Transitando la incertidumbre

This work approaches the creative process as a journey through uncertainty. It delves into the state of openness that opens up to surprise and discovery from a gaze that denaturalises the world.Este trabajo aborda el proceso creativo como un “transitar en la incertidumbre”. Ahonda en el estado de apertura que abre a la sorpresa y al descubrimiento desde una mirada que desnaturaliza el mundo.Este trabalho aborda o processo criativo como uma jornada pela incerteza. Ele investiga o estado de abertura que se abre para a surpresa e a descoberta a partir de um olhar que desnaturaliza o mundo

Cuerpo. Vestido. Paisaje

Clothing, as the first space of living, raises a deep consciousness on the relation between body and space. Itaims at the wonderful notion of mutual affectation and at the possibility of understanding this bond like an infinite continuity between landscape and life.El vestido como primer espacio del habitar plantea una profunda conciencia sobre la relación entre el cuerpo y el espacio. Apunta a la maravillosa noción de afectación mutua y desde allí a laposibilidad de entender este vínculo como una continuidad infinita entre el paisaje y la vida.O vestido como primeiro espaço do habitar propõe uma profunda consciência sobre a relação entre o corpo eo espaço. Aponta à maravilhosa noção de afetação mútua e desde ali à possibilidade de entender este vínculo como umacontinuidade infinita entre a paisagem e a vida

Piel cuerpo danza y desborde transdisciplinar

 This text dives into the creative process from the metaphor of the skin as a vital and connecting metaphor. The skin is established as an imaginary that values the body as an organism interwoven and deployed from its multiple perceptions. Este texto bucea en el proceso creativo desde la metáfora de la piel como metáfora vital y conectora. La piel, se establece como imaginario que pone en valor al cuerpo como organismo entramado y desplegado desde sus múltiples percepciones. Resumo: Este texto mergulha no processo criativo a partir da metáfora da pele como uma metáfora vital e de conexão. A pele é estabelecida como um imaginário que valoriza o corpo como um organismo entrelaçado e implantado a partir de suas múltiplas percepções

Museo, tramas, cuerpo y experiencia

 This text, in the form of an epistolary dialogue, approaches the imaginary of the Museum from three particular points of view that intertwine and complement each other. Este texto, en formato de diálogo epistolar, aborda el imaginario del Museo desde tres miradas particulares que se entraman y complementan.&nbsp

Biodegradable PEG-poly(ω-pentadecalactone- co - p -dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors

Intracranial delivery of therapeutic agents is limited by penetration beyond the blood-brain barrier (BBB) and rapid metabolism of the drugs that are delivered. Convection-enhanced delivery (CED) of drugloaded nanoparticles (NPs) provides for local administration, control of distribution, and sustained drug release. While some investigators have shown that repeated CED procedures are possible, longer periods of sustained release could eliminate the need for repeated infusions, which would enhance safety and translatability of the approach. Here, we demonstrate that nanoparticles formed from poly(ethylene glycol)-poly(u-pentadecalactone-co-p-dioxanone) block copolymers [PEG-poly(PDL-co- DO)] are highly efficient nanocarriers that provide long-term release: small nanoparticles (less than 100 nm in diameter) continuously released a radiosensitizer (VE822) over a period of several weeks in vitro, provided widespread intracranial drug distribution during CED, and yielded significant drug retention within the brain for over 1 week. One advantage of PEG-poly(PDL-co-DO) nanoparticles is that hydrophobicity can be tuned by adjusting the ratio of hydrophobic PDL to hydrophilic DO monomers, thus making it possible to achieve a wide range of drug release rates and drug distribution profiles. When administered by CED to rats with intracranial RG2 tumors, and combined with a 5-day course of fractionated radiation therapy, VE822-loaded PEG-poly(PDL-co-DO) NPs significantly prolonged survival when compared to free VE822. Thus, PEG-poly(PDL-co-DO) NPs represent a new type of versatile nanocarrier system with potential for sustained intracranial delivery of therapeutic agents to treat brain tumors

Evaluating drug targets through human loss-of-function genetic variation

Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets using human loss-of-function variants. First, even essential genes, in which loss-of-function variants are not tolerated, can be highly successful as targets of inhibitory drugs. Second, in most genes, loss-of-function variants are sufficiently rare that genotype-based ascertainment of homozygous or compound heterozygous ‘knockout’ humans will await sample sizes that are approximately 1,000 times those presently available, unless recruitment focuses on consanguineous individuals. Third, automated variant annotation and filtering are powerful, but manual curation remains crucial for removing artefacts, and is a prerequisite for recall-by-genotype efforts. Our results provide a roadmap for human knockout studies and should guide the interpretation of loss-of-function variants in drug development.</p

Synchronous volcanic eruptions and abrupt climate change ∼17.7 ka plausibly linked by stratospheric ozone depletion.

Glacial-state greenhouse gas concentrations and Southern Hemisphere climate conditions persisted until ∼17.7 ka, when a nearly synchronous acceleration in deglaciation was recorded in paleoclimate proxies in large parts of the Southern Hemisphere, with many changes ascribed to a sudden poleward shift in the Southern Hemisphere westerlies and subsequent climate impacts. We used high-resolution chemical measurements in the West Antarctic Ice Sheet Divide, Byrd, and other ice cores to document a unique, ∼192-y series of halogen-rich volcanic eruptions exactly at the start of accelerated deglaciation, with tephra identifying the nearby Mount Takahe volcano as the source. Extensive fallout from these massive eruptions has been found >2,800 km from Mount Takahe. Sulfur isotope anomalies and marked decreases in ice core bromine consistent with increased surface UV radiation indicate that the eruptions led to stratospheric ozone depletion. Rather than a highly improbable coincidence, circulation and climate changes extending from the Antarctic Peninsula to the subtropics-similar to those associated with modern stratospheric ozone depletion over Antarctica-plausibly link the Mount Takahe eruptions to the onset of accelerated Southern Hemisphere deglaciation ∼17.7 ka

Speciation analysis of iodine and bromine at picogram-per-gram levels in polar ice

Iodine and bromine species participate in key atmospheric reactions including the formation of cloud con- densation nuclei and ozone depletion. We present a novel method coupling a high-performance liquid chromatogra- phy with ion chromatography and inductively coupled plas- ma mass spectrometry, which allows the determination of iodine (I) and bromine (Br) species (IO3−, I−, Br−, BrO3−) at the picogram-per-gram levels presents in Antarctic ice. Chromatographic separation was achieved using an ION- PAC® AS16 Analytical Column with NaOH as eluent. Detection limits for I and Br species were 5 to 9 pg g−1 with an uncertainty of less than 2.5% for all considered species. Inorganic iodine and bromine species have been determined in Antarctic ice core samples, with concentrations close to the detection limits for iodine species, and approximately 150 pg g−1 for Br−. Although iodate (IO3−) is the most abundant iodine species in the atmosphere, only the much rarer iodide (I−) species was present in Antarctic Holocene ice. Bromine was found to be present in Antarctic ice as Br−

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing