bluuebunny/crossref_metadata_2025 huggingface dataset:
Elongational viscosity scaling of polymer melts with different chemical constituents
Authors: Narimissa Esmaeil , Poh Leslie , Wagner Manfred H.
Published: March 2021

Morelly et al. (Macromolecules 52:915-922, 2019) reported transient and steady-state elongational viscosity data of monodisperse linear polymer melts obtained by filament-stretching rheometry with locally controlled strain and strain rate and found different power law scaling of the elongational viscosities of polystyrene, poly(tert-butylstyrene) and poly(methyl-methacrylate). Very good agreement is achieved between data and predictions of the extended interchain pressure (EIP) model (Narimissa et al. J. Rheol. 64, 95-110 (2020)), based solely on linear viscoelastic characterization and the Rouse time τR of the melts. The analysis reveals that both the normalized elongational viscosity and the normalized elongational stress are dependent on the number of entanglements (Z) and the ratio of entanglement molar mass Mem to critical molar mass Mcm of the melts in the linear viscoelastic regime through $$ {\eta}_E^0/\left({G}_N{\tau}_R\right)\propto {\left({M}_{\mathrm{em}}/{M}_{\mathrm{cm}}\right)}^{2.4}{Z}^{1.4} $$

η
E
0

/

G
N

τ
R

∝

M
em

/

M
cm

2.4

Z
1.4

and $$ {\sigma}_E^0/{G}_N\propto {\left({M}_{\mathrm{em}}/{M}_{\mathrm{cm}}\right)}^{2.4}{Z}^{1.4} Wi $$

σ
E
0

/

G
N

∝

M
em

/

M
cm

2.4

Z
1.4

W
i
, while in the limit of fast elongational flow with high Weissenberg number $$ Wi={\tau}_R\dot{\varepsilon} $$
Wi
=

τ
R

ε
̇

, both viscosity and stress become independent of Z and Mem/Mcm, and approach a scaling which depends only on Wi, i.e. ηE/(GNτR) ∝ Wi−1/2 and σE/GN ∝ Wi1/2. When expressed by an effective power law, the broad transition from the linear viscoelastic to the high Wi regime leads to chemistry-dependent scaling at intermediate Wi depending on the number of entanglements and the ratio between entanglement molar mass and critical molar mass.
Entscheidungshilfe zur Patientenzuweisung bei Verdacht auf COVID-19
Authors: Thies N. , Urban B. , Kraus M. , Kohlmann T. , Niedermirtl F. , Prückner S.
Published: March 2021

Während einer Pandemielage sind Patienten mit Verdacht auf COVID-19 auch im Rahmen von Rettungsdienstalarmierungen zu versorgen. Um ein adäquates Vorgehen zu etablieren, ist die Entscheidungshilfe zur Patientenzuweisung bei Verdacht auf COVID-19 für die Rettungsdienstmitarbeiter sowie für die Notärzte im bayerischen Rettungsdienst erstellt worden. Die Entscheidungshilfe schließt die aktuellen Leitlinien und Empfehlungen zum Thema COVID-19 ein. Für die Darstellung der Entscheidungshilfe wurde ein Flussdiagramm in DIN-A4-Format gewählt, welches nach dem im Rettungsdienst etablierten ABCDE-Schema (A-Airway, B-Breathing, C-Circulation, D-Disability, E-Environment/Exposure)aufgebaut ist. Das Flussdiagramm ermöglicht eine Kategorisierung der Patienten in drei Stufen, welche anhand von (Vital‑)Parametern und Kriterien wie Risikofaktoren und spezifischen Rahmenbedingungen erfolgt. Ziel ist es, Notärzten und Rettungsdienstmitarbeitern eine Orientierungshilfe für die Beurteilung der Patienten sowie daraus entstehende Transportentscheidung mit gegebenenfalls geeigneter Zielklinik an die Hand zu geben.
COVID-19 Infection Detection from Chest X-Ray Images Using Hybrid Social Group Optimization and Support Vector Classifier
Authors: Singh Asu Kumar , Kumar Anupam , Mahmud Mufti , Kaiser M Shamim , Kishore Akshat
Published: March 2021

A novel strain of Coronavirus, identified as the Severe Acute Respiratory Syndrome-2 (SARS-CoV-2), outbroke in December 2019 causing the novel Corona Virus Disease (COVID-19). Since its emergence, the virus has spread rapidly and has been declared a global pandemic. As of the end of January 2021, there are almost 100 million cases worldwide with over 2 million confirmed deaths. Widespread testing is essential to reduce further spread of the disease, but due to a shortage of testing kits and limited supply, alternative testing methods are being evaluated. Recently researchers have found that chest X-Ray (CXR) images provide salient information about COVID-19. An intelligent system can help the radiologists to detect COVID-19 from these CXR images which can come in handy at remote locations in many developing nations. In this work, we propose a pipeline that uses CXR images to detect COVID-19 infection. The features from the CXR images were extracted and the relevant features were then selected using Hybrid Social Group Optimization algorithm. The selected features were then used to classify the CXR images using a number of classifiers. The proposed pipeline achieves a classification accuracy of 99.65% using support vector classifier, which outperforms other state-of-the-art deep learning algorithms for binary and multi-class classification.
Direct numerical simulation of TS-waves over suction panel steps from manufacturing tolerances
Authors: Lüdeke H. , von Soldenhoff R.
Published: March 2021

