Social Capital, Creative Destruction and Economic Growth

The dynamic structure of profit rates for 156 US manufacturing companies is analyzed by means of fractional integration techniques as an alternative to the commolny used ARMIA models with respect to the "persistence of profits". The results show - despite the short lengths of the series - that 35,5% of the series have long range dependence and 54% are nonstationary. This is a confirmation of the strong challenge to the competitive environment hypothesis obtained by previous studies.

The Role of Optimism and Working Alliance and its Utility in Predicting Therapeutic Outcomes in Counseling Relationships

Achieving positive therapeutic outcomes is the goal of all involved in the mental health field. The last 10 years have seen ever increasing demands for recognition of the elements that constitute empirically supported treatments (EST) and research on those elements, not only by professionals in the mental health field but also by third party providers (health insurance companies) and clients. Yet over the course of this increasing demand, research has repeatedly, and authoritatively, demonstrated that the most significant and consistent contributor to therapeutic outcome is the working relationship between client and counselor, not specific theoretically-bound techniques. In spite of the recognition of the importance of the working relationship, and the many efforts to isolate the ingredients that insure a therapeutic outcome, there is a dearth of consensus on those ingredients. With that lack of consensus in mind this research project sought to explore the interrelationship of three constructs in achieving therapeutic outcomes. The constructs that were investigated were dispositional optimism, the working alliance, and counselor experience. Participants were counselors who worked with clients presenting with depression. The research was conducted via an Internet based survey. Participants were asked to complete instruments that measured dispositional optimism and working alliance. The amount of counselors experience was determined via self-report on a demographic information sheet. The Working Alliance Inventory (WAI: Horvath & Greenberg, 1989) was used to measure perceived working alliance and the Life Orientation Test—Revised (LOT-R; Scheier, Carver, & Bridges. 1994) was used to measure dispositional optimism. Both instruments have evidence of validity and reliability in measuring the pertinent constructs, and are easily administered and scored. Upon completion of this study, statistical analyses were completed to determine the degree of relationship among the variables (dispositional optimism, perceived working alliance, and the amount of counselor\u27s experience). In addition to identifying potential relationships, multiple regression analysis was used to determine if either dispositional optimism or the working alliance was useful in the prediction of premature unilateral termination of therapy by clients. The results indicate that there is a statistically significant relationship among all three of the constructs studied herein. The results gave no support for the use of optimism or working alliance data as a means of predicting premature unilateral client termination. Implications of these results are discussed

Tests of the Efficient Markets Hypothesis

This paper surveys various statistical methods that have been proposed for the examination of the efficiency of financial markets and proposes a novel procedure for testing the predictability of a time series. For illustration, this procedure is applied to Austrian stock return series

In situ synthesis of size-controlled, stable silver nanoparticles within ultrashort peptide hydrogels and their anti-bacterial properties

We have developed a silver-releasing biomaterial with promising potential for wound healing applications. The material is made of ultrashort peptides which can self-assemble in water to form hydrogels. Silver nanoparticles (Ag NPs) were synthesized in situ within the biomaterial, using only UV irradiation and no additional chemical reducing agents. The synthetic strategy allows precise control of the nanoparticle size, with the network of peptide fibers preventing aggregation of Ag NPs. The biomaterial shows increased mechanical strength compared to the hydrogel control. We observed a sustained release of Ag NPs over a period of 14 days. This is a crucial prerequisite for effective anti-bacterial therapy. The ability to inhibit bacterial growth was tested using different bacterial strains, namely gram-negative Escherichia coli and Pseudomonas aeruginosa and gram-positive Staphylococcus aureus. Inhibition of bacterial growth was observed for all strains. The best results were obtained for Pseudomonas aeruginosa which is known for exhibiting multidrug resistance. Biocompatibility studies on HDFa cells, using Ag NP-containing hydrogels, did not show any significant influence on cell viability. We propose this silver-releasing hydrogel as an excellent biomaterial with great potential for applications in wound healing due to its low silver content, sustained silver nanoparticle release and biocompatibility

Synthesis and bioactivity of a conjugate composed of green tea catechins and hyaluronic acid

(-)-Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol that has several biological activities, including anti-cancer activity and anti-inflammation. Hyaluronic acid (HA) is a naturally-occurring polysaccharide that is widely used as a biomaterial for drug delivery and tissue engineering due to its viscoelastic, biocompatible and biodegradable properties. By conjugating HA with EGCG, the resulting HA-EGCG conjugate is expected to exhibit not only the inherent properties of HA but also the bioactivities of EGCG. Toward this end, we report the synthesis of an amine-functionalized EGCG as an intermediate compound for conjugation to HA. EGCG was reacted with 2,2-diethoxyethylamine (DA) under acidic conditions, forming ethylamine-bridged EGCG dimers. The EGCG dimers were composed of four isomers, which were characterized by HPLC, high-resolution mass spectrometry and NMR spectroscopy. The amine-functionalized EGCG dimers were conjugated to hyaluronic acid (HA) through the formation of amide bonds. HA-EGCG conjugates demonstrated several bioactivities which were not present in unmodified HA, including resistance to hyaluronidase-mediated degradation, inhibition of cell growth and scavenging of radicals. The potential applications of HA-EGCG conjugates are discussed

Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy

Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells

Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells.BackgroundThe immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (FK506) are extruded from cells by the multidrug resistance P-glycoprotein (P-gp), an efflux pump for drugs and xenobiotics, which may limit their therapeutic effectiveness and/or incidence of toxic side effects. In the present study, we investigated the effect of therapeutic concentrations of CsA and FK506 on the expression of P-gp in cultured endothelial and proximal tubule cells.MethodsP-gp expression in human arterial endothelial (HAEC) and rat proximal tubule cells (RPTC) was determined by immunoblotting and immunocytochemistry, and correlated with P-gp-mediated transport by measuring the intracellular accumulation of the fluorescent probe calcein.ResultsFollowing incubation of HAEC with therapeutic concentrations of 0.1 to 1.6 μm CsA up to seven days, P-gp expression increased in a time- and concentration-dependent manner, maximally to 291 ± 42% of controls with 0.8 μm CsA for seven days. Similar effects of CsA were observed in RPTC. In contrast, therapeutic concentrations of FK506 (0.01 to 0.2 μm up to 7days) did not change P-gp expression in either cell type, though at higher, supratherapeutic concentrations of FK506 (0.6 to 1.2 μm) P-gp expression was also increased. Immunocytochemistry revealed increased P-gp expression in the plasma membrane of HAEC and RPTC treated with 0.8 μm CsA, which was reflected by a decrease of P-gp-mediated accumulation of calcein in both cell types.ConclusionsThe data suggest that the induction of P-gp expression in HAEC and RPTC at concentrations of CsA or FK506 above 0.5 μm is part of the protective answer of cells to toxic concentrations of the drugs and could therefore interfere with the therapeutic effectiveness of CsA in vivo

Ligation of anti-cancer drugs to self-assembling ultrashort peptides by click chemistry for localized therapy

Self-assembling ultrashort peptides from aliphatic amino acids were functionalized with platinum anti-cancer drugs by click chemistry. Oxaliplatin-derived hybrid peptide hydrogels with up to 40% drug loading were tested for localized breast cancer therapy. Stably injected gels showed significant tumor growth inhibition in mice and a better tolerance compared to the free platinum drug

Searching for epistatic interactions in nuclear families using conditional linkage analysis

BACKGROUND: Genomic screens generally employ a single-locus strategy for linkage analysis, but this may have low power in the presence of epistasis. Ordered subsets analysis (OSA) is a method for conditional linkage analysis using continuous covariates. METHODS: We used OSA to evaluate two-locus interactions in the simulated Genetic Analysis Workshop 14 dataset. We used all nuclear families ascertained by Aipotu, Karangar, and Danacaa. Using the single-nucleotide polymorphism map, multipoint affected-sibling-pair (ASP) linkage analysis was performed on all 100 replicates for each chromosome using SIBLINK. OSA was used to examine linkage on each chromosome using LOD scores at each 3-cM location on every other chromosome as covariates. Two methods were used to identify positive results: one searching across the entire covariate chromosome, the other conditioning on location of known disease loci. RESULTS: Single-locus linkage analysis revealed very high LOD scores for disease loci D1 through D4, with mean LOD scores over 100 replicates ranging from 4.0 to 7.8. Although OSA did not obscure this linkage evidence, it did not detect the simulated interactions between any of the locus pairs. We found inflated type I error rates using the first OSA method, highlighting the need to correct for multiple comparisons. Therefore, using "null chromosome pairs" without simulated disease loci, we calculated a corrected alpha-level. CONCLUSION: We were unable to detect two-locus interactions using OSA. This may have been due to lack of incorporation of phenotypic subgroups, or because linkage evidence as summarized by LOD scores performs poorly as an OSA covariate. We found inflated type I error rates, but were able to calculate a corrected alpha-level for future analyses employing this strategy to search for two-locus interactions