HCF-2 inhibits cell proliferation and activates differentiation-gene expression programs.

HCF-2 is a member of the host-cell-factor protein family, which arose in early vertebrate evolution as a result of gene duplication. Whereas its paralog, HCF-1, is known to act as a versatile chromatin-associated protein required for cell proliferation and differentiation, much less is known about HCF-2. Here, we show that HCF-2 is broadly present in human and mouse cells, and possesses activities distinct from HCF-1. Unlike HCF-1, which is excluded from nucleoli, HCF-2 is nucleolar-an activity conferred by one and a half C-terminal Fibronectin type 3 repeats and inhibited by the HCF-1 nuclear localization signal. Elevated HCF-2 synthesis in HEK-293 cells results in phenotypes reminiscent of HCF-1-depleted cells, including inhibition of cell proliferation and mitotic defects. Furthermore, increased HCF-2 levels in HEK-293 cells lead to inhibition of cell proliferation and metabolism gene-expression programs with parallel activation of differentiation and morphogenesis gene-expression programs. Thus, the HCF ancestor appears to have evolved into a small two-member protein family possessing contrasting nuclear versus nucleolar localization, and cell proliferation and differentiation functions

Lily Day, Wednesday, March 4, 1964

Comments on past research in Ohio on Lilies / D. C. Kiplinger -- Lily investigations / Abdel-Alim M. Shoushan -- Further studies on causes and control of leaf scorch in Croft Easter lily / N. W. Stuart, William Skou, and D. C. Kiplinger -- Fertilizer and lime affect amount of leaf scorch in Croft Easter lilies / Neil W. Stuart, K. S. Nelson and D. C. Kiplinger -- Comparative development of Ace and Nellie White lilies / Dennis Rider and D. C. Kiplinger -- Experiments with potted lilies, 1961-1962 / D. C. Kiplinger, Robert O. Miller, Howard Jones, and Dennis Rider -- Lily culture and timing for Easter, 1964 / D. C. Kiplinger and Robert O. Miller -- High temperature treatment of Easter lily bulbs / Robert O. Miller and D. C. Kiplinger -- An investigation of causes of variation in the growth of commercial and experimental lilies / Robert O. Miller and D. C. Kiplinger -- Applying terraclor with or without dexon / D. C. Kiplinger, Robert O. Miller and Leonard J. Her

Introduced plants as novel Anthropocene habitats for insects

Major environmental changes in the history of life on Earth have given rise to novel habitats, which gradually accumulate species. Human‐induced change is no exception, yet the rules governing species accumulation in anthropogenic habitats are not fully developed. Here we propose that nonnative plants introduced to Great Britain may function as analogues of novel anthropogenic habitats for insects and mites, analysing a combination of local‐scale experimental plot data and geographic‐scale data contained within the Great Britain Database of Insects and their Food Plants. We find that novel plant habitats accumulate the greatest diversity of insect taxa when they are widespread and show some resemblance to plant habitats which have been present historically (based on the relatedness between native and nonnative plant species), with insect generalists colonizing from a wider range of sources. Despite reduced per‐plant diversity, nonnative plants can support distinctive insect communities, sometimes including insect taxa that are otherwise rare or absent. Thus, novel plant habitats may contribute to, and potentially maintain, broader‐scale (assemblage) diversity in regions that contain mixtures of long‐standing and novel plant habitats

An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.

Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells

A solution of the coincidence problem based on the recent galactic core black hole mass density increase

A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial

Background: Open radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. Objective: To compare perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. Design, setting, and participants: A prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. Intervention: Standard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Outcome measurements and statistical analysis: Primary outcomes were overall 90-d grade 2-5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3-and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. Results and limitations: The trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2-5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, -21% to -13%; p = 0.7). The similar rates of grade 2-5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss (p = 0.027) but significantly longer operative time than the ORC group (p \u3c 0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p = 0.5). Three-and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. Conclusions: This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3-and 6-mo QOL outcomes were observed regardless of surgical technique. Patient summary: Of 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. Trial Registration: ClinicalTrials. gov identifier NCT01076387, www.clinicaltrials.gov. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved

Interferometry with Bose-Einstein Condensates in Microgravity

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Due to their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this paper we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far-field of a double-slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.Comment: 8 pages, 3 figures; 8 pages of supporting materia

Does Higher Cost Inefficiency Imply Higher Profit Inefficiency? Evidence on Inefficiency and Ownership of German Hospitals

This paper investigates cost and profit efficiency of German hospitals. More specifically, it deals with the question how hospital efficiency varies with ownership, patient structure,and other exogenous factors, which are neither inputs nor outputs of the production process. We conduct a Stochastic Frontier Analysis (SFA) on a multifaceted administrative German dataset combined with the balance sheets of 374 hospitals for the years 2002 to 2005.The results indicate that private (for-profit) and (private) non-profit hospitals are on average less cost efficient but more profit efficient than publicly owned hospitals