On Neurons Invariant to Sentence Structural Changes in Neural Machine Translation

We present a methodology that explores how sentence structure is reflected in neural representations of machine translation systems. We demonstrate our model-agnostic approach with the Transformer English-German translation model. We analyze neuron-level correlation of activations between paraphrases while discussing the methodology challenges and the need for confound analysis to isolate the effects of shallow cues. We find that similarity between activation patterns can be mostly accounted for by similarity in word choice and sentence length. Following that, we manipulate neuron activations to control the syntactic form of the output. We show this intervention to be somewhat successful, indicating that deep models capture sentence-structure distinctions, despite finding no such indication at the neuron level. To conduct our experiments, we develop a semi-automatic method to generate meaning-preserving minimal pair paraphrases (active-passive voice and adverbial clause-noun phrase) and compile a corpus of such pairs

MuLER: Detailed and Scalable Reference-based Evaluation

We propose a novel methodology (namely, MuLER) that transforms any reference-based evaluation metric for text generation, such as machine translation (MT) into a fine-grained analysis tool. Given a system and a metric, MuLER quantifies how much the chosen metric penalizes specific error types (e.g., errors in translating names of locations). MuLER thus enables a detailed error analysis which can lead to targeted improvement efforts for specific phenomena. We perform experiments in both synthetic and naturalistic settings to support MuLER's validity and showcase its usability in MT evaluation, and other tasks, such as summarization. Analyzing all submissions to WMT in 2014-2020, we find consistent trends. For example, nouns and verbs are among the most frequent POS tags. However, they are among the hardest to translate. Performance on most POS tags improves with overall system performance, but a few are not thus correlated (their identity changes from language to language). Preliminary experiments with summarization reveal similar trends

Noncontact Diffuse Optical Assessment of Blood Flow Changes in Head and Neck Free Tissue Transfer Flaps

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning “1”) for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89±0.15, 2.26±0.13, and 2.43±0.13 (mean±standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (

Norspermidine is not a self-produced trigger for biofilm disassembly

SummaryFormation of Bacillus subtilis biofilms, consisting of cells encapsulated within an extracellular matrix of exopolysaccharide and protein, requires the polyamine spermidine. A recent study reported that (1) related polyamine norspermidine is synthesized by B. subtilis using the equivalent of the Vibrio cholerae biosynthetic pathway, (2) exogenous norspermidine at 25 μM prevents B. subtilis biofilm formation, (3) endogenous norspermidine is present in biofilms at 50–80 μM, and (4) norspermidine prevents biofilm formation by condensing biofilm exopolysaccharide. In contrast, we find that, at concentrations up to 200 μM, exogenous norspermidine promotes biofilm formation. We find that norspermidine is absent in wild-type B. subtilis biofilms at all stages, and higher concentrations of exogenous norspermidine eventually inhibit planktonic growth and biofilm formation in an exopolysaccharide-independent manner. Moreover, orthologs of the V. cholerae norspermidine biosynthetic pathway are absent from B. subtilis, confirming that norspermidine is not physiologically relevant to biofilm function in this species

Case-fatality rate of major bleeding events in patients on dual antiplatelet therapy after percutaneous coronary intervention: A systematic review and meta-analysis.

Background Assessment of the case-fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI). Objectives To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT. Methods Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic. Results Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow-up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1-16.2; I 2 = 50%) in the entire study population, and 13.8% (95% CI, 6.5-27.1; I 2 = 28%), 11.2% (95% CI, 6.7-18.0; I 2 = 0%), and 5.8% (95% CI, 3.0-11.1; I 2 = 0%) in those on short-term (≤6 months; n = 16,553), standard-term (12 months; n = 19,453), and long-term DAPT (>12 months; n = 10,238), respectively. Conclusion Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long-term DAPT

Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the β-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies

Systematic analysis of the entire second extracellular loop of the V 1a vasopressin receptor :Key residues, conserved throughout a G-protein-coupled receptor family, identified

The roles of extracellular residues of G-protein-coupled receptors (GPCRs) are not well defined compared with residues in transmembrane helices. Nevertheless, it has been established that extracellular domains of both peptide-GPCRs and amine-GPCRs incorporate functionally important residues. Extracellular loop 2 (ECL2) has attracted particular interest, because the x-ray structure of bovine rhodopsin revealed that ECL2 projects into the binding crevice within the transmembrane bundle. Our study provides the first comprehensive investigation into the role of the individual residues comprising the entire ECL2 domain of a small peptide-GPCR. Using the V1a vasopressin receptor, systematic substitution of all of the ECL2 residues by Ala generated 30 mutant receptors that were characterized pharmacologically. The majority of these mutant receptor constructs (24 in total) had essentially wild-type ligand binding and intracellular signaling characteristics, indicating that these residues are not critical for normal receptor function. However, four aromatic residues Phe189, Trp206, Phe209, and Tyr218 are important for agonist binding and receptor activation and are highly conserved throughout the neurohypophysial hormone subfamily of peptide-GPCRs. Located in the middle of ECL2, juxtaposed to the highly conserved disulfide bond, Trp206 and Phe209 project into the binding crevice. Indeed, Phe209 is part of the Cys-X-X-X-Ar (where Ar is an aromatic residue) motif, which is well conserved in both peptide-GPCRs and amine-GPCRs. In contrast, Phe189 and Tyr218, located at the extreme ends of ECL2, may be important for determining the position of the ECL2 cap over the binding crevice. This study provides mechanistic insight into the roles of highly conserved ECL2 residues

The updated spectral catalogue of INTEGRAL Gamma-Ray Bursts

We present a catalogue with the properties of all the bursts detected and localized by the IBIS instrument onboard the INTEGRAL satellite from November 2002 to September 2008. The sample is composed of 56 bursts, corresponding to a rate of ~ 0.8 GRB per month. Thanks to the performances of the INTEGRAL Burst Alert System, 50% of the IBIS GRBs have detected afterglows, while 5% have redshift measurements. A spectral analysis of the 43 bursts in the INTEGRAL public archive has been carried out using the most recent software and calibration, deriving an updated, homogeneous and accurate catalogue with the spectral features of the sample. When possible also a time-resolved spectral analysis has been carried out. The GRBs in the sample have 20-200 keV fluences in the range 5 x 1E-8 --2.5 x 1E-4 erg cm-2, and peak fluxes in the range 0.11 - 56 ph cm-2 s-1. While most of the spectra are well fitted by a power law with photon index ~ 1.6, we found that 9 bursts are better described by a cut-off power law, resulting in Ep values in the range 35--190 keV. Altough these results are comparable with those obtained with BAT onboard Swift, there is a marginal evidence that ISGRI detects dimmer bursts than Swift/BAT. Using the revised spectral parameters and an updated sky exposure map that takes into account also the effects of the GRB trigger efficiency, we strengthen the evidence for a spatial correlation with the super galactic plane of the faint bursts with long spectral lag (Foley et al.,2008).Comment: Corrected some typos, added some references; Accepted by Astronomy & Astrophysics, in pres