Domain-General and Domain-Specific Electrophysiological Markers of Cognitive Distance Coding for What, Where, and When Memory Retrieval.

The what, where, and when components of episodic memory can be differentiated based on their distinctive domain-specific underlying neural correlates. However, recent studies have proposed that a common neural mechanism of conceptual mapping may be involved in the coding of cognitive distance across all domains. In this study, we provide evidence that both domain-specific and domain-general processes occur simultaneously during memory retrieval by identifying distinctive and common neural representations for mapping what (i.e., semantic distance), where (i.e., spatial distance), and when (i.e., temporal distance) using scalp EEG from 47 healthy participants (age 21-30, 26 male and 21 female). First, we found that all three components commonly showed a positive correlation between cognitive distance and slow theta power (2.5-5 Hz) in parietal channels. Meanwhile, fast theta power (5-8.5 Hz) specifically represented spatial and temporal distance in occipital and parietal channels, respectively. Additionally, we identified a unique correlate of temporal distance coding in frontal/parietal slow theta power during the early phase of retrieval. All of the above neural markers of cognitive mapping, both domain-general and specific, were associated with individual differences in what, where, and when memory accuracy.SIGNIFICANCE STATEMENT The Cognitive Map Theory was originally founded to explain how we remember and organize the immense amount of spatial information that we face when we navigate. However, memory research has recently trended in the direction of emphasizing the generalizability of cognitive mapping mechanisms to information in any domain, represented as distances in an abstract conceptual space. In a single study, we show that both common and unique neural coding of semantic distance (i.e., what), spatial distance (i.e., where), and temporal distance (i.e., when) simultaneously support episodic memory retrieval. Our results suggest that our ability to accurately distinguish between memories is achieved through an integration of domain-specific and domain-general neurocognitive mechanisms that work in parallel.

Cognotyping by What-Where-When Retrieval Reveals the Potential Role of Temporal Memory and Its Neural Correlates in Understanding Individual Differences across Aging and Alzheimer Disease.

Despite distinct neural representation of what, where, and when information, studies of individual differences in episodic memory have neglected to test the three components separately. Here, we used a componential episodic memory task to measure cognitive profiles across a wide age range and in Alzheimer disease (AD) and to examine the role of theta oscillations in explaining performance. In Experiment 1, we tested a group of 47 young adults (age 21-30 years, 21 women) while recording their scalp EEG. A separate behavioral experiment (Experiment 2) was performed in 42 older adults (age 66-85 years, 29 women) and in a group of 16 AD patients (age 80-90 years, 12 women). In Experiment 1, K-means clustering based on behavioral data resulted in three "cognotypes" whose memory profiles showed corresponding differences in their EEG markers: What and where memory depended on frontal theta power and when memory depended on theta modulation by temporal distance between retrieved items. In Experiment 2, healthy older adults showed three cognotypes similar to those found in younger adults; moreover, AD patients had an overlapping profile with one specific cognotype, characterized by marked difficulties in when memory. These findings highlight the utility of componential episodic memory tests and cognotyping in understanding individual strengths and vulnerabilities in age-related neurocognitive decline.

Laser frequency stabilization in the 10 -14 range via optimized modulation transfer spectroscopy on the 87Rb D2 line.

We present a high-performance laser frequency stabilization method using modulation transfer spectroscopy (MTS) on the rubidium 87D2 transition line. A substantial improvement of the laser frequency stability was achieved by searching for the optimal diameter and intensity settings of the probe and pump beam. The frequency instability measured from the beat frequency of two locked external cavity diode lasers (ECDLs) reached a short-term stability of 4.5×10-14/τ and did not exceed 2 × 10-12 until 105 s, which is the best performance reported thus far with a D2 transition. The long-term stability is limited by the offset fluctuations of the baseline induced by the residual amplitude modulation (RAM), which can be further improved by reducing the current temperature variation of about 0.2 K by means of temperature stabilization or through a further reduction of the RAM.

Moving-frame imaging of transiting cold atoms for precise long-range transport.

Transporting cold atoms between interconnected vacuum chambers is an important technique for increasing the versatility of cold atom setups, particularly for those that couple atoms to photonic devices. In this report, we introduce a method where we are able to image the atoms at all points during transport via moving optical dipole trap. Cooled 87Rb atoms are transported ∼50 cm into an auxiliary vacuum chamber while being monitored with a moving-frame imaging system for which in-situ characterization of the atom transport is demonstrated. Precise positioning of the atoms near photonic devices is also tested across several tapered fibers showing an axial positioning resolution of ∼450 µm.

