Tetraspanin CD9: Contributions to Cancer Cell and Vascular Cell Phenotypes from the Sixth Man

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate that CD9 expression promotes human fibrosarcoma cell invasion by upregulating matrixmetalloproteinase-9 expression. These effects were dependent upon an extracellular region of CD9 and involved the presence and activity of the epidermal growth factor receptor. In the vascular cell model, CD9 elicited the actin arrangement and contraction of human aortic smooth muscle cells in a RhoA dependent manner. Taken together these provide insight on how tetraspanins regulate diverse cellular phenotypes

Photonic chip based optical frequency comb using soliton induced Cherenkov radiation

By continuous wave pumping of a dispersion engineered, planar silicon nitride microresonator, continuously circulating, sub-30fs short temporal dissipative solitons are generated, that correspond to pulses of 6 optical cycles and constitute a coherent optical frequency comb in the spectral domain. Emission of soliton induced Cherenkov radiation caused by higher order dispersion broadens the spectral bandwidth to 2/3 of an octave, sufficient for self referencing, in excellent agreement with recent theoretical predictions and the broadest coherent microresonator frequency comb generated to date. In a further step, this frequency comb is fully phase stabilized. The ability to preserve coherence over a broad spectral bandwidth using soliton induced Cherenkov radiation marks a critical milestone in the development of planar optical frequency combs, enabling on one hand application in e.g. coherent communications, broadband dual comb spectroscopy and Raman spectral imaging, while on the other hand significantly relaxing dispersion requirements for broadband microresonator frequency combs and providing a path for their generation in the visible and UV. Our results underscore the utility and effectiveness of planar microresonator frequency comb technology, that offers the potential to make frequency metrology accessible beyond specialized laboratories.Comment: Changes: - Added data (new Fig.4) on the first full phase stabilization of a dissipative Kerr soliton (or dissipative cavity soliton) in a microresonator - Extended Fig. 8 in the SI - Introduced nomenclature of dissipative Kerr solitons - Minor other change

Algorithms for highly symmetric linear and integer programs

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimension

Algorithms for highly symmetric linear and integer programs

This paper deals with exploiting symmetry for solving linear and integer programming problems. Basic properties of linear representations of finite groups can be used to reduce symmetric linear programming to solving linear programs of lower dimension. Combining this approach with knowledge of the geometry of feasible integer solutions yields an algorithm for solving highly symmetric integer linear programs which only takes time which is linear in the number of constraints and quadratic in the dimensio

Regionalität: Wettbewerbliche Überlegungen zum Krankenhausmarkt

In den letzten Jahren haben die durch das Bundeskartellamt behandelten Fusionskontrollverfahren im Krankenhaussektor zu einer anhaltenden wettbewerbsökonomischen Debatte geführt. Als eine wichtige Erkenntnis hat sich hierbei ergeben, dass für den überwiegenden Bereich der akutstationären Krankenhausversorgung von einer vergleichsweise engen räumlichen Marktabgrenzung auszugehen ist, der Wettbewerb zwischen Krankenhäusern daher in der Region ausgetragen wird. Das vorliegende Papier untersucht Regionalität und Krankenhauswettbewerb unter verschiedenen Aspekten: Insbesondere beleuchten wir die marktverschließenden Wirkungen der dualistischen Krankenhausfinanzierung, gehen auf die besondere Problematik von Krankenhäusern in der Fusionskontrolle ein und arbeiten das Ob und Wie wesentlicher Konsequenzen von Regionalität in der Versorgung mit Krankenhausleistungen heraus. Zudem greifen wir den Vorschlag der Monopolkommission auf, die Fusionskontrolle im Krankenhausbereich zu verschärfen, um der Regionalität der Krankenhausmärkte gerecht zu werden. -- The increasing number of hospital mergers over the last few years has lead to some debate over the form and degree of competition between hospitals. An important conclusion has been that the geographic definition of the relevant market should be rather narrow when considering inpatient care units. Thus, competition between hospitals takes place in the region. This paper analyses regionalism and hospital competition, highlighting several aspects: We shed light on the market-foreclosing effects of the dual financing system, discuss the special features of hospitals within the German merger control regime and underline the consequences of regionalism for the provision of hospital care. In addition, we follow the proposal made by the German Monopolies Commission to strengthen the merger control regime in order to subject more regional mergers to merger control.

Role of the HCF-1 Basic Region in Sustaining Cell Proliferation

BACKGROUND: The human herpes simplex virus-associated host cell factor 1 (HCF-1) is a conserved human transcriptional co-regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors. It is synthesized as a 2035 amino acid precursor that is cleaved to generate an amino- (HCF-1(N)) terminal subunit, which promotes G1-to-S phase progression, and a carboxy- (HCF-1(C)) terminal subunit, which controls multiple aspects of cell division during M phase. The HCF-1(N) subunit contains a Kelch domain that tethers HCF-1 to sequence-specific DNA-binding transcription factors, and a poorly characterized so called "Basic" region (owing to a high ratio of basic vs. acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC) component. Here we studied the role of the Basic region in cell proliferation and G1-to-S phase transition assays. METHODOLOGY/PRINCIPAL FINDINGS: Surprisingly, much like the transcriptional activation domains of sequence-specific DNA-binding transcription factors, there is no unique sequence within the Basic region required for promoting cell proliferation or G1-to-S phase transition. Indeed, the ability to promote these activities is size dependent such that the shorter the Basic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferation in a temperature-sensitive tsBN67 cell assay are more stringent than for G1-to-S phase progression in an HCF-1 siRNA-depletion HeLa-cell assay. Thus, either half of the Basic region alone can support G1-to-S phase progression but not cell proliferation effectively in these assays. Nevertheless, the Basic region displays considerable structural plasticity because each half is able to promote cell proliferation when duplicated in tandem. Consistent with a potential role in promoting cell-cycle progression, the Sin3a HDAC component can associate independently with either half of the Basic region fused to the HCF-1 Kelch domain. CONCLUSIONS/SIGNIFICANCE: While conserved, the HCF-1 Basic region displays striking structural flexibility for controlling cell proliferation

Wettbewerbspotenziale im deutschen Apothekenmarkt

Der vorliegende Beitrag analysiert den Ordnungsrahmen für den deutschen Apothekenmarkt und die dortigen Konkurrenzbeziehungen, welche durch signifikante Wettbewerbsdefizite gekennzeichnet sind. Ausgehend von unserer Diagnose und den Befunden werden die Vor- und Nachteile von zwei Therapieoptionen als diskutiert: Das sogenannte Selektivertragsmodell, bei dem Apotheken um das Kollektiv der Versichertengemeinschaft einer jeden Krankenkasse konkurrieren, und das Modell der Apothekentaxe, bei dem die Patienten die Leistung der Apotheke direkt vergüten. Für das Modell der Apothekentaxe werden in drei Szenarien die Wettbewerbswirkungen und das mögliche Einsparpotenzial pro Jahr ermittelt, dass sich auf bis zu 448 Mio. EUR beläuft. -- This paper analyses the institutional framework for pharmacies in Germany and competition in that sector, which is characterized by significant competition deficits. Based on our diagnosis and findings the advantages and disadvantages of two therapies are discussed: The selective contracting model, where pharmacies compete for the collective group of all members of every health insurance company, and the pharmacy fee model, where patients have to directly pay for pharmacy services. For the latter model we analyze, under three different scenarios, the competitive effects and annual saving potentials which can amount up to 448 million euro.Apotheke,Wettbewerb,Gesundheitsausgaben,Effizienz,Nachhaltigkeit,pharmacies,competition,health-care expenditures,efficiency,sustainability