Behavior of heuristics and state space structure near SAT/UNSAT transition

We study the behavior of ASAT, a heuristic for solving satisfiability problems by stochastic local search near the SAT/UNSAT transition. The heuristic is focused, i.e. only variables in unsatisfied clauses are updated in each step, and is significantly simpler, while similar to, walksat or Focused Metropolis Search. We show that ASAT solves instances as large as one million variables in linear time, on average, up to 4.21 clauses per variable for random 3SAT. For K higher than 3, ASAT appears to solve instances at the ``FRSB threshold'' in linear time, up to K=7.Comment: 12 pages, 6 figures, longer version available as MSc thesis of first author at http://biophys.physics.kth.se/docs/ardelius_thesis.pd

Observation of a Free-Shercliff-Layer Instability in Cylindrical Geometry

We report on observations of a free-Shercliff-layer instability in a Taylor-Couette experiment using a liquid metal over a wide range of Reynolds numbers, $Re\sim 10^3-10^6$. The free Shercliff layer is formed by imposing a sufficiently strong axial magnetic field across a pair of differentially rotating axial endcap rings. This layer is destabilized by a hydrodynamic Kelvin-Helmholtz-type instability, characterized by velocity fluctuations in the $r-\theta$ plane. The instability appears with an Elsasser number above unity, and saturates with an azimuthal mode number $m$ which increases with the Elsasser number. Measurements of the structure agree well with 2D global linear mode analyses and 3D global nonlinear simulations. These observations have implications for a range of rotating MHD systems in which similar shear layers may be produced.Comment: 5 pages, 4 figure

A new model for preclinical testing of dermal substitutes for human skin reconstruction

Background: Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage. Methods: Bioengineered grafts consisting of collagen type I hydrogels with incorporated human fibroblasts and human keratinocytes seeded on these gels were produced. Two different dermal substitutes, namely Matriderm®, and an acellular collagen type I hydrogel, were applied onto full-thickness skin wounds created on the back of immuno-incompetent rats. As control, no dermal substitute was used. As coverage for the dermal substitutes either the bioengineered grafts were used, or, as controls, human split-thickness skin or neonatal rat epidermis were used. Grafts were excised 21days post-transplantation. Histology and immunofluorescence was performed to investigate survival, epidermis formation, and vascularization of the grafts. Results: The bioengineered grafts survived on all tested dermal substitutes. Epidermis formation and vascularization were comparable to the controls. Conclusion: We could successfully use human bioengineered grafts to test different dermal substitutes. This novel model can be used to investigate newly designed dermal substitutes in detail and in a standardized wa

Multiple Approaches to Investigate the Transport and Activity-Dependent Release of BDNF and Their Application in Neurogenetic Disorders

Studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (BDNF). Currently, this knowledge of BDNF function is being translated into improvement strategies for several debilitating neurological disorders in which BDNF abnormalities play a prominent role. Common among the BDNF-related disorders are irregular trafficking and release of mature BDNF (mBDNF) and/or its prodomain predecessor, proBDNF. Thus, investigating the conditions required for proper trafficking and release of BDNF is an essential step toward understanding and potentially improving these neurological disorders. This paper will provide examples of disorders related to BDNF release and serve as a review of the techniques being used to study the trafficking and release of BDNF

Bringing the Entrepreneurial Mindset into Mining Engineering Education

There has been an ongoing debate on how to transform engineering education to better prepare students for today`s professional world that is characterized by increasingly complex problems and challenges that engineers are tasked with upon entering the industry. Within the conceive–design–implement–operate (CDIO) framework, entrepreneurship education presents a valuable pedagogical approach to foster the necessary skills of the students through integrated, hands-on, active learning experiences. While numerous publications have addressed possibilities of how experiential, problem-based, project-based and active learning can be integrated into engineering curriculum, there has been hardly any attention on mining engineering with respect to adopting this approach. This paper will address the possibilities of integrating entrepreneurship education into mining engineering programs in particular. This paper will enhance and foster discussion among academics from mining engineering on how to integrate elements of entrepreneurship education on a course, program and departmental level to infuse value creation experiences across the curriculum

Targeted next-generation sequencing of cancer genes in poorly differentiated thyroid cancer

Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy with higher mortality than well-differentiated thyroid carcinoma. The histological diagnosis can be difficult as well as the therapy. Improved diagnosis and new targeted therapies require knowledge of DNA sequence changes in cancer-relevant genes. The TruSeq Amplicon Cancer Panel was used to screen cancer genomes from 25 PDTC patients for somatic single-nucleotide variants in 48 genes known to represent mutational hotspots. A total of 4490 variants were found in 23 tissue samples of PDTC. Ninety-eight percent (4392) of these variants did not meet the inclusion criteria, while 98 potentially pathogenic or pathogenic variants remained after filtering. These variants were distributed over 33 genes and were all present in a heterozygous state. Five tissue samples harboured not a single variant. Predominantly, variants in P53 (43% of tissue samples) were identified, while less frequently, variants in APC, ERBB4, FLT3, KIT, SMAD4 and BRAF (each in 17% of tissue samples) as well as ATM, EGFR and FBXW7 (each in 13% of tissue samples) were observed. This study identified new potential genetic targets for further research in PDTC. Of particular interest are four observed ERBB4 (alias HER4) variants, which have not been connected to this type of thyroid carcinoma so far. In addition, APC and SMAD4 mutations have not been reported in this subtype of cancer either. In contrast to other reports, we did not find CTNNB1 variants

Transcripts Encoding the Androgen Receptor and IGF-Related Molecules Are Differently Expressed in Human Granulosa Cells From Primordial and Primary Follicles

Bidirectional cross talk between granulosa cells and oocytes is known to be important in all stages of mammalian follicular development. Insulin-like growth factor (IGF) signaling is a prominent candidate to be involved in the activation of primordial follicles, and may be be connected to androgen-signaling. In this study, we interrogated transcriptome dynamics in granulosa cells isolated from human primordial and primary follicles to reveal information of growth factors and androgens involved in the physiology of ovarian follicular activation. Toward this, a transcriptome comparison study on primordial follicles (n = 539 follicles) and primary follicles (n = 261 follicles) donated by three women having ovarian tissue cryopreserved before chemotherapy was performed. The granulosa cell contribution in whole follicle isolates was extracted in silico. Modeling of complex biological systems was performed using IPA® software. We found the granulosa cell compartment of the human primordial and primary follicles to be extensively enriched in genes encoding IGF-related factors, and the Androgen Receptor (AR) enriched in granulosa cells of primordial follicles. Our study hints the possibility that primordial follicles may indeed be androgen responsive, and that the action of androgens represents a connection to the expression of key players in the IGF-signaling pathway including IGF1R, IGF2, and IGFBP3, and that this interaction could be important for early follicular activation. In line with this, several androgen-responsive genes were noted to be expressed in both oocytes and granulosa cells from human primordial and primary follicle. We present a detailed description of AR and IGF gene activities in the human granulosa cell compartment of primordial and primary follicles, suggesting that these cells may be or prepare to be responsive toward androgens and IGFs

Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer

<p>Abstract</p> <p>Background</p> <p>We have previously reported that expression of the Wnt antagonist genes <it>SFRP1 </it>and <it>SFRP5 </it>is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether <it>SFRP2 </it>promoter methylation might serve as a potential tumor biomarker.</p> <p>Methods</p> <p>We analyzed <it>SFRP2 </it>mRNA expression and <it>SFRP2 </it>promoter methylation in 10 breast cell lines, 199 primary breast carcinomas, 20 matched normal breast tissues and 17 cancer-unrelated normal breast tissues using RT-PCR, realtime PCR, methylation-specific PCR and Pyrosequencing, respectively. SFRP2 protein expression was assessed by immunohistochemistry on a tissue microarray. Proliferation assays after transfection with an <it>SFRP2 </it>expression vector were performed with mammary MCF10A cells. Statistical evaluations were accomplished with SPSS 14.0 software.</p> <p>Results</p> <p>Of the cancerous breast cell lines, 7/8 (88%) lacked <it>SFRP2 </it>mRNA expression due to <it>SFRP2 </it>promoter methylation (<it>P </it>< 0.001). <it>SFRP2 </it>expression was substantially restored in most breast cell lines after treatment with 5-aza-2'-deoxycytidine and trichostatin A. In primary breast carcinomas SFRP2 protein expression was strongly reduced in 93 of 125 specimens (74%). <it>SFRP2 </it>promoter methylation was detected in 165/199 primary carcinomas (83%) whereas all cancer-related and unrelated normal breast tissues were not affected by <it>SFRP2 </it>methylation. <it>SFRP2 </it>methylation was not associated with clinicopathological factors or clinical patient outcome. However, loss of SFRP2 protein expression showed a weak association with unfavorable patient overall survival (<it>P </it>= 0.071). Forced expression of <it>SFRP2 </it>in mammary MCF10A cells substantially inhibited proliferation rates (<it>P </it>= 0.045).</p> <p>Conclusion</p> <p>The <it>SFRP2 </it>gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation of <it>SFRP2 </it>expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of <it>SFRP2</it>. Although clinical patient outcome was not associated with <it>SFRP2 </it>methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify <it>SFRP2 </it>promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.</p

Incorporating molecular data in fungal systematics: a guide for aspiring researchers

The last twenty years have witnessed molecular data emerge as a primary research instrument in most branches of mycology. Fungal systematics, taxonomy, and ecology have all seen tremendous progress and have undergone rapid, far-reaching changes as disciplines in the wake of continual improvement in DNA sequencing technology. A taxonomic study that draws from molecular data involves a long series of steps, ranging from taxon sampling through the various laboratory procedures and data analysis to the publication process. All steps are important and influence the results and the way they are perceived by the scientific community. The present paper provides a reflective overview of all major steps in such a project with the purpose to assist research students about to begin their first study using DNA-based methods. We also take the opportunity to discuss the role of taxonomy in biology and the life sciences in general in the light of molecular data. While the best way to learn molecular methods is to work side by side with someone experienced, we hope that the present paper will serve to lower the learning threshold for the reader.Comment: Submitted to Current Research in Environmental and Applied Mycology - comments most welcom