To determine allowable tolerances between successive suction panels at hybrid laminar wings with suction surfaces, direct numerical simulations of Tollmien–Schlichting waves over different steps are carried out for realistic suction rates on a wind tunnel configuration. Simulations at given suction panel positions over forward and backward facing steps are carried out by the use of a high-order method for the direct simulation of Tollmien–Schlichting wave growth. Comparisons between high-fidelity direct numerical simulations and quick linear stability calculations have shown capabilities and limits of the well-validated linear stability theory design approach.
Digging in the dark: reviewing international literature to address impending policy challenges for Swedish and Finnish mining
Authors: Poelzer Gregory , Linde Stefan , Jagers Sverker C. , Matti Simon
Published: March 2021

The mining industries of Sweden and Finland currently face several policy issues around investment, stakeholder involvement, and sustainability. Since the two countries garnered significant attention during the mining boom, research from a social sciences perspective grew significantly. One approach to understanding how these issues in Sweden and Finland compare to international examples is through an analysis of the policy development framework. Looking at three factors—institutions, actors, and process—gives a broad overview of the imminent challenges in both Sweden and Finland and potential lessons from existing research that point to similar problems and their solutions. As the mining operations continue to sit at the center of different values, capable policy is required.
Consistency and mechanical properties of sustainable concrete blended with brick dust waste cementitious materials
Authors: Amakye S. Y. , Abbey S. J. , Olubanwo A. O.
Published: March 2021

The reuse of waste materials in civil engineering projects has become the topic for many researchers due to their economic and environmental benefits. In this study, brick dust waste (BDW) derived from cutting of masonry bricks and demolition waste which are normally dumped as land fill is used as partial replacement of cement in a concrete mix at 10%, 20% and 30% respectively, with the aim of achieving high strength in concrete using less cement due to the environmental problems associated with the cement production. To ascertain the effects of BDW on the consistency and mechanical performance of concrete mix, laboratory investigations on the workability of fresh concrete and the strength of hardened concrete were carried out. Slump and compaction index test were carried out on fresh concrete mix and unconfined compressive strength (UCS) test and tensile strength test were conducted on hardened concrete specimen after 7, 14 and 28 days of curing. The results showed high UCS and tensile strength with the addition of 10% BDW to the concrete mix, hence achieving the set target in accordance with the relevant British standards. A gradual reduction in strength was observed as BDW content increases, however, recording good workability as slump and compaction index results fell within the set target range in accordance with relevant British standards. Findings from this study concluded that BDW can partially replace cement in a concrete mix to up to 30% igniting the path to a cleaner production of novel concrete using BDW in construction work.
Light therapy for seasonal affective disorder in visual impairment and blindness – a pilot study
Authors: Madsen Helle Østergaard , Ba-Ali Shakoor , Hageman Ida , Lund-Andersen Henrik , Martiny Klaus
Published: March 2021

Objective:

Seasonal and non-seasonal depression are prevalent conditions in visual impairment (VI). We assessed the effects and side effects of light therapy in persons with severe VI/blindness who experienced recurrent depressive symptoms in winter corresponding to seasonal affective disorder (SAD) or subsyndromal SAD (sSAD).

Results:

We included 18 persons (11 with severe VI, 3 with light perception and 4 with no light perception) who met screening criteria for sSAD/SAD in a single-arm, assessor-blinded trial of 6 weeks light therapy. In the 12 persons who completed the 6 weeks of treatment, the post-treatment depression score was reduced (p < 0.001), and subjective wellbeing (p = 0.01) and sleep quality were improved (p = 0.03). In 6/12 participants (50%), the post-treatment depression score was below the cut-off set for remission. In four participants with VI, side effects (glare or transiently altered visual function) led to dropout or exclusion.

