84 research outputs found
Designing self-assembling kinetics with differentiable statistical physics models
The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems
Dependency Theory and the Aesthetics of Contrast in Fernando Solanasâs La hora de los hornos and Memoria del saqueo
This paper is a comparative analysis of two key documentaries by Fernando Solanas: La hora de los hornos / The Hour of the Furnaces (1966â68) and Memoria del saqueo / Social Genocide (2003). It argues that Solanas produces documentaries when the representative link that ties the political representatives to the represented (the people) is suspended or breaks down, as experienced during the times of the proscription of Peronism (1955â73) and in the more recent crisis of representation in Argentine institutional politics (1989â2001). The comparison follows two axes: political arguments and the aesthetics of contrast. Regarding the first criterion, the paper highlights the current persistence, in Solanasâs political argumentation, of externalist-mechanistic versions of dependency theory of the late 1960s and early 1970s. In relation to the aesthetics of contrast, it analyses the stark oppositions in Solanasâs documentaries as a visual rhetoric which can be read as an essentialist false-bottom economy that opposes âappearanceâ to ârealityâ. The article concludes that these political and aesthetic polarizations are essentializing and literalizing discursive strategies that denounce the excesses of political representation from an unmediated and transparent site of full popular presence. Within such strategies, there is no room for the constitutive opacity intrinsic to representation and articulatory politics
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (ORâ=â2.44, Pâ=â0.034 and ORâ=â3.79; Pâ=â0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (ORâ=â1.96; Pâ=â0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10â392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group
PDRs4All IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
(Abridged) Mid-infrared observations of photodissociation regions (PDRs) are
dominated by strong emission features called aromatic infrared bands (AIBs).
The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 m. The
most sensitive, highest-resolution infrared spectral imaging data ever taken of
the prototypical PDR, the Orion Bar, have been captured by JWST. We provide an
inventory of the AIBs found in the Orion Bar, along with mid-IR template
spectra from five distinct regions in the Bar: the molecular PDR, the atomic
PDR, and the HII region. We use JWST NIRSpec IFU and MIRI MRS observations of
the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288).
We extract five template spectra to represent the morphology and environment of
the Orion Bar PDR. The superb sensitivity and the spectral and spatial
resolution of these JWST observations reveal many details of the AIB emission
and enable an improved characterization of their detailed profile shapes and
sub-components. While the spectra are dominated by the well-known AIBs at 3.3,
6.2, 7.7, 8.6, 11.2, and 12.7 m, a wealth of weaker features and
sub-components are present. We report trends in the widths and relative
strengths of AIBs across the five template spectra. These trends yield valuable
insight into the photochemical evolution of PAHs, such as the evolution
responsible for the shift of 11.2 m AIB emission from class B in
the molecular PDR to class A in the PDR surface layers. This
photochemical evolution is driven by the increased importance of FUV processing
in the PDR surface layers, resulting in a "weeding out" of the weakest links of
the PAH family in these layers. For now, these JWST observations are consistent
with a model in which the underlying PAH family is composed of a few species:
the so-called 'grandPAHs'.Comment: 25 pages, 10 figures, to appear in A&
PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar
(Abridged) We investigate the impact of radiative feedback from massive stars
on their natal cloud and focus on the transition from the HII region to the
atomic PDR (crossing the ionisation front (IF)), and the subsequent transition
to the molecular PDR (crossing the dissociation front (DF)). We use
high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST
to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science
Program. The NIRSpec data reveal a forest of lines including, but not limited
to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence
lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and
their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from
H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the
first time towards a PDR. Their spatial distribution resolves the H and He
ionisation structure in the Huygens region, gives insight into the geometry of
the Bar, and confirms the large-scale stratification of PDRs. We observe
numerous smaller scale structures whose typical size decreases with distance
from Ori C and IR lines from CI, if solely arising from radiative recombination
and cascade, reveal very high gas temperatures consistent with the hot
irradiated surface of small-scale dense clumps deep inside the PDR. The H2
lines reveal multiple, prominent filaments which exhibit different
characteristics. This leaves the impression of a "terraced" transition from the
predominantly atomic surface region to the CO-rich molecular zone deeper in.
This study showcases the discovery space created by JWST to further our
understanding of the impact radiation from young stars has on their natal
molecular cloud and proto-planetary disk, which touches on star- and planet
formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&
A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk
Most low-mass stars form in stellar clusters that also contain massive stars,
which are sources of far-ultraviolet (FUV) radiation. Theoretical models
predict that this FUV radiation produces photo-dissociation regions (PDRs) on
the surfaces of protoplanetary disks around low-mass stars, impacting planet
formation within the disks. We report JWST and Atacama Large Millimetere Array
observations of a FUV-irradiated protoplanetary disk in the Orion Nebula.
Emission lines are detected from the PDR; modelling their kinematics and
excitation allows us to constrain the physical conditions within the gas. We
quantify the mass-loss rate induced by the FUV irradiation, finding it is
sufficient to remove gas from the disk in less than a million years. This is
rapid enough to affect giant planet formation in the disk
PDRs4All II: JWST's NIR and MIR imaging view of the Orion Nebula
The JWST has captured the most detailed and sharpest infrared images ever
taken of the inner region of the Orion Nebula, the nearest massive star
formation region, and a prototypical highly irradiated dense photo-dissociation
region (PDR). We investigate the fundamental interaction of far-ultraviolet
photons with molecular clouds. The transitions across the ionization front
(IF), dissociation front (DF), and the molecular cloud are studied at
high-angular resolution. These transitions are relevant to understanding the
effects of radiative feedback from massive stars and the dominant physical and
chemical processes that lead to the IR emission that JWST will detect in many
Galactic and extragalactic environments. Due to the proximity of the Orion
Nebula and the unprecedented angular resolution of JWST, these data reveal that
the molecular cloud borders are hyper structured at small angular scales of
0.1-1" (0.0002-0.002 pc or 40-400 au at 414 pc). A diverse set of features are
observed such as ridges, waves, globules and photoevaporated protoplanetary
disks. At the PDR atomic to molecular transition, several bright features are
detected that are associated with the highly irradiated surroundings of the
dense molecular condensations and embedded young star. Toward the Orion Bar
PDR, a highly sculpted interface is detected with sharp edges and density
increases near the IF and DF. This was predicted by previous modeling studies,
but the fronts were unresolved in most tracers. A complex, structured, and
folded DF surface was traced by the H2 lines. This dataset was used to revisit
the commonly adopted 2D PDR structure of the Orion Bar. JWST provides us with a
complete view of the PDR, all the way from the PDR edge to the substructured
dense region, and this allowed us to determine, in detail, where the emission
of the atomic and molecular lines, aromatic bands, and dust originate
The ABC130 barrel module prototyping programme for the ATLAS strip tracker
For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector,
consisting of silicon pixel, silicon strip and transition radiation
sub-detectors, will be replaced with an all new 100 % silicon tracker, composed
of a pixel tracker at inner radii and a strip tracker at outer radii. The
future ATLAS strip tracker will include 11,000 silicon sensor modules in the
central region (barrel) and 7,000 modules in the forward region (end-caps),
which are foreseen to be constructed over a period of 3.5 years. The
construction of each module consists of a series of assembly and quality
control steps, which were engineered to be identical for all production sites.
In order to develop the tooling and procedures for assembly and testing of
these modules, two series of major prototyping programs were conducted: an
early program using readout chips designed using a 250 nm fabrication process
(ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm
processing (ABC130 and HCC130 chips). This second generation of readout chips
was used for an extensive prototyping program that produced around 100
barrel-type modules and contributed significantly to the development of the
final module layout. This paper gives an overview of the components used in
ABC130 barrel modules, their assembly procedure and findings resulting from
their tests.Comment: 82 pages, 66 figure
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