knn-seq: Efficient, Extensible kNN-MT Framework

k-nearest-neighbor machine translation (kNN-MT) boosts the translation quality of a pre-trained neural machine translation (NMT) model by utilizing translation examples during decoding. Translation examples are stored in a vector database, called a datastore, which contains one entry for each target token from the parallel data it is made from. Due to its size, it is computationally expensive both to construct and to retrieve examples from the datastore. In this paper, we present an efficient and extensible kNN-MT framework, knn-seq, for researchers and developers that is carefully designed to run efficiently, even with a billion-scale large datastore. knn-seq is developed as a plug-in on fairseq and easy to switch models and kNN indexes. Experimental results show that our implemented kNN-MT achieves a comparable gain to the original kNN-MT, and the billion-scale datastore construction took 2.21 hours in the WMT'19 German-to-English translation task. We publish our knn-seq as an MIT-licensed open-source project and the code is available on https://github.com/naist-nlp/knn-seq . The demo video is available on https://youtu.be/zTDzEOq80m0

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy

The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection

Viral infection and stimulation with lipopolysaccharide (LPS) or double stranded RNA (dsRNA) induce phosphorylation of interferon (IFN) regulatory factor (IRF)-3 and its translocation to the nucleus, thereby leading to the IFN-β gene induction. Recently, two IκB kinase (IKK)–related kinases, inducible IκB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-β production in Toll-like receptor (TLR) signaling and viral infection. In this work, we investigated the physiological roles of these kinases by gene targeting. TBK1-deficient embryonic fibroblasts (EFs) showed dramatic decrease in induction of IFN-β and IFN-inducible genes in response to LPS or dsRNA as well as after viral infection. However, dsRNA-induced expression of these genes was residually detected in TBK1-deficient cells and intact in IKK-i–deficient cells, but completely abolished in IKK-i/TBK1 doubly deficient cells. IRF-3 activation, in response not only to dsRNA but also to viral infection, was impaired in TBK1-deficient cells. Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-β and IFN-inducible genes in both TLR-stimulated and virus-infected EFs

Association between intensive care unit delirium and delusional memory after critical care in mechanically ventilated patients

AimTo determine the relationship between the delirium of patients with mechanical ventilation during intensive care unit (ICU) stay and delusional memory after ICU discharge.DesignProspective cohort study.MethodsDelirium in adult patients who received mechanical ventilation for more than 24 hr was assessed twice daily using the Confusion Assessment Method for the ICU. Delusional memories were evaluated using the ICU Memory Tool 5–10 days after ICU discharge. The associations between the presence of delirium during the ICU stay and delusional memories were evaluated.ResultsOf 60 enrolled patients, 62% had delirium during their ICU stay, and 68% experienced delusional memories 5–10 days after discharge. Delirium during ICU stay was an independent factor to experience delusional memories following discharge. Preventing delirium during ICU stay might reduce delusional memory. We recommend that patients with delirium during their ICU stay should be carefully followed up after discharge from the ICU

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Pyrroloquinoline Quinone-Dependent Dehydrogenases from Ketogulonicigenium vulgare Catalyze the Direct Conversion of l-Sorbosone to l-Ascorbic Acid

A novel enzyme, l-sorbosone dehydrogenase 1 (SNDH1), which directly converts l-sorbosone to l-ascorbic acid (l-AA), was isolated from Ketogulonicigenium vulgare DSM 4025 and characterized. This enzyme was a homooligomer of 75-kDa subunits containing pyrroloquinoline quinone (PQQ) and heme c as the prosthetic groups. Two isozymes of SNDH, SNDH2 consisting of 75-kDa and 55-kDa subunits and SNDH3 consisting of 55-kDa subunits, were also purified from the bacterium. All of the SNDHs produced l-AA, as well as 2-keto-l-gulonic acid (2KGA), from l-sorbosone, suggesting that tautomerization of l-sorbosone causes the dual conversion by SNDHs. The sndH gene coding for SNDH1 was isolated and analyzed. The N-terminal four-fifths of the SNDH amino acid sequence exhibited 40% identity to the sequence of a soluble quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus. The C-terminal one-fifth of the sequence exhibited similarity to a c-type cytochrome with a heme-binding motif. A lysate of Escherichia coli cells expressing sndH exhibited SNDH activity in the presence of PQQ and CaCl(2). Gene disruption analysis of K. vulgare indicated that all of the SNDH proteins are encoded by the sndH gene. The 55-kDa subunit was derived from the 75-kDa subunit, as indicated by cleavage of the C-terminal domain in the bacterial cells

Distinction between Two Molecular Species of Type V Collagen from Human Post-Burn Granulation Tissues

Human type V collagen was purified form post-burn granulation tissues, and was demonstrated to exist in two different molecular assemblies consisting of [α1 (V)]2α2(V) and α1(V)α2(V)α3(V) heterotrimers which are designated as type V (112) and V(123) collagens, respectively, in this paper. Two two molecular species were separated by salt fractionation at neutral pH under non-denaturing conditions. When crude type V collagen was dialyzed against phosphate-buffered saline at 4°C, mainly collagen V(112) precipitated, leaving collagen V(123) in the solution, Type V(112) collagen, but not type V (123), precipitated at 0.15 M NaCl in 50 mM Tris-HCI buffer (pH 7.5), whereas the type V(123) molecule precipitated at 4.5 M NaCI in the same buffer. when the crude type V collagen was electrophoresed under non-denaturing conditions, tow bands were observed; and it was confirmed that the fast-migrating band was composed of [α1(V)]2α2(V) and the slow-migrating band was α1(V)α2(V)α3(V). Both α1 and α2 chains of V(112) showed biochemical properties that were very similar, if not identical, to those of the corresponding α chains of V(123) judging from amino acid compositions, peptide mapping patterns obtained following treatment with cyanogen bromide and lysyl endopeptidase, and periodic acid Schiff and concanavalin A stainings. Alpha 3 chain, in contrast, was distinct from both α1 and α2 chains. The amino acid composition and peptide maps of α3 chain were similar to some extent, but not identical, to those of the α1 chain. The intensity of carbohydrate stainings of the α3 chain was clearly different form that of the α1 chain. The negatively stained segment-long-spacing crystallites of the two molecular species exhibited an identical banding pattern. The crystallite derived from collagen V(112) was usually in a dimeric form exhibiting the C-C terminal junction, but that of collagen V(123) was mostly in a monomeric form. Differences between the two molecular species is ascribed to the presence of the α3 chain in collagen V(123)