Microfluidic fabrication of advanced microcapsules for use in self-healing materials

The proposed work aims to facilitate the development of a microfluidic platform for the production of advanced microcapsules containing active agents which can be the functional constituents of self-healing composites. The creation of such microcapsules is enabled by the unique flow characteristics within microchannels including precise control over shear and interfacial forces for droplet creation and manipulation as well as the ability to form a solid shell either chemically or via the addition of thermal or irradiative energy. Microchannel design and a study of the fluid dynamics and mechanisms for shell creation are undertaken in order to establish a fabrication approach capable of producing healing-agent-containing microcapsules. An in-depth study of the process parameters has been undertaken in order to elucidate the advantages of this production technique including precise control of size (i.e., monodispersity) and surface morphology of the microcapsules. This project also aims to aid the optimization of the mechanical properties as well as healing performance of self-healing composites by studying the effects of the advantageous properties of the as-produced microcapsules. Scale-up of the microfluidic fabrication using parallel devices on a single chip as well as on-chip microcapsule production and shape control will also be investigated. It will be demonstrated that microfluidic fabrication is a versatile approach for the efficient creation of functional microcapsules allowing for superior design of self-healing composites.

NON-CHROMATOGRAPHIC PURIFICATION OF SYNTHETIC BIO-OLIGOMERS

Synthetic oligonucleotides and peptides have found wide applications in industry and academic research labs. There are ~60 peptide drugs on the market and over 500 under development. The global annual sale of peptide drugs in 2010 was estimated to be $13 billion. There are three oligonucleotide-based drugs on market; among them, the FDA newly approved Kynamro was predicted to have a $100 million annual sale. The annual sale of oligonucleotides to academic labs was estimated to be $700 million. Both bio-oligomers are mostly synthesized on automated synthesizers using solid phase synthesis technology, in which nucleoside or amino acid monomers are added sequentially until the desired full-length sequence is reached. The additions cannot be complete, which generates truncated undesired failure sequences. For almost all applications, these impurities must be removed. The most widely used method is HPLC. However, the method is slow, expensive, labor-intensive, not amendable for automation, difficult to scale up, and unsuitable for high throughput purification. It needs large capital investment, and consumes large volumes of harmful solvents. The purification costs are estimated to be more than 50% of total production costs. Other methods for bio-oligomer purification also have drawbacks, and are less favored than HPLC for most applications. To overcome the problems of known biopolymer purification technologies, we have developed two non-chromatographic purification methods. They are (1) catching failure sequences by polymerization, and (2) catching full-length sequences by polymerization. In the first method, a polymerizable group is attached to the failure sequences of the bio-oligomers during automated synthesis; purification is achieved by simply polymerizing the failure sequences into an insoluble gel and extracting full-length sequences. In the second method, a polymerizable group is attached to the full-length sequences, which are then incorporated into a polymer; impurities are removed by washing, and pure product is cleaved from polymer. These methods do not need chromatography, and all drawbacks of HPLC no longer exist. Using them, purification is achieved by simple manipulations such as shaking and extraction. Therefore, they are suitable for large scale purification of oligonucleotide and peptide drugs, and also ideal for high throughput purification, which currently has a high demand for research projects involving total gene synthesis. The dissertation will present the details about the development of the techniques. Chapter 1 will make an introduction to oligodeoxynucleotides (ODNs), their synthesis and purification. Chapter 2 will describe the detailed studies of using the catching failure sequences by polymerization method to purify ODNs. Chapter 3 will describe the further optimization of the catching failure sequences by polymerization ODN purification technology to the level of practical use. Chapter 4 will present using the catching full-length sequence by polymerization method for ODN purification using acid-cleavable linker. Chapter 5 will make an introduction to peptides, their synthesis and purification. Chapter 6 will describe the studies using the catching full-length sequence by polymerization method for peptide purification.

Paediatric antiretroviral treatment programmes in sub-Saharan Africa: a review of published clinical studies

Knowledge of the experience and outcomes of current paediatric antiretroviral treatment (ART) programmes in sub-Saharan Africa can inform new programmes in the region as well as enhance existing ones. This is urgently needed to facilitate the scale-up of treatment, which is needed to address the burden of paediatric HIV cases on the continent. We reviewed the characteristics and outcomes of programmes with clinical paediatric ART studies published prior to 1 January 2008. The outcomes of the studies were comparable to similar ones from developed countries; however, the duration of follow-up was relatively limited in almost all the studies reviewed. One-year survival probability was between 84% and 91%, and considerable improvement in the clinical, immunologic and iral status of the paediatric patients was generally recorded. Loss to follow-up was less than 10% in all but two studies. Adherence to treatment was good and few adverse events were reported. This is despite the fact that many programmes were subject to enormous constraints in terms of health services, and despite widespread use of adult fixed-dose combinations for paediatric patients, including young infants. While the majority of children commencing ART were severely ill, most children were old (median age >5 years for almost all studies) with relatively few infants and young children (age <2 years) receiving treatment. This is in contrast to knowledge of rapid disease progression in the majority of HIV-infected infants and despite the World Health Organization’s recent recommendations to commence ART in all HIV-infected infants less than one year old. There is an urgent need to address barriers to ART for infants. Studies of the outcomes of programmes treating infants as well as those with longer-term follow-up are also needed.

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

Introduction: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results: Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73-1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20-1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51-0.93). Conclusions: In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals.

Toward global prevention of sexually transmitted infections (STIs): The need for STI vaccines.

An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts.

Mobility and Bandwidth Prediction as a Service in Virtualized LTE Systems

Recently telecommunication industry benefits from infrastructure sharing, one of the most fundamental enablers of cloud computing, leading to emergence of the Mobile Virtual Network Operator (MVNO) concept. The most momentous intents by this approach are the support of on-demand provisioning and elasticity of virtualized mobile network components, based on data traffic load. To realize it, during operation and management procedures, the virtualized services need be triggered in order to scale-up/down or scale-out/in an instance. In this paper we propose an architecture called MOBaaS (Mobility and Bandwidth Availability Prediction as a Service), comprising two algorithms in order to predict user(s) mobility and network link bandwidth availability, that can be implemented in cloud based mobile network structure and can be used as a support service by any other virtualized mobile network services. MOBaaS can provide prediction information in order to generate required triggers for on-demand deploying, provisioning, disposing of virtualized network components. This information can be used for self-adaptation procedures and optimal network function configuration during run-time operation, as well. Through the preliminary experiments with the prototype implementation on the OpenStack platform, we evaluated and confirmed the feasibility and the effectiveness of the prediction algorithms and the proposed architecture.

An Insight Into Cervical Cancer Screening and Treatment Capacity in Sub Saharan Africa.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia.

Pediatric antiretroviral adherence and child disclosure in Botswana

The scale-up of antiretrovirals (ARVs) to treat HIV/AIDS in Africa has been rapid over the last five years. Botswana was the first African nation to roll out a comprehensive ARV program, where ARVs are available to all citizens who qualify. Excellent adherence to these ARVs is necessary to maintain HIV suppression and on-going health of all individuals taking them. Children rely almost entirely on their caregivers for the administration of these medications, and very little research has been done to examine the factors which affect both adherence and disclosure to the child of their HIV status. ^ Methods. This cross-sectional study used multiple methods to examine adherence, disclosure, and stigma across various dimensions of the child and caregiver's lives, including 30 caregiver questionnaires, interviewer-administered 3-day adherence recalls, pharmacy pill counts, and chart reviews. Fifty in-depth interviews were conducted with caregivers, male caregivers, teenagers, and health care providers. ^ Results. Perceived family stigma was found to be a predictor of excellent adherence. After controlling for age, children who live with their mothers were significantly less likely to know their HIV status than children living with any other relative (OR=0.403, p=0.014). Children who have a grandmother living in the household or taking care of them each day are significantly more likely to have optimal adherence than children who don't have grandmother involvement in their daily lives. ^ Discussion. Visible illness plays an intermediary role between adherence and perceived family stigma: Caregivers know that ARVs suppress physical manifestations of HIV, and in an effort to avoid unnecessary disclosure of the child's status to family members, therefore have children with excellent adherence. Grandmothers play a vital role in supporting the care and treatment of children in Botswana. ^

A costing exercise of provision of prevention of HIV transmission from mother to child services in Vietnam