A New Method of Myostatin Inhibition in Mice via Oral Administration of Lactobacillus casei Expressing Modified Myostatin Protein, BLS-M22.

Myostatin is a member of the transforming growth factor-beta superfamily and is an endogenous negative regulator of muscle growth. This study aimed to determine whether an oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) could elicit sufficient levels of myostatin-specific antibody and improve the dystrophic features of an animal model of Duchenne muscular dystrophy (DMD; mdx mouse). BLS-M22 is a recombinant L. casei engineered to harbor the pKV vector and poly-gamma-glutamic acid gene linked to a modified human myostatin gene. Serological analysis showed that anti-myostatin IgG titers were significantly increased, and serum creatine kinase was significantly reduced in the BLS-M22-treated mdx mice compared to the control mice. In addition, treatment of BLS-M22 resulted in a significant increase in body weight and motor function (Rotarod behavior test). Histological analysis showed an improvement in the dystrophic features (fibrosis and muscle hypertrophy) of the mdx mice with the administration of BLS-M22. The circulating antibodies generated after BLS-M22 oral administration successfully lowered serum myostatin concentration. Myostatin blockade resulted in serological, histological, and functional improvements in mdx mice. Overall, the findings suggest the potential of BLS-M22 to treat DMD; however, further clinical trials are essential to ascertain its efficacy and safety in humans.

The LHC Olympics 2020 a community challenge for anomaly detection in high energy physics.

A new paradigm for data-driven, model-agnostic new physics searches at colliders is emerging, and aims to leverage recent breakthroughs in anomaly detection and machine learning. In order to develop and benchmark new anomaly detection methods within this framework, it is essential to have standard datasets. To this end, we have created the LHC Olympics 2020, a community challenge accompanied by a set of simulated collider events. Participants in these Olympics have developed their methods using an R&D dataset and then tested them on black boxes: datasets with an unknown anomaly (or not). Methods made use of modern machine learning tools and were based on unsupervised learning (autoencoders, generative adversarial networks, normalizing flows), weakly supervised learning, and semi-supervised learning. This paper will review the LHC Olympics 2020 challenge, including an overview of the competition, a description of methods deployed in the competition, lessons learned from the experience, and implications for data analyses with future datasets as well as future colliders.

Maximized atom number for a grating magneto-optical trap via machine-learning assisted parameter optimization.

We present a parameter set for obtaining the maximum number of atoms in a grating magneto-optical trap (gMOT) by employing a machine learning algorithm. In the multi-dimensional parameter space, which imposes a challenge for global optimization, the atom number is efficiently modeled via Bayesian optimization with the evaluation of the trap performance given by a Monte-Carlo simulation. Modeling gMOTs for six representative atomic species - 7Li, 23Na, 87Rb, 88Sr, 133Cs, 174Yb - allows us to discover that the optimal grating reflectivity is consistently higher than a simple estimation based on balanced optical molasses. Our algorithm also yields the optimal diffraction angle which is independent of the beam waist. The validity of the optimal parameter set for the case of 87Rb is experimentally verified using a set of grating chips with different reflectivities and diffraction angles.

Industrial carbon dioxide capture and utilization: state of the art and future challenges.

Dramatically increased CO2 concentration from several point sources is perceived to cause severe greenhouse effect towards the serious ongoing global warming with associated climate destabilization, inducing undesirable natural calamities, melting of glaciers, and extreme weather patterns. CO2 capture and utilization (CCU) has received tremendous attention due to its significant role in intensifying global warming. Considering the lack of a timely review on the state-of-the-art progress of promising CCU techniques, developing an appropriate and prompt summary of such advanced techniques with a comprehensive understanding is necessary. Thus, it is imperative to provide a timely review, given the fast growth of sophisticated CO2 capture and utilization materials and their implementation. In this work, we critically summarized and comprehensively reviewed the characteristics and performance of both liquid and solid CO2 adsorbents with possible schemes for the improvement of their CO2 capture ability and advances in CO2 utilization. Their industrial applications in pre- and post-combustion CO2 capture as well as utilization were systematically discussed and compared. With our great effort, this review would be of significant importance for academic researchers for obtaining an overall understanding of the current developments and future trends of CCU. This work is bound to benefit researchers in fields relating to CCU and facilitate the progress of significant breakthroughs in both fundamental research and commercial applications to deliver perspective views for future scientific and industrial advances in CCU.

Chip-Scale Ultra-Low Field Atomic Magnetometer Based on Coherent Population Trapping.

We report a chip-scale atomic magnetometer based on coherent population trapping, which can operate near zero magnetic field. By exploiting the asymmetric population among magnetic sublevels in the hyperfine ground state of cesium, we observe that the resonance signal acquires sensitivity to magnetic field in spite of degeneracy. A dispersive signal for magnetic field discrimination is obtained near-zero-field as well as for finite fields (tens of micro-tesla) in a chip-scale device of 0.94 cm3 volume. This shows that it can be readily used in low magnetic field environments, which have been inaccessible so far in miniaturized atomic magnetometers based on coherent population trapping. The measured noise floor of 300 pT/Hz1/2 at the zero-field condition is comparable to that of the conventional finite-field measurement obtained under the same conditions. This work suggests a way to implement integrated atomic magnetometers with a wide operating range.

Anti-Fibrotic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1.

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2-5-month-old mdx mice intravenously injected with 1 × 105 Wharton's jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

Pressure Stimuli Improve the Proliferation of Wharton's Jelly-Derived Mesenchymal Stem Cells under Hypoxic Culture Conditions.

Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells' niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton's jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications.

Optical phase-locking of two extended-cavity diode lasers by serrodyne modulation.

We report the optical phase-locking of two extended-cavity diode lasers with a frequency difference of 6.9 GHz by serrodyne modulation. The bandwidth of the phase-locking loop is extended up to 9.5 MHz. The residual phase noise of the two phase-locked lasers reaches -130 dBrad2/Hz in the offset frequency range of 1.5 kHz to 9 kHz and below -120 dBrad2/Hz in the range of 150 Hz to 350 kHz, respectively. It is expected that the sensitivity limit of atom interferometers will be enhanced when the phase-locked lasers are used.

The Influence of Segond Fracture on Outcomes After Anterior Cruciate Ligament Reconstruction.

PURPOSE: To determine the prevalence of Segond fractures using computed tomography (CT) and to investigate the effects of Segond fractures on the outcomes of primary anterior cruciate ligament (ACL) reconstruction for isolated ACL injuries. METHODS: Between January 2010 and July 2015, we retrospectively evaluated 383 patients who underwent primary ACL reconstruction, who underwent CT scans immediately after surgery, and who were available at 2 years of follow-up. The absence or presence of a Segond fracture was confirmed using CT. The following parameters were evaluated in all patients at the 2-year follow-up visit: clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity score) and knee joint stability (anterior drawer test, Lachman test, pivot-shift test, and side-to-side difference in anterior tibial translation on Telos stress radiographs). RESULTS: Among 383 patients with primary ACL tears, a Segond fracture was confirmed in 8.9% (n = 34) using 3-dimensional CT. We placed 349 patients into the group with ACL tears without Segond fractures (group A) and the other 34 into the group with ACL tears with Segond fractures (group B). Between the 2 groups, there were no significant differences in the postoperative International Knee Documentation Committee subjective score (P = .97), Lysholm score (P = .17), or Tegner activity score (P = .95). No significant differences in the anterior drawer test (P = .28), Lachman test (P = .45), pivot-shift test (P = .14), and side-to-side difference in anterior tibial translation on Telos stress radiographs (P = .93) between the 2 groups were found preoperatively and postoperatively. CONCLUSIONS: The presence of a Segond fracture did not affect knee joint stability in patients with ACL tears. Moreover, the 2 groups did not show significant differences in clinical scores or knee joint stability after undergoing ACL reconstruction. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Novelty of Dynamic Process in the Synthesis of Biocompatible Silica Nanotubes by Biomimetic Glycyldodecylamide as a Soft Template.

A dynamic process in the synthesis of silica nanotubes (SNTs) by utilizing glycyldodecylamide (GDA) as a soft template was thoroughly investigated. The morphological evolution from GDA to SNTs was deeply explored to elucidate the formation mechanism for optimizing the synthesis procedure. Various analytical tools, namely, XRD, FTIR, SEM, TEM, Z-potential, and N2 adsorption/desorption isotherms, were employed during the synthesis procedure. The interactive structure of GDA was also investigated using TEM-EDX as a function of aging time. These studies revealed the stepwise morphology of nanograin, nanofiber, curved plate, and nanotube in the ethanol/water solution when aged at room temperature. The supramolecular GDA molded the vesicle type nanostructure which was surrounded by silica and facilitated the formation of uniform SNTs. The stimulus for GDA to be curved into a vesicle was the intermolecular hydrogen bonding between adjacent amide groups of the template molecules. This was illustrated by FTIR spectra of GDA-silica intermediate by detecting the transition of amide I peak from 1678 to 1635 cm-1. The effect of hydrogen bonding became stronger when the sample was aged.

