bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-rank representation of omnidirectional subsurface extended image volumes
Authors: Yang Mengmeng , Graff Marie , Kumar Rajiv , Herrmann Felix J.
Published: January 2021

Subsurface-offset gathers play an increasingly important role in seismic imaging. These gathers are used during velocity model building and inversion of rock properties from amplitude variations. Although powerful, these gathers come with high computational and storage demands to form and manipulate these high-dimensional objects. This explains why only limited numbers of image gathers are computed over a limited offset range. We avoid these high costs by working with highly compressed low-rank factorizations. These factorizations are obtained via a combination of probings with the double two-way wave equation and randomized singular-value decompositions. In turn, the resulting factorizations give us access to all subsurface offsets without having to form the full extended image volumes (EIVs) that are at best quadratic in image size. As a result, we can easily handle situations in which conventional horizontal offset gathers are no longer focused. More importantly, the factorization also provides a mechanism to use the invariance relation of EIVs for velocity continuation. With this technique, EIVs for one background velocity model can be directly mapped to those of another background velocity model. Our low-rank factorization inherits this invariance property, so that factorization costs arise only once when examining different imaging scenarios. Because all imaging experiments only involve the factors, they are computationally efficient with costs that scale with the rank of the factorization. Examples using 2D synthetics, including a challenging imaging example with salt, validate the methodology. Instead of brute-force explicit crosscorrelations between shifted source and receiver wavefields, our approach relies on the underlying linear-algebra structure that enables us to work with these objects without incurring unfeasible demands on computation and storage.
An interview with Swathi Arur
Authors: Eve Alex
Published: January 2021

Swathi Arur is an Associate Professor for the Department of Genetics at the MD Anderson Cancer Center, USA, where she uses multidisciplinary approaches to understand female germline development and fertility. She has received numerous accolades, including the MD Anderson Distinguished Research Faculty Mentor Award in 2017. In 2020, she was elected to the American Association for the Advancement of Science (AAAS). Swathi joined the team at Development as an Academic Editor in 2020, and we met with her over Zoom to hear more about her life, her career and her love for C. elegans.
Requirement of CRAMP for mouse macrophages to eliminate phagocytosedE. colithrough an autophagy pathway
Authors: Chen Keqiang , Yoshimura Teizo , Gong Wanghua , Tian Cuimeng , Huang Jiaqiang , Trinchieri Giorgio , Wang Ji Ming
Published: January 2021

Host-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild-type, WT) mouse macrophages increased their expression of cathelin-related antimicrobial peptide (CRAMP, encoded by Camp) after infection by viable E. coli or stimulation with inactivated E. coli and its product lipopolysaccharide (LPS), a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages for elimination of phagocytosed E. coli, with participation of autophagy-related proteins ATG5, LC3-II and LAMP-1, as well as for aggregation of the bacteria with p62 (also known as SQSTM1). This process was impaired in CRAMP−/− macrophages, resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate that CRAMP is a critical component in autophagy-mediated clearance of intracellular E. coli by mouse macrophages.
Characterization of Organic Biomolecules (Monosaccharide, Fatty Acid, and Amino Acid) by Losses on Ignition under Stepwise Increases in Temperature
Authors: Satoh Yuhi , Wada Shigeki
Published: January 2021

The characteristics of loss on ignition (LOI) at 200–500 °C of three types of authentic organic biomolecules (monosaccharides: MSs, fatty acids: FAs, and amino acids: AAs) are evaluated and compared to those of reference organic natural samples. FAs and branched-chain AAs degraded almost completely by 300 °C, whereas MSs and unbranched AAs degraded at a slower rate. The exponential regression coefficients matched closely between the references and the authentic compounds, and lipid content was correlated with rate of LOI.
Resenha do livro “Racismo linguístico: os subterrâneos da linguagem e do racismo”
Authors: Missiatto Leandro Aparecido Fonseca
Published: January 2021

Racismo linguístico: os subterrâneos da linguagem e do racismo, livro de autoria de Gabriel Nascimento, aborda a linguagem como mecanismo de produção, disseminação e sedimentação do racismo. Ao fazer os caminhos de pensadores decolonialistas e de uma linguística crítica, o autor aponta para complexidade do racismo e suas interfaces com a linguagem. Com uma escrita potente, meticulosamente arquitetada em uma vasta literatura da área, essa obra é um convite para pensar a linguagem como instrumento de poder e de subalternização de vidas que são produzidas nos horizontes da linguagem como se humanos não fossem.
As cotas raciais na construção da democracia
Authors: Oliveira da Silva Eliaidina Wagna , Lima Alba Janes
Published: January 2021