Conclusion:

Light therapy was associated with a reduction in depressive symptoms in persons with severe VI/blindness. Eye safety remains a concern in persons with residual sight.
Aristotle and Scientific Experiments
Authors: Byrne Christopher
Published: March 2021

Many have argued that there is no room for experiments in Aristotle's natural science: experiments intervene in nature, but Aristotle holds that we must simply observe nature; if we intervened, the result would be something artificial or contrary to nature. Against this, I argue that Aristotle not only performed experiments, but also holds that there is much about nature that can be discovered experimentally.
Généalogie de la pensée perspectiviste : les figures inversées de Pascal et de Leibniz dans l’œuvre de Nietzsche
Authors: Lebreton Lucie
Published: March 2021

Lorsque les commentateurs s'interrogent sur les sources d'inspiration du perspectivisme nietzschéen, leur réponse la plus constante est de le rapporter à la monadologie de Leibniz. C'est oublier que Pascal — dont Leibniz avait lu les écrits — fut le premier à introduire l'idée de perspective en philosophie. C'est négliger surtout les indications de Nietzsche lui-même puisque, s'il loue en Pascal l'un de ces «bons Européens» qui précipitent la dévalorisation des valeurs chrétiennes et, singulièrement, de celle de vérité, il considère au contraire Leibniz comme l'une des plus «grandes entraves à la probité intellectuelle de l'Europe».
Attitude reconstruction from strap-down rate gyros using power series
Authors: Ghanbarpourasl Habib
Published: March 2021

This paper introduces a power series based method for attitude reconstruction from triad orthogonal strap-down gyros. The method is implemented and validated using quaternions and direction cosine matrix in single and double precision implementation forms. It is supposed that data from gyros are sampled with high frequency and a fitted polynomial is used for an analytical description of the angular velocity vector. The method is compared with the well-known Taylor series approach, and the stability of the coefficients’ norm in higher-order terms for both methods is analysed. It is shown that the norm of quaternions’ derivatives in the Taylor series is bigger than the equivalent terms coefficients in the power series. In the proposed method, more terms can be used in the power series before the saturation of the coefficients and the error of the proposed method is less than that for other methods. The numerical results show that the application of the proposed method with quaternions performs better than other methods. The method is robust with respect to the noise of the sensors and has a low computational load compared with other methods.
Altered Gesture Imitation and Brain Anatomy in Adult Prader–Willi Syndrome Patients
Authors: Caixàs Assumpta , Blanco-Hinojo Laura , Pujol Jesús , Deus Joan , Giménez-Palop Olga , Torrents-Rodas David , Coronas Ramon , Novell Ramon , Esteba-Castillo Susanna
Published: March 2021

Objective:

To explore motor praxis in adults with Prader–Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements.

Method:

Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis.

Results:

Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas.

Conclusions:

Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.
Rationale and Design of the National Neuropsychology Network
Authors: Loring David W. , Bauer Russell M. , Cavanagh Lucia , Drane Daniel L. , Enriquez Kristen D. , Reise Steven P. , Shih KuoChung , Umfleet Laura Glass , Wahlstrom Dustin , Whelan Fiona , Widaman Keith F. , Bilder Robert M. ,   for the NNN Study Group
Published: March 2021

Objective.

The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology’s transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency.

Method:

The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures.

Results:

NNN is acquiring item-level data from 500–10,000 patients across 47 widely used Neuropsychology (NP) tests and sharing these data via the NIMH Data Archive. Modern psychometric methods (e.g., item response theory) will specify the constructs measured by different tests and determine their positive/negative predictive power regarding diagnostic outcomes and relationships to other clinical, historical, and demographic factors. The Structured History Protocol for NP (SHiP-NP) helps standardize acquisition of relevant history and self-report data.

Conclusions:

NNN is a proof-of-principle collaboration: by addressing logistical challenges, NNN aims to engage other clinics to create a national and ultimately an international network. The mature NNN will provide mechanisms for data aggregation enabling shared analysis and collaborative research. NNN promises ultimately to enable robust diagnostic inferences about neuropsychological test patterns and to promote the validation of novel adaptive assessment strategies that will be more efficient, more precise, and more sensitive to clinical contexts and individual/cultural differences.
LOCAL COORDINATES FOR COMPLEX AND QUATERNIONIC HYPERBOLIC PAIRS
Authors: GONGOPADHYAY KRISHNENDU , KALANE SAGAR B.
Published: March 2021

Let$G(n)={\textrm {Sp}}(n,1)$or${\textrm {SU}}(n,1)$. We classify conjugation orbits of generic pairs of loxodromic elements in$G(n)$. Such pairs, called ‘nonsingular’, were introduced by Gongopadhyay and Parsad for${\textrm {SU}}(3,1)$. We extend this notion and classify$G(n)$-conjugation orbits of such elements in arbitrary dimension. For$n=3$, they give a subspace that can be parametrized using a set of coordinates whose local dimension equals the dimension of the underlying group. We further construct twist-bend parameters to glue such representations and obtain local parametrization for generic representations of the fundamental group of a closed (genus$g \geq 2$) oriented surface into$G(3)$.
NB-IoT devices in reverberation chambers: a comprehensive uncertainty analysis
Authors: Hubrechsen Anouk , Remley Kate A. , Jones Robert D. , Horansky Robert D. , Neylon Vincent T. , Bronckers Laurens A.
Published: March 2021