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1.

The role of Wharton's jelly-derived human mesenchymal stem cells (WJ-MSCs) in inhibiting muscle cell death has been elucidated in this study. Apoptosis induced by serum deprivation in mouse skeletal myoblast cell lines (C2C12) was significantly reduced when the cell lines were cocultured with WJ-MSCs. Antibody arrays indicated high levels of chemokine (C motif) ligand (XCL1) secretion by cocultured WJ-MSCs and XCL1 protein treatment resulted in complete inhibition of apoptosis in serum-starved C2C12 cells. Apoptosis of C2C12 cells and loss of differentiated C2C12 myotubes induced by lovastatin, another muscle cell death inducer, was also inhibited by XCL1 treatment. However, XCL1 treatment did not inhibit apoptosis of cell lines other than C2C12. When XCL1-siRNA pretreated WJ-MSCs were cocultured with serum-starved C2C12 cells, apoptosis was not inhibited, thus confirming that XCL1 is a key factor in preventing C2C12 cell apoptosis. We demonstrated the therapeutic effect of XCL1 on the zebrafish myopathy model, generated by knock down of a causative gene ADSSL1. Furthermore, the treatment of XCL1 resulted in significant recovery of the zebrafish skeletal muscle defects. These results suggest that human WJ-MSCs and XCL1 protein may act as promising and novel therapeutic agents for treatment of myopathies and other skeletal muscle diseases.

Dual control of the vestibulosympathetic reflex following hypotension in rats.

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

Mie resonance-enhanced pumping and detection efficiency for shallow nitrogen-vacancy centers in diamond.

We investigate Mie resonances of a diamond nano-resonator as a means to enhance the pumping and detection efficiency of shallow nitrogen-vacancy color centers. We show it is possible to tune a couple of high-order modes of a single resonator to each absorption and emission spectrum of the color center, and thereby the resonator plays a dual role of pump field concentration and emission field guiding. Furthermore superposition of the resonator field and the uncoupled near field results in even stronger pump intensity in the shallow top layer of the resonator. We also examine possible coupling between adjacent resonators when they form a periodic array. This approach allows us to achieve lower excitation power and higher signal intensity at local sites defined by resonators providing a way to enhance wide-field metrology in the sampled region of shallow color centers.

Decreased hemoglobin levels, cerebral small-vessel disease, and cortical atrophy: among cognitively normal elderly women and men.

BACKGROUND: Decreased hemoglobin levels increase the risk of developing dementia among the elderly. However, the underlying mechanisms that link decreased hemoglobin levels to incident dementia still remain unclear, possibly due to the fact that few studies have reported on the relationship between low hemoglobin levels and neuroimaging markers. We, therefore, investigated the relationships between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and cortical atrophy in cognitively healthy women and men. METHODS: Cognitively normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and magnetic resonance imaging (MRI) were enrolled at a health promotion center. We measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes, and microbleeds. Cortical thickness was automatically measured using surface based methods. Multivariate regression analyses were performed after controlling for possible confounders. RESULTS: Decreased hemoglobin levels were not associated with the presence of WMH, lacunes, or microbleeds in women and men. Among women, decreased hemoglobin levels were associated with decreased cortical thickness in the frontal (Estimates, 95% confidence interval, -0.007, (-0.013, -0.001)), temporal (-0.010, (-0.018, -0.002)), parietal (-0.009, (-0.015, -0.003)), and occipital regions (-0.011, (-0.019, -0.003)). Among men, however, no associations were observed between hemoglobin levels and cortical thickness. CONCLUSION: Our findings suggested that decreased hemoglobin levels affected cortical atrophy, but not increased CSVD, among women, although the association is modest. Given the paucity of modifiable risk factors for age-related cognitive decline, our results have important public health implications.

Association between body mass index and cortical thickness: among elderly cognitively normal men and women.

BACKGROUND: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. METHODS: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. RESULTS: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. CONCLUSIONS: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

BACKGROUND: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). METHODS: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). RESULTS: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. CONCLUSION: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.