G1 checkpoint protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder

The G1 cell cycle checkpoint regulates entry into S phase for normal cells. Components of the G1 checkpoint, including retinoblastoma (Rb) protein, cyclin D1 and p16INK4a, are commonly altered in human malignancies, abrogating cell cycle control. Using immunohistochemistry, we examined 79 invasive transitional cell carcinomas of the urinary bladder treated by cystectomy, for loss of Rb or p16INK4a protein and for cyclin D1 overexpression. As p53 is also involved in cell cycle control, its expression was studied as well. Rb protein loss occurred in 23/79 cases (29%); it was inversely correlated with loss of p16INK4a, which occurred in 15/79 cases (19%). One biphenotypic case, with Rb+p16– and Rb-p16+ areas, was identified as well. Cyclin D1 was overexpressed in 21/79 carcinomas (27%), all of which retained Rb protein. Fifty of 79 tumours (63%) showed aberrant accumulation of p53 protein; p53 staining did not correlate with Rb, p16INK4a, or cyclin D1 status. Overall, 70% of bladder carcinomas showed abnormalities in one or more of the intrinsic proteins of the G1 checkpoint (Rb, p16INK4a and cyclin D1). Only 15% of all bladder carcinomas (12/79) showed a normal phenotype for all four proteins. In a multivariate survival analysis, cyclin D1 overexpression was linked to less aggressive disease and relatively favourable outcome. In our series, Rb, p16INK4a and p53 status did not reach statistical significance as prognostic factors. In conclusion, G1 restriction point defects can be identified in the majority of bladder carcinomas. Our findings support the hypothesis that cyclin D1 and p16INK4a can cooperate to dysregulate the cell cycle, but that loss of Rb protein abolishes the G1 checkpoint completely, removing any selective advantage for cells that alter additional cell cycle proteins. © 1999 Cancer Research Campaig

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Novel self-cleaning coatings: Development and testing

Self-cleaning coatings, which follow the concepts of photocatalysis, superhydrophobicity or superhydrophilicity, are commercially available. The self-cleaning properties of such coatings, however, are significantly degraded, when they are exposed to scratching or surface tension affecting substances. Within this work a novel concept to generate surfaces with self-cleaning properties is proved. This concept bases on a usage of UV/IR-reflecting additives in organic or inorganic/organic hybrid coatings. The self-cleaning properties of these coatings are evaluated by the outdoor exposure and with a novel quantitative short-time test. The results obtained show a good correlation. Additional methods for the quantification of the UV-induced degradation of coatings are proposed

Customized Software Environment for Remote Learning: Providing Students a Specialized Learning Experience

The Covid-19 pandemic has challenged educators across the world to move their teaching and mentoring from in-person to remote. During nonpandemic semesters at their institutes (e.g. universities), educators can directly provide students the software environment needed to support their learning - either in specialized computer laboratories (e.g. computational chemistry labs) or shared computer spaces. These labs are often supported by staff that maintains the operating systems (OS) and software. But how does one provide a specialized software environment for remote teaching? One solution is to provide students a customized operating system (e.g., Linux) that includes open-source software for supporting your teaching goals. However, such a solution should not require students to install the OS alongside their existing one (i.e. dual/multi-booting) or be used as a complete replacement. Such approaches are risky because of a) the students' possible lack of software expertise, b) the possible disruption of an existing software workflow that is needed in other classes or by other family members, and c) the importance of maintaining a working computer when isolated (e.g. societal restrictions). To illustrate possible solutions, we discuss our approach that used a customized Linux OS and a Docker container in a course that teaches computational chemistry and Python3

Association of Periprocedural Inflammatory Activation With Increased Risk for Early Coronary Stent Thrombosis

Background Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis. Methods and Results Within a prospective single‐center registry, the association between preprocedural acute inflammatory activation, defined as C‐reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P<0.00001), independent of age, sex, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor, and clinical presentation. Elevated laboratory markers of acute inflammation were associated with the occurrence of stent thrombosis in both patients with acute coronary syndrome (hazard ratio, 2.63; P<0.001) and in patients with stable ischemic heart disease (hazard ratio, 3.57; P<0.001). Conclusions An acute inflammatory state at the time of PCI was associated with a significantly increased risk of early stent thrombosis. Evidence of acute inflammation should result in deferred PCI in elective patients, while future studies are needed for patients with acute coronary syndrome