New protocols related to Internet-of-things applications may introduce previously unnoticed measurement effects in reverberation chambers (RCs) due to the narrowband nature of these protocols. Such technologies also require less loading to meet the coherence-bandwidth conditions, which may lead to higher variations, hence uncertainties, across the channel. In this work, we extend a previous study of uncertainty in NB-IoT and CAT-M1 device measurements in RCs by providing, for the first time, a comprehensive uncertainty analysis of the components related to the reference and DUT measurements. By use of a significance test, we show that certain components of uncertainty become more dominant for such narrowband protocols, and cannot be considered as negligible, as in current standardized test methods. We show that the uncertainty, if not accounted for by using the extended formulation, will be greatly overestimated and could lead to non-compliance to standards.
Chekhov's Environmental Psychology: Medicine and the Early Stories
Authors: Mangold Matthew
Published: March 2021

In light of the historical circumstances surrounding Anton Chekhov's early writing career and his own statements about the importance of medicine to it, there is surprisingly little scholarship on how medicine shaped his prose. What ideas was he introduced to in medical school and how did he apply them? Which of these drew his attention as he strove to articulate a new artistic vision? How did Chekhov draw on his experience with medicine to experiment with new themes and forms in his literary writing? This article addresses these questions by focusing on the aspects of medicine that had the most discernable influence on Chekhov as he developed his literary writing: hygiene, clinical medicine, and psychiatry. It argues that Chekhov engaged with core issues of medicine not only as a medical student who wrote case histories of his patients, but also as a groundbreaking writer. As he transcodes insights from the clinic into his prose, he creates a new conception of details that disclose relationships between settings and characters and an environmental psychology emerges across his medical writing and fiction. His stories envision relationships between physical and mental life with such originality that he becomes a new literary force not long after completing his medical education.
The Relation Between Loneliness or Positive Solitude with Posttraumatic Symptoms of Holocaust Survivors
Authors: Palgi Yuval , Hayun Yonat , Greenblatt-Kimron Lee
Published: March 2021

Abstract. The current study examined how reported early life experiences of isolation encountered by Holocaust survivors affect the relationship between their current feeling of loneliness/feeling of positive solitude and their level of posttraumatic stress symptoms. To this end, using a convenient sampling methodology 81 community-dwelling older adults reported the number of years they had been alone or the level of loneliness they had experienced during the Holocaust, their level of current loneliness/positive solitude, and their level of posttraumatic stress symptoms. More years spent alone during the Holocaust were related to a stronger positive association between loneliness and posttraumatic stress symptoms; feeling lonelier was also related to a stronger negative association between positive solitude and posttraumatic stress symptoms. The findings emphasize that survivors who reported more years of isolation during the Holocaust are prone to be more sensitive when associated with current loneliness to the deleterious results of posttraumatic stress symptoms. However, survivors who felt lonelier during the Holocaust demonstrate lower levels of posttraumatic stress symptoms when reporting on a higher level of positive solitude. Intervention focus on improving positive solitude capability may become beneficial for those suffering from loneliness and posttraumatic stress symptoms.
Correction to: DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis
Authors: Yuan Menglang , Zhang Xinsheng , Zhang Jingbo , Wang Keyong , Zhang Yu , Shang Wei , Zhang Yinan , Cui Jingyi , Shi Xiaomeng , Na Heya , Fang Deyu , Zuo Yunfei , Ren Shuangyi
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41418-021-00736-9
Correction to: PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis
Authors: Zhao Bin , Liu Lei , Mao Jun , Zhang Zhiwei , Wang Qifei , Li Quanlin
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03387-3
Long noncoding RNA LINC00518 induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop in melanoma
Authors: Liu Yan , He Dong , Xiao Mengqing , Zhu Yuxing , Zhou Jianda , Cao Ke
Published: March 2021

The long noncoding RNA, LINC00518, is highly expressed in various types of cancers and is involved in cancer progression. Although LINC00518 promotes the metastasis of cutaneous malignant melanoma (CMM), the mechanism underlaying its effects on CMM radiosensitivity remains unclear. In this study, LINC00518 expression was significantly upregulated in CMM samples, and LINC00518 levels were associated with poor prognosis of patients with CMM. Knockdown of LINC00518 in CMM cells significantly inhibited cell invasion, migration, proliferation, and clonogenicity. LINC00518-mediated invasion, migration, proliferation, and clonogenicity were negatively regulated by the microRNA, miR-33a-3p, in vitro, which increased sensitivity to radiotherapy via inhibition of the hypoxia-inducible factor 1α (HIF-1α)/lactate dehydrogenase A glycolysis axis. Additionally, HIF-1α recognized the miR-33a-3p promoter region and recruited histone deacetylase 2, which decreased the expression of miR-33a-3p and formed an LINC00518/miR-33a-3p/HIF-1α negative feedback loop. Furthermore, signaling with initially activated glycolysis and radioresistance in CMM cells was impaired by Santacruzamate A, a histone deacetylase inhibitor, and 2-deoxy-D-glucose, a glycolytic inhibitor. Lastly, knockdown of LINC00518 expression sensitized CMM cancer cells to radiotherapy in an in vivo subcutaneously implanted tumor model. In conclusion, LINC00518 was confirmed to be an oncogene in CMM, which induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop. Our study, may provide a potential strategy to improve the treatment outcome of radiotherapy in CMM.
Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer
Authors: Weeks Shannon E. , Kammerud Sarah C. , Metge Brandon J. , AlSheikh Heba A. , Schneider David A. , Chen Dongquan , Wei Shi , Mobley James A. , Ojesina Akinyemi I. , Shevde Lalita A. , Samant Rajeev S.
Published: March 2021

Triple-negative breast cancer (TNBC) patients with upregulated Wnt/β-catenin signaling often have poor clinical prognoses. During pathological examinations of breast cancer sections stained for β-catenin, we made the serendipitous observation that relative to non-TNBC, specimens from TNBC patients have a greater abundance of nucleoli. There was a remarkable direct relationship between nuclear β-catenin and greater numbers of nucleoli in TNBC tissues. These surprising observations spurred our investigations to decipher the differential functional relevance of the nucleolus in TNBC versus non-TNBC cells. Comparative nucleolar proteomics revealed that the majority of the nucleolar proteins in TNBC cells were potential targets of β-catenin signaling. Next, we undertook an analysis of the nucleolar proteome in TNBC cells in response to β-catenin inhibition. This effort revealed that a vital component of pre-rRNA processing, LAS1 like ribosome biogenesis factor (LAS1L) was significantly decreased in the nucleoli of β-catenin inhibited TNBC cells. Here we demonstrate that LAS1L protein expression is significantly elevated in TNBC patients, and it functionally is important for mammary tumor growth in xenograft models and enables invasive attributes. Our observations highlight a novel function for β-catenin in orchestrating nucleolar activity in TNBCs.
Small intestinal immune-environmental changes induced by oral tolerance inhibit experimental atopic dermatitis
Authors: Um Han-Na , Baek Jin-Ok , Park Sohyeon , Lee Eun-Hui , Jang Jinsun , Park Woo-Jae , Roh Joo-Young , Jung YunJae
Published: March 2021

Atopic dermatitis is a chronic skin inflammatory disease mediated by Th2-type immune responses. Although intestinal immune responses have been shown to play a critical role in the development or prevention of atopic dermatitis, the precise influence of intestinal immunity on atopic dermatitis is incompletely understood. We show here that orally tolerized mice are protected from experimental atopic dermatitis induced by sensitization and epicutaneous (EC) challenge to ovalbumin. Although the expression of Th2-type cytokines in the small intestine of orally tolerized and EC-challenged mice did not change significantly, these mice showed decreased inflammatory responses in the small intestine with restoration of microbial change elicited by the EC challenge. Interestingly, an increase in small intestinal eosinophils was observed with the EC challenge, which was also inhibited by oral tolerance. The role of small intestinal eosinophils and microbiota in the pathogenesis of experimental atopic dermatitis was further substantiated by decreased inflammatory mediators in the small intestine and attenuated Th2-type inflammation in the skin of eosinophil-deficient and microbiota-ablated mice with EC challenges. Based on these data, we propose that the bidirectional interaction between the skin and the intestine has a role in the pathogenesis of atopic dermatitis and that modulation of the intestinal microenvironments could be a therapeutic approach to atopic dermatitis.
Enzymatic spiroketal formation via oxidative rearrangement of pentangular polyketides
Authors: Frensch Britta , Lechtenberg Thorsten , Kather Michel , Yunt Zeynep , Betschart Martin , Kammerer Bernd , Lüdeke Steffen , Müller Michael , Piel Jörn , Teufel Robin
Published: March 2021

The structural complexity and bioactivity of natural products often depend on enzymatic redox tailoring steps. This is exemplified by the generation of the bisbenzannulated [5,6]-spiroketal pharmacophore in the bacterial rubromycin family of aromatic polyketides, which exhibit a wide array of bioactivities such as the inhibition of HIV reverse transcriptase or DNA helicase. Here we elucidate the complex flavoenzyme-driven formation of the rubromycin pharmacophore that is markedly distinct from conventional (bio)synthetic strategies for spiroketal formation. Accordingly, a polycyclic aromatic precursor undergoes extensive enzymatic oxidative rearrangement catalyzed by two flavoprotein monooxygenases and a flavoprotein oxidase that ultimately results in a drastic distortion of the carbon skeleton. The one-pot in vitro reconstitution of the key enzymatic steps as well as the comprehensive characterization of reactive intermediates allow to unravel the intricate underlying reactions, during which four carbon-carbon bonds are broken and two CO2 become eliminated. This work provides detailed insight into perplexing redox tailoring enzymology that sets the stage for the (chemo)enzymatic production and bioengineering of bioactive spiroketal-containing polyketides.
Ultrastable liquid crystalline blue phase from molecular synergistic self-assembly
Authors: Hu Wei , Wang Ling , Wang Meng , Zhong Tingjun , Wang Qian , Zhang Lanying , Chen Feiwu , Li Kexuan , Miao Zongcheng , Yang Dengke , Yang Huai
Published: March 2021

