Flexibility properties in Complex Analysis and Affine Algebraic Geometry

In the last decades affine algebraic varieties and Stein manifolds with big (infinite-dimensional) automorphism groups have been intensively studied. Several notions expressing that the automorphisms group is big have been proposed. All of them imply that the manifold in question is an Oka-Forstneri\v{c} manifold. This important notion has also recently merged from the intensive studies around the homotopy principle in Complex Analysis. This homotopy principle, which goes back to the 1930's, has had an enormous impact on the development of the area of Several Complex Variables and the number of its applications is constantly growing. In this overview article we present 3 classes of properties: 1. density property, 2. flexibility 3. Oka-Forstneri\v{c}. For each class we give the relevant definitions, its most significant features and explain the known implications between all these properties. Many difficult mathematical problems could be solved by applying the developed theory, we indicate some of the most spectacular ones.Comment: thanks added, minor correction

approach to a water safety plan for recreational waters disinfection of a drainage pumping station as an unconventional point source of fecal contamination

Abstract In the context of the management of bathing water quality, the intermittent contamination of rainwater drainage pumps (unconventional point sources) could be controlled by peracetic acid disinfection. Thus, a field experimental study was carried out to set up a water safety plan, determining the monitoring parameters and the critical limit for corrective actions. With a 0.5 mg/l dosage, the average logarithmic microbial reduction was 0.50 ± 0.48 for Escherichia coli (EC) and 0.43 ± 0.54 for intestinal enterococci. Among the chemical and physical parameters that could be monitored in real time, the oxidation–reduction potential was the only one able to predict the microbial concentration discharged from a drainage pump and the logarithmic abatement of EC. Considering the possible impact of this source on bathing waters in terms of additional risk of gastrointestinal infections, the critical limit for continuous monitoring was established using a quantitative microbial risk assessment (QMRA) model

Hydatid disease of the liver: thirty years of surgical experience.

Hydatid disease of the liver is a relatively frequent disease. Although the natural history is almost completely known, several complications may occur. The aim of this study was to show that radical surgical resection of the hepatic hydatid cyst is a safe and very effective technique, based on our results after 30-year experience. A review of most significant studies was carried out. We retrospectively evaluated our surgical cases. From January 1973 to December 2003 we treated 216 patients, 98 males and 118 females. Survival was compared with the Kaplan-Meier test, using log-rank analysis to compare data. Differences with a p value less than 0.05 were considered significant. A total of 279 cysts were excised. We performed pericystectomy in 122 cases, 73 of which closed. We also performed 19 atypical resections, 10 segmentectomies, 20 lobectomies and 2 percutaneous treatments. In more than 90% of cases, preoperative data collection was completed by preoperative ultrasound. The cumulative morbidity was 13%. The recurrence rate amounted to 4.3% at 5 years and 7% at 10 years: of these, 6 occurred after non-radical surgery and 2 after total pericystectomy or liver resection (p < 0.001). Technical advances and accumulated experience permit safe treatment of hepatic hydatid cysts by radical resection, with an almost zero recurrence rate, making it the treatment of choice over partial resection. The utility of percutaneous treatment remains confined to limited indications, such as laparoscopy

A ligand-based system for receptor-specific delivery of proteins

Gene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand\u2019s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases

Are the hosts of gamma-ray bursts sub-luminous and blue galaxies?

