W. M. Keck Foundation 2010 Annual Report

Contains board chair's message, 2010 program highlights and grantee profiles, grants list, financial statements, and lists of board members and committee members

Bio-inspired approaches for critical infrastructure protection: Application of clonal selection principle for intrusion detection and FACTS placement

In this research, Clonal Selection, an immune system inspired approach, is utilized along with Evolutionary Algorithms to solve complex engineering problems such as Intrusion Detection and optimization of Flexible AC Transmission System (FACTS) device placement in a power grid. The clonal selection principle increases the strength of good solutions and alters their properties to find better solutions in a problem space. A special class of evolutionary algorithms that utilizes the clonal selection principle to guide its heuristic search process is termed Clonal EA. Clonal EAs can be used to solve complex pattern recognition and function optimization problems, which involve searching an enormous problem space for a solution. Intrusion Detection is modeled, in this research, as a pattern recognition problem wherein efficient detectors are to be designed to detect intrusive behavior. Optimization of FACTS device placement in a power grid is modeled as a function optimization problem wherein optimal placement positions for FACTS devices are to be determined, in order to balance load across power lines. Clonal EAs are designed to implement the solution models. The benefits and limitations of using Clonal EAs to solve the above mentioned problems are discussed and the performance of Clonal EAs is compared with that of traditional evolutionary algorithms and greedy algorithms --Abstract, page iii

Triple Helix, Fall 2018

Table of Contents: Science Agenda: The Politics of Grant Writing / by Kavya Rajesh (p. 4) -- From the Experts / by Katherine Bruner (p. 5) -- 3D Printed Drugs: The Future of Pharmaceuticals / by Ethan Wang (p. 6) -- Computerized Markets: Wall Street Takeover / by James Kiraly (p. 10) -- The Evolution of Fear / by Alisha Ahmed (p. 14) -- ADDing Up / by Victor Liaw (p. 18) -- The Clone Wars / by Jina Zhou (p. 22) -- Physician-Assisted Suicide: Drawing the Line / by Haley Wolf (p. 26) -- Supervised Injection Sites / by Alex Gajewski (p. 30) -- On Emerging Medicalization and Health Care / by Patrick Lee (p. 33) -- The Future of Human Gene Modifications / by Elizabeth Robinson (p. 36)College of Natural SciencesUT LibrariesLiberal Art

Micro/nanofluidic and lab-on-a-chip devices for biomedical applications

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [1]. Because of their adaptability, feasibility, and cost-efficiency, these devices can revolutionize the future of preclinical technologies. Furthermore, they allow insights into the performance and toxic effects of responsive drug delivery nanocarriers to be obtained, which consequently allow the shortcomings of two/three-dimensional static cultures and animal testing to be overcome and help to reduce drug development costs and time [2–4]. With the constant advancements in biomedical technology, the development of enhanced microfluidic devices has accelerated, and numerous models have been reported. Given the multidisciplinary of this Special Issue (SI), papers on different subjects were published making a total of 14 contributions, 10 original research papers, and 4 review papers. The review paper of Ko et al. [1] provides a comprehensive overview of the significant advancements in engineered organ-on-a-chip research in a general way while in the review presented by Kanabekova and colleagues [2], a thorough analysis of microphysiological platforms used for modeling liver diseases can be found. To get a summary of the numerical models of microfluidic organ-on-a-chip devices developed in recent years, the review presented by Carvalho et al. [5] can be read. On the other hand, Maia et al. [6] report a systematic review of the diagnosis methods developed for COVID-19, providing an overview of the advancements made since the start of the pandemic. In the following, a brief summary of the research papers published in this SI will be presented, with organs-on-a-chip, microfluidic devices for detection, and device optimization having been identified as the main topics.info:eu-repo/semantics/publishedVersio

The domestication of the probiotic bacterium Lactobacillus acidophilus

Lactobacillus acidophilus is a Gram-positive lactic acid bacterium that has had widespread historical use in the dairy industry and more recently as a probiotic. Although L. acidophilus has been designated as safe for human consumption, increasing commercial regulation and clinical demands for probiotic validation has resulted in a need to understand its genetic diversity. By drawing on large, well-characterised collections of lactic acid bacteria, we examined L. acidophilus isolates spanning 92 years and including multiple strains in current commercial use. Analysis of the whole genome sequence data set (34 isolate genomes) demonstrated L. acidophilus was a low diversity, monophyletic species with commercial isolates essentially identical at the sequence level. Our results indicate that commercial use has domesticated L. acidophilus with genetically stable, invariant strains being consumed globally by the human population

