Changes in fMRI BOLD dynamics reflect anticipation to moving objects

The human brain is thought to respond differently to novel versus predictable neural input. In human visual cortex, neural response amplitude to visual input might be determined by the degree of predictability. We investigated how fMRI BOLD responses in human early visual cortex reflect the anticipation of a single moving bar's trajectory. We found that BOLD signals decreased linearly from onset to offset of the stimulus trajectory. Moreover, decreased amplitudes of BOLD responses coincided with an increased initial dip as the stimulus moved along its trajectory. Importantly, motion anticipation effects were absent, when motion coherence was disrupted by means of stimulus contrast reversals. These results show that human early visual cortex anticipates the trajectory of a coherently moving object at the initial stages of visual motion processing. The results can be explained by suppression of predictable input, plausibly underlying the formation of stable visual percepts

Singularities of the Magnon Boundstate S-Matrix

We study the conjectured exact S-matrix for the scattering of BPS magnon boundstates in the spin-chain description of planar N=4 SUSY Yang-Mills. The conjectured S-matrix exhibits both simple and double poles at complex momenta. Some of these poles lie parametrically close to the real axis in momentum space on the branch where particle energies are positive. We show that all such poles are precisely accounted for by physical processes involving one or more on-shell intermediate particles belonging to the known BPS spectrum.Comment: 32 pages, 9 figure

Basal topographic controls on rapid retreat of Humboldt Glacier, northern Greenland

Discharge from marine-terminating outlet glaciers accounts for up to half the recent mass loss from the Greenland ice sheet, yet the causal factors are not fully understood. Here we assess the factors controlling the behaviour of Humboldt Glacier (HG), allowing us to evaluate the influence of basal topography on outlet glacier response to external forcing since part of HG’s terminus occupies a large overdeepening. HG’s retreat accelerated dramatically after 1999, coinciding with summer atmospheric warming of up to 0.19°C a–1 and sea-ice decline. Retreat was an order of magnitude greater in the northern section of the terminus, underlain by a major basal trough, than in the southern section, where the bedrock is comparatively shallow. Velocity change following retreat was spatially non-uniform, potentially due to a pinning point near HG’s northern lateral margin. Consistent with observations, numerical modelling demonstrates an order-of-magnitude greater sensitivity to sea-ice buttressing and crevasse depth (used as a proxy for atmospheric warming) in the northern section. The trough extends up to 72 km inland, so it is likely to facilitate sustained retreat and ice loss from HG during the 21st century

Dyonic Giant Magnons

We study the classical spectrum of string theory on AdS_5 X S^5 in the Hofman-Maldacena limit. We find a family of classical solutions corresponding to Giant Magnons with two independent angular momenta on S^5. These solutions are related via Pohlmeyer's reduction procedure to the charged solitons of the Complex sine-Gordon equation. The corresponding string states are dual to BPS boundstates of many magnons in the spin-chain description of planar N=4 SUSY Yang-Mills. The exact dispersion relation for these states is obtained from a purely classical calculation in string theory.Comment: LaTeX file, 16 pages. One figure. Corrected reference

Diagnostic Value of Microbial Cell-free DNA Sequencing for Suspected Invasive Fungal Infections:A Retrospective Multicenter Cohort Study

Background: An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis. Materials: In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a "research use only test"on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT. Results: Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non-Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2-57.7) and 96.6% (95% CI, 88.5%-99.1%). Sensitivity of the KT was higher in non-Aspergillus IFD (Mucorales:2/3, Pneumocystis jirovecii: 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1-96.3), and specificity 83.3% (95% CI, 49.1-87.5). Conclusions: Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non-Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a "rule-out"test.</p

Neutrophil killing of Mycobacterium abscessus by intra- and extracellular mechanisms

