How Open Is the Maker Movement?:Integrative Literature Review of the Openness Practices in the Global Maker Movement

This article explores the multiple meanings of the concept of openness in the global maker movement. Openness is viewed as one of the key principles of the maker movement. As the global maker movement is a bricolage of diverse and situated practices and traditions, there are also many different interpretations and ways of practicing openness. We have explored this diversity with an integrative literature review, relying on the Web of Science™ database. We identified three interrelated but also, in part, mutually contested approaches to openness. Firstly, openness often refers to applying open hardware. Secondly, it is in many cases related to the inclusion and empowerment of various groups in making. Thirdly, openness appears to be seen as a means to pursue economic growth through increasing innovation activity and entrepreneurship. Our results also highlight the substantial barriers encountered by makers while aiming to open up their practices. These barriers include: value conflicts in which openness is overridden by other important values; exclusion of lower income groups from making due to a lack of resources; and difficulties in maintaining long-term activities. The different meanings of openness together with the barriers create tensions within the maker movement while implementing openness. We propose that engaging in a reflexive futures dialogue on the consequences of these tensions can enhance the maker movement to become more open, inclusive and resilient

How Open Is the Maker Movement?:Integrative Literature Review of the Openness Practices in the Global Maker Movement

This article explores the multiple meanings of the concept of openness in the global maker movement. Openness is viewed as one of the key principles of the maker movement. As the global maker movement is a bricolage of diverse and situated practices and traditions, there are also many different interpretations and ways of practicing openness. We have explored this diversity with an integrative literature review, relying on the Web of Science™ database. We identified three interrelated but also, in part, mutually contested approaches to openness. Firstly, openness often refers to applying open hardware. Secondly, it is in many cases related to the inclusion and empowerment of various groups in making. Thirdly, openness appears to be seen as a means to pursue economic growth through increasing innovation activity and entrepreneurship. Our results also highlight the substantial barriers encountered by makers while aiming to open up their practices. These barriers include: value conflicts in which openness is overridden by other important values; exclusion of lower income groups from making due to a lack of resources; and difficulties in maintaining long-term activities. The different meanings of openness together with the barriers create tensions within the maker movement while implementing openness. We propose that engaging in a reflexive futures dialogue on the consequences of these tensions can enhance the maker movement to become more open, inclusive and resilient.EC/H2020/101006285/EU/Critical Making: Studying RRI Principles in the Maker Community/Critical Makin

Comparative study on the rheological properties and tablettability of various APIs and their composites with titanate nanotubes

The present study aimed to investigate the processability of API-titanate nanotube composites into direct compressed tablets and therefore to reveal the benefits of the composite formation provided in tablet manufacturing. Diltiazem hydrochloride, diclofenac sodium, atenolol, hydrochlorothiazide and their 1:1 ratio composites formed with titanate nanotubes (TNTs) were used for the comparative investigations focusing on flowability, compaction behaviour and post-compressional property measurements. The flowability was studied by measuring the flow time, the angle of repose, the Hausner Ratio and the Compressibility Index, while the compaction properties were estimated by the use of out-of-the-die method applying Kawakita and Walker models. The tablet properties were described by determining the apparent tablet density, the breaking strength and the disintegration time. Based on the experimental results, the composites have superior flowability and display better compactibility and compressibility than the pure APIs. These findings were supported by the more favourable post-compressional properties shown by the composite containing tablets. However, the measurements also revealed that the advantageous effect of TNTs on drug tablettability depends on the efficiency of the incorporation process. © 2017 Elsevier B.V

Identification of epidermal Pdx1 expression discloses different roles of Notch1 and Notch2 in murine KrasG12D-induced skin carcinogenesis in vivo

