Multiplexed biochemical assays with biological chips

High density peptide and oligonucleotide chips are fabricated using semiconductor-based technologies. These chips have a variety of biological applications.     

Cover Picture: Toward Large‐Scale Alignment of Electrohydrodynamic Patterning of Thin Polymer Films (Adv. Funct. Mater. 15/2006)

By integrating lithography and self‐assembly via electrohydrodynamic instabilities, Russel and co‐workers are able to guide initially flat polymer films to evolve into periodic arrays of pillars over regions much greater in extent than their natural domain sizes, as detailed on p. 1992. Novel structures that involve a combination of linear ridges and pillars are also produced, mainly as as result of the dynamic merging among preformed pillars. To pattern thin polymer films via electrohydrodynamic instabilities, we design and utilize two different kinds of mask patterns to guide pillars into alignment over regions much greater in extent than their natural domain sizes. First, narrow protruding ridges that intersect to form regular patterns on the mask trigger the growth of pillars beneath. Later, square and triangular packings of pillars develop in the regions enclosed by those ridges, preserving the registry from one domain to the next over a much larger area than within individual domains in unpatterned portions of the mask. Second, small square protrusions that are prealigned into a large regular array on the mask guide the formation of square packings of pillars in domains that conform to the mask, forming a large array of pillars. Novel structures involving a combination of linear ridges and pillars are also produced mainly due to the dynamic merging among preformed pillars. Finally, we find vertex symmetry of the mask pattern is necessary for generating and preserving ordered patterns on the polymer film.     

Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy

Although studies generally support a positive association between alcohol consumption and lung-cancer risk, the relationship between specific alcoholic beverages and lung-cancer risk has been inconsistent. We examined recent and past alcoholic beverage intake among 261 incident cases and 615 population controls enrolled in a lung-cancer case-control study of African Americans and Caucasians in Los Angeles County between 1991 and 1994. An in-person interview elicited information about past alcohol intake from ages 30 to 40 y, smoking, other lung-cancer risk factors, as well as recent intake of alcohol, and recent dietary intake. An association was observed between recent hard-liquor consumption and lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL) per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per month), adjusted for smoking, the matching factors, saturated fat and other alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No appreciable association was observed for total alcohol, whereas small inverse associations were observed for beer and wine, although confidence intervals were wide. An elevated lung-cancer risk was also observed for past liquor consumption (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of liquor compared with infrequent drinkers was 1.83 (95% CI = 1. 06-3.15). Confounding of the association between alcohol and lung cancer by smoking was apparent. Although we devoted considerable efforts to adjusting for smoking in our analyses, residual confounding is still possible because smoking and alcohol are closely associated. In addition, case-control studies including this study should be viewed with caution because of possible selection bias. An increased risk of lung cancer might occur with moderate drinking of hard liquor but confirmation is required in larger studies.     

Theory blending: extended algorithmic aspects and examples

In Cognitive Science, conceptual blending has been proposed as an important cognitive mechanism that facilitates the creation of new concepts and ideas by constrained combination of available knowledge. It thereby provides a possible theoretical foundation for modeling high-level cognitive faculties such as the ability to understand, learn, and create new concepts and theories. Quite often the development of new mathematical theories and results is based on the combination of previously independent concepts, potentially even originating from distinct subareas of mathematics. Conceptual blending promises to offer a framework for modeling and re-creating this form of mathematical concept invention with computational means. This paper describes a logic-based framework which allows a formal treatment of theory blending (a subform of the general notion of conceptual blending with high relevance for applications in mathematics), discusses an interactive algorithm for blending within the framework, and provides several illustrating worked examples from mathematics.     

The UCSC Kestrel parallel processor

The architectural landscape of high-performance computing stretches from superscalar uniprocessor to explicitly parallel systems, to dedicated hardware implementations of algorithms. Single-purpose hardware can achieve the highest performance and uniprocessors can be the most programmable. Between these extremes, programmable and reconfigurable architectures provide a wide range of choice in flexibility, programmability, computational density, and performance. The UCSC Kestrel parallel processor strives to attain single-purpose performance while maintaining user programmability. Kestrel is a single-instruction stream, multiple-data stream (SIMD) parallel processor with a 512-element linear array of 8-bit processing elements. The system design focuses on efficient high-throughput DNA and protein sequence analysis, but its programmability enables high performance on computational chemistry, image processing, machine learning, and other applications. The Kestrel system has had unexpected longevity in its utility due to a careful design and analysis process. Experience with the system leads to the conclusion that programmable SIMD architectures can excel in both programmability and performance. This work presents the architecture, implementation, applications, and observations of the Kestrel project at the University of California at Santa Cruz.     