Objectives. This dissertation focuses on estimating the cost of providing a minimum package of prevention of mother-to-child HIV transmission (PMTCT) in Vietnam from a societal perspective and discussing the issues of scaling-up the minimum package nationwide. ^ Methods. Through collection of cost-related data of PMTCT services at 22 PMTCT sites in 5 provinces (Hanoi, Quang Ninh, Thai Nguyen, Hochiminh City, and An Giang) in Vietnam, the research investigates the item cost of each service in minimum PMTCT packages and the actual cost per PMTCT site at different organizational levels including central, provincial, and district. Next, the actual cost per site at each organizational level is standardized by adjusting for HIV prevalence rate to arrive at standardized costs per site. This study then uses the standardized costs per site to project, by different scenarios, the total cost to scale-up the PMTCT program in Vietnam. ^ Results. The cost for HIV tests, infant formula, and salary of health workers are consistently found to be the biggest expenditures in the PMTCT minimum package program across all organizational levels. Annual cost for drugs for prophylaxis treatment, operating and capital, and training costs are not substantial (less than 5% of total costs at all levels). The actual annual estimated cost for a PMTCT site at the central level is nearly VND 1.9 billion or US$ 107,650 (exchange rate US$ 1 = VND 17,500) while the annual cost for a provincial site is VND 375 million or US$ 21,400. The annual cost for a district site is VND 139 million (∼US$ 8,000). ^ The estimated total annual cost to roll out the PMTCT minimum package to the 5 studied provinces is approximately US$ 1.1 million. If the PMTCT program is to be scaled-up to 14 provinces until 2008 and up to 40 provinces through the end of 2010 as planned by the Ministry of Health, it would cost the health system an approximate annual amount of US$ 2.1 million and US$ 5.04 million, respectively. The annual cost for scaling-up the PMTCT minimum package nationwide is around US$ 7.6 million. Meanwhile, the total annual cost to implement PMTCT minimum packages to achieve PMTCT national targets in 2010 (providing counseling service to 90% of all pregnant women; 60% of them will receive HIV tests and 100% of HIV (+) mother and their newborn will receive prophylaxis treatment) would be US$ 6.1 million. ^ Recommendations. This study recommends: (1) the Ministry of Health of Vietnam should adjust its short-term national targets to a more feasible and achievable level given the current level of available resources; (2) a detailed budget for scaling-up the PMTCT program should be developed together with the national PMTCT action plan; (3) the PMTCT scaling-up plan developed by the Ministry of Health should focus on coverage of high prevalence population and quality of services provided rather than number of physical provinces reached; (4) exclusive breastfeeding strategy should be promoted as part of the PMTCT program; and (5) for a smooth and effective rolling out of PMTCT services nationwide, development of a national training plan and execution of this plan must precede any other initiations of the PMTCT scaling-up plan. ^

Proceedings of the 23rd Annual Biochemical Engineering Symposium

The 23rd Annual Biochemical Engineering Symposium was held at the University of Oklahoma on April 17, 1993. The objectives of the symposium were to provide 1) a forum for informal discussion of biochemical engineering research being carried at the participating universities and 2) an opportunity for students to present and publish their work. Thirteen papers presented at the symposium are included in the proceedings. Because final publication usually takes place in refereed journals, the articles included here are typically brief and often cover work in progress. The program of the symposium and a list of participants are included in the proceedings. ContentsA Low-Cost Bioreactor Strategy for RNA Synthesis, H. Anthony Marble, Eleni Chrisikos, and Robert H. Davis Development of a CELSS Bioreactor: Oxygen Transfer and Micromixing in Parabolic Flight, P.E. Villeneuve, K.S. Wenger, B.G. Thompson, T. Kedar, and E.H. Dunlop Scale-up of Dexter Murine Bone Marrow Cultures Utilizing a Three-Dimensional Fiberglass Support Matrix, John G. Highfill, Paul Todd, Steve Haley, and Dhinaker Kompala Modeling and Estimation of States of Recombinant Fermentations Using Nonlinear Input/Output Models, Vicotr M. Saucedo and M. Nazmul Karim Deadent Microfiltration of Bovine Serum Albumin Suspension Through Yeast Cake Layers and Assymetric Polymeric Membranes, Naveen Arora and Robert H. Davis Monitoring the Fate of Toluene and Phenol in the Rhizosphere, N. Muralidharan, Lawrence C. Davis, and Larry E. Erickson Hydrodynamic Motions Associated with Bubble Coalescence and Breakup, T.Y. Yiin, L.A. Glasgow, and L.E. Erickson Expression and Purification of a-Human Atrial Natriuretic Peptide in Escherichia coli by Fusion with L-Asparaginase, Nien-Tung Ma and Roger G. Harrison High Pressure Crystallization of Proteins, Mungara V. Saikumar, Charles E. Glatz, and Maurice A. Larson Structure/Function Relationships in the Catalytic and Starch Binding Domains of Glucoamylase, Pedro M. Coutinho, Clark Ford, Peter J. Reilly Cellular Responses of Insect Cell Spodoptera frugiperda to Environmental Stresses, Paul Yeh, Grace Y. Sun, Gary A. Weisman, Rakesh Bajpai A Novel Approach to Understanding the Antimicrobial Activity of Peptides, Naveen Pathak, Marie-Helene Janna, Gael Ruche, David McCarthy, and Roger Harrison Mass Transfer in the Bioremediation of Soils Contaminated with Trapped Non-Aqueous Phase Liquids, Xiaoqing Yang, Larry E. Jacobson, and L.T. Fan

Saving Young Lives: Pathfinder International’s Youth-Friendly Postabortion Care Project

As many as 2.5 million adolescent women seek abortion each year, and nearly 70,000 women die from complications related to unsafe abortion, of which almost half are women under the age of 25. A further 5 million women suffer disability due to unsafe abortion yearly. In most developing countries, abortion is legally restricted or highly inaccessible, which leads young women to seek services from unskilled practitioners often leading to incomplete, septic abortions and massive bleeding, which can result in permanent injury, infertility, and death. Based on our deeply held belief that all people, including adolescents, have a right to sexual and reproductive health services and the importance of addressing adolescent needs within Postabortion Care (PAC) services, Pathfinder used private funds to initiate a Youth-Friendly Postabortion Care (YFPAC) program in eight sub-Saharan African countries. Implemented between June 2007 and May 2008, the YFPAC program offered an opportunity to apply the PAC Consortium’s Technical Guidance on Youth-Friendly PAC, generating promising approaches and lessons learned. The goal of the YFPAC initiative was to increase access to PAC services that are responsive to adolescent needs in sub-Saharan Africa. While outcomes varied according to the country, the overall outcomes included: Increased community support for services and activities that prevent unwanted pregnancy, decreased stigma around abortion, and awareness of the issue of unsafe abortion among adolescent women: 311 peer educators reached almost 17,487 youth and other community members; 171 stakeholders (e.g., religious and traditional leaders, health officials, and local government officials) were sensitized on YFPAC, resulting in a positive shift in communities’ attitudes toward youth in need of PAC services. 125 service providers were trained to deliver YFPAC services and three doctors in Ghana were provided with a technical update on YFPAC. YFPAC services are available in Angola, Ghana, Nigeria, Mozambique, Tanzania, Uganda, Ethiopia, and Kenya. Pathfinder introduced YFPAC services into 25 facilities (in 27 service delivery points), and provided more than 3,800 clients with YFPAC services throughout the eight countries. The number of adolescent PAC clients seen at the project facilities increased— 710 clients were seen in the first quarter, 1,144 were seen in the fourth. The number of adolescent PAC clients who adopt a contraceptive method to prevent future unintended pregnancies has increased. Statistics show an average postabortion contraceptive acceptance of 69%, with the highest acceptance being 83% and the lowest being 44%. Evidence-based approaches, tools, and lessons learned are being disseminated and used for scale-up or replication of YFPAC interventions.

Harmony: Towards automated self-adaptive consistency in cloud storage

In just a few years cloud computing has become a very popular paradigm and a business success story, with storage being one of the key features. To achieve high data availability, cloud storage services rely on replication. In this context, one major challenge is data consistency. In contrast to traditional approaches that are mostly based on strong consistency, many cloud storage services opt for weaker consistency models in order to achieve better availability and performance. This comes at the cost of a high probability of stale data being read, as the replicas involved in the reads may not always have the most recent write. In this paper, we propose a novel approach, named Harmony, which adaptively tunes the consistency level at run-time according to the application requirements. The key idea behind Harmony is an intelligent estimation model of stale reads, allowing to elastically scale up or down the number of replicas involved in read operations to maintain a low (possibly zero) tolerable fraction of stale reads. As a result, Harmony can meet the desired consistency of the applications while achieving good performance. We have implemented Harmony and performed extensive evaluations with the Cassandra cloud storage on Grid?5000 testbed and on Amazon EC2. The results show that Harmony can achieve good performance without exceeding the tolerated number of stale reads. For instance, in contrast to the static eventual consistency used in Cassandra, Harmony reduces the stale data being read by almost 80% while adding only minimal latency. Meanwhile, it improves the throughput of the system by 45% while maintaining the desired consistency requirements of the applications when compared to the strong consistency model in Cassandra.

Simplifying data acquisition in plant canopies- Measurements of leaf angles with a cell phone

1. Canopies are complex multilayered structures comprising individual plant crowns exposing a multifaceted surface area to sunlight. Foliage arrangement and properties are the main mediators of canopy functions. The leaves act as light traps whose exposure to sunlight varies with time of the day, date and latitude in a trade-off between photosynthetic light harvesting and excessive or photoinhibitory light avoidance. To date, ecological research based upon leaf sampling has been limited by the available echnology, with which data acquisition becomes labour intensive and time-consuming, given the verwhelming number of leaves involved. 2. In the present study, our goal involved developing a tool capable of easuring a sufficient number of leaves to enable analysis of leaf populations, tree crowns and canopies.We specifically tested whether a cell phone working as a 3Dpointer could yield reliable, repeatable and valid leaf anglemeasurements with a simple gesture. We evaluated the accuracy of this method under controlled conditions, using a 3D digitizer, and we compared performance in the field with the methods commonly used. We presented an equation to estimate the potential proportion of the leaf exposed to direct sunlight (SAL) at any given time and compared the results with those obtained bymeans of a graphicalmethod. 3. We found a strong and highly significant correlation between the graphical methods and the equation presented. The calibration process showed a strong correlation between the results derived from the two methods with amean relative difference below 10%. Themean relative difference in calculation of instantaneous exposure was below 5%. Our device performed equally well in diverse locations, in which we characterized over 700 leaves in a single day. 4. The newmethod, involving the use of a cell phone, ismuchmore effective than the traditionalmethods or digitizers when the goal is to scale up from leaf position to performance of leaf populations, tree crowns or canopies. Our methodology constitutes an affordable and valuable tool within which to frame a wide range of ecological hypotheses and to support canopy modelling approaches.

Change-Impact driven Agile Architecting.

Software architecture is a key factor to scale up Agile Software Development ASD in large softwareintensive systems. Currently, software architectures are more often approached through mechanisms that enable to incrementally design and evolve software architectures aka. agile architecting. Agile architecting should be a light-weight decision-making process, which could be achieved by providing knowledge to assist agile architects in reasoning about changes. This paper presents the novel solution of using change-impact knowledge as the main driver for agile architecting. The solution consists of a Change Impact Analysis technique and a set of models to assist agile architects in the change -decision-making- process by retrieving the change-impact architectural knowledge resulting from adding or changing features iteration after iteration. To validate our approach, we have put our solution into practice by running a project of a metering management system in electric power networks in an i-smart software factory.

Probabilistic reasoning with an enzyme-driven DNA device

We present a biomolecular probabilistic model driven by the action of a DNA toolbox made of a set of DNA templates and enzymes that is able to perform Bayesian inference. The model will take single-stranded DNA as input data, representing the presence or absence of a specific molecular signal (the evidence). The program logic uses different DNA templates and their relative concentration ratios to encode the prior probability of a disease and the conditional probability of a signal given the disease. When the input and program molecules interact, an enzyme-driven cascade of reactions (DNA polymerase extension, nicking and degradation) is triggered, producing a different pair of single-stranded DNA species. Once the system reaches equilibrium, the ratio between the output species will represent the application of Bayes? law: the conditional probability of the disease given the signal. In other words, a qualitative diagnosis plus a quantitative degree of belief in that diagno- sis. Thanks to the inherent amplification capability of this DNA toolbox, the resulting system will be able to to scale up (with longer cascades and thus more input signals) a Bayesian biosensor that we designed previously.