Fabricating functional materials via molecular self-assembly is a promising approach, and precisely controlling the molecular building blocks of nanostructures in the self-assembly process is an essential and challenging task. Blue phase liquid crystals are fascinating self-assembled three-dimensional nanomaterials because of their potential information displays and tuneable photonic applications. However, one of the main obstacles to their applications is their narrow temperature range of a few degrees centigrade, although many prior studies have broadened it to tens via molecular design. In this work, a series of tailored uniaxial rodlike mesogens disfavouring the formation of blue phases are introduced into a blue phase system comprising biaxial dimeric mesogens, a blue phase is observed continuously over a temperature range of 280 °C, and the range remains over 132.0 °C after excluding the frozen glassy state. The findings show that the molecular synergistic self-assembly behavior of biaxial and uniaxial mesogens may play a crucial role in achieving the ultrastable three-dimensional nanostructure of blue phases.
Transcriptome and chromatin landscape of iNKT cells are shaped by subset differentiation and antigen exposure
Authors: Murray Mallory Paynich , Engel Isaac , Seumois Grégory , Herrera-De la Mata Sara , Rosales Sandy Lucette , Sethi Ashu , Logandha Ramamoorthy Premlal Ashmitaa , Seo Goo-Young , Greenbaum Jason , Vijayanand Pandurangan , Scott-Browne James P. , Kronenberg Mitchell
Published: March 2021

Invariant natural killer T cells (iNKT cells) differentiate into thymic and peripheral NKT1, NKT2 and NKT17 subsets. Here we use RNA-seq and ATAC-seq analyses and show iNKT subsets are similar, regardless of tissue location. Lung iNKT cell subsets possess the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. Following antigenic stimulation, iNKT cells undergo chromatin and transcriptional changes delineating two populations: one similar to follicular helper T cells and the other NK or effector like. Phenotypic analysis indicates these changes are observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to additional subsets.
The methyltransferase SETD2 couples transcription and splicing by engaging mRNA processing factors through its SHI domain
Authors: Bhattacharya Saikat , Levy Michaella J. , Zhang Ning , Li Hua , Florens Laurence , Washburn Michael P. , Workman Jerry L.
Published: March 2021

Heterogeneous ribonucleoproteins (hnRNPs) are RNA binding molecules that are involved in key processes such as RNA splicing and transcription. One such hnRNP protein, hnRNP L, regulates alternative splicing (AS) by binding to pre-mRNA transcripts. However, it is unclear what factors contribute to hnRNP L-regulated AS events. Using proteomic approaches, we identified several key factors that co-purify with hnRNP L. We demonstrate that one such factor, the histone methyltransferase SETD2, specifically interacts with hnRNP L in vitro and in vivo. This interaction occurs through a previously uncharacterized domain in SETD2, the SETD2-hnRNP Interaction (SHI) domain, the deletion of which, leads to a reduced H3K36me3 deposition. Functionally, SETD2 regulates a subset of hnRNP L-targeted AS events. Our findings demonstrate that SETD2, by interacting with Pol II as well as hnRNP L, can mediate the crosstalk between the transcription and the splicing machinery.
Real-time determination of earthquake focal mechanism via deep learning
Authors: Kuang Wenhuan , Yuan Congcong , Zhang Jie
Published: March 2021

An immediate report of the source focal mechanism with full automation after a destructive earthquake is crucial for timely characterizing the faulting geometry, evaluating the stress perturbation, and assessing the aftershock patterns. Advanced technologies such as Artificial Intelligence (AI) has been introduced to solve various problems in real-time seismology, but the real-time source focal mechanism is still a challenge. Here we propose a novel deep learning method namely Focal Mechanism Network (FMNet) to address this problem. The FMNet trained with 787,320 synthetic samples successfully estimates the focal mechanisms of four 2019 Ridgecrest earthquakes with magnitude larger than Mw 5.4. The network learns the global waveform characteristics from theoretical data, thereby allowing the extensive applications of the proposed method to regions of potential seismic hazards with or without historical earthquake data. After receiving data, the network takes less than two hundred milliseconds for predicting the source focal mechanism reliably on a single CPU.
Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics
Authors: Weng Qinjie , Sun Heng , Fang Chunyan , Xia Fan , Liao Hongwei , Lee Jiyoung , Wang Jincheng , Xie An , Ren Jiafeng , Guo Xia , Li Fangyuan , Yang Bo , Ling Daishun
Published: March 2021

Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.
Biodiversity of non-Saccharomyces yeasts associated with spontaneous fermentation of Cabernet Sauvignon wines from Shangri-La wine region, China
Authors: Zhao Yue , Sun Qingyang , Zhu Shusheng , Du Fei , Mao Ruzhi , Liu Lijing , Tian Bin , Zhu Yifan
Published: March 2021

Shangri-La is a wine region that has the highest altitude vineyards in China. This is the first study investigated the biodiversity of non-Saccharomyces yeasts associated with spontaneous fermentation of Cabernet Sauvignon wines produced from two sub-regions (Lancang River and Jinsha River) of Shangri-La. The culturable yeasts were preliminarily classified based on their colonial morphology on the Wallerstein Laboratory nutrient agar plates. Yeast species were identified by the sequencing of the 26S rRNA D1/D2 region and the 5.8S rRNA ITS region. Twenty-five non-Saccharomyces yeast species belonging to sixteen genera were isolated and identified in Shangri-La wine region. Candida, Hanseniaspora, Pichia, and Starmerella were found in both sub-regions, but the Lancang River showed more diverse yeast species than the Jinsha River. Shangri-La not only exhibited high diversity of non-Saccharomyces yeasts, and furthermore, seven species of non-Saccharomyces yeasts were exclusively found in this region, including B. bruxellensis, D. hansenii, M. guilliermondii, S. vini, S. diversa, T. delbrueckii and W. anomalus, which might play an important role in distinctive regional wine characteristics. This study provide a relatively comprehensive analysis of indigenous non-Saccharomyces yeasts associated with Cabernet Sauvignon from Shangri-La, and has significance for exploring ‘microbial terroir’ of wine regions in China.
A large-scale retrospective study of opioid poisoning in New York State with implications for targeted interventions
Authors: Chen Xin , Hou Wei , Rashidian Sina , Wang Yu , Zhao Xia , Leibowitz George Stuart , Rosenthal Richard N. , Saltz Mary , Saltz Joel H. , Schoenfeld Elinor Randi , Wang Fusheng
Published: March 2021

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP). To discover trends and patterns of opioid poisoning and the demographic and regional disparities, we analyzed large scale patient visits data in New York State (NYS). Demographic, spatial, temporal and correlation analyses were performed for all OP patients extracted from the claims data in the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016, along with Decennial US Census and American Community Survey zip code level data. 58,481 patients with at least one OP diagnosis and a valid NYS zip code address were included. Main outcome and measures include OP patient counts and rates per 100,000 population, patient level factors (gender, age, race and ethnicity, residential zip code), and zip code level social demographic factors. The results showed that the OP rate increased by 364.6%, and by 741.5% for the age group > 65 years. There were wide disparities among groups by race and ethnicity on rates and age distributions of OP. Heroin and non-heroin based OP rates demonstrated distinct temporal trends as well as major geospatial variation. The findings highlighted strong demographic disparity of OP patients, evolving patterns and substantial geospatial variation.
Elucidating the genetics of grain yield and stress-resilience in bread wheat using a large-scale genome-wide association mapping study with 55,568 lines
Authors: Juliana Philomin , Singh Ravi Prakash , Poland Jesse , Shrestha Sandesh , Huerta-Espino Julio , Govindan Velu , Mondal Suchismita , Crespo-Herrera Leonardo Abdiel , Kumar Uttam , Joshi Arun Kumar , Payne Thomas , Bhati Pradeep Kumar , Tomar Vipin , Consolacion Franjel , Campos Serna Jaime Amador
Published: March 2021

Wheat grain yield (GY) improvement using genomic tools is important for achieving yield breakthroughs. To dissect the genetic architecture of wheat GY potential and stress-resilience, we have designed this large-scale genome-wide association study using 100 datasets, comprising 105,000 GY observations from 55,568 wheat lines evaluated between 2003 and 2019 by the International Maize and Wheat Improvement Center and national partners. We report 801 GY-associated genotyping-by-sequencing markers significant in more than one dataset and the highest number of them were on chromosomes 2A, 6B, 6A, 5B, 1B and 7B. We then used the linkage disequilibrium (LD) between the consistently significant markers to designate 214 GY-associated LD-blocks and observed that 84.5% of the 58 GY-associated LD-blocks in severe-drought, 100% of the 48 GY-associated LD-blocks in early-heat and 85.9% of the 71 GY-associated LD-blocks in late-heat, overlapped with the GY-associated LD-blocks in the irrigated-bed planting environment, substantiating that simultaneous improvement for GY potential and stress-resilience is feasible. Furthermore, we generated the GY-associated marker profiles and analyzed the GY favorable allele frequencies for a large panel of 73,142 wheat lines, resulting in 44.5 million datapoints. Overall, the extensive resources presented in this study provide great opportunities to accelerate breeding for high-yielding and stress-resilient wheat varieties.
Metabolomics shows the Australian dingo has a unique plasma profile
Authors: Yadav Sonu , Pickford Russell , Zammit Robert A. , Ballard J. William O.
Published: March 2021

Dingoes occupy a wide range of the Australian mainland and play a crucial role as an apex predator with a generalist omnivorous feeding behaviour. Dingoes are ecologically, phenotypically and behaviourally distinct from modern breed dogs and have not undergone artificial selection since their arrival in Australia. In contrast, humans have selected breed dogs for novel and desirable traits. First, we examine whether the distinct evolutionary histories of dingoes and domestic dogs has lead to differences in plasma metabolomes. We study metabolite composition differences between dingoes (n = 15) and two domestic dog breeds (Basenji n = 9 and German Shepherd Dog (GSD) n = 10). Liquid chromatography mass spectrometry, type II and type III ANOVA with post-hoc tests and adjustments for multiple comparisons were used for data evaluation. After accounting for within group variation, 62 significant metabolite differences were detected between dingoes and domestic dogs, with the majority of differences in protein (n = 14) and lipid metabolites (n = 12), mostly lower in dingoes. Most differences were observed between dingoes and domestic dogs and fewest between the domestic dog breeds. Next, we collect a second set of data to investigate variation between pure dingoes (n = 10) and dingo-dog hybrids (n = 10) as hybridisation is common in regional Australia. We detected no significant metabolite differences between dingoes and dingo-dog hybrids after Bonferroni correction. However, power analysis showed that increasing the sample size to 15 could result in differences in uridine 5′-diphosphogalactose (UDPgal) levels related to galactose metabolism. We suggest this may be linked to an increase in Amylase 2B copy number in hybrids. Our study illustrates that the dingo metabolome is significantly different from domestic dog breeds and hybridisation is likely to influence carbohydrate metabolism.
IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development
Authors: Hasegawa Hideaki , Mizoguchi Izuru , Orii Naoko , Inoue Shinya , Katahira Yasuhiro , Yoneto Toshihiko , Xu Mingli , Miyazaki Toru , Yoshimoto Takayuki
Published: March 2021

Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4+T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4+T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4+T cells. Both CD4+T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF+CD4+T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation.
A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China
Authors: Yin Yiya , Li Ting , Wang Chaohao , Liu Xiaoya , Ouyang Hehao , Ji Wanfeng , Liu Jiahao , Liao Xueyu , Li Junyi , Hu Changmin
Published: March 2021

Feline infectious peritonitis (FIP) is a systemic, potentially fatal viral disease. The objectives of this study were to review clinical and laboratory features and treatment of cats highly suspected of FIP in Wuhan, China. The clinical records of 127 cats highly suspected of FIP were reviewed for history, clinical signs, physical findings, and diagnostic test results. Sex, neutering status, breed, age, and month of onset of disease were compared with the characteristics of the clinic population. Age and neutering status were significantly correlated with FIP-suspicion. Sex, breed and onset month were not associated with FIP. There were many more FIP-suspected cases in cats in young cats or male intact cats. Effusion was observed in 85.8% of the FIP-suspected cats. Increased serum amyloid A (SAA) and lymphopenia were common laboratory abnormalities in the FIP cases. Furthermore, 91.7% of the cats highly suspected of FIP had an albumin/globulin (A/G) ratio < 0.6, while 85.3% had an A/G ratio < 0.5. The mortality rate for FIP-suspected cats was 67%, and six submitted cases were confirmed by FIP-specific immunohistochemistry. Of the 30 cats treated with GS-441524 and/or GC376, 29 were clinically cured. The study highlights the diverse range of clinical manifestations by clinicians in diagnosing this potentially fatal disease. A/G ratio and SAA were of higher diagnostic value. GS-441524 and GC376 were efficient for the treatment of FIP-suspected cats.
Mendelian randomization analysis of the association between human blood cell traits and uterine polyps
Authors: Sun Shuliu , Liu Yan , Li Lanlan , Jiao Minjie , Jiang Yufen , Li Beilei , Gao Wenrong , Li Xiaojuan
Published: March 2021

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.
Cytosolic delivery of membrane-penetrating QDs into T cell lymphocytes: implications in immunotherapy and drug delivery
Authors: Jing Haoran , Pálmai Marcell , Saed Badeia , George Anne , Snee Preston T. , Hu Ying S.
Published: March 2021

Single-particle studies of intracellular delivery of DSS-QDs into T cell lymphocytes.