Congenital anomalies from a physics perspective. The key role of "manufacturing" volatility

Genetic and environmental factors are traditionally seen as the sole causes of congenital anomalies. In this paper we introduce a third possible cause, namely random "manufacturing" discrepancies with respect to ``design'' values. A clear way to demonstrate the existence of this component is to ``shut'' the two others and to see whether or not there is remaining variability. Perfect clones raised under well controlled laboratory conditions fulfill the conditions for such a test. Carried out for four different species, the test reveals a variability remainder of the order of 10%-20% in terms of coefficient of variation. As an example, the CV of the volume of E.coli bacteria immediately after binary fission is of the order of 10%. In short, ``manufacturing'' discrepancies occur randomly, even when no harmful mutation or environmental factors are involved. Not surprisingly, there is a strong connection between congenital defects and infant mortality. In the wake of birth there is a gradual elimination of defective units and this screening accounts for the post-natal fall of infant mortality. Apart from this trend, post-natal death rates also have humps and peaks associated with various inabilities and defects.\qL In short, infant mortality rates convert the case-by-case and mostly qualitative problem of congenital malformations into a global quantitative effect which, so to say, summarizes and registers what goes wrong in the embryonic phase. Based on the natural assumption that for simple organisms (e.g. rotifers) the manufacturing processes are shorter than for more complex organisms (e.g. mammals), fewer congenital anomalies are expected. Somehow, this feature should be visible on the infant mortality rate. How this conjecture can be tested is outlined in our conclusion.Comment: 43 pages, 9 figure

CRISPR/Cas9 system and fluorescence enhanced BA-LIFT bioprinting technique as a toolbox for the study of the Immune System

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 24-09-2020In this work, the CRISPR/Cas system genome editing toolbox and the fluorescence enhanced BA-LIFT laser bioprinting tools have been used to study the immune system cells behavior. CD69 is tightly regulated at the transcription level by the CNS2 regulatory region, whose epigenetic marks define as a bivalent regulatory element that match with the previously definition of CD69 as a bivalent gene. By CRISPR/Cas9 transcriptional assays and genome editing, two major areas within the CNS2 enhancer with antagonistic but complementary regulatory activities in vivo were defined in T cells: a Core E region of ~60 bp with a dual repressor and activator function; and a 5’ region adjacent to the Core E (5’C) of ~160 bp where the major activation transcriptional machinery is associated. Deletion of the Core E led to a CD69 overexpression both at resting and after stimulation, supporting its repressive role at steady state and avoiding CD69 overexpression upon stimulation. The Core E is enriched in the Oct1 and Chd4 TFs, whose bivalent function have been previously defined. RNA-seq analysis of ΔCore E T cells showed that CD69 overexpression is associated with an increase of the chemokine receptors CCR1, CCR2 and CCR5 at steady state, and of its ligands CCL3L3, CCL4 and CCL4L1 after stimulation, highlighting the role of CD69 in the regulation of chemokines and its receptors, as has been previously observed in mouse models. The role of the human ERAP2 aminopeptidase in the antigen presentation was assessed by generating a functional ERAP2 KO in B cells. Comparison of the HLA-B*27:05 ligandomes of ERAP+/+ and ERAP-/- cells determine that ERAP2 destroy ligands with N-terminal basic residues and peptides with minority anchor motifs at P2 (K and Q). A compensation effect in other peptide positions was observed, since the overall stability of the peptides remained constant. A newly developed fluorescence enhanced BA-LIFT laser bioprinting technique has been integrated. A laser-based bioprinting device for accurate identification, selection and printing of single or grouped cells within a complex population was developed and validated. FE BA-LIFT has proven to be an efficient and precise tool with high viability and resolution when depositing biological material in hydrogels or scaffolds with different characteristics. An IFN-γ human NK cell reporter has been generated by CRISPR/Cas9 to be used for the validation of the FE BA-LIFT bioprinte