We determine the infrared behaviour of the BFKL forward amplitude for gluon–gluon scattering. Our approach, based on the discrete pomeron solution, leads to an excellent description of the new ...combined inclusive HERA data at low values of
x
(<0.01) and at the same time determines the unintegrated gluon density inside the proton, for squared transverse momenta of the gluon less than 100 GeV
2
. The phases of this amplitude are sensitive to the non-perturbative gluonic dynamics and could be sensitive to the presence of Beyond-the-Standard-Model particles at very high energies.
The London dispersion interactions between systems undergoing bond breaking, twisting, or compression are not well studied due to the scarcity and the high computational cost of methods being able to ...describe both the dynamic correlation and the multireference character of the system. Recently developed methods based on the Generalized Valence Bond wave function, such as EERPA-GVB and SAPT(GVB) (SAPT = symmetry-adapted perturbation theory), allow one to accurately compute and analyze noncovalent interactions between multireference systems. Here, we augment this analysis by introducing a local indicator for dispersion interactions inspired by Mata and Wuttke’s Dispersion Interaction Density J. Comput. Chem. 2017, 38, 15−23 applied on top of an EERPA-GVB computation. Using a few model systems, we show what insights into the nature and evolution of the dispersion interaction during bond breaking and twisting such an approach is able to offer. The new indicator can be used at a minimal cost additional to an EERPA-GVB computation and can be complemented by an energy decomposition employing the SAPT(GVB) method. We explain the physics behind the initial increase, followed by a decrease in the interaction of linear molecules upon bond stretching. Namely, the elongation of covalent bonds leads to the enhancement of attractive dispersion interactions. For even larger bond lengths, this effect is canceled by the increase of the repulsive exchange forces resulting in a suppression of the interaction and finally leading to repulsion between monomers.
Due to the tendency of polychlorinated biphenyls (PCB) to accumulate in matrixes with high lipid content, the contamination of the breast milk with these compounds is a serious issue, mainly to the ...newborn. In this study, milk samples were collected from breastfeeding mothers belonging to 4 Brazilian regions (south, southeast, northeast and north). Twelve PCB were analyzed by HS-SPME-GC-ECD and the corresponding peak areas were correlated to the answers to a questionnaire of general habits, breastfeeding and characteristics of the living places. To realize this exploratory analyze, self-organizing maps generated applying Kohonen neural network were applied. It was possible to verify the occurrence of different PCB congeners in the breast milk relating to the region of the Brazil that the breastfeeding lives, the proximity to an industry, the proximity to a contaminated river or sea, the type of milk (colostrum, foremilk and hindmilk) and the number of past pregnancies.
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•The breast milk contamination by PCB in Brazil was evaluated by Kohonen neural network.•Mothers who live in large and industrialized cities had greatest amounts of PCB in the milk.•Samples of mature milk were more contaminated than samples of colostrum or transition milk.•Milk of first-time mothers was most contaminated implying in a higher exposition to the first child.•A strong relation was observed between the milk contamination and the proximity to rivers and seas.
The exclusive deep inelastic electroproduction of ψ(2S) and J/ψ(1S) at an ep centre-of-mass energy of 317 GeV has been studied with the ZEUS detector at HERA in the kinematic range 2<Q2<80 GeV2, ...30<W<210 GeV and |t|<1 GeV2, where Q2 is the photon virtuality, W is the photon–proton centre-of-mass energy and t is the squared four-momentum transfer at the proton vertex. The data for 2<Q2<5 GeV2 were taken in the HERA I running period and correspond to an integrated luminosity of 114 pb−1. The data for 5<Q2<80 GeV2 are from both HERA I and HERA II periods and correspond to an integrated luminosity of 468 pb−1. The decay modes analysed were μ+μ− and J/ψ(1S)π+π− for the ψ(2S) and μ+μ− for the J/ψ(1S). The cross-section ratio σψ(2S)/σJ/ψ(1S) has been measured as a function of Q2,W and t. The results are compared to predictions of QCD-inspired models of exclusive vector-meson production.
A
bstract
Charm production in charged current deep inelastic scattering has been measured for the first time in
e
±
p
collisions, using data collected with the ZEUS detector at HERA, corresponding to ...an integrated luminosity of 358 pb
−1
. Results are presented separately for
e
+
p
and
e
−
p
scattering at a centre-of-mass energy of
s
= 318 GeV within a kinematic phase-space region of 200 GeV
2
<
Q
2
< 60000 GeV
2
and
y
< 0.9, where
Q
2
is the squared four-momentum transfer and
y
is the inelasticity. The measured cross sections of electroweak charm production are consistent with expectations from the Standard Model within the large statistical uncertainties.
Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity regulated by the cleavage and polyadenylation (CPA) machinery. To better understand how these ...proteins govern polyA site choice, we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 CPA regulators with a 3′ scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a framework to detect perturbation-dependent changes in polyadenylation and characterize modules of co-regulated polyA sites. We find groups of intronic polyA sites regulated by distinct components of the nuclear RNA life cycle, including elongation, splicing, termination, and surveillance. We train and validate a deep neural network (APARENT-Perturb) for tandem polyA site usage, delineating a cis-regulatory code that predicts perturbation response and reveals interactions between regulatory complexes. Our work highlights the potential for multiplexed single-cell perturbation screens to further our understanding of post-transcriptional regulation.
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•Genetic perturbations of CPA regulators reveal coordinated changes in polyA site usage•PASTA quantifies heterogeneity in polyA site usage in scRNA-seq data•Distinct components of RNA life cycle affect intronic polyA site usage•Deep learning identifies sequence features that dictate perturbation response
CRISPR perturbation screens of 42 cleavage and polyadenylation regulators followed by 3′ scRNA-seq (CPA-Perturb-seq) identifies modules of co-regulated polyA sites, their connection with distinct components of the RNA life cycle, and the sequence determinants that drive perturbation responses.
Aspergillus fumigatus isolates display significant heterogeneity in growth, virulence, pathology, and inflammatory potential in multiple murine models of invasive aspergillosis. Previous studies have ...linked the initial germination of a fungal isolate in the airways to the inflammatory and pathological potential, but the mechanism(s) regulating A. fumigatus germination in the airways is unresolved. To explore the genetic basis for divergent germination phenotypes, we utilized a serial passaging strategy in which we cultured a slow germinating strain (AF293) in a murine-lung-based medium for multiple generations. Through this serial passaging approach, a strain emerged with an increased germination rate that induces more inflammation than the parental strain (herein named LH-EVOL for
ung
omogenate
ved). We identified a potential loss-of-function allele of
(
) in the LH-EVOL strain. The LH-EVOL strain had a decreased ability to induce the SakA-dependent stress pathway, similar to AF293 Δ
and CEA10. In support of the whole-genome variant analyses,
,
, or
loss-of-function strains in the AF293 parental strain increased germination both
and
. Since the airway surface liquid of the lungs contains low glucose levels, the relationship of low glucose concentration on germination of these mutant AF293 strains was examined; interestingly, in low glucose conditions, the
pathway mutants exhibited an enhanced germination rate. In conclusion, A. fumigatus germination in the airways is regulated by SskA through the SakA mitogen-activated protein kinase (MAPK) pathway and drives enhanced disease initiation and inflammation in the lungs.
Aspergillus fumigatus is an important human fungal pathogen particularly in immunocompromised individuals. Initiation of growth by A. fumigatus in the lung is important for its pathogenicity in murine models. However, our understanding of what regulates fungal germination in the lung environment is lacking. Through a serial passage experiment using lung-based medium, we identified a new strain of A. fumigatus that has increased germination potential and inflammation in the lungs. Using this serially passaged strain, we found it had a decreased ability to mediate signaling through the osmotic stress response pathway. This finding was confirmed using genetic null mutants demonstrating that the osmotic stress response pathway is critical for regulating growth in the murine lungs. Our results contribute to the understanding of A. fumigatus adaptation and growth in the host lung environment.
Eric H Kowalski,1 Diana Kneiber,1 Manuel Valdebran,2 Umangi Patel,1 Kyle T Amber11Department of Dermatology, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Dermatology, ...University of California-Irvine, Irvine, CA, USAKolli et al shed light on a pertinent issue of poor adherence to therapy in the treatment of prurigo nodularis (PN).1 While our intention was to cover recalcitrance in the sense of medical failure, Kolli et al bring up an extremely valuable point: adherence to therapy is dismal.2 Escalation of therapy as a result of poor compliance may result in unintended adverse effects from the more potent systemic therapies delineated in the treatment of PN. Thus, ensuring compliance with the treatment protocol should be a priority.In our view, PN is most often a phenotypic manifestation of chronic pruritus secondary to a host of diseases. Presumably, the relative adherence to treatment for the underlying cause of the PN, in cases where there is one, has a large role to play in the recalcitrance of the PN. This is perhaps most glaring in the case of atopic dermatitis (AD). AD has been identified to contribute to PN development in nearly 50% of PN patients.3 Assessment of nonadherence, as well as steroid phobia has been well documented in the AD population and almost certainly contributes to the development of clinically deemed recalcitrant PN in this population.4,5 Because of the well-established efficacy of topical corticosteroids in the treatment of atopic dermatitis, it is likely that atopic PN would prove more responsive. Thus, “treatment resistant” atopic PN, requires serious con- sideration of nonadherence. Clinical data on nonadherence in nonatopic PN patients, however, remains undetermined.Regardless of the primary underlying cause, patients receiving supervised phototherapy in the outpatient setting offer insight into truly recalcitrant PN due to complete adherence. A recent review on phototherapy in treatment of PN showed that in 5 out of 11 studies, patients experienced recalcitrant disease.6 Thus, even in a supervised setting where adherence could be monitored,numerous cases were recalcitrant.Innovation in adherence strategies across a wide spectrum of therapies ideally will result in fewer “treatment-resistant” cases.7–9 We agree with Kolli et al, that it remains vital to distinguish between poor adherence and medical failure.This is in response to the Letter to the Editor
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