Esse estudo expõe aos movimentos representativos atuantes contra as disparidades sociorraciais e educacionais, uma leitura das ações afirmativas como remédio de garantia da igualdade material. Aponta o caminhar do Estado Democrático de Direito rumo a uma nação participativa e multicultural, militando inclusões sociais positivas em cujo manifesto pelas diversidades rompem invisibilidades das minorias negras ao compartilhar espaços acadêmicos por meio das cotas raciais. Trata-se de artigo bibliográfico com análise descritiva respaldada na Constituição Federal e produções de Fernandes (2008a, 2008b, 2013, 2017) dialogadas com estudiosos da causa negra, para compreensão do impacto do racismo sobre os corpos negros e das proteções constitucionais contra grupos reacionários.
INTERESSES DO EMPRESARIADO EM TORNO DO PROJETO ESCOLA VIVA
Authors: Lima Marcelo , Sperandio Renan Dos Santos , Costa Debora Freitas
Published: January 2021

O trabalho tem como objetivo analisar em que medida o programa “Escola Viva” (Lei Estadual n° 799/2015) se antecipa em relação a implementação da Reforma do Ensino Médio (lei nº 13.415/2017), cujas soluções incorporam formas de privatização da escola pública. Metodologicamente, realizamos uma análise documental percorrendo os registros presentes em fontes extraídas do relatório legislativo local, sites de parlamentares, documentos do conselho estadual de educação, manifestos de instituições de alunos e professores e notícias de jornais de grande circulação do estado. O que percebemos é que tanto nacionalmente quanto em âmbito estadual, apenas a demanda do setor empresarial foi acatada na implementação do projeto, além do uso de recursos autoritários do executivo para aprovação do projeto sem a garantia de um amplo debate com os professores, pais e alunos.
FUNDAMENTOS DE UMA ANÁLISE HISTÓRICO-CRÍTICA SOBRE OS DESAFIOS DO ENSINO MÉDIO PARA A DÉCADA DE 2020
Authors: Turini Mateus Henrique , Villela Fábio Fernandes
Published: January 2021

A partir das reflexões obtidas durante uma pesquisa de mestrado, o presente trabalho sistematiza um conjunto de pressupostos teórico-metodológicos para se refletir sobre os desafios do Ensino Médio para a década de 2020. Orientados pela Pedagogia Histórico-crítica (PHC), a concepção de mediação pedagógica apresenta-se como uma atividade dialética, em constante movimento, imersa na prática social e que valoriza o conhecimento produzido, acumulado e reinterpretado historicamente. Nessa perspectiva e observando a Base Nacional Comum Curricular (BNCC), é possível viabilizar potenciais caminhos de estímulo ao exercício crítico da atividade pedagógica, tendo bem delineados o papel social da escola, sua atividade nuclear, sua relação com a sociedade e sua contribuição para a formação humana.
A CIÊNCIA E A TECNOLOGIA NOS INSTITUTOS FEDERAIS E SEU POTENCIAL TRANSFORMADOR: UM BREVE DIÁLOGO COM ÁLVARO VIEIRA PINTO (E O MATERIALISMO HISTÓRICO-DIALÉTICO)
Authors: Madureira João Cláudio
Published: January 2021

O presente trabalho apresenta um breve ensaio a respeito da compreensão da concepção e diretrizes dos institutos federais, instituições públicas de educação profissional e tecnológica do país, a partir da perspectiva da filosofia da técnica desenvolvida por Álvaro Vieira Pinto, na obra “O Conceito de Tecnologia”, por meio da categoria central de análise Trabalho em suas dimensões ontológica e histórica. A partir dos conceitos de tecnologia e razão técnica e sua relação dialética com a produção da existência material humana realiza-se inferências quanto ao potencial revolucionário da formação tecnológica pretendida pelos institutos federais, ao tomar o trabalho como princípio educativo, assim como a pesquisa como princípio pedagógico e científico, na contribuição ao processo de tomada de consciência para si dos/as estudantes trabalhadores/as nestas instituições.
APONTAMENTOS SOBRE A REVOLUÇÃO BURGUESA NO BRASIL NA OBRA DE FLORESTAN FERNANDES
Authors: Cassin Márcia Pereira da Silva
Published: January 2021

O artigo desenvolve uma síntese sobre os principais aspectos acerca do tema da revolução burguesa no Brasil presentes na obra de Florestan Fernandes. A primeira parte versa sobre a formação do Estado nacional a partir da independência, buscando identificar as raízes da dominação burguesa no Brasil e de sua natureza autocrática. A segunda parte se debruça sobre o desenvolvimento do capitalismo dependente, em suas diferentes fases, e o processo de consolidação da revolução burguesa no Brasil.Palavras-chave: Revolução burguesa no Brasil; Capitalismo dependente; Autocracia burguesa.
FERNANDES, Florestan. O QUE É REVOLUÇÃO?. SÃO PAULO: EXPRESSÃO POPULAR, 2018.
Authors: Oliveira Tiago Fávero de
Published: January 2021

