8917640 fatcat:i2nnfqk7rre7ld32wal3rplwia
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