Enhancement of the surface expression of tumor necrosis factor alpha (TNFalpha) but not the p55 TNFalpha receptor in the THP-1 monocytic cell line by matrix metalloprotease inhibitors

The monocytic cell line THP-1 can be induced to express and release tumor necrosis factor alpha (TNFalpha) and both TNFalpha receptors (p55 and p75) upon exposure to bacterial lipopolysaccharide (LPS). The broad-spectrum matrix metalloprotease (MMP) inhibitors [4-(N-hydroxyamino)-2R-isobutyl-3S-(phenylthiomethyl)succinyl]-L-p henylalanine-N-methylamide (GI-129471) and marimastat [2S-[N4(R*),2R*,3S*]]-N4[2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-N 1,2-dihydroxy-3-(2-methylpropyl)butanediamide (BB-2516) were effective inhibitors of LPS-induced TNFalpha (soluble) release with IC50 values of 0.2 and 4.0 microM, respectively. Upon LPS stimulation, the expression of pro-TNFalpha (membrane associated) on the cell surface (FACS analysis) could not be observed. However, in the presence of GI-129471, a concentration-dependent increase in TNFalpha surface expression was observed. Peak expression (percentage of cells expressing pro-TNFalpha and mean fluorescence units) in the presence of GI-129471 was at 2 hr, and steadily declined to return to near control levels by 8 hr. This time course was similar to TNFalpha release, which also peaked at 2-4 hr after LPS exposure and then declined. Stimulation of THP-1 cells with LPS + phorbol myristate acetate increased the percentage of cells expressing pro-TNFalpha by 10-fold. In the presence of GI-129471, these increases were augmented further and peaked between 2 and 4 hr, but also returned to near control levels of expression by 24 hr. This was in contrast to the release of soluble TNFalpha, which continued to accumulate over a 24-hr time course. TNFalpha receptor I (p55, TNFRI) and II (p75, TNFRII) shedding was also inhibited by GI-129471 (IC50 = 1.5 and 3.1 microM, respectively) and BB-2516 (IC50 = 14 and 15 microM, respectively). Unlike pro-TNFalpha surface expression, surface expression of both TNFalpha receptors steadily increased over 72 hr. In contrast to pro-TNFalpha surface expression, TNFRI surface expression was not augmented by these MMP inhibitors in THP-1 cells after LPS stimulation. Surface expression of TNFRII was augmented by these MMP inhibitors. These results suggest that even in the continued presence of LPS stimulation and an inhibitor of TNFalpha processing, the augmented surface expression of TNFalpha is transient. The potential "deleterious" implications of high levels of surface pro-TNFalpha expression in the presence of these inhibitors may be lessened by its transient nature.     

Zero base budgeting for human service agencies

This paper describes the development of a zero base budgeting process as part of an integral planning-budgeting-control system relating client needs with service programs. Particular attention is focused on designing, gaining acceptance for and implementing a new budgeting system for the human services agencies of a rural county government. The relationship of the zero base budgeting process to the client case management and evaluation system are explored. Problems encountered in implementing the system and an evaluation of the results are discussed.     

Cyclodextrin-based carbohydrate clusters by amide bond formation

Per-6-amino-2,3-dimethyl-ß-cyclodextrin was prepared very efficiently as its hydrochloride salt from native ß-cyclodextrin in four steps and 89% overall yield. O-Acetyl-protected ß-D-thioglucose and ß-D-thiolactose derivatives, containing short spacer arms terminated with carboxylic acid functions, were prepared by the BF₃·OEt₂-catalyzed thioglycosylation of ß-D-glucose pentaacetate and ß-lactose octaacetate with 3-mercaptopropionic acid, respectively. Utilizing amide bond formation as the key step, these thio-ß-D-glucosyl and lactosyl derivatives were coupled to per-6-amino-2,3-dimethyl-ß-cyclodextrin to afford, after deprotection, perfunctionalized ß-cyclodextrin-based clusters containing seven thio-ß-D-glucosyl and seven ß-lactosyl appendages, respectively. Molecular modeling of both these ß-cyclodextrin-based clusters revealed the glucose and lactose clusters to be approximately 23 Å and 27 Å in diameter, respectively, and approximately 19 Å in height in both cases. The association constants for the complexation of the anti-inflammatory drug naproxen by ß-cyclodextrin, per-2,3-dimethyl-ß-cyclodextrin, and the lactose cluster of ß-cyclodextrin in 0.01 M phosphate buffered saline solution (pH 7.4) were found by UV-vis spectrophotometric titration to be 374 ± 75 M⁻¹, 351 ± 70 M⁻¹, and 165 ± 33 M⁻¹, respectively.     

Stakeholder ranking of watershed goals with the vector analytic hierarchy process: Effects of participant grouping scenarios

More effective methods of eliciting and summarizing stakeholders' goals can assist in improving watershed management. This paper discusses the process of summarizing the goals that were generated during a workshop of watershed stakeholders in Virginia by using the Vector Analytic Hierarchy Process, and then grouping them into homogeneous subgroups by using two different methods: 1) assigning subgroups based on individuals' stated affiliations from a participant bio-sheet; and 2) assigning subgroups based on the similarity of individuals' actual preferences between the goals. Several different clustering approaches are considered for creating the preference-based subgroups, and the relative advantages and disadvantages of each approach are discussed. The process of combining the subgroups to generate a single overall preference structure for the group as a whole is also considered, and the final results are compared based on both the resulting rankings and the coherence, or variability of opinion, that they reflect. Determining the “best” set of subgroups can be valuable not only in exploring the underlying nature of the population's preferences, but also in supporting additional discussion and analysis of the results. As such, it can ultimately lead to much stronger and better informed decision-making by the stakeholders.