Resenha da obra "O que é revolução?" de Florestan Fernandes. A importância do pensamento e da militância de Florestan Fernandes para a história da democracia no país é reconhecida por muitos teóricos e cidadãos. Num momento de crise democrática e de novos padrões de socialização, refletir sobre “O que é revolução” é atual e necessário. A obra em análise foi originalmente publicada, em parceria com Caio Prado Júnior, no ano de 1981 dentro do livro “Clássicos sobre a revolução brasileira” (PRADO JÚNIOR; FERNANDES, 2000). Utilizou-se, nesta resenha, a nova edição de 2018 da Editora Expressão Popular (FERNANDES, 2018), dentro da qual foi publicada apenas o texto do sociólogo paulista. O autor analisa, em seu texto, a trajetória histórica da revolução burguesa no capitalismo dependente brasileiro, sinalizando para a necessária revolução operária, vista como caminho para a realização de um Estado democrático independente. O livro é dividido em seis partes, apresentadas pelo autor como questões, a saber: o que se deve entender por revolução?; “quem faz” a revolução?; é possível “impedir” ou “atrasar” a revolução?; como “fortalecer a revolução” e “leva-la até o fim”?; revolução nacional ou revolução proletária?; como “lutar pela revolução proletária” no Brasil?. Nesta resenha, optou-se por dar centralidade à obra, com muitas citações do texto original, a partir do agrupamento de temas que são relevantes, sem se preocupar em acompanhar cada parte de modo específico.
Reversible DNA codes from skew cyclic codes over a ring of order 256
Authors: CENGELLENMİS Yasemin , AYDİN Nuh , DERTLİ Abdullah
Published: January 2021

We introduce skew cyclic codes over the finite ring $\R$, where $u^{2}=0,v^{2}=v,w^{2}=w,uv=vu,uw=wu,vw=wv$ and use them to construct reversible DNA codes. The 4-mers are matched with the elements of this ring. The reversibility problem for DNA 4-bases is solved and some examples are provided.
Landslide detection and susceptibility mapping using geological and remote sensing data: A case study of Azad Kashmir, NW Sub-Himalayas
Authors: Zeeshan Muhammad
Published: January 2021

Azad Kashmir has undergone sever landslide episodes in the past. The main reasons behind the occurrence of landslides in this area are heavy rainfall, weak geological strata, seismic zones and active faults. Several episodes of roads blockage due to landslide is one of the major problem in this area, therefore, this study is carried out for landslide susceptibility analysis along the roads of Kotli to Trar Khel, Azad Kashmir, NW Sub-Himalayas. Geographic information system (GIS) is used to interpret remote sensing, geological strata and topographical data. Total ten anthropogenic and physical factors (aspects, fault, lithology, drainage density, curvature, distance to roads, landuse landcover, slope, seismic and elevation) were examined by Multi-criteria Decision Analysis (MCDA) technique. The thematic layers of all factors were prepared for the preparation of the final susceptibility map by using a weighted overlay method (WOM). The susceptibility map classified the study area into four susceptible classes of low, moderate, high and very high. The spatial analysis and result outcomes depicted that active faults, slope gradient and landuse landcover may facilitate landslide phenomena. The results were verified by landslide density analyses (LDA), receiver operator characteristics (ROC) and area under curve (AUC) with predictive accuracy of 77 % that is rated as satisfactory by many researchers.
‘It may not be due to illness’: social rights for applicants for incapacity benefits
Authors: Arlesten Sara , Ulmestig Rickard
Published: January 2021

The aim of this article is to understand the materialisation of social rights for citizens in need of incapacity benefits by analysing the institution of welfare inter-agency collaboration. We achieve this through an analysis of 12 observation sessions of inter-agency collaboration where incapacity benefits are being processed between several agencies. Social rights are materialised behind closed doors. The decisions are affected by suspicions of social explanations of incapacity while medical knowledge is prioritised. The laws and resources are used to suit the explanations from the officials. In such cases inter-agency collaboration risks disempowering the citizens.
Romance, companionship and masculinities in establishing relationships by Mexican Mormon men
Authors: Siles Ali
Published: January 2021

The contradictory pressures that Mormon belief and practice create for men’s gender identity and sexuality give reason to reconsider the concept of ‘hegemonic masculinity’. Starting from Connell’s conceptualisation, this article analyses narratives by 25 Mexican Mormon men of establishing ‘romantic’ relationships. Participants were recruited through three different Mormon organisations in Mexico City. I explore emotional/affective notions constitutive of masculinity at play in their narratives and how they influenced the experiences and trajectories of their romantic relationships. I argue that relationships framed by hegemonic Mormon masculinity incorporate ‘traditional’ elements associated with long-lasting Judaeo-Christian normativity, such as (self-) control over physical attraction and marriage as the only context for it, simultaneously emphasising modern/post-modern forms of masculinity through ideas of love, companionship and emotional connection. The incorporation of these affective notions in the analysis can expand the concept of ‘hegemonic masculinity’, illuminating ways in which men adopt, negotiate or contest hegemonic patterns of masculinity.
Understanding the economics of abuse: an assessment of the economic abuse definition within the Domestic Abuse Bill
Authors: Sharp-Jeffs Nicola
Published: January 2021

