Expression of CCN family of genes in human skin in vivo and alterations by solar-simulated ultraviolet irradiation

The CCN family of proteins is involved in diverse biological functions such as cell growth, adhesion, migration, angiogenesis, and regulation of extracellular matrix. We have investigated expression of CCN family genes and alternations induced by solar-simulated ultraviolet irradiation in human skin in vivo. Transcripts of all six CCN genes were expressed in human skin in vivo. CCN5 was most abundantly expressed followed by CCN2>CCN3>CCN1>CCN4>CCN6. Solar-simulated ultraviolet irradiation increased mRNA expression of CCN1 and CCN2. In contrast, mRNA levels of CCN3, CCN4, CCN5, and CCN6, were reduced. Knowledge gained from this study provides the foundation to explore the functional roles of CCN gene products in cutaneous biology and responses to solar ultraviolet irradiation

Ward's Hierarchical Clustering Method: Clustering Criterion and Agglomerative Algorithm

The Ward error sum of squares hierarchical clustering method has been very widely used since its first description by Ward in a 1963 publication. It has also been generalized in various ways. However there are different interpretations in the literature and there are different implementations of the Ward agglomerative algorithm in commonly used software systems, including differing expressions of the agglomerative criterion. Our survey work and case studies will be useful for all those involved in developing software for data analysis using Ward's hierarchical clustering method.Comment: 20 pages, 21 citations, 4 figure

Recognizing Members of the Tournament Equilibrium Set is NP-hard

A recurring theme in the mathematical social sciences is how to select the "most desirable" elements given a binary dominance relation on a set of alternatives. Schwartz's tournament equilibrium set (TEQ) ranks among the most intriguing, but also among the most enigmatic, tournament solutions that have been proposed so far in this context. Due to its unwieldy recursive definition, little is known about TEQ. In particular, its monotonicity remains an open problem up to date. Yet, if TEQ were to satisfy monotonicity, it would be a very attractive tournament solution concept refining both the Banks set and Dutta's minimal covering set. We show that the problem of deciding whether a given alternative is contained in TEQ is NP-hard.Comment: 9 pages, 3 figure

SAT-based Explicit LTL Reasoning

We present here a new explicit reasoning framework for linear temporal logic (LTL), which is built on top of propositional satisfiability (SAT) solving. As a proof-of-concept of this framework, we describe a new LTL satisfiability tool, Aalta\_v2.0, which is built on top of the MiniSAT SAT solver. We test the effectiveness of this approach by demonnstrating that Aalta\_v2.0 significantly outperforms all existing LTL satisfiability solvers. Furthermore, we show that the framework can be extended from propositional LTL to assertional LTL (where we allow theory atoms), by replacing MiniSAT with the Z3 SMT solver, and demonstrating that this can yield an exponential improvement in performance

Growth in solvable subgroups of GL_r(Z/pZ)

Let $K=Z/pZ$ and let $A$ be a subset of \GL_r(K) such that is solvable. We reduce the study of the growth of $A$ under the group operation to the nilpotent setting. Specifically we prove that either $A$ grows rapidly (meaning $|A\cdot A\cdot A|\gg |A|^{1+\delta}$), or else there are groups $U_R$ and $S$, with $S/U_R$ nilpotent such that $A_k\cap S$ is large and $U_R\subseteq A_k$, where $k$ is a bounded integer and $A_k = \{x_1 x_2...b x_k : x_i \in A \cup A^{-1} \cup {1}}$. The implied constants depend only on the rank $r$ of $\GL_r(K)$. When combined with recent work by Pyber and Szab\'o, the main result of this paper implies that it is possible to draw the same conclusions without supposing that is solvable.Comment: 46 pages. This version includes revisions recommended by an anonymous referee including, in particular, the statement of a new theorem, Theorem

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus

Negotiation in strategy making teams : group support systems and the process of cognitive change

This paper reports on the use of a Group Support System (GSS) to explore at a micro level some of the processes manifested when a group is negotiating strategy-processes of social and psychological negotiation. It is based on data from a series of interventions with senior management teams of three operating companies comprising a multi-national organization, and with a joint meeting subsequently involving all of the previous participants. The meetings were concerned with negotiating a new strategy for the global organization. The research involved the analysis of detailed time series data logs that exist as a result of using a GSS that is a reflection of cognitive theory

Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice

Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4–5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating l-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5–16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34 ± 0.32), arginine (Arg, 1.66 ± 0.39), glutamine (Gln, 1.75 ± 0.60), and proline (Pro, 1.48 ± 0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56 ± 0.30). However, essential amino acids mixtures (BCAA + Arg + Gln, BCAA + Gln, and BCAA + Pro) significantly increased the FSR (2.07 ± 0.58, 2.04 ± 0.54, 2.01 ± 0.50 and 2.07 ± 0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation

Quantification of Biomolecular Dynamics Inside Real and Synthetic Nuclear Pore Complexes Using Time-Resolved Atomic Force Microscopy

Over the past decades, atomic force microscopy (AFM) has emerged as an increasingly powerful tool to study the dynamics of biomolecules at nanometer length scales. However, the more stochastic the nature of such biomolecular dynamics, the harder it becomes to distinguish them from AFM measurement noise. Rapid, stochastic dynamics are inherent to biological systems comprising intrinsically disordered proteins. One role of such proteins is in the formation of the transport barrier of the nuclear pore complex (NPC): the selective gateway for macromolecular traffic entering or exiting the nucleus. Here, we use AFM to observe the dynamics of intrinsically disordered proteins from two systems: the transport barrier of native NPCs and the transport barrier of a mimetic NPC made using a DNA origami scaffold. Analyzing data recorded with 50-200 ms temporal resolution, we highlight the importance of drift correction and appropriate baseline measurements in such experiments. In addition, we describe an autocorrelation analysis to quantify time scales of observed dynamics and to assess their veracity-an analysis protocol that lends itself to the quantification of stochastic fluctuations in other biomolecular systems. The results reveal the surprisingly slow rate of stochastic, collective transitions inside mimetic NPCs, highlighting the importance of FG-nup cohesive interactions