bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled HRpQCT Study
Authors: WARDEN STUART J. , WRIGHT CHRISTIAN S. , FUCHS ROBYN K.
Published: December 2020

Purpose

Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 yr) physical activity on trabecular microarchitectural properties and microfinite element analyses of estimated bone strength.

Methods

Female collegiate-level tennis players (n = 15; age = 20.3 ± 0.9 yr) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral quantitative computed tomography. The distal tibia and the tibial diaphysis in both legs were also assessed, and cross-country runners (n = 15; age = 20.8 ± 1.2 yr) included as controls.

Results

The distal radius of the racquet arm had 11.8% (95% confidence interval [CI] = 7.9% to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than that in the nonracquet arm (all P < 0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI = 13.0% to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI = 6.7% to 12.6%) greater in the racquet versus nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI = 1.7% to 7.1%) greater strength than the contralateral leg.

Conclusion

Chronically elevated physical activity enhances trabecular microarchitecture and microfinite element estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate that tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared with in the contralateral leg.
Running into Fatigue: The Effects of Footwear on Kinematics, Kinetics, and Energetics
Authors: SANNO MAXIMILIAN , EPRO GASPAR , BRÜGGEMANN GERT-PETER , WILLWACHER STEFFEN
Published: December 2020

Purpose

Recent studies identified a redistribution of positive mechanical work from distal to proximal joints during prolonged runs, which might partly explain the reduced running economy observed with running-induced fatigue. Higher mechanical demand of plantar flexor muscle–tendon units, for example, through minimal footwear, can lead to an earlier onset of fatigue, which might affect the redistribution of lower extremity joint work during prolonged runs. Therefore, the purpose of this study was to examine the effects of a racing flat and cushioned running shoe on the joint-specific contributions to lower extremity joint work during a prolonged fatiguing run.

Methods

On different days, 18 runners performed two 10-km runs with near-maximal effort in a racing flat and a cushioned shoe on an instrumented treadmill synchronized with a motion capture system. Joint kinetics and kinematics were calculated at 13 predetermined distances throughout the run. The effects of shoes, distance, and their interaction were analyzed using a two-factor repeated-measures ANOVA.

Results

For both shoes, we found a redistribution of positive joint work from the ankle (−6%) to the knee (+3%) and the hip (+3%) throughout the entire run. Negative ankle joint work was higher (P < 0.01) with the racing flat compared with the cushioned shoe. Initial differences in foot strike patterns between shoes disappeared after 2 km of running distance.

Conclusions

Irrespective of the shoe design, alterations in the running mechanics occurred in the first 2 km of the run, which might be attributed to the existence of a habituation rather than fatigue effect. Although we did not find a difference between shoes in the fatigue-related redistribution of joint work from distal to more proximal joints, more systematical studies are needed to explore the effects of specific footwear design features.
Physiological Changes Differ between Responders and Nonresponders to Pulmonary Rehabilitation in COPD
Authors: BUEKERS JOREN , DE BOEVER PATRICK , THEUNIS JAN , HOUBEN-WILKE SARAH , VAES ANOUK W. , FRANSSEN FRITS M. E. , WOUTERS EMIEL F. M. , SIMONS SAMI O. , AERTS JEAN-MARIE , SPRUIT MARTIJN A.
Published: December 2020

Purpose

Not all patients with chronic obstructive pulmonary disease (COPD) experience similar benefits after pulmonary rehabilitation (PR). This pre–post PR study used a large sample of patients with COPD to determine whether PR-induced changes of oxygen uptake (V˙O2) kinetics and exercise responses of V˙O2, carbon dioxide output (V˙CO2), minute ventilation (V˙E), V˙E/V˙CO2, breathing frequency, and tidal volume differed between responders and nonresponders to PR.

Methods

Responders to PR were defined as patients with a minimal clinically important increase in endurance time of 105 s. Isotime (=180 s) values of V˙O2, V˙CO2, V˙E, V˙E/V˙CO2, breathing frequency, and tidal volume; gains of V˙O2, V˙CO2, and V˙E; and V˙O2 mean response time of 183 patients with COPD (forced expiratory volume in 1 s: 56% ± 19% predicted) were compared between pre- and post-PR constant work rate tests.

Results

After PR, only the group of responders significantly decreased V˙O2 mean response time (P < 0.05), V˙CO2 gain, V˙E gain, and isotime values of V˙CO2, V˙E, and V˙E/V˙CO2 (all, P < 0.001), while also improving their breathing pattern (e.g., decreased breathing frequency isotime value; P < 0.0001). These changes were not observed in the group of nonresponders. Changes in physiological exercise responses were correlated with changes in physical performance (e.g., correlation between changes in V˙O2 mean response time and endurance time: P = 0.0002, r = −0.32).

Conclusions

PR-induced changes in physiological exercise responses differed between responders and nonresponders. Physiological changes are relevant to explain the variable improvements of physical performance after PR in patients with COPD.
Lack of Selection and Limits to Delegation: Firm Dynamics in Developing Countries
Authors: Akcigit Ufuk , Alp Harun , Peters Michael
Published: December 2020

Delegating managerial tasks is essential for firm growth. Most firms in developing countries, however, do not hire outside managers but instead rely on family members. In this paper, we ask if this lack of managerial delegation can explain why firms in poor countries are small and whether it has important aggregate consequences. We construct a model of firm growth where entrepreneurs have a fixed time endowment to run their daily operations. As firms grow large, the need to hire outside managers increases. Firms’ willingness to expand therefore depends on the ease with which delegation can take place. We calibrate the model to plant-level data from the United States and India. We identify the key parameters of our theory by targeting the experimental evidence on the effect of managerial practices on firm performance from Bloom et al. (2013). We find that inefficiencies in the delegation environment account for 11 percent of the income per capita difference between the United States and India. They also contribute to the small size of Indian producers, but would cause substantially more harm for US firms. The reason is that US firms are larger on average and managerial delegation is especially valuable for large firms, thus making delegation efficiency and other factors affecting firm growth complements. (JEL D22, G32, L25, L26, O14)
Politically Feasible Reforms of Nonlinear Tax Systems
Authors: Bierbrauer Felix J. , Boyer Pierre C. , Peichl Andreas
Published: December 2020

We study reforms of nonlinear income tax systems from a political economy perspective. We present a median voter theorem for monotonic tax reforms, reforms so that the change in the tax burden is a monotonic function of income. We also provide an empirical analysis of tax reforms, with a focus on the United States. We show that past reforms have, by and large, been monotonic. We also show that support by the median voter was aligned with majority support in the population. Finally, we develop sufficient statistics that enable to test whether a given tax system admits a politically feasible reform. (JEL D72, H21, H24)
Filter Bank Multi-Carrier Modulation Technique for Vehicle-to-Vehicle Communication
Authors:   Centre of Advanced Electronic and Communication Engineering (PAKET), Universiti Kebangsaan Malaysia, 43600 UKM Bangi Selangor, Malaysia, Alrubaee Saif H. , Ismail Mahamod , Altahrawi Mohammed A. , Burhan Bara B.
Published: December 2020

Modern wireless communication like 5G systems are expected to serve a wider range of scenarios than current mobile communications systems. One of the major network applications related to 5G is Vehicle-to-Vehicle (V2V) communication that improves vehicle road safety, enhances traffic and travel efficiency, and provides convenience and comfort for passengers and drivers. However, supporting high mobility is a challenge on the air interface. Accordingly, multicarrer modulation as a multiple access is used to enhance the connection between vehicles and to overcome this challenge. In this paper, two multicarrier modulations are simulated. The first one is the Orthogonal Frequency Division Multiplexing (OFDM) while the second one is the Filter Bank Multi-Carrier with Offset Quadrature Amplitude Modulation (FBMC/OQAM) which is called FBMC. Simulation results show that all waveforms have comparable BER performance. The throughput of the FBMC is greater than the OFDM and the spectral efficiency is increased according to the use of the OQAM modulation. The FBMC throughput reaches 5 Mbps while the OFDM reaches 4 Mbps; these results are due to the higher usable bandwidth and because of using filters in FBMC which reduces the effect of Cyclic Prefix (CP) on the signal especially when CP is large in OFDM.
Indoor Location Tracking System Based on Android Application Using Bluetooth Low Energy Beacons for Ubiquitous Computing Environment
Authors:   Department of Electrical Engineering and Information Technology, Faculty of Engineering, Universitas Gadjah Mada, Yogyakarta, Indonesia, NonAlinsavath Khamla , Nugroho Lukito Edi , Widyawan Widyawan , Hamamoto Kazuhiko
Published: December 2020

Indoor positioning and tracking systems have become enormous issue in location awareness computing due to its improvement of location detection and positioning identification. The locations are normally detected using position technologies such as Global Positioning System, radio frequency identification, Bluetooth Beacon, Wi-Fi fingerprinting, pedometer and so on. This research presents an indoor positioning system based on Bluetooth low energy 4.0 Beacons; we have implemented Bluetooth signal strength for tracking the specific location and detect the movement of user through Android application platform. Bluetooth low energy was addressed to be an experiment technique to set up into the real environment of interior the building. The signal strength of beacons is evaluated and measured the quality of accuracy as well as the improvement of provide raw data from Beacons to the system to get better performance of the direction map and precise distance from current location to desire’s positioning. A smartphone application detects the location-based Bluetooth signal strength accurately and can be achieved the destination by provided direction map and distance perfectly.
Cooperative Relay Transmission under Physical Layer Security for Non-Orthogonal Networks
Authors:   Faculty of Engineering and technology, Multimedia university, Malacca 75450, Malaysia, Salem Mohammed A. , Aziz Azlan B. Abd. , Alias Mohamad Y.
Published: December 2020

In this paper, the secrecy performance for a downlink cooperative non-orthogonal multiple access (NOMA) communication system is studied under two cases. In the first case, the presence of an untrusted user is studied. While, the presence of an eavesdropper node is considered in the second case. The base station transmits superimposed information signals to the half-duplex two-way relay node. The relay amplifies-and-forwards the received signal towards the users. This paper studies the effectiveness of two factors on the secrecy performance in terms of secrecy capacity. these factors are the power allocated for each user, and the distance between the untrusted user and the cooperative relay node with respect to the strong user. Moreover, this paper proposes the shared jamming signal strategy in order to enhance the physical layer security of the cooperative NOMA in the presence of an eavesdropper node. Furthermore, simulations of the secrecy capacity are presented and compared with a conventional scheme based on null-steering jamming scheme. Based on the result the proposed technique outperforms the conventional technique in terms the of secrecy capacity.
Performance of TCP CUBIC and TCP BBR on IEEE802.11s Mesh Network
Authors:   Tokyo Denki University, Tokyo, Japan, Atsuta Katsuya , Kouya Satoshi , Sakamoto Naoshi
Published: December 2020

In this study, IEEE802.11s mesh networking was formulated as it expected to be widely used because of its convenience. The properties of IEEE802.11s mesh networking were investigated and the results revealed its faulty communication performance in a multi-hop network. This could be explained based on Mathis’s theory for loss-based TCP congestion control algorithm that suggests that with an increase in delay, the loss probability decreases the communication performance. Recently, Google proposed TCP Bottleneck Bandwidth and Round-trip propagation time (BBR), both of which may tolerate a high bit error rate. This algorithm does not follow Mathis’s model. In this study, we measure the performance of TCP CUBIC and TCP BBR on a mesh network, followed by an evaluation of the properties of this mesh network.
Practice Summary: Le Macaron Implements Ordering Optimization
Authors: Gorman Michael F.
Published: December 2020

Le Macaron French Pastries is based in Sarasota, Florida. Its central commissary specializes in baking macarons, a small, French-style pastry. It has more than 60 retail franchises throughout the United States, which order in large lots from the commissary. We developed a low-cost, user-friendly, and creative solution for the franchises to easily improve their orders to minimize costs and maintain product freshness. Implemented benefits include an 80% improvement in inventory at time of order, a 75% reduction in the number of orders, and an improvement in product freshness.
Profit Estimation Error in the Newsvendor Model Under a Parametric Demand Distribution
Authors: Siegel Andrew F. , Wagner Michael R.
Published: December 2020

We consider the newsvendor model in which uncertain demand is assumed to follow a probabilistic distribution with known functional form but unknown parameters. These parameters are estimated, unbiasedly and consistently, from data. We show that the classic maximized expected profit expression exhibits a systematic expected estimation error. We provide an asymptotic adjustment so that the estimate of maximized expected profit is unbiased. We also study expected estimation error in the optimal order quantity, which depends on the distribution: (1) if demand is exponentially or normally distributed, the order quantity has zero expected estimation error; (2) if demand is log-normally distributed, there is a nonzero expected estimation error in the order quantity that can be corrected. Numerical experiments, for light- and heavy-tailed distributions, confirm our theoretical results.

This paper was accepted by Vishal Gaur, operations management.
Does Immediate Feedback Make You Not Try as Hard? A Study on Automotive Telematics
Authors: Choudhary Vivek , Shunko Masha , Netessine Serguei
Published: December 2020

Problem definition: Mobile and internet-of-things (IoT) devices increasingly enable tracking of user behavior, and they often provide real-time or immediate feedback to consumers in an effort to improve their conduct. Growing adoption of such technologies leads to an important question: “Does reviewing immediate feedback improve user behavior?” We study immediate (close to real-time) feedback in the context of automotive telematics, which has been recognized as the most disruptive technology in the automotive insurance industry. Academic/practical relevance: Numerous automotive telematics providers claim unsubstantiated benefits from immediate feedback, while we still barely understand the implications of such feedback on user behavior. Given the high adoption of these technologies in automotive applications, it is important to study the effect of such feedback on behavior. This understanding is important, given that other attempts to make driving safer have led to unintended consequences in the past. Methodology: Using proprietary data on driving behavior, as measured by several parameters, such as harsh braking, speeding, and steep acceleration, we investigate the impact of the driver’s decision to review immediate feedback on driving behavior. We use instrumental variable regression to estimate the effect. Results: Contrary to the claims from multiple telematics providers, we find that, on average, users’ driving performance after they review detailed feedback is nearly 14.9% worse than that of users who do not review their detailed feedback. This impairment in performance translates to 6.9%, or a one-year reduction in interaccident time. Strong negative feedback (e.g., a sharp deterioration in performance) exerts a positive effect on short-term performance, but this only happens for very large drops in performance (3% of cases). Furthermore, we demonstrate that drivers just below the insurance-incentive thresholds exert greater effort following immediate feedback. Managerial implications: Our results provide a key message to firms employing immediate feedback—specifically, that such technology can yield unintended consequences. Furthermore, we show that drivers should receive only strong negative (but not positive) feedback to improve their performance. Finally, our results suggest that insurance incentives should be continuous rather than a step function.
Why Do Banks Favor Employee-Friendly Firms? A Stakeholder-Screening Perspective
Authors: Qian Cuili , Crilly Donal , Wang Ke , Wang Zheng
Published: December 2020

We investigate why employee-friendly firms often benefit from lower costs of debt financing. We theorize that banks use employee treatment as a screen to assess firms’ trustworthiness, which encompasses not only confidence in firms’ ability to perform well but also the belief that they will act with good intent toward their creditors. We integrate screening theory and stakeholder theory to explain the—oftentimes unintended—consequences that firms’ actions toward employees have on their relationships with other stakeholders. An analysis of U.S. firms between 2003 and 2010 shows that favorable employee treatment reduces the cost of bank loans, and this relationship is stronger when banks cannot infer firms’ intent from their relations with stakeholders other than employees. A policy-capturing study provides further support that employee treatment serves as a screen for intent. We discuss the implications of our stakeholder-screening perspective as a novel way to understand the second-order, unintended effects of a focal stakeholder relationship on firms’ relations with other stakeholders.
Meeting the UN's development targets in Cuba: lessons from the global
south
Authors: Kirk Emily J. , Walker Chris
Published: December 2020

Para muchos el análisis de los Objetivos de Desarrollo del Milenio de las
Naciones Unidas (MDG en inglés) deja unas imágenes de comunidades pobres y
marginalizadas en el sur global que reciben apoyo financiero, préstamos, y apoyo
de varias ONG del norte global. Pero, ¿puede un país del sur global, con
recursos muy limitados, alcanza tanto los MDG como los Objetivos de Desarrollo
Sostenible (SDG en inglés), y hacerlo sin el apoyo, apoyo financiero del norte
global y la industria de desarrollo? El caso de Cuba, y su estrategia de
desarrollo sostenible, podría ofrecernos algunas pautas sobre la forma de
superar estos retos. En particular este artículo analiza los éxitos de Cuba al
cumplir con los objetivos, tanto de MDG como de SDG, en cuestiones de salud
pública, educación, igualdad de género y medio ambiente.
Social Management Training in Males With 47,XXY (Klinefelter Syndrome): A Pilot Study of a Neurocognitive-Behavioral Treatment Targeting Social, Emotional, and Behavioral Problems
Authors: Martin Francien , van Rijn Sophie , Bierman Marit , Swaab Hanna
Published: December 2020

Klinefelter syndrome (47,XXY) is associated with problems in social interaction and behavioral adaptation. Sixteen adolescents and adult men with 47,XXY enrolled in a pilot-study evaluating the effectiveness of Social Management Training (SMT), a novel neurocognitive-behavioral treatment program targeted at improving social, emotional, and behavioral functioning. Participants reported improved emotional stability from pre- to post-test (5 months). Informants reported reductions in internalizing and externalizing symptoms, including improvement in self-regulation. Although informants did not report changes in autism-like symptoms, increased awareness of social challenges was found. SMT may improve emotional stability, self-regulation, and self-reflection in people males with Klinefelter syndrome. This potentially efficacious treatment approach may prove to be a promising psychosocial therapeutic intervention for this population.
On the Developmental Trajectories of Relational Concepts Among Children and Adolescents With Intellectual Disability of Undifferentiated Etiology
Authors: Facon Bruno , Magis David , Courbois Yannick
Published: December 2020

The aim of this study was to examine the developmental trajectories of comprehension of relational concepts among 557 participants with intellectual disability (ID) of undifferentiated etiology (M age  =  12.20 years, SD  =  3.18) and 557 typically developing (TD) participants (M age  =  4.57 years, SD  =  0.80). Logistic regression analyses, with nonverbal cognitive level entered first in the equations, showed only negligible differences with regard to the discriminative power of each of the 72 concepts used as outcome variables, and moderate differences in difficulty for only three items. A moderate mixed effect (i.e., combining a group difference in difficulty and discriminative power) was observed for a fourth item. It is concluded that the developmental trajectories of relational concepts are similar for participants with or without ID. The implications and limitations of the study are discussed.
Language Improvement Following Pivotal Response Treatment for Children With Developmental Disorders
Authors: Schwartzman Jessica M. , Strong Kristen , Ardel Christina M. , Schuck Rachel K. , Millan M. Estefania , Phillips Jennifer M. , Hardan Antonio Y. , Gengoux Grace W.
Published: December 2020

Given the high prevalence of communication deficits in developmental disorders, there is need for efficient early interventions. The aim of this pilot study is to examine benefits of pivotal response treatment (PRT) for improving language in young children with developmental disorders without autism spectrum disorder. Parents of 15 children with developmental disorders received weekly PRT parent training for 12 weeks. Standardized parent-rated assessments were administered at baseline and post-treatment to measure changes in language. Structured laboratory observation indicated children demonstrated significantly greater frequency of utterances and improvement on standardized questionnaires measuring expressive language and adaptive communication skills following PRT. Findings suggest that PRT may be efficacious in improving language abilities among children with developmental disorders.
Passive imaging at 250 GHz for detection of face presentation attacks
Authors: Kowalski Marcin
Published: December 2020

Face presentation attacks are becoming more efficient since new 3D facial masks are used. Passive terahertz imaging offers specific physical properties that may improve presentation attack detection capabilities. The non-zero transmission capability through a variety of non-metallic materials may provide necessary information for presentation attack detection. The aim of this paper is to present outcomes of a study on face presentation attack detection using passive imaging at 250 GHz. An analysis of presentation attacks for facial recognition systems using custom displayed and printed photographs, 3D-printed and full-face flexible 3D-latex masks, is provided together with spectral characterization of various presentation attack instruments. A set of experiments with various instruments and various sets of clothing is described and discussed. Finally, two presentation attack detection methods are proposed. The first method is based on a threshold corresponding to a difference between mean intensities of selected regions of interests while the second method uses eight different deep learning classifiers to detect presentation attacks. Results of two validation schemes are presented.
Achromatic optical system with diffractive-refractive hybrid lenses for multifocusing of ultrashort pulse beams
Authors: Amako Jun , Nakano Hidetoshi
Published: December 2020

We report an achromatic cascade optical system for multifocusing ultrashort pulse beams with a diffractive beam splitter. Distortion compensation requires the removal of pulse front distortions from arrayed pulses, which originate from beam-radius-dependent group delay dispersions. The inclusion of hybrid diffractive-refractive lenses can effectively manage system dispersions. Simple design formulas are derived using the ray-matrix analysis and the designed system is evaluated using 20-fs pulses. We confirm that the hybridized system can remove not only chromatic aberrations but also pulse front distortions, hence improving the system spatio-temporal focusing resolutions. The proposed pulse delivery technique enhances the practicality of materials processing with ultrashort pulses.
Enhancement in optically induced ultrafast THz response of MoSe2MoS2 heterobilayer
Authors: Kumar Sunil , Singh Arvind , Kumar Sandeep , Nivedan Anand , Tondusson Marc , Degert Jérôme , Oberlé Jean , Yun Seok Joon , Lee Young Hee , Freysz Eric
Published: December 2020

THz conductivity of large area MoS2 and MoSe2 monolayers as well as their vertical heterostructure, MoSe2MoS2 is measured in the 0.3–5 THz frequency range. Compared to the monolayers, the ultrafast THz reflectivity of the MoSe2MoS2 heterobilayer is enhanced many folds when optically excited above the direct band gap energies of the constituting monolayers. The free carriers generated in the heterobilayer evolve with the characteristic times found in each of the two monolayers. Surprisingly, the same enhancement is recorded in the ultrafst THz reflectivity of the heterobilayer when excited below the MoS2 bandgap energy. A mechanism accounting for these observations is proposed.
Three-wavelength measurement of aerosol absorption using a multi-resonator coupled photoacoustic spectrometer
Authors: Cao Yuan , Liu Kun , Wang Ruifeng , Chen Weidong , Gao Xiaoming
Published: December 2020

Aerosol optical absorption measurements are important for the prediction of climate change, as aerosols directly disturb Earth’s radiation balance by absorbing or scattering solar radiation. Although photoacoustic spectroscopy is commonly recognized as one of the best candidates to measure the absorption of aerosols, multi-wavelength measurements of aerosols optical absorption remain challenging. Here, a method based on photoacoustic spectroscopy that can simultaneously measure the aerosol absorption characteristics of three wavelengths (404, 637 and 805 nm) is proposed. In the three-wavelength photoacoustic spectrometer (TW-PAS), a photoacoustic cell with three acoustic resonators operating at different resonant frequencies was designed for offering multi-laser (multi-wavelength) operation simultaneously, and only one microphone was used to measure the acoustic signals of all resonators. The performance of TW-PAS was demonstrated and evaluated by measuring and analyzing the wavelength-dependent absorption coefficients of carbonaceous aerosols, which shows good agreement with previously reported results. The developed TW-PAS exhibits high potential for classifying and quantifying different types of light-absorbing aerosols by analyzing its absorption wavelength dependence characteristics.
Effects of pump pulse energy and repetition rate on beam quality in a high-power mid-infrared ZnGeP2 OPO
Authors: Piotrowski Marcin , Alessandro Medina Manuel , Schellhorn Martin , Spindler Gerhard , Hildenbrand-Dhollande Anne
Published: December 2020

We report on changes of beam quality with rising pump pulse energy and repetition rate in a high-power mid-infrared ZnGeP2 (ZGP) OPO in a non-planar cavity. The ZGP OPO generates 25 W in 3 – 5 μm pumped by a 10 kHz Q-switched Ho:LLF MOPA system at 2 μm. The beam quality factor increases from nearly diffraction-limited at OPO threshold to a M2 = 1.8 at maximum pump power. The degradation can be attributed to thermal lensing and gain guiding effects in the nonlinear crystal. To discriminate between those effects, we monitored the beam quality as a function of the repetition rate at the highest pump pulse energy using a Pockels cell as a pulse picker. Therefore, the heat load inducing thermal lensing increases linearly, whereas gain guiding remains nearly unaffected. M2 shows a minimum of 1.2 at 1 kHz, starting from 1.3 at 100 Hz and rising to 1.8 at 10 kHz. Those findings have been reproduced by numerical simulations. Further investigations show the transient evolution of beam quality, revealing the thermal lens build-up process to the steady-state.
Coherent Fourier scatterometry using orbital angular momentum beams for defect detection
Authors: Wang Bin , Tanksalvala Michael , Zhang Zhe , Esashi Yuka , Jenkins Nicholas W. , Murnane Margaret M. , Kapteyn Henry C. , Liao Chen-Ting
Published: December 2020

Defect inspection on lithographic substrates, masks, reticles, and wafers is an important quality assurance process in semiconductor manufacturing. Coherent Fourier scatterometry (CFS) using laser beams with a Gaussian spatial profile is the standard workhorse routinely used as an in-line inspection tool to achieve high throughput. As the semiconductor industry advances toward shrinking critical dimensions in high volume manufacturing using extreme ultraviolet lithography, new techniques that enable high-sensitivity, high-throughput, and in-line inspection are critically needed. Here we introduce a set of novel defect inspection techniques based on bright-field CFS using coherent beams that carry orbital angular momentum (OAM). One of these techniques, the differential OAM CFS, is particularly unique because it does not rely on referencing to a pre-established database in the case of regularly patterned structures with reflection symmetry. The differential OAM CFS exploits OAM beams with opposite wavefront or phase helicity to provide contrast in the presence of detects. We numerically investigated the performance of these techniques on both amplitude and phase defects and demonstrated their superior advantages—up to an order of magnitude higher in signal-to-noise ratio—over the conventional Gaussian beam CFS. These new techniques will enable increased sensitivity and robustness for in-line nanoscale defect inspection and the concept could also benefit x-ray scattering and scatterometry in general.
Long-term experimental evolution of HIV-1 reveals effects of environment and mutational history
Authors: Bons Eva , Leemann Christine , Metzner Karin J. , Regoes Roland R.
Published: December 2020

An often-returning question for not only HIV-1, but also other organisms, is how predictable evolutionary paths are. The environment, mutational history, and random processes can all impact the exact evolutionary paths, but to which extent these factors contribute to the evolutionary dynamics of a particular system is an open question. Especially in a virus like HIV-1, with a large mutation rate and large population sizes, evolution is expected to be highly predictable if the impact of environment and history is low, and evolution is not neutral. We investigated the effect of environment and mutational history by analyzing sequences from a long-term evolution experiment, in which HIV-1 was passaged on 2 different cell types in 8 independent evolutionary lines and 8 derived lines, 4 of which involved a switch of the environment. The experiments lasted for 240–300 passages, corresponding to approximately 400–600 generations or almost 3 years. The sequences show signs of extensive parallel evolution—the majority of mutations that are shared between independent lines appear in both cell types, but we also find that both environment and mutational history significantly impact the evolutionary paths. We conclude that HIV-1 evolution is robust to small changes in the environment, similar to a transmission event in the absence of an immune response or drug pressure. We also find that the fitness landscape of HIV-1 is largely smooth, although we find some evidence for both positive and negative epistatic interactions between mutations.
Structural analyses of the PKA RIIβ holoenzyme containing the oncogenic DnaJB1-PKAc fusion protein reveal protomer asymmetry and fusion-induced allosteric perturbations in fibrolamellar hepatocellular carcinoma
Authors: Lu Tsan-Wen , Aoto Phillip C. , Weng Jui-Hung , Nielsen Cole , Cash Jennifer N. , Hall James , Zhang Ping , Simon Sanford M. , Cianfrocco Michael A. , Taylor Susan S.
Published: December 2020

When the J-domain of the heat shock protein DnaJB1 is fused to the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), replacing exon 1, this fusion protein, J-C subunit (J-C), becomes the driver of fibrolamellar hepatocellular carcinoma (FL-HCC). Here, we use cryo-electron microscopy (cryo-EM) to characterize J-C bound to RIIβ, the major PKA regulatory (R) subunit in liver, thus reporting the first cryo-EM structure of any PKA holoenzyme. We report several differences in both structure and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Most striking is the asymmetry caused by the absence of the second cyclic nucleotide binding (CNB) domain and the J-domain in one of the RIIβ:J-C protomers. Using molecular dynamics (MD) simulations, we discovered that this asymmetry is already present in the wild-type (WT) RIIβ2C2 but had been masked in the previous crystal structure. This asymmetry may link to the intrinsic allosteric regulation of all PKA holoenzymes and could also explain why most disease mutations in PKA regulatory subunits are dominant negative. The cryo-EM structure, combined with small-angle X-ray scattering (SAXS), also allowed us to predict the general position of the Dimerization/Docking (D/D) domain, which is essential for localization and interacting with membrane-anchored A-Kinase-Anchoring Proteins (AKAPs). This position provides a multivalent mechanism for interaction of the RIIβ holoenzyme with membranes and would be perturbed in the oncogenic fusion protein. The J-domain also alters several biochemical properties of the RIIβ holoenzyme: It is easier to activate with cAMP, and the cooperativity is reduced. These results provide new insights into how the finely tuned allosteric PKA signaling network is disrupted by the oncogenic J-C subunit, ultimately leading to the development of FL-HCC.
Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments
Authors: Rastogi Ananya , Robert Philippe A. , Halle Stephan , Meyer-Hermann Michael
Published: December 2020

In vivoimaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs. We developed a three-dimensional agent-based model to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photonin vivoobservations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor. However, when allowingin silicoT cells to initiate new interactions with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with experimental datasets. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided readouts to distinguish CTL killing models.
The COVID-19 outbreak in Sichuan, China: Epidemiology and impact of interventions
Authors: Liu Quan-Hui , Bento Ana I. , Yang Kexin , Zhang Hang , Yang Xiaohan , Merler Stefano , Vespignani Alessandro , Lv Jiancheng , Yu Hongjie , Zhang Wei , Zhou Tao , Ajelli Marco
Published: December 2020

In January 2020, a COVID-19 outbreak was detected in Sichuan Province of China. Six weeks later, the outbreak was successfully contained. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of interventions in limiting SARS-CoV-2 transmission. We analyzed patient records for all laboratory-confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimated the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. We estimated R0 at 2.4 (95% CI: 1.6–3.7). The epidemic was self-sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95% CI: 31–68 days), causing 9,216 more cases (95% CI: 1,317–25,545).
Measuring spectrally-resolved information transfer
Authors: Pinzuti Edoardo , Wollstadt Patricia , Gutknecht Aaron , Tüscher Oliver , Wibral Michael
Published: December 2020

Information transfer, measured by transfer entropy, is a key component of distributed computation. It is therefore important to understand the pattern of information transfer in order to unravel the distributed computational algorithms of a system. Since in many natural systems distributed computation is thought to rely on rhythmic processes a frequency resolved measure of information transfer is highly desirable. Here, we present a novel algorithm, and its efficient implementation, to identify separately frequencies sending and receiving information in a network. Our approach relies on the invertible maximum overlap discrete wavelet transform (MODWT) for the creation of surrogate data in the computation of transfer entropy and entirely avoids filtering of the original signals. The approach thereby avoids well-known problems due to phase shifts or the ineffectiveness of filtering in the information theoretic setting. We also show that measuring frequency-resolved information transfer is a partial information decomposition problem that cannot be fully resolved to date and discuss the implications of this issue. Last, we evaluate the performance of our algorithm on simulated data and apply it to human magnetoencephalography (MEG) recordings and to local field potential recordings in the ferret. In human MEG we demonstrate top-down information flow in temporal cortex from very high frequencies (above 100Hz) to both similarly high frequencies and to frequencies around 20Hz, i.e. a complex spectral configuration of cortical information transmission that has not been described before. In the ferret we show that the prefrontal cortex sends information at low frequencies (4-8 Hz) to early visual cortex (V1), while V1 receives the information at high frequencies (> 125 Hz).
Optimal learning with excitatory and inhibitory synapses
Authors: Ingrosso Alessandro
Published: December 2020

Characterizing the relation between weight structure and input/output statistics is fundamental for understanding the computational capabilities of neural circuits. In this work, I study the problem of storing associations between analog signals in the presence of correlations, using methods from statistical mechanics. I characterize the typical learning performance in terms of the power spectrum of random input and output processes. I show that optimal synaptic weight configurations reach a capacity of 0.5 for any fraction of excitatory to inhibitory weights and have a peculiar synaptic distribution with a finite fraction of silent synapses. I further provide a link between typical learning performance and principal components analysis in single cases. These results may shed light on the synaptic profile of brain circuits, such as cerebellar structures, that are thought to engage in processing time-dependent signals and performing on-line prediction.
Differential effects of RASA3 mutations on hematopoiesis are profoundly influenced by genetic background and molecular variant
Authors: Robledo Raymond F. , Ciciotte Steven L. , Graber Joel H. , Zhao Yue , Lambert Amy J. , Gwynn Babette , Maki Nathaniel J. , Brindley Elena C. , Hartman Emily , Blanc Lionel , Peters Luanne L.
Published: December 2020

Studies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5–13.5 due to severe hemorrhage. Here, conditional deletion in hematopoietic stem and progenitor cells (HSPCs) using Vav-iCre recapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, leading to pancytopenia and death within two weeks. Notably, RASA3 missense mutations in two mouse models, scat (G125V) and hlb381 (H794L), show dramatically different hematopoietic consequences specific to both genetic background and molecular variant. The mutation effect is mediated at least in part by differential effects on RAS and RAP activation. In addition, we show that the role of RASA3 is conserved during human terminal erythropoiesis, highlighting a potential function for the RASA3-RAS axis in disordered erythropoiesis in humans. Finally, global transcriptomic studies in scat suggest potential targets to ameliorate disease progression.
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density
Authors: Swan Anna L. , Schütt Christine , Rozman Jan , del Mar Muñiz Moreno Maria , Brandmaier Stefan , Simon Michelle , Leuchtenberger Stefanie , Griffiths Mark , Brommage Robert , Keskivali-Bond Piia , Grallert Harald , Werner Thomas , Teperino Raffaele , Becker Lore , Miller Gregor , Moshiri Ala , Seavitt John R. , Cissell Derek D. , Meehan Terrence F. , Acar Elif F. , Lelliott Christopher J. , Flenniken Ann M. , Champy Marie-France , Sorg Tania , Ayadi Abdel , Braun Robert E. , Cater Heather , Dickinson Mary E. , Flicek Paul , Gallegos Juan , Ghirardello Elena J. , Heaney Jason D. , Jacquot Sylvie , Lally Connor , Logan John G. , Teboul Lydia , Mason Jeremy , Spielmann Nadine , McKerlie Colin , Murray Stephen A. , Nutter Lauryl M. J. , Odfalk Kristian F. , Parkinson Helen , Prochazka Jan , Reynolds Corey L. , Selloum Mohammed , Spoutil Frantisek , Svenson Karen L. , Vales Taylor S. , Wells Sara E. , White Jacqueline K. , Sedlacek Radislav , Wurst Wolfgang , Lloyd K. C. Kent , Croucher Peter I. , Fuchs Helmut , Williams Graham R. , Bassett J. H. Duncan , Gailus-Durner Valerie , Herault Yann , Mallon Ann-Marie , Brown Steve D. M. , Mayer-Kuckuk Philipp , Hrabe de Angelis Martin ,   IMPC Consortium
Published: December 2020

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.
GATA factor-regulated solute carrier ensemble reveals a nucleoside transporter-dependent differentiation mechanism
Authors: Zwifelhofer Nicole M. , Cai Xiaoli , Liao Ruiqi , Mao Bin , Conn Daniel J. , Mehta Charu , Keles Sunduz , Xia Yang , Bresnick Emery H.
Published: December 2020

Developmental-regulatory networks often include large gene families encoding mechanistically-related proteins like G-protein-coupled receptors, zinc finger transcription factors and solute carrier (SLC) transporters. In principle, a common mechanism may confer expression of multiple members integral to a developmental process, or diverse mechanisms may be deployed. Using genetic complementation and enhancer-mutant systems, we analyzed the 456 member SLC family that establishes the small molecule constitution of cells. This analysis identified SLC gene cohorts regulated by GATA1 and/or GATA2 during erythroid differentiation. As >50 SLC genes shared GATA factor regulation, a common mechanism established multiple members of this family. These genes included Slc29a1 encoding an equilibrative nucleoside transporter (Slc29a1/ENT1) that utilizes adenosine as a preferred substrate. Slc29a1 promoted erythroblast survival and differentiation ex vivo. Targeted ablation of murine Slc29a1 in erythroblasts attenuated erythropoiesis and erythrocyte regeneration in response to acute anemia. Our results reveal a GATA factor-regulated SLC ensemble, with a nucleoside transporter component that promotes erythropoiesis and prevents anemia, and establish a mechanistic link between GATA factor and adenosine mechanisms. We propose that integration of the GATA factor-adenosine circuit with other components of the GATA factor-regulated SLC ensemble establishes the small molecule repertoire required for progenitor cells to efficiently generate erythrocytes.