The term ‘economic abuse’ was first introduced into discourse when it was identified as a tactic used by perpetrators within the Duluth Power and Control Wheel. Yet it is only recently that researchers have turned their attention to defining and understanding it. This article draws on a review of the global and UK specific academic research literature to assess the suitability of the definition of economic abuse put forward within the Westminster government’s Domestic Abuse Bill. It recommends that a) the term ‘any behaviour’ within the definition is understood to include controlling tactics which sit under the constructs of economic restriction, exploitation and/or sabotage, b) the definition recognises perpetrators will also prevent a partner from using/maintaining goods or services and, c) attention is given to the suggestion that single incidents of economic abuse would not fall under this definition. While the focus of this article is on Westminster policy in the UK, the case for ‘naming’ and defining economic abuse in statute has wider resonance, not least because it provides a framework within which to report on prevalence, hold perpetrators accountable and for services (statutory and voluntary) to respond.
‘A life barely half lived’: domestic abuse and sexual violence practitioners’ experiences and perceptions of providing care to survivors of non-physical abuse within intimate partner relationships
Authors: Halliwell Gemma , Daw Jennifer , Hay Susie , Dheensa Sandi , Jacob Suzanne
Published: January 2021

Non-physically abusive acts (underpinned by coercive control) are more prevalent than physical or sexual violence within intimate partner relationships. Yet, little is known about survivors’ help-seeking journeys or the efficacy of existing services in addressing this need. We present findings from a survey of UK-based domestic violence and abuse (DVA) and sexual violence (SV) practitioners (n = 279) exploring experiences of providing care to women with histories of non-physical abuse. Our findings suggest that survivors often seek help for non-physical abuse from specialist DVA and SV services, but wider professional agencies often overlook the severity of this experience of abuse in the absence of physical or sexual violence. The impacts of non-physical abuse on survivors’ health and wellbeing are severe and there are multiple barriers to support, particularly within the criminal justice system. Our findings highlight the urgent need to increase public and professional awareness of non-physical abuse and its consequences for training of wider agencies (for example, police, child protection, legal services) and for sustainable funding that increases long-term support options for survivors and their children.
No-core fiber interferometry pH sensor based on a polyvinyl alcohol/polyacrylic acid and silica/polyvinyl alcohol/polyacrylic acid hydrogel coating
Authors: Abdzaid Thimar A. , Taher Hanan J.
Published: January 2021

In this paper, we present an investigation on the sensing performance of a pH sensor based on a modal interferometer formed by a simple NO-core fiber interferometer (NCFI) that operates in transmission mode. The fundamental configuration of this sensor encompasses a single-mode-no-core-single-mode fiber (SMF-NCF-SMF “SNCS”) segment chain. The chemical etching method has been used with hydrofluoric (HF) acid to prepare diverse NCF diameters. This was proposed to expand the evanescent fields and enhance sensor sensitivity. Then, the two diverse segments of etched NCF were cladded with polymeric composite fabricated by polyvinyl alcohol/polyacrylic acid (PVA/PAA) hydrogel and pure silica nanoparticles embedded in polyvinyl alcohol/polyacrylic acid (

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is more appropriate for the base sensing, in which these coating materials show enhancement in the sensitivity above the NCF structure before an uncoated sensor due to greater enhancement of the evanescent field affected by the coating layer. The experimental results demonstrate a high average sensitivity of 3.42 nm/pH unit for the 11 w.t.% PVA/PAA coated sensor in the pH range from 1 to 7 and 3.2 nm/pH unit in the pH range from 8 to 14. The sensor also displays high repeatability and stability and low cross-sensitivity to temperature. The simple fabrication and high sensitivity of this sensor may prompt many potential applications in the fields of biology and chemistry.
Fiber-optic sensor measuring spatial distributions of refractive index and temperature
Authors: Pfalzgraf Ivonne , Suntsov Sergiy , Kip Detlef
Published: January 2021

In this work, we present a fiber sensor designed to measure simultaneously spatial inhomogeneities of the refractive index and temperature in liquid media, for example, induced by biochemical reactions. The sensor’s constituent elements are Fabry–Perot microresonators fabricated in standard single-mode optical fibers by diamond blade dicing. To allow simultaneous measurements of different refractive indices, the sensor comprises two open cavities approximately 2 mm apart. With a small Si inlay inserted into one of the resonators used for temperature measurements, the sensor allows for immediate compensation of crosstalk between temperature- and composition-induced fluids’ refractive index changes. The measurements were evaluated by phase tracking of the characteristic Fourier transform components of the sensor’s backreflected spectra. The temperature sensitivity of the Si inlay is 0.063 rad/°C (79 pm/°C), and an accuracy of 0.01°C is obtained. Meanwhile, the two refractive index sensing (open) cavities show a sensitivity of 1168 and 1153 nm/RIU for temperature-compensated measurements. Finally, the sensor performance to measure spatial distributions is demonstrated by measuring the diffusion behavior of sucrose in water, which allows precise monitoring of hydration effects and breaking of bonds at elevated temperatures.
Real-time tool to layer distance estimation for robotic subretinal injection using intraoperative 4D OCT
Authors: Sommersperger Michael , Weiss Jakob , Ali Nasseri M. , Gehlbach Peter , Iordachita Iulian , Navab Nassir
Published: January 2021

The emergence of robotics could enable ophthalmic microsurgical procedures that were previously not feasible due to the precision limits of manual delivery, for example, targeted subretinal injection. Determining the distance between the needle tip, the internal limiting membrane (ILM), and the retinal pigment epithelium (RPE) both precisely and reproducibly is required for safe and successful robotic retinal interventions. Recent advances in intraoperative optical coherence tomography (iOCT) have opened the path for 4D image-guided surgery by providing near video-rate imaging with micron-level resolution to visualize retinal structures, surgical instruments, and tool-tissue interactions. In this work, we present a novel pipeline to precisely estimate the distance between the injection needle and the surface boundaries of two retinal layers, the ILM and the RPE, from iOCT volumes. To achieve high computational efficiency, we reduce the analysis to the relevant area around the needle tip. We employ a convolutional neural network (CNN) to segment the tool surface, as well as the retinal layer boundaries from selected iOCT B-scans within this tip area. This results in the generation and processing of 3D surface point clouds for the tool, ILM and RPE from the B-scan segmentation maps, which in turn allows the estimation of the minimum distance between the resulting tool and layer point clouds. The proposed method is evaluated on iOCT volumes from ex-vivo porcine eyes and achieves an average error of 9.24 µm and 8.61 µm measuring the distance from the needle tip to the ILM and the RPE, respectively. The results demonstrate that this approach is robust to the high levels of noise present in iOCT B-scans and is suitable for the interventional use case by providing distance feedback at an average update rate of 15.66 Hz.
Generation of quantum entanglement based on electromagnetically induced transparency media
Authors: Chuang You-Lin , Lee Ray-Kuang , Yu Ite A.
Published: January 2021

Quantum entanglement is an essential ingredient for the absolute security of quantum communication. Generation of continuous-variable entanglement or two-mode squeezing between light fields based on the effect of electromagnetically induced transparency (EIT) has been systematically investigated in this work. Here, we propose a new scheme to enhance the degree of entanglement between probe and coupling fields of coherent-state light by introducing a two-photon detuning in the EIT system. This proposed scheme is more efficient than the conventional one, utilizing the ground-state relaxation (population decay or dephasing) rate to produce entanglement or two-mode squeezing which adds far more excess fluctuation or noise to the system. In addition, maximum degree of entanglement at a given optical depth can be achieved with a wide range of the coupling Rabi frequency and the two-photon detuning, showing our scheme is robust and flexible. It is also interesting to note that while EIT is the effect in the perturbation limit, i.e. the probe field being much weaker than the coupling field and treated as a perturbation, there exists an optimum ratio of the probe to coupling intensities to achieve the maximum entanglement. Our proposed scheme can advance the continuous-variable-based quantum technology and may lead to applications in quantum communication utilizing squeezed light.
Influence of the delay line jitter on the SHG FROG reconstruction
Authors: Veselá Petra , Žídek Karel
Published: January 2021

Frequency-resolved optical gating (FROG) counts among the most used methods to characterize complex femtosecond pulses. The multishot FROG experiment, studied in this work, relies on varying a delay between two replicas of the measured pulse, where the delay accuracy can suffer from delay line imperfections, setup instability, or minimization of the acquisition time. We present a detailed study on the effect of the delay line jitter on the pulse retrieval. We carried out simulations with the jitter values ranging from high-precision delay lines (100 nm) up to extremely unstable measurements (>1000 nm). For three sets of pulses, we quantified criteria assuring reliable reconstruction, using ptychographic algorithm, of a complex pulse based on the experimentally available FROG trace error. We observe that the effect of the jitter scales together with the spectral bandwidth. However, the pulse reconstruction is relatively robust against the jitter and, even for a severe distortion of the FROG trace (e.g., a jitter of 500 nm for broadband pulses), the main features of all pulses are retrieved with high fidelity. Our results provide guidance for the limitations based on the delay imperfections in the FROG experiment.
Optimization of the silicon-based aperiodic optical phased array antenna
Authors: Kazemian Arash , Wang Pengdi , Zhuang Yating , Yi Yasha
Published: January 2021

Beam engineering is one of the most important functionalities in light detection and ranging (LiDAR). In this work, a silicon optical phased array (OPA) is employed to control the beam profile. Machine-learning-based genetic algorithm optimization is utilized to suppress the sidelobes of the far field pattern assuming the random distribution of aperiodic arrays. The optimized mainlobe position versus wavelength relationship in two-dimensional aperiodic arrays is distinctly different from prior works. Analysis was performed to show the effect of fabrication error of arrays on the side mode suppression ratio. Our study provides an effective pathway to optimize the random distributed OPAs within a controllable time frame among the vast number of parameters.
Realization of directional single-mode lasing by a GaN-based warped microring
Authors: Zhang Shengnan , Li Yufeng , Hu Peng , Tian Zhenhuan , Li Qiang , Li Aixing , Zhang Ye , Yun Feng
Published: January 2021

Multimode and random directionalities are major issues restricting the application of whispering gallery mode microcavity lasers. We demonstrated a 40 μm diameter microring with an off-centered embedded hole and warped geometry from strained III-nitride quantum well multilayers. Single-mode directional whispering gallery mode lasing was achieved by the warped structure and high-order mode suppression induced by the off-centered hole. In addition, the introduction of the off-centered hole reduced the lasing threshold from 3.24 to

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compared with the warped microdisk without an embedded hole while maintaining a high-quality factor of more than 4000. Directional light emission in 3D was achieved and attributed to the warped structure, which provides a vertical component of the light emission, making it promising for building multifunctional coherent light sources in optoelectronic integration.
Reconstructing tumor evolutionary histories and clone trees in polynomial-time with SubMARine
Authors: Sundermann Linda K. , Wintersinger Jeff , Rätsch Gunnar , Stoye Jens , Morris Quaid
Published: January 2021

Tumors contain multiple subpopulations of genetically distinct cancer cells. Reconstructing their evolutionary history can improve our understanding of how cancers develop and respond to treatment. Subclonal reconstruction methods cluster mutations into groups that co-occur within the same subpopulations, estimate the frequency of cells belonging to each subpopulation, and infer the ancestral relationships among the subpopulations by constructing a clone tree. However, often multiple clone trees are consistent with the data and current methods do not efficiently capture this uncertainty; nor can these methods scale to clone trees with a large number of subclonal populations.

Here, we formalize the notion of a partially-defined clone tree (partial clone tree for short) that defines a subset of the pairwise ancestral relationships in a clone tree, thereby implicitly representing the set of all clone trees that have these defined pairwise relationships. Also, we introduce a special partial clone tree, the Maximally-Constrained Ancestral Reconstruction (MAR), which summarizes all clone trees fitting the input data equally well. Finally, we extend commonly used clone tree validity conditions to apply to partial clone trees and describe SubMARine, a polynomial-time algorithm producing the subMAR, which approximates the MAR and guarantees that its defined relationships are a subset of those present in the MAR. We also extend SubMARine to work with subclonal copy number aberrations and define equivalence constraints for this purpose. Further, we extend SubMARine to permit noise in the estimates of the subclonal frequencies while retaining its validity conditions and guarantees. In contrast to other clone tree reconstruction methods, SubMARine runs in time and space that scale polynomially in the number of subclones.

We show through extensive noise-free simulation, a large lung cancer dataset and a prostate cancer dataset that the subMAR equals the MAR in all cases where only a single clone tree exists and that it is a perfect match to the MAR in most of the other cases. Notably, SubMARine runs in less than 70 seconds on a single thread with less than one Gb of memory on all datasets presented in this paper, including ones with 50 nodes in a clone tree. On the real-world data, SubMARine almost perfectly recovers the previously reported trees and identifies minor errors made in the expert-driven reconstructions of those trees.

The freely-available open-source code implementing SubMARine can be downloaded at https://github.com/morrislab/submarine.
Selection for rapid uptake of scarce or fluctuating resource explains vulnerability of glycolysis to imbalance
Authors: Janulevicius Albertas , van Doorn G. Sander
Published: January 2021

Glycolysis is a conserved central pathway in energy metabolism that converts glucose to pyruvate with net production of two ATP molecules. Because ATP is produced only in the lower part of glycolysis (LG), preceded by an initial investment of ATP in the upper glycolysis (UG), achieving robust start-up of the pathway upon activation presents a challenge: a sudden increase in glucose concentration can throw a cell into a self-sustaining imbalanced state in which UG outpaces LG, glycolytic intermediates accumulate and the cell is unable to maintain high ATP concentration needed to support cellular functions. Such metabolic imbalance can result in “substrate-accelerated death”, a phenomenon observed in prokaryotes and eukaryotes when cells are exposed to an excess of substrate that previously limited growth. Here, we address why evolution has apparently not eliminated such a costly vulnerability and propose that it is a manifestation of an evolutionary trade-off, whereby the glycolysis pathway is adapted to quickly secure scarce or fluctuating resource at the expense of vulnerability in an environment with ample resource. To corroborate this idea, we perform individual-based eco-evolutionary simulations of a simplified yeast glycolysis pathway consisting of UG, LG, phosphate transport between a vacuole and a cytosol, and a general ATP demand reaction. The pathway is evolved in constant or fluctuating resource environments by allowing mutations that affect the (maximum) reaction rate constants, reflecting changing expression levels of different glycolytic enzymes. We demonstrate that under limited constant resource, populations evolve to a genotype that exhibits balanced dynamics in the environment it evolved in, but strongly imbalanced dynamics under ample resource conditions. Furthermore, when resource availability is fluctuating, imbalanced dynamics confers a fitness advantage over balanced dynamics: when glucose is abundant, imbalanced pathways can quickly accumulate the glycolytic intermediate FBP as intracellular storage that is used during periods of starvation to maintain high ATP concentration needed for growth. Our model further predicts that in fluctuating environments, competition for glucose can result in stable coexistence of balanced and imbalanced cells, as well as repeated cycles of population crashes and recoveries that depend on such polymorphism. Overall, we demonstrate the importance of ecological and evolutionary arguments for understanding seemingly maladaptive aspects of cellular metabolism.
Reconciling kinetic and thermodynamic models of bacterial transcription
Authors: Morrison Muir , Razo-Mejia Manuel , Phillips Rob
Published: January 2021

The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on thermodynamic and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the thermodynamic models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.
Bacterial fitness landscapes stratify based on proteome allocation associated with discrete aero-types
Authors: Chen Ke , Anand Amitesh , Olson Connor , Sandberg Troy E. , Gao Ye , Mih Nathan , Palsson Bernhard O.
Published: January 2021

The fitness landscape is a concept commonly used to describe evolution towards optimal phenotypes. It can be reduced to mechanistic detail using genome-scale models (GEMs) from systems biology. We use recently developed GEMs of Metabolism and protein Expression (ME-models) to study the distribution ofEscherichia coliphenotypes on the rate-yield plane. We found that the measured phenotypes distribute non-uniformly to form a highly stratified fitness landscape. Systems analysis of the ME-model simulations suggest that this stratification results from discrete ATP generation strategies. Accordingly, we define “aero-types”, a phenotypic trait that characterizes how a balanced proteome can achieve a given growth rate by modulating 1) the relative utilization of oxidative phosphorylation, glycolysis, and fermentation pathways; and 2) the differential employment of electron-transport-chain enzymes. This global, quantitative, and mechanistic systems biology interpretation of fitness landscape formed upon proteome allocation offers a fundamental understanding of bacterial physiology and evolution dynamics.
A theory of memory for binary sequences: Evidence for a mental compression algorithm in humans
Authors: Planton Samuel , van Kerkoerle Timo , Abbih Leïla , Maheu Maxime , Meyniel Florent , Sigman Mariano , Wang Liping , Figueira Santiago , Romano Sergio , Dehaene Stanislas
Published: January 2021

Working memory capacity can be improved by recoding the memorized information in a condensed form. Here, we tested the theory that human adults encode binary sequences of stimuli in memory using an abstract internal language and a recursive compression algorithm. The theory predicts that the psychological complexity of a given sequence should be proportional to the length of its shortest description in the proposed language, which can capture any nested pattern of repetitions and alternations using a limited number of instructions. Five experiments examine the capacity of the theory to predict human adults’ memory for a variety of auditory and visual sequences. We probed memory using a sequence violation paradigm in which participants attempted to detect occasional violations in an otherwise fixed sequence. Both subjective complexity ratings and objective violation detection performance were well predicted by our theoretical measure of complexity, which simply reflects a weighted sum of the number of elementary instructions and digits in the shortest formula that captures the sequence in our language. While a simpler transition probability model, when tested as a single predictor in the statistical analyses, accounted for significant variance in the data, the goodness-of-fit with the data significantly improved when the language-based complexity measure was included in the statistical model, while the variance explained by the transition probability model largely decreased. Model comparison also showed that shortest description length in a recursive language provides a better fit than six alternative previously proposed models of sequence encoding. The data support the hypothesis that, beyond the extraction of statistical knowledge, human sequence coding relies on an internal compression using language-like nested structures.
Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans
Authors: Priest Shelby J. , Coelho Marco A. , Mixão Verónica , Clancey Shelly Applen , Xu Yitong , Sun Sheng , Gabaldón Toni , Heitman Joseph
Published: January 2021

Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis. Loss of Msh2 results in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungalCryptococcusspecies,Cryptococcus neoformansandCryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary betweenC.neoformansandC.deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel phenotype inCryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways or other mismatch repair components limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomyceteCryptococcusspecies.
Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect
Authors: Böck Julia , Krogsaeter Einar , Passon Marcel , Chao Yu-Kai , Sharma Sapna , Grallert Harald , Peters Annette , Grimm Christian
Published: January 2021

The endo-lysosomal two-pore channel (TPC2) has been established as an intracellular cation channel of significant physiological and pathophysiological relevance in recent years. For example, TPC2-/- mice show defects in cholesterol degradation, leading to hypercholesterinemia; TPC2 absence also results in mature-onset obesity, and a role in glucagon secretion and diabetes has been proposed. Infections with bacterial toxins or viruses e.g., cholera toxin or Ebola virus result in reduced infectivity rates in the absence of TPC2 or after pharmacological blockage, and TPC2-/- cancer cells lose their ability to migrate and metastasize efficiently. Finally, melanin production is affected by changes in hTPC2 activity, resulting in pigmentation defects and hair color variation. Here, we analyzed several publicly available genome variation data sets and identified multiple variations in the TPC2 protein in distinct human populations. Surprisingly, one variation, L564P, was found to be the predominant TPC2 isoform on a global scale. By applying endo-lysosomal patch-clamp electrophysiology, we found that L564P is a prerequisite for the previously described M484L gain-of-function effect that is associated with blond hair. Additionally, other gain-of-function variants with distinct geographical and ethnic distribution were discovered and functionally characterized. A meta-analysis of genome-wide association studies was performed, finding the polymorphisms to be associated with both distinct and overlapping traits. In sum, we present the first systematic analysis of variations in TPC2. We functionally characterized the most common variations and assessed their association with various disease traits. With TPC2 emerging as a novel drug target for the treatment of various diseases, this study provides valuable insights into ethnic and geographical distribution of TPC2 polymorphisms and their effects on channel activity.
Estimating FST and kinship for arbitrary population structures
Authors: Ochoa Alejandro , Storey John D.
Published: January 2021

FSTand kinship are key parameters often estimated in modern population genetics studies in order to quantitatively characterize structure and relatedness. Kinship matrices have also become a fundamental quantity used in genome-wide association studies and heritability estimation. The most frequently-used estimators ofFSTand kinship are method-of-moments estimators whose accuracies depend strongly on the existence of simple underlying forms of structure, such as the independent subpopulations model of non-overlapping, independently evolving subpopulations. However, modern data sets have revealed that these simple models of structure likely do not hold in many populations, including humans. In this work, we analyze the behavior of these estimators in the presence of arbitrarily-complex population structures, which results in an improved estimation framework specifically designed for arbitrary population structures. After generalizing the definition ofFSTto arbitrary population structures and establishing a framework for assessing bias and consistency of genome-wide estimators, we calculate the accuracy of existingFSTand kinship estimators under arbitrary population structures, characterizing biases and estimation challenges unobserved under their originally-assumed models of structure. We then present our new approach, which consistently estimates kinship andFSTwhen the minimum kinship value in the dataset is estimated consistently. We illustrate our results using simulated genotypes from an admixture model, constructing a one-dimensional geographic scenario that departs nontrivially from the independent subpopulations model. Our simulations reveal the potential for severe biases in estimates of existing approaches that are overcome by our new framework. This work may significantly improve future analyses that rely on accurate kinship andFSTestimates.
Htt is a repressor of Abl activity required for APP-induced axonal growth
Authors: Marquilly Claire , Busto Germain U. , Leger Brittany S. , Boulanger Ana , Giniger Edward , Walker James A. , Fradkin Lee G. , Dura Jean-Maurice
Published: January 2021

Huntington’s disease is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of a polyglutamine tract at the N-terminus of a large cytoplasmic protein. TheDrosophila huntingtin(htt) gene is widely expressed during all developmental stages from embryos to adults. However,Drosophila httmutant individuals are viable with no obvious developmental defects. We asked if such defects could be detected inhttmutants in a background that had been genetically sensitized to reveal cryptic developmental functions. Amyloid precursor protein (APP) is linked to Alzheimer’s disease. Appl is theDrosophilaAPP ortholog andApplsignaling modulates axon outgrowth in the mushroom bodies (MBs), the learning and memory center in the fly, in part by recruiting Abl tyrosine kinase. Here, we find thathttmutations suppress axon outgrowth defects of αβ neurons inApplmutant MB by derepressing the activity of Abl. We show thatAblis required in MB αβ neurons for their axon outgrowth. Importantly, bothAbloverexpression and lack of expression produce similar phenotypes in the MBs, indicating the necessity of tightly regulating Abl activity. We find that Htt behaves genetically as a repressor of Abl activity, and consistent with this,in vivoFRET-based measurements reveal a significant increase in Abl kinase activity in the MBs when Htt levels are reduced. Thus, Appl and Htt have essential but opposing roles in MB development, promoting and suppressing Abl kinase activity, respectively, to maintain the appropriate intermediate level necessary for axon growth.