Background The Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis. To study the role of Notch and oncogenic Kras signaling in a progenitor cell population, Pdx1-Cre mice were utilized to generate conditional oncogenic KrasG12D mice with ablation of Notch1 and/or Notch2. Methodology/Principal Findings Surprisingly, mice with activated KrasG12D and Notch1 but not Notch2 ablation developed skin papillomas progressing to squamous cell carcinoma providing evidence for Pdx1 expression in the skin. Immunostaining and lineage tracing experiments indicate that PDX1 is present predominantly in the suprabasal layers of the epidermis and rarely in the basal layer. Further analysis of keratinocytes in vitro revealed differentiation-dependent expression of PDX1 in terminally differentiated keratinocytes. PDX1 expression was also increased during wound healing. Further analysis revealed that loss of Notch1 but not Notch2 is critical for skin tumor development. Reasons for this include distinct Notch expression with Notch1 in all layers and Notch2 in the suprabasal layer as well as distinctive p21 and β-catenin signaling inhibition capabilities. Conclusions/Significance Our results provide strong evidence for epidermal expression of Pdx1 as of yet not identified function. In addition, this finding may be relevant for research using Pdx1-Cre transgenic strains. Additionally, our study confirms distinctive expression and functions of Notch1 and Notch2 in the skin supporting the importance of careful dissection of the contribution of individual Notch receptors

Morphological evidence for enhanced kisspeptin and neurokinin B signaling in the infundibular nucleus of the aging man.

Peptidergic neurons synthesizing kisspeptin (KP) and neurokinin B (NKB) in the hypothalamic infundibular nucleus have been implicated in negative sex steroid feedback to GnRH neurons. In laboratory rodents, testosterone decreases KP and NKB expression in this region. In the present study, we addressed the hypothesis that the weakening of this inhibitory testosterone feedback in elderly men coincides with enhanced KP and NKB signaling in the infundibular nucleus. This central hypothesis was tested in a series of immunohistochemical studies on hypothalamic sections of male human individuals that were divided into arbitrary "young" (21-49 yr, n = 11) and "aged" (50-67 yr, n = 9) groups. Quantitative immunohistochemical experiments established that the regional densities of NKB-immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, exceeded several times those of the KP-IR elements. Robust aging-dependent enhancements were identified in the regional densities of KP-IR perikarya and fibers and the incidence of afferent contacts they established onto GnRH neurons. The abundance of NKB-IR perikarya, fibers, and axonal appositions to GnRH neurons also increased with age, albeit to lower extents. In dual-immunofluorescent studies, the incidence of KP-IR NKB perikarya increased from 36% in young to 68% in aged men. Collectively, these immunohistochemical data suggest an aging-related robust enhancement in central KP signaling and a moderate enhancement in central NKB signaling. These changes are compatible with a reduced testosterone negative feedback to KP and NKB neurons. The heavier KP and NKB inputs to GnRH neurons in aged, compared with young, men may play a role in the enhanced central stimulation of the reproductive axis. It requires clarification to what extent the enhanced KP and NKB signaling upstream from GnRH neurons is an adaptive response to hypogonadism or, alternatively, a consequence of a decline in the androgen sensitivity of KP and NKB neurons

In vitro binding and functional studies of Ac-RYYRIK-ol and its derivatives, novel partial agonists of the nociceptin/orphanin F/Q receptor.

Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NOP receptor affinity and selectivity were identified. On the basis of this information we developed a number of novel compounds. The detailed structure-activity studies on the partial agonist Ac-RYYRIK-NH(2) are reported in this communication. Besides the modifications on N- and C-terminal, Arg-Cit exchange was performed on the template structure. The novel hexapeptides were analyzed in radioligand binding, functional biochemical [(35)S]GTPgammaS binding assays by using membranes from rat brains and Chinese hamster ovary cells expressing human NOP receptor. The agonist/antagonist properties were also tested on in the mouse vas deferens bioassay. C-terminal modification yielded a high affinity, selective and potent NOP ligand (Ac-RYYRIK-ol) with a partial agonist property. Several analogs of this compound were synthesized. The presence of the positively charged arginine residue at the first position turned out to be crucial for the biological activity of the hexapeptide. The N-terminal modifications with various acyl groups (ClAc, pivaloyl, formyl, benzoyl, mesyl) decreased the affinity of the ligand towards the receptor and the intrinsic activity for stimulating the G-protein activation was also decreased. The structure-activity studies on the hexapeptide derivatives provided some basic information on the structural requirements for receptor binding and activation

Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory