Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(−/−)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction

Atomistic origin of metal versus charge-density-wave phase separation in indium atomic wires on Si(111)

We investigate in atomic scale the electronic phase separation occurring in the well known quasi 1D charge-density wave (CDW) phase of the In atomic wire array on a Si(111) surface. The characteristic atomic scale defects, originated from excess In atoms, are found to be actively involved in the formation of the phase boundary between the metallic and the CDW phases by extensive analysis of scanning tunneling microscopy images at various temperatures. These particular defects flip the phase of the quasi 1D CDW to impose strong local constraints in the CDW correlation. We show that such local constraints and the substantial interwire CDW interaction induce local condensates of CDW and the phase separation between the metallic and the CDW phases. This work unveils the atomistic origin of the electronic phase separation, highlighting the importance of atomic scale structures of defects and their collective interaction in electronically inhomogeneous materials

Pseudogap and weak multifractality in disordered Mott charge-density-wave insulator

The competition, coexistence and cooperation of various orders in low-dimensional materials like spin, charge, topological orders and charge-density-wave has been one of the most intriguing issues in condensed matter physics. In particular, layered transition metal dichalcogenides provide an ideal platform for studying such an interplay with a notable case of 1${T}$-TaS$_{2}$ featuring Mott-insulating ground state, charge-density-wave, spin frustration and emerging superconductivity together. We investigated local electronic states of Se-substituted 1${T}$-TaS$_{2}$ by scanning tunneling microscopy/spectroscopy (STM/STS), where superconductivity emerges from the unique Mott-CDW state. Spatially resolved STS measurements reveal that an apparent V-shape pseudogap forms at the Fermi Level (E$_{F}$), with the origin of the electronic states splitting and transformation from the Mott states, and the CDW gaps are largely preserved. The formation of the pseudogap has little correlation to the variation of local Se concentration, but appears to be a global characteristics. Furthermore, the correlation length of local density of states (LDOS) diverges at the Fermi energy and decays rapidly at high energies. The spatial correlation shows a power-law decay close to the Fermi energy. Our statistics analysis of the LDOS indicates that our system exhibits weak multifractal behavior of the wave functions. These findings strongly support a correlated metallic state induced by disorder in our system, which provides an new insight into the novel mechanism of emerging superconductivity in the two-dimensional correlated electronic systems

Damped Population Oscillation in a Spontaneously Decaying Two-Level Atom Coupled to a Monochromatic Field

We investigate the time evolution of atomic population in a two-level atom driven by a monochromatic radiation field, taking spontaneous emission into account. The Rabi oscillation exhibits amplitude damping in time caused by spontaneous emission. We show that the semiclassical master equation leads in general to an overestimation of the damping rate and that a correct quantitative description of the damped Rabi oscillation can thus be obtained only with a full quantum mechanical theory.Comment: 5 pages, 5 figure

Nonlinear Optical Corneal Crosslinking, Mechanical Stiffening, and Corneal Flattening Using Amplified Femtosecond Pulses.

Purpose:We have shown that nonlinear optical corneal crosslinking (NLO CXL) and stiffening can be achieved in ex vivo rabbit corneas using an 80-MHz, 760-nm femtosecond (FS) laser, however the required power was beyond the American National Standard Institute limit. The purpose of this study was to test the efficacy of amplified FS pulses to perform CXL to reduce power by increasing pulse energy. Methods:A variable numerical aperture laser scanning delivery system was coupled to a 1030-nm laser with a noncollinear optical parametric amplifier to generate 760 nm, 50 to 150 kHz amplified FS pulses with 79.5-μm axial and 2.9-μm lateral two-photon focal volume. Ex vivo rabbit corneas received NLO CXL, and effectiveness was assessed by measuring collagen autofluorescence (CAF) and mechanical stiffening. NLO CXL was also performed in 14 live rabbits, and changes in corneal topography were measured using an Orbscan. Results:Amplified pulses (0.3 μJ) generated significant CAF that increased logarithmically with decreasing scan speed; achieving equivalent CAF to UVA CXL at 15.5 mm/s. Indentation testing detected a 62% increase in stiffness compared to control, and corneal topography measurements revealed a significant decrease of 1.0 ± 0.8 diopter by 1 month (P < 0.05). Conclusions:These results show that NLO CXL using amplified pulses can produce corneal collagen CXL comparable to UVA CXL. Translational Relevance:NLO CXL using amplified pulses can produce corneal CXL comparable to UVA CXL, suggesting a potential clinical application in which NLO CXL can be used to perform personalized crosslinking for treatment of refractive errors and keratoconus

Remarks on Noun Phrases in English

In this paper, we deal with some facts concerning the movement out of and within noun phrases in English. For a proper analysis, subject (SPEC) positions of NP are divided into two kinds: A-position and A'-position. The NP with A subject, which is nexal in its nature, is a barrier if the NP is not L·marked, whereas the NP with A' ·subject as well as the NP with non-specific determiner, i. e., non·nexal NPs are an inherent barrier, for they cannot be L·marked. The original version of the Minimality Condition proposed in Chomsky (1986) is modified in a substantive way to accomodate the facts of nominals in English. With the proposals described above, along with the assumption that the noun is not a proper governor, as many linguists including Kayne claim, it is possible to explain some facts about movement in NPs in a consistent way with the help of the Empty Category Principle (ECP)

A Study on the Light Verb Construction in English and Korean

This paper is an attempt to analyze the light verb construction of Korean, based on the recent proposal of Hale and Keyser (1993a, 1993b, among others) regarding minimal X′-structure. This paper is primarily concerned with the grammatical difference found in the examples below: (1) a. *Chelswu-ka malwu-lul ti ha-n chengsoi -nom floor-acc do-rel cleaning 'lit: the cleaning that Chelswu did to the floor' b. Chelswu-ka Yenghi-wa ti ha-n hapseki -nom -with do-rel table-sharing 'lit: the table-sharing that Chelswu did with Yenghi' The relative clause (1a) is formed with the verb chengsohata 'to clean' and (1b) comes from hapsekhata 'to table-share', both of which consist of a verbal noun plus a verb hata 'to do'. Where does the difference come from? At first glance, it is obvious that chengsohata is a transitive verb while hapsekhata in an (unergative) intransitive verb. However, the distinction of transtivity itself cannot form any reason for the grammaticality difference shown in (1)

On the Syntax of Unusual Subjects: Exceptional Case Marking Constructions

This study aims to explain the mixed properties of the ECM subject in Korean and Mongolian in terms of the Relator Phrase (RP) analysis proposed by den Dikken (2007, 2017a, 2017b). The embedded subject in the Korean ECM is known to exhibit both higher/lower and A/A' properties. How can an XP have several locus properties at the same time? To address this question, the present study proposes the following insights: Predication relations constitute an inherent RP phase (den Dikken 2007, 2017a, 2017b; Wurmbrand, 2021); The ECM subject is base-generated in the Spec-RP position in Korean, which is an A-position by definition; R assumes a null state or becomes C+R if C is elevated to R; A null operator (O) binds the overt/covert pronoun in the embedded TP; The ECM subject is related to the embedded CP in terms of predication, akin to Browning's (1991) perspective. The proposed analysis explains the Korean ECM and its difference from Mongolian. The proposal resolves the ongoing discourse on whether the ECM subject moves or stays in situ. Additionally, significant similarities between ECM construction and the multiple nominative constructions (MNC) in Korean are also explained in terms of RP, a correlation previously understudied in previous studies.An earlier version of this paper was presented in the Theoretical and Experimental Approaches to Comparative Linguistics Workshop at University of the Basque Country (UPV/EHU), 2023. The author also owes much to three anonymous reviewers of Language Research, by whose help some earlier ideas of this paper could be further clarified. This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2022S1A5A2A0103824711)

AAD-2004, a potent spin trapping molecule and microsomal prostaglandin E synthase-1 inhibitor, shows safety and efficacy in a mouse model of ALS

While free radicals and inflammation constitute major routes of neuronal injury occurring in neurodegenerative diseases, neither antioxidants nor nonsteroidal anti-inflammatory drugs (NSAIDs) have shown significant efficacy in human clinical trials. To explore the possibility that concurrent blockade of free radicals and PGE2-mediated inflammation might constitute a safe and effective therapeutic approach to certain neurodegenerative diseases, we have developed 2-hydroxy-5-[2-(4-trifluoromethylphenyl)-ethylaminobezoic acid (AAD-2004) as a derivative of aspirin. AAD-2004 completely removed free radicals at 50 nM as a potent spin trapping molecule and inhibited microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 230 nM. Oral administration of AAD-2004 blocked free radical formation, PGE2 formation, and microglial activation in the spinal motor neurons of SOD1G93A mice. As a consequence, AAD-2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD-2004 was superior to ibuprofen or riluzole. Gastric bleeding was not induced by AAD-2004 even at a dose 400-fold higher than that required to obtain maximal therapeutic efficacy in SOD1G93A mice. Targeting both mPGES-1 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases

Engineering of Corynebacterium glutamicum for the secretory production of recombinant proteins via Tat-dependent pathway

Corynebacterium glutamicum, which has been an industrial producer of various L-amino acids, nucleic acids, and vitamins, is now also regarded as a potential host for the secretory production of recombinant proteins since it exhibits numerous ideal features for protein secretion: (i) it has a single cellular membrane as a gram-positive bacterium, which allows proteins to be easily secreted into the extracellular medium. (ii) C. glutamicum secretes only a few endogenous proteins into the culture medium, which allows the simpler purification of target proteins in downstream process. (iii), secreted proteins from C. glutamicum can be kept stable because extracellular protease activity is rarely detectable. To harness its potential as an industrial platform for recombinant protein production, the development of an efficient secretion system is necessary. To achieve this goal first, we engineered several genetic parts in C. glutamicum: (i) synthetic promoters, (ii) plasmid copy number, (iii) signal peptides, (iv) co-expression of secretion machinery proteins. Using the engineered host-vector systems, gram-scale production of recombinant proteins could be achieved in fed-batch cultivation