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, are increasingly present in soft tissue infections and chronic lung diseases, including cystic fibrosis, and infections are characterized by growth in neutrophil-rich environments. M. abscessus is observed as two distinct smooth and rough morphotypes. The environmental smooth morphotype initiates infection and has a relatively limited ability to activate neutrophils. The rough morphotype has increased virulence and immunogenicity. However, the neutrophil response to the rough morphotype has not been explored. Killing of the smooth and rough strains, including cystic fibrosis clinical isolates, was equivalent. Neutrophil uptake of M. abscessus was similar between morphotypes. Mechanistically, both rough and smooth morphotypes enhanced neutrophil reactive oxygen species generation but inhibition of NADPH oxidase activity did not affect M. abscessus viability. However, inhibition of phagocytosis and extracellular traps reduced killing of the smooth morphotype with lesser effects against the rough morphotype. Neutrophils treated with M. abscessus released a heat-labile mycobactericidal activity against the rough morphotype, but the activity was heat-tolerant against the smooth morphotype. Overall, M. abscessus stimulates ineffective neutrophil reactive oxygen species generation, and key mechanisms differ in killing of the smooth (phagocytosis-dependent, extracellular traps, and heat-tolerant secreted factor) and rough (extracellular traps and a heat-labile secreted factor) morphotypes. These studies represent an essential advancement in understanding the host response to M. abscessus, and help explain the recalcitrance of infection

Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor

BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts. METHODS: Included were MBC patients with a HER2-negative primary tumor, with ≥1 detectable CTC, starting a new line of treatment. CTCs were enumerated using the CellSearch system, characterized for HER2 with the CellSearch anti-HER2 phenotyping reagent, and characterized for ER mRNA expression. Primary end point was pr

Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients

Mutations and splice variants in the estrogen receptor (ER) gene, ESR1, may yield endocrine resistance in metastatic breast cancer (MBC) patients. These putative endocrine resistance markers are likely to emerge during treatment, and therefore, its detection in liquid biopsies, such as circulating tumor cells (CTCs) and cell-free DNA (cfDNA), is of great interest. This research aimed to determine whether ESR1 mutations and splice variants occur more frequently in CTCs of MBC patients progressing on endocrine treatment. In addition, the presence of ESR1 mutations was evaluated in matched cfDNA and compared to CTCs. CellSearch-enriched CTC fractions (≥5/7.5 mL) of two MBC cohorts were evaluated, namely (a) patients starting first-line endocrine therapy (n = 43, baseline cohort) and (b) patients progressing on any line of endocrine therapy (n = 40, progressing cohort). ESR1 hotspot mutations (D538G and Y537S/N/C) were evaluated in CTC-enriched DNA using digital PCR and compared with matched cfDNA (n = 18 baseline cohort; n = 26 progressing cohort). Expression of ESR1 full-length and 4 of its splice variants ((increment)5, (increment)7, 36 kDa, and 46 kDa) was evaluated in CTC-enriched mRNA. It was observed that in the CTCs, the ESR1 mutations were not enriched in the progressing cohort (8%), when compared with the baseline cohort (5%) (P = 0.66). In the cfDNA, however, ESR1 mutations were more prevalent in the progressing cohort (42%) than in the baseline cohort (11%) (P = 0.04). Three of the same mutations were observed in both CTCs and cfDNA, 1 mutation in CTCs only, and 11 in cfDNA only. Only the (increment)5 ESR1 splice variant was CTC-specific expressed, but was not enriched in the progressing cohort. In conclusion, sensitivity for detecting ESR1 mutations in CTC-enriched fractions was lower than for cfDNA. ESR1 mutations detected in cfDNA, rarely present at the start of first-line endocrine therapy, were enriched at progression, strongly suggesting a role in conferring endocrine resistance in MBC

Decoherence and CPT Violation in a Stringy Model of Space-Time Foam

I discuss a model inspired from the string/brane framework, in which our Universe is represented as a three brane, propagating in a bulk space time punctured by D0-brane (D-particle) defects. As the D3-brane world moves in the bulk, the D-particles cross it, and from an effective observer on D3 the situation looks like a ``space-time foam'' with the defects ``flashing'' on and off (``D-particle foam''). The open strings, with their ends attached on the brane, which represent matter in this scenario, can interact with the D-particles on the D3-brane universe in a topologically non-trivial manner, involving splitting and capture of the strings by the D0-brane defects. Such processes are described by logarithmic conformal field theories on the world-sheet. Physically, they result in effective decoherence of the string matter on the D3 brane, and as a result, of CPT Violation, but of a type that implies an ill-defined nature of the effective CPT operator. Due to electric charge conservation, only electrically neutral (string) matter can exhibit such interactions with the D-particle foam. This may have unique, experimentally detectable, consequences for electrically-neutral entangled quantum matter states on the brane world, in particular the modification of the pertinent EPR Correlation of neutral mesons in a meson factory.Comment: 41 pages Latex, five eps figures incorporated. Uses special macro