Non-obviousness and Screening

The paper offers a novel justification for the non-obviousness patentability requirement. An innovation involves two stages: research results in a technology blueprint, which development transforms into a profitable activity. An innovator, who is either efficient or inefficient, must rely on outside finance for the development. Only patented technologies are developed. Strengthening the non-obviousness requirement alleviates adverse selection by discouraging inefficient innovators from doing research, but creates inefficiencies by excluding marginal innovations. We show that it is socially optimal to raise the non-obviousness requirement so as to exclude bad innovators; we also provide several robustness checks and discuss the policy implications

Observations of Toroidal Coupling for Low-N Alfven Modes in the Tca Tokamak

The antenna structure in the TCA tokamak is phased to excite preferentially Alfven waves with known toroidal and poloidal wave numbers. Surprisingly, the loading spectrum includes both discrete and continuum modes with poloidal wave numbers incompatible with the antenna phasing. These additional modes, which are important for our heating experiments, can be attributed to linear mode coupling induced by the toroidicity of the plasma column, when we take into account ion-cyclotron effects

Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) ‘resets’ these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices—which do not have the constraints of bioprinted scaffolds—the ‘reset’ vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call ‘Organ-On-VascularNet’. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting

The use of mesh in acute hernia: frequency and outcome in 99 cases

Background: Incarceration of inguinal, umbilical and cicatricial hernias is a frequent problem. However, little is known about the relationship between the use of mesh and outcome after surgery. The goal of this study was to describe the relationship between the use of mesh in incarcerated hernia and the clinical outcome. Patients and methods: Correspondence, operation reports and patient files between January 1995 and December 2005 of patients presented at one academic and one teaching hospital in Rotterdam were searched for the following keywords: incarceration, strangulation and hernia. The patient characteristics, clinical presentation, pre-operative findings and clinical course were scored and analysed. Results: A total of 203 patients could be identified: 76 inguinal, 52 umbilical, 39 incisional, 14 epigastric, 14 femoral, five trocar and three spigelian hernias. In the statistical analysis, epigastric, femoral, trocar and spigelian hernias were pooled, due to their small group sizes. One patient was excluded from the analysis because the hernia was not corrected during operation. In total, 99 hernias were repaired using mesh versus 103 primary suture repairs. Twenty-five wound infections were registered (12.3%). One mesh was removed during a reintervention for anastomotic leakage, although no signs of wound infection were present. Nine patients died, none of them due to wound-related problems [one cardiovascular, one ruptured aneurysm, two anastomotic leakage, two sepsis e causa incognita (e.c.i.), three pulmonary complications]. Univariate analysis showed that female patients (P = 0.007), adipose patients (P = 0.016), patients with an umbilical hernia (P = 0.01) and patients who underwent a bowel resection (P = 0.015) had a significantly higher rate of wound infections. The type of repair (e.g. primary suture or mesh), use of antibiotic prophylaxis, gender, ASA class and age showed no significant relation with post-operative wound infection. After logistic regression analysis, only bowel resection (P = 0.020) showed a significant relation with post-operative wound infection. Conclusions: Wound infection rates are high after the correction of acute hernia, but clinical consequences are relatively low. Mesh correction of an acute hernia seems to be safe and should be considered in every incarcerated hernia

Repetition, expectation, and the perception of time

Prior experience with a stimulus profoundly affects how it is processed, perceived, and acted upon. One striking finding is that repeated items seem to last for less time than novel or rare ones. This link between the processing of stimulus identity and the perception of stimulus duration has important implications for theories of timing, and for broader accounts of the organization, purpose, and neural basis of perception. Here, we examine the nature and basis of the repetition effect on subjective duration. Contrary to unitary accounts which equate repetition effects with implicit expectations about forthcoming stimuli, new work suggests that first-order repetition and second-order repetition?expectations differentially affect the perception of time. We survey emerging evidence from behavioural studies of time perception and neuroscientific studies of stimulus encoding which support this view, and outline key questions for the future

Whole Genome Sequencing Highlights Genetic Changes Associated with Laboratory Domestication of C. elegans

Defining the mutational landscape when individuals of a species grow separately and diverge over many generations can provide insights into trait evolution. A specific example of this involves studying changes associated with domestication where different lines of the same wild stock have been cultivated independently in different standard environments. Whole genome sequence comparison of such lines permits estimation of mutation rates, inference of genes' ancestral states and ancestry of existing strains, and correction of sequencing errors in genome databases. Here we study domestication of the C. elegans Bristol strain as a model, and report the genome sequence of LSJ1 (Bristol), a sibling of the standard C. elegans reference wild type N2 (Bristol). The LSJ1 and N2 lines were cultivated separately from shortly after the Bristol strain was isolated until methods to freeze C. elegans were developed. We find that during this time the two strains have accumulated 1208 genetic differences. We describe phenotypic variation between N2 and LSJ1 in the rate at which embryos develop, the rate of production of eggs, the maturity of eggs at laying, and feeding behavior, all the result of post-isolation changes. We infer the ancestral alleles in the original Bristol isolate and highlight 2038 likely sequencing errors in the original N2 reference genome sequence. Many of these changes modify genome annotation. Our study provides a starting point to further investigate genotype-phenotype association and offers insights into the process of selection as a result of laboratory domestication

Reaction of rat connective tissue to mineral trioxide aggregate and diaket

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare the reaction of rat connective tissue to two root-end filling materials: white Mineral Trioxide Aggregate (WMTA) and Diaket.</p> <p>Methods</p> <p>Each of the materials was placed in dentine tubes and implanted subcutaneously in the dorsal connective tissue of 21 Wistar albino rats. Tissue biopsies were collected 7, 30, and 60 days after the implantation procedure. The specimens were processed and stained with hematoxylin and eosin and examined microscopically. After determining inflammatory cell numbers in sections from each specimen, inflammatory reaction scores were defined as follows: 0; no or few inflammatory cells (no reaction), 1; less than 25 cells (mild reaction), 2; 25 to 125 cells, (moderate reaction), and 3; 125 or more cells (severe reaction). Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney tests.</p> <p>Results</p> <p>There were statistically significant differences in the median inflammatory cell numbers throughout the three test periods, with the most severe degree of inflammation observed at the one-week period. Few cases of necrosis were observed with WMTA. Diaket exhibited the most severe degree of inflammation and necrosis. After 30 days, both materials provoked moderate inflammatory reaction. The eight-week period showed the least severe degree of inflammation in all groups.</p> <p>Conclusions</p> <p>It was concluded that WMTA exhibits a more favourable tissue response compared with Diaket which induced more severe inflammatory reaction than WMTA and the control.</p