We present K-band imaging observations of ten gamma-ray burst (GRB) host galaxies for which an optical and/or radio afterglow associated with the GRB event was clearly identified. Data were obtained with the Very Large Telescope and New Technology Telescope at ESO (Chile), and with the Gemini-North telescope at Mauna Kea (Hawaii). Adding to our sample nine other GRB hosts with K-band photometry and determined redshifts published in the literature, we compare their observed and absolute K magnitudes as well as their R − K colours with those of other distant sources detected in various optical, nearinfrared, mid-infrared and submillimeter deep surveys. We find that the GRB host galaxies, most of them lying at 0.5 ≲ z ≲ 1.5, exhibit very blue colours, comparable to those of the faint blue star-forming sources at high redshift. They are sub-luminous in the K-band, suggesting a low stellar mass content. We do not find any GRB hosts harbouring R- and K-band properties similar to those characterizing the luminous infrared/submillimeter sources and the extremely red starbursts. Should GRBs be regarded as an unbiased probe of star-forming activity, this lack of luminous and/or reddened objects among the GRB host sample might reveal that the detection of GRB optical afterglows is likely biased toward unobscured galaxies. It would moreover support the idea that a large fraction of the optically-dark GRBs occur within dust-enshrouded regions of star formation. On the other hand, our result might also simply reflect intrinsic properties of GRB host galaxies experiencing a first episode of very massive star formation and characterized by a rather weak underlying stellar population. Finally, we compute the absolute B magnitudes for the whole sample of GRB host galaxies with known redshifts and detected at optical wavelengths. We find that the latter appear statistically even less luminous than the faint blue sources which mostly contributed to the B-band light emitted at high redshift. This indicates that the formation of GRBs could be favoured in particular systems with very low luminosities and, therefore, low metallicities. Such an intrinsic bias toward metal-poor environments would be actually consistent with what can be expected from the currently-favoured scenario of the “collapsar”. The forthcoming launch of the SWIFT mission at the end of 2003 will provide a dramatic increase of the number of GRB-selected sources. A detailed study of the chemical composition of the gas within this sample of galaxies will thus allow us to further analyse the potential effect of metallicity in the formation of GRB events.Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

A Hybrid Model for Dynamic Simulation of Custom Software Projects in a Multiproject Environment

This paper describes SimHiProS, a hybrid simulation model of software production. The goal is to gain insight on the dynamics induced by resource sharing in multiproject management. In order to achieve it the hierarchy of decisions in a multiproject organization is modeled and some resource allocation methods based on algorithms from the OR/AI domain are used. Other critical issues such as the hybrid nature of software production and the effects of measurement and control are also incorporated in the model. Some first results are presented.Ministerio de Ciencia e Innovación TIN2004-06689-C03-03Ministerio de Ciencia e Innovación TIN2007-67843-C06-0

Degradation of Cdc25A by \u3b2-TrCP during S phase and in response to DNA damage

The Cdc25A phosphatase is essential for cell-cycle progression because of its function in dephosphorylating cyclin-dependent kinases. In response to DNA damage or stalled replication, the ATM and ATR protein kinases activate the checkpoint kinases Chk1 and Chk2, which leads to hyperphosphorylation of Cdc25A1\u20133. These events stimulate the ubiquitin-mediated pro- teolysis of Cdc25A1,4,5 and contribute to delaying cell-cycle progression, thereby preventing genomic instability1\u20137. Here we report that b-TrCP is the F-box protein that targets phosphory- lated Cdc25A for degradation by the Skp1/Cul1/F-box protein complex. Downregulation of b-TrCP1 and b-TrCP2 expression by short interfering RNAs causes an accumulation of Cdc25A in cells progressing through S phase and prevents the degradation of Cdc25A induced by ionizing radiation, indicating that b-TrCP may function in the intra-S-phase checkpoint. Consistent with this hypothesis, suppression of b-TrCP expression results in radioresistant DNA synthesis in response to DNA damage\u2014a phenotype indicative of a defect in the intra-S-phase checkpoint that is associated with an inability to regulate Cdc25A properly. Our results show that b-TrCP has a crucial role in mediating the response to DNA damage through Cdc25A degradation

New GTC spectroscopic data and a statistical study to better constrain the redshift of the BL Lac RGB J2243 + 203

We present new spectroscopic data of the BL Lac RGB 2243 + 203, and its surroundings, obtained with the OSIRIS Multi Object Spectrograph (MOS) mounted in the Gran Telescopio Canarias (GTC). The spectra of neither the BL Lac nor its host galaxy show any spectral feature, thus hindering direct determination of its redshift. The spectroscopic redshift distribution of objects in the MOS field of view shows four galaxies with redshift between 0.5258 and 0.5288. We make use of a statistical analysis to test the possibility that the targeted BL Lac may be a member of that group. By using the spectroscopic redshifts obtained with our GTC observations, we found that this probability is between 86 and 93 per cent.Fil: Rosa González, D. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Muriel, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Mayya, Y. D.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Aretxaga, I.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Becerra González, J.. Instituto de Astrofisica de Canarias; EspañaFil: Carramiñana, Alberto. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Méndez-Abreu, J.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Vega, O. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Terlevich, E-. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Coutiño de León, S.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Furniss, A.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Longinotti, A. L.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Terlevich, R. J.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Donzelli, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentin

Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth

: Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations