bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncolytic effect of Midkine promoter–based conditionally replicating adenoviruses expressing EGFR siRNA in head and neck squamous cancer cell line T891
Authors: Uehara Natsumi , Otsuki Naoki , Kubo Mie , Kitamoto Junko , Kojima Yasutaka , Teshima Masanori , Shinomiya Hirotaka , Shirakawa Toshiro , Nibu Ken‐ichi
Published: February 2020

Background

Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinomas (HNSCCs). Midkine expression is restricted in adult tissues but is increased in several malignant tumors, including HNSCCs.

Aim

Here, we evaluated the antitumor effect of Midkine promoter–based conditionally replicative adenovirus expressing siRNA against EGFR for targeting HNSCCs expressing Midkine.

Methods and results

A conditionally replicative adenovirus vector controlled by the Midkine promoter, Ad‐MK‐siEGFR, was generated by integrating gene‐expressing siRNA against EGFR. Antitumor effect of Ad‐MK‐siEGFR was tested in vitro using established HNSCC cell line, T891 with strong Midkine expression. Expression of EGFR in T891 infected with Ad‐MK‐siEGFR was significantly lower than that of T891 infected with control. Cytotoxicity assays showed significant growth suppression of Ad‐MK‐siEGFR in T891 cells.

Conclusions

This study demonstrated the possibility of oncolytic therapy using the Midkine promoter–based conditional replication‐selective adenovirus containing siRNA against EGFR in HNSCC cell line T891. Further validation of the findings in more cell lines and in vivo should be performed to clarify the potential clinical application.
Synthesis of 2′‐Deoxyuridine Modified with a 3,5‐Difluoro‐4‐Methoxybenzylidene Imidazolinone Derivative for Incorporation into Oligonucleotide Probes for Detection of HER2 Breast Cancer Marker
Authors: Saady Abed , Steinman Noam Y. , Wojtyniak Melissa , Ducho Christian , Fischer Bilha
Published: February 2020

Nucleoside intercalator conjugates (NICs) describe an innovative methodology developed in our research group for preparation of fluorescence turn‐on DNA hybridization probes targeting specific mRNA sequences (e.g., breast cancer markers). In this methodology, we conjugate a non‐fluorescent intercalator to the base of a nucleic acid (e.g., uracil) via a flexible spacer. This modified monomer can be incorporated into oligonucleotides by solid‐phase synthesis and a large fluorescence enhancement is observed when the modified oligonucleotide is hybridized with its complementary strand due to intercalation of the fluorophore between the two strands. 5‐(6‐p‐Methoxybenzylidene imidazolinone‐1‐hexene)‐2′‐deoxyuridine (dUMBI) is a synthetic monomer to which 4‐methoxybenzylidene imidazolinone (MBI), the fluorescent chromophore of green fluorescent protein (GFP), has been conjugated via a flexible spacer. The detection of human epidermal growth factor receptor 2 (HER2) mRNA by this probe has already been established by our group. The fluorescent intensity of the single‐strand DNA can be considered as negligible due to the free rotation of the fluorophore. Upon hybridization, however, the flexible spacer allows for the intercalation of the fluorophore between the hybridized strands, giving rise to enhanced fluorescence and indicating the presence of target mRNA. 3,5‐Difluoro‐4‐methoxybenzylidene (DFMBI) has enhanced photophysical properties compared to MBI fluorophore. This protocol describes a simple, reliable, efficient, and general method for the synthesis of improved derivative dUDFMBI as a monomer of fluorescent turn‐on DNA hybridization probe with application for detection of HER2 mRNA. © 2020 by John Wiley & Sons, Inc.

Basic Protocol: Synthesis of 5‐[(6)‐3,5‐difluoro‐4‐methoxybenzylidene imidazolinone‐1‐hexene]‐2′‐deoxyuridine
Genetic variation of the fungus Atkinsonella hypoxylon infecting poverty oat grass
Authors: Warnke Scott E. , Thammina Chandra S. , Amundsen Keenan
Published: February 2020

Poverty oat grass [Danthonia spicata (L.) P. Beauv. ex Roem. & Schult.] is a perennial bunch‐type grass native to North America. Poverty oat grass is often present in managed turfgrass areas of the United States where cool‐season grasses are adapted and has potential for development as a seeded low‐input turfgrass option. Naturally occurring poverty oat grass plants occasionally exhibit choke on the flowering stems because of a proliferation of fungal hyphae by the ascomycete Atkinsonella hypoxylon (Peck) Diehl. (family Clavicipitaceae). Twenty‐five A. hypoxylon isolates were cultured from choke‐exhibiting poverty oat grass plants collected from five different populations. DNA variation was evaluated at the 5.8S ribosomal ribonucleic acid (rRNA) internal transcribed spacer (ITS) first (ITS‐1) and second (ITS‐2) regions and 10 simple sequence repeat (SSR) loci. Five single nucleotide polymorphisms (SNPs) in the ITS‐1 region and an addition–deletion in the ITS‐2 region identified two isolate groups present in four of the five populations. The 10 SSR loci exhibited 28 scorable alleles and support the two groupings with variation appearing as random mutations and high linkage disequilibrium providing no evidence for sexual recombination within or between the two identified groups.
Baseline serum albumin and its dynamic change is associated with type 2 diabetes risk: A large cohort study in China
Authors: Hu Fulan , Lou Yanmei , Shi Jing , Cao Liming , Wang Changyi , Ma Jianping , Peng Xiaolin , Xu Shan , Chen Hongen , Zhao Dan , Zhao Yang , Guo Chunmei , Liu Dechen , Zhou Qionggui , Li Quanman , Liu Feiyan , Tian Gang , Wu Xiaoyan , Qie Ranran , Han Minghui , Huang Shengbing , Zhao Ping , Zhang Ming , Hu Dongsheng , Qin Pei
Published: February 2020

Background

The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study.

Methods

This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow‐up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check‐up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow‐up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models.

Results

During 7 years of follow‐up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (−0.2 ≤ ∆ALB <1.0 g/L), the risk of T2DM increased for ∆ALB < −2.0 g/L (HR 1.44, 95% CI 1.24‐1.68) and decreased for ∆ALB ≥3.0 g/L (0.81, 0.68‐0.97) after adjusting for potential confounding factors. Restricted cubic splines showed a linear dose‐response association between baseline serum albumin level and T2DM risk (Pnonlinearity 0.715) and a nonlinear dose‐response association between ∆ALB and T2DM risk (Pnonlinearity 0.011).

Conclusions

Baseline serum albumin level appears to be inversely associated with T2DM risk. Adults with reduced serum albumin level could be early identified for diabetes risk in clinical practice.
S1PR4‐dependent CCL2 production promotes macrophage recruitment in a murine psoriasis model
Authors: Schuster Christian , Huard Arnaud , Sirait‐Fischer Evelyn , Dillmann Christina , Brüne Bernhard , Weigert Andreas
Published: February 2020

The sphingolipid sphingosine‐1‐phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein‐coupled receptors. The immune cell‐specific sphingosine‐1‐phosphate receptor 4 (S1pr4) was connected to the generation of IL‐17‐producing T cells through regulation of cytokine production in innate immune cells. Therefore, we explored whether S1pr4 affected imiquimod‐induced murine psoriasis via regulation of IL‐17 production. We did not observe altered IL‐17 production, although psoriasis severity was reduced in S1pr4‐deficient mice. Instead, ablation of S1pr4 attenuated the production of CCL2, IL‐6, and CXCL1 and subsequently reduced the number of infiltrating monocytes and granulocytes. A connection between S1pr4, CCL2, and Mϕ infiltration was also observed in Zymosan‐A induced peritonitis. Boyden chamber migration assays functionally linked reduced CCL2 production in murine skin and attenuated monocyte migration when S1pr4 was lacking. Mechanistically, S1pr4 signaling synergized with TLR signaling in resident Mϕs to produce CCL2, likely via the NF‐κB pathway. We propose that S1pr4 activation enhances TLR response of resident Mϕs to increase CCL2 production, which attracts further Mϕs. Thus, S1pr4 may be a target to reduce perpetuating inflammatory responses.
Biodistribution and toxicity of epitope‐functionalized dextran iron oxide nanoparticles in a pregnant murine model
Authors: Bolandparvaz Amir , Vapniarsky Natalia , Harriman Rian , Alvarez Kenneth , Saini Jasmeen , Zang Zexi , Van De Water Judy , Lewis Jamal S.
Published: February 2020

In pursuit of a preventive therapeutic for maternal autoantibody‐related (MAR) autism, we assessed the toxicity, biodistribution, and clearance of a MAR specific peptide‐functionalized dextran iron oxide nanoparticle system in pregnant murine dams. We previously synthesized ~15 nm citrate‐coated dextran iron oxide nanoparticles (DIONPs), surface‐modified with polyethylene glycol and MAR peptides to produce systems for nanoparticle‐based autoantibody reception and entrapments (SNAREs). First, we investigated their immunogenicity and MAR lactate dehydrogenase B antibody uptake in murine serum in vitro. To assess biodistribution and toxicity, as well as systemic effects, we performed in vivo clinical and post mortem pathological evaluations. We observed minimal production of inflammatory cytokines—interleukin 10 (IL‐10) and IL‐12 following in vitro exposure of macrophages to SNAREs. We established the maximum tolerated dose of SNAREs to be 150 mg/kg at which deposition of iron was evident in the liver and lungs by histology and magnetic resonance imaging but no concurrent evidence of liver toxicity or lung infarction was detected. Further, SNAREs exhibited slower clearance from the maternal blood in pregnant dams compared to DIONPs based on serum total iron concentration. These findings demonstrated that the SNAREs have a prolonged presence in the blood and are safe for use in pregnant mice as evidenced by no associated organ damage, failure, inflammation, and fetal mortality. Determination of the MTD dose sets the basis for future studies investigating the efficacy of our nanoparticle formulation in a MAR autism mouse model.
A multi‐model analysis of the East Asian monsoon changes in the Medieval Climate Anomaly and Little Ice Age
Authors: Yang Kaiqing , Hua Wei , Hu Qin
Published: February 2020

Using nine climate model simulations from the Paleoclimate Modelling Intercomparison Project Phase 3, the changes in the East Asian summer and winter monsoon, together with their associated atmospheric circulations in the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA), were investigated in this study. The East Asian summer monsoon strengthened (weakened) as a consequence of the increased (decreased) land–sea thermal contrast between the East Asian continent and the adjacent western North Pacific and South China Sea in the MCA (LIA). The East Asian winter monsoon (EAWM) changes varied across models, and differences were shown between the low latitudes and mid‐to‐high latitudes of the EAWM region. In the northern area, the EAWM intensified slightly due to a reinforced Aleutian Low during the MCA and decreased slightly because of the suppression of the Siberian High and the weakening and northward shift of the Aleutian Low during the LIA. In contrast, there are large inconsistencies among models during both periods in the southern EAWM region. Our results imply that model improvement is needed to reproduce the complex interacting processes over the low latitudes of East Asia.
Sensory and monosaccharide analysis of drip brew coffee fractions versus brewing time
Authors: Batali Mackenzie E , Frost Scott C , Lebrilla Carlito B , Ristenpart William D , Guinard Jean‐Xavier
Published: February 2020

BACKGROUND

The composition of drip brew coffee versus brewing time has been chemically characterized in previous studies, and it is known that the total dissolved solids (TDS) systematically decreases with each fraction during the brew. Little information exists regarding the corresponding sensory attributes versus time, however, and it is unclear how TDS correlates with flavor profile.

RESULTS

Standard drip brews were fractionated into distinct samples by switching in an empty carafe every 30 s during the brew. Using a trained sensory descriptive panel, we found that most taste and flavor attributes decreased with brew time; for example, the earlier fractions were systematically more bitter and more sour than later fractions. Surprisingly, however, several flavor and taste attributes increased in time; for example, later fractions were systematically sweeter and more floral than earlier fractions. Since later fractions had lower TDS, these results indicate that perceived sweetness in drip brew coffee is negatively correlated with TDS. Mass spectrometry measurements of the monosaccharide content in the brews showed that none of the fractions had perceptible concentrations of any monosaccharide.

CONCLUSION

The results of the sensory analysis and the monosaccharide analysis suggest that perceptible sweetness in coffee is a consequence of masking effects and/or the presence of sweet‐associated aromas and flavors. The results further suggest that unique flavor profiles could be obtained from the same coffee grounds by judicious combinations of specific fractions. © 2020 Society of Chemical Industry
Parallel Laser Micro/Nano‐Processing for Functional Device Fabrication
Authors: Li Yang , Hong Minghui
Published: February 2020

Photolithography is one of the most commonly used techniques in semiconductor manufacturing, which is the foundation for all the modern electronic device fabrication. However, deep and extreme ultraviolet lithographic systems as well as the corresponding photomasks are both relatively expensive. The fabrication methods are based on the low‐speed high‐cost electron‐beam lithography or focused‐ion‐beam etching. Therefore, a maskless high‐speed method is highly recommended for the micro/nano‐structure fabrication. Among all these maskless methods, direct laser writing (DLW) is an important and widely adopted micro‐processing technique. Based on the nonlinear exposure, the feature size can achieve down to tens of nanometers. However, the speed of DLW is a technical bottleneck. To overcome this issue, parallel DLW methods are developed, including the self‐assembly microspheres laser patterning, laser interference lithography, and multifocal array DLW. Herein, the principles, advantages, challenges, and applications of these parallel processing technologies are summarized. Nanoscale resolution for large area arbitrary periodic pattern fabrication is achieved. Meanwhile, these technologies have the unique ability to build 3D structures instead of conventional 2D patterns, which is the direction of future micro/nano‐fabrication. These techniques are widely applied to surface processing and functional device fabrication in the field of sensing, solar cells, and metamaterials.
Reputation and lying aversion in the die roll paradigm: Reducing ambiguity fosters honest behavior
Authors: Crede Ann‐Kathrin , von Bieberstein Frauke
Published: February 2020

This paper examines reputation as motive for lying aversion. In a control treatment, participants roll a six‐sided die and report the outcome, which the experimenter cannot observe. In a digital die treatment, the outcome of the die roll is determined randomly on the computer. Contrary to prior literature, we reduce ambiguity in the digital die treatment by making observability common knowledge. We find that partial lying and full lying disappear when the experimenter can track participants' behavior. This result can be explained by reputational costs: Participants care about how they are viewed by the experimenter and abstain from lying.
Determination and assessment of fatigue stresses on concrete bridges
Authors: Hansen Michael
Published: February 2020

Dynamic loads reduce the load bearing capacity and the service life of structural components and constructions. This article discusses fatigue stresses and their effects on uncracked concrete structures using the example of concrete bridges. In standard proofs, a distinction is made between the stresses on and the resistance of structural components. Thus, first the determination of the damage‐equivalent stresses on constructions will be considered. Subsequently, the resistance of construction materials, structural components, and the whole construction has to be determined. Based on these input data for the verification, the load bearing capacity and service life under fatigue loading shall be assessed.
Dysphasia is associated with diffusion-weighted MRI abnormalities in patients with transient neurological symptoms
Authors: Jia Zejin , Song Yangguang , Hu Wenli
Published: February 2020

Background

The clinical characteristics of diffusion-weighted imaging (DWI) abnormalities after transient neurological symptoms are of great significance for the early diagnosis and urgent intervention of transient ischemic attack (TIA). This study was aimed to investigate the clinical characteristics associated with acute DWI lesions in transient neurological symptoms.

Methods

We retrospectively recruited 302 patients with transient neurological symptoms. According to DWI findings, they were divided into DWI positive and DWI negative group. The clinical characteristics and the TIA-related scores such as ABCD2, ABCD3, ABCD3I, Dawson score, and the Diagnosis of TIA (DOT) score were compared between the two groups. Logistic regression analysis and receiver operating characteristic curves were used to identify the independent factors and compare the predictive value of different TIA scores for acute DWI lesions.

Results

A total of 302 patients were enrolled in this study. The mean age was 61.8 years, and 67.2% were male. We found 89 (29.5%) patients with DWI positivity. Logistic regression analysis showed the characteristic associated with DWI lesions was dysphasia (OR 2.226, 95% CI 1.220–4.062). The area under the curve for Dawson score and the DOT score was 0.610 (95% CI 0.543–0.678) and 0.625 (95% CI 0.559–0.691), respectively.

Conclusion

We found that DWI lesions were detected in 29.5% of patients with transient neurological symptoms and were associated with dysphasia. Dawson score and DOT score could have a higher predictability of DWI lesions in patients with transient neurological symptoms.
Fluid–Structure Interaction Models of Bioprosthetic Heart Valve Dynamics in an Experimental Pulse Duplicator
Authors: Lee Jae H. , Rygg Alex D. , Kolahdouz Ebrahim M. , Rossi Simone , Retta Stephen M. , Duraiswamy Nandini , Scotten Lawrence N. , Craven Brent A. , Griffith Boyce E.
Published: February 2020

Computer modeling and simulation is a powerful tool for assessing the performance of medical devices such as bioprosthetic heart valves (BHVs) that promises to accelerate device design and regulation. This study describes work to develop dynamic computer models of BHVs in the aortic test section of an experimental pulse-duplicator platform that is used in academia, industry, and regulatory agencies to assess BHV performance. These computational models are based on a hyperelastic finite element extension of the immersed boundary method for fluid–structure interaction (FSI). We focus on porcine tissue and bovine pericardial BHVs, which are commonly used in surgical valve replacement. We compare our numerical simulations to experimental data from two similar pulse duplicators, including a commercial ViVitro system and a custom platform related to the ViVitro pulse duplicator. Excellent agreement is demonstrated between the computational and experimental results for bulk flow rates, pressures, valve open areas, and the timing of valve opening and closure in conditions commonly used to assess BHV performance. In addition, reasonable agreement is demonstrated for quantitative measures of leaflet kinematics under these same conditions. This work represents a step towards the experimental validation of this FSI modeling platform for evaluating BHVs.
Seismic characterization of a rapidly-rising jökulhlaup cycle at the A.P. Olsen Ice Cap, NE-Greenland
Authors: Behm Michael , Walter Jacob I. , Binder Daniel , Cheng Feng , Citterio Michele , Kulessa Bernd , Langley Kirsty , Limpach Phillipe , Mertl Stefan , Schöner Wolfgang , Tamstorf Mikkel , Weyss Gernot
Published: February 2020

Rapidly-rising jökulhlaups, or glacial outburst floods, are a phenomenon with a high potential for damage. The initiation and propagation processes of a rapidly-rising jökulhlaup are still not fully understood. Seismic monitoring can contribute to an improved process understanding, but comprehensive long-term seismic monitoring campaigns capturing the dynamics of a rapidly-rising jökulhlaup have not been reported so far. To fill this gap, we installed a seismic network at the marginal, ice-dammed lake of the A.P. Olsen Ice Cap (APO) in NE-Greenland. Episodic outbursts from the lake cause flood waves in the Zackenberg river, characterized by a rapid discharge increase within a few hours. Our 6 months long seismic dataset comprises the whole fill-and-drain cycle of the ice-dammed lake in 2012 and includes one of the most destructive floods recorded so far for the Zackenberg river. Seismic event detection and localization reveals abundant surface crevassing and correlates with changes of the river discharge. Seismic interferometry suggests the existence of a thin basal sedimentary layer. We show that the ballistic part of the first surface waves can potentially be used to infer medium changes in both the ice body and the basal layer. Interpretation of time-lapse interferograms is challenged by a varying ambient noise source distribution.
Posivotes, recommandations et autres «j'aime» : les heuristiques numériques d'acceptabilité sociale comme vecteur d'homogénéisation en contexte délibératif
Authors: Duguay Philippe A.
Published: February 2020

Mobilisant un sondage avec un devis expérimental, cet article cherche à comprendre l'effet que peuvent avoir les heuristiques numériques d'acceptabilité sociale sur la capacité de convaincre. L'expérience expose les répondants à un article de nouvelle sur les réfugiés syriens et irakiens et, selon le traitement, à un fil de discussion comprenant différentes heuristiques numériques d'acceptabilité sociale. L’étude démontre que la présence d'un fil de discussion modifie l'effet à court terme que peut avoir l'article d'actualité initial et démontre également et surtout la façon dont les heuristiques numériques d'acceptabilité sociale ont un effet d'amplification sur la capacité de convaincre et les émotions évoquées par les commentaires. Chaque unité d'heuristique ou chaque recommandation n'augmente pas nécessairement d'autant le pouvoir de convaincre des commentaires associés et, pour les commentaires que les individus ne sont pas prédisposés à appuyer, servent plutôt à consolider les attitudes préexistantes et à polariser.
DOMESTICATION, DEGENERATION, AND THE ESTABLISHMENT OF THE ADDO ELEPHANT NATIONAL PARK IN SOUTH AFRICA, 1910s–1930s
Authors: SKOTNES-BROWN JULES
Published: February 2020

This article examines conflict between farmers and elephants in the Addo region in 1910s–1930s South Africa to explore the porosity of the concepts ‘wild’, ‘tame’, and ‘domestic’, and their relationship to race, degeneration, nature conservation, and colonialism. In the 1910s, settler farmers indicted the ‘Addo Elephants’, as ‘vicious’ thieves who raided crops and ‘hunted’ farmers. This view conflicted with a widespread perception of elephants as docile, sagacious, and worthy of protection. Seeking to reconcile these views, bureaucrats were divided between exterminating the animals, creating a game reserve, and drawing upon the expertise of Indianmahoutsto domesticate them. Ultimately, all three options were attempted: the population was decimated by hunter Phillip Jacobus Pretorius, an elephant reserve was created, the animals were tamed to ‘lose their fear of man’ and fed oranges. Despite the presence of tame elephants and artificial feeding, the reserve was publicized as a natural habitat, and a window onto the prehistoric. This was not paradoxical but provokes a need to rethink the relationship between wildness, tameness, and domesticity. These concepts were not implicitly opposed but existed on a spectrum paralleling imperialist hierarchies of civilization, race, and evolution, upon which tame elephants could still be considered wild.
Die Folgen von Kindesmisshandlung und ihre psychotherapeutische Behandlung: Eine praxisorientierte Übersicht
Authors: Rassenhofer Miriam
Published: February 2020

Zusammenfassung. Kindesmisshandlung ist ein gesamtgesellschaftliches Problem, dessen Dimension und Auftretenshäufigkeit oft unterschätzt wird. Misshandlungserfahrungen stellen einen großen Anteil aller traumatischen Erlebnisse in Kindheit und Jugend dar. Da sich in der psychiatrisch-psychotherapeutischen Versorgung misshandelter Kinder immer noch Lücken auftun und auf Seiten der Fachkräfte Unsicherheiten im Umgang mit Fällen von Misshandlung bestehen, wird in dieser praxisorientierten Übersicht grundlegendes Wissen zum Thema vermittelt. Es werden zunächst die Definitionen der verschiedenen Misshandlungsformen erläutert sowie die Prävalenzen dargestellt. Die möglichen Folgeerscheinungen werden mit dem Fokus auf die psychischen Folgen kurz zusammengefasst und im Anschluss werden allgemeine Hinweise zur Diagnostik und Behandlung misshandelter, missbrauchter und vernachlässigter Kinder und Jugendlicher gegeben sowie einzelne Diagnostikinstrumente und traumafokussierte Behandlungsansätze kurz vorgestellt. Die Frage nach Misshandlungserfahrungen sollte immer Teil der Anamneseerhebung sein. Misshandlungsfolgen sollten gestuft mit Screeninginstrumenten und sich gegebenenfalls anschließenden klinischen Interviews erfasst werden. Die Behandlung sollte anhand von evidenzbasierten traumafokussierten Ansätzen für Kinder und Jugendliche erfolgen, welche nachweislich Misshandlungsfolgen lindern können.
Impact of environmental temperature on production traits in pigs
Authors: Rauw Wendy M. , de Mercado de la Peña Eduardo , Gomez-Raya Luis , García Cortés Luis Alberto , Ciruelos Juan José , Gómez Izquierdo Emilio
Published: February 2020

There is an urgent need to identify the effects of temperature on production traits. This study aimed to determine the impact of pig production in three environments (T°Cgrowing-°Cfattening-°Cfinishing = T24-24-21, T19-19-19, and T23-17-15) on growth curve parameters, body weight gain (DBWG), feed intake (DFI), and feed efficiency during the growing, fattening and finishing stages, and on carcass yield of primal cuts (ham, shoulder, and loin) in 158 Duroc × Iberian pigs. Maturation rate was higher in T23-17-15than in T19-19-19(P < 0.001). Pigs in T23-17-15reached a lower mature body weight (P < 0.05). During the growing stage, pigs in T23-17-15had higher DFI than those in T24-24-21and T19-19-19(P < 0.05); during the fattening stage, DFI was lowest in T24-24-21(P < 0.001). In the growing stage, pigs had highest DBWG in the warmest environments (T24-24-21and T23-17-15) and lowest in the coldest environment (T19-19-19; P < 0.001). Feed efficiency was highest in warmer environments (P < 0.01). Temperature T24-24-21favored loin yield, T19-19-19favored ham yield, and T23-17-15favored shoulder yield (P < 0.01). The results imply a favorable effect of temperature on feed efficiency, however, possible negative implications for animal health and welfare should be considered.
Migratory ability of quinone methide-generating acridine conjugates in DNA
Authors: Deeyaa Blessing D. , Rokita Steven E.
Published: February 2020

Conversion of a bisquinone methide–acridine conjugate to its monofunctional analogue releases the constraints that limit migration of its reversible adducts within DNA.
The Eaf3 chromodomain acts as a pH sensor for gene expression by altering its binding affinity for histone methylated-lysine residues
Authors: Okuda Masahiko , Nishimura Yoshifumi
Published: February 2020

During gene expression, histone acetylation by histone acetyltransferase (HAT) loosens the chromatin structure around the promoter to allow RNA polymerase II (Pol II) to initiate transcription, while de-acetylation by histone deacetylase (HDAC) tightens the structure in the transcribing region to repress false initiation. Histone acetylation is also regulated by intracellular pH (pHi) with global hypoacetylation observed at low pHi, and hyperacetylation, causing proliferation, observed at high pHi. However, the mechanism underlying the pHi-dependent regulation of gene expression remains elusive. Here, we have explored the role of the chromodomain (CD) of budding yeast Eaf3, a common subunit of both HAT and HDAC that is thought to recognize methylated lysine residues on histone H3. We found that Eaf3 CD interacts with histone H3 peptides methylated at Lys4 (H3K4me, a promoter epigenetic marker) and Lys36 (H3K36me, a coding region epigenetic marker), as well as with many dimethyl-lysine peptides and even arginine-asymmetrically dimethylated peptides, but not with unmethylated, phosphorylated or acetylated peptides. The Eaf3 CD structure revealed an unexpected histidine residue in the aromatic cage essential for binding H3K4me and H3K36me. pH titration experiments showed that protonation of the histidine residue around physiological pH controls the charge state of the aromatic cage to regulate binding to H3K4me and H3K36me. Histidine substitution and NMR experiments confirmed the correlation of histidine pKa with binding affinity. Collectively, our findings suggest that Eaf3 CD functions as a pHi sensor and a regulator of gene expression via its pHi-dependent interaction with methylated nucleosomes.
Deceptively cold dust in the massive starburst galaxy GN20 at z ∼ 4
Authors: Cortzen Isabella , Magdis Georgios E. , Valentino Francesco , Daddi Emanuele , Liu Daizhong , Rigopoulou Dimitra , Sargent Mark , Riechers Dominik , Cormier Diane , Hodge Jacqueline A. , Walter Fabian , Elbaz David , Béthermin Matthieu , Greve Thomas R. , Kokorev Vasily , Toft Sune
Published: February 2020

We present new observations, carried out with IRAM NOEMA, of the atomic neutral carbon transitions [C I](3P1–3P0) at 492 GHz and [C I](3P2–3P1) at 809 GHz of GN20, a well-studied star-bursting galaxy at z = 4.05. The high luminosity line ratio [C I](3P2–3P1) /[C I](3P1–3P0) implies an excitation temperature of 48+14−9 K, which is significantly higher than the apparent dust temperature of Td = 33 ± 2 K (β = 1.9) derived under the common assumption of an optically thin far-infrared dust emission, but fully consistent with Td = 52 ± 5 K of a general opacity model where the optical depth (τ) reaches unity at a wavelength of λ0 = 170 ± 23 μm. Moreover, the general opacity solution returns a factor of ∼2× lower dust mass and, hence, a lower molecular gas mass for a fixed gas-to-dust ratio, than with the optically thin dust model. The derived properties of GN20 thus provide an appealing solution to the puzzling discovery of starbursts appearing colder than main-sequence galaxies above z >  2.5, in addition to a lower dust-to-stellar mass ratio that approaches the physical value predicted for starburst galaxies.
The Effect of Aeration on River Water Receiving Industrial Discharges to Its Quality and Toxicity
Authors: Salami Indah R S , Pradita Dea Putri
Published: February 2020

Citarum River in West Java Province was an important river that supported more than 25 million people in the region. It was considered highly polluted by many sources of wastes. This study was aimed to evaluate the effect of aeration process on river water quality and toxicity in Citarum tributary receiving industrial wastes as river restoration alternative. Three types of aeration methods namely mechanical, hydraulic, and diffused air were studied in laboratory scale. Water quality parameters analyzed were TSS, TDS, COD, nitrate, phosphate, nitrite, phenol, and acute toxicity LC50 96 hrs on Daphnia magna was tested to obtain TUa value. Results showed TUa of water samples collected at daytime was 0.467±0.12, whereas night time water samples resulted higher toxicity of TUa 1.36±0.3. Aeration of daytime river water by diffuser, mechanical aeration, and cascade aeration, reduced toxicity to TUa of 0.01±0.002, 0.08±0.04, and 0.30±0.2 respectively. On the other hand, aeration for night time river water samples still posed higher acute toxicity showing TUa respectively of 0.13±0.02, 0.44±0.13, and 1.04±0.13. These showed that aeration type has different capacity in lowering water toxicity and improving water quality. Study suggested that contaminated river water quality and toxicity could be improved by aeration processes.
Functionalization of Si-C Using TEOS (Tetra Ethyl Ortho Silica) as Precursor and Organic Catalyst
Authors: Ayu Lestari Riani , Elma Muthia , Rampun Erdina Lulu Atika , Sumardi Anna , Paramitha Adhe , Eka Lestari Aptar , Rabiah Sadidan , Assyaifi Zaini Lambri , Satriaji Gesit
Published: February 2020

Silica network was tailored configuring siloxane (Si-O-Si) and silanol (Si-OH) groups which are essential to produce porous-structured materials. As silanols are hydrophilic, react with water to form fouling. This research address to actualize strategy for synthesizing highly functionalized silica carbon (Si-C) using hybrid organic-inorganic structures as the primary method for improving hydro-stability by employing precursor TEOS and organic catalyst through a sol-gel process. Catalysis employs citric acid or citric acid-ammonia whereas carbon templated into silica network. The synthesis scheme involves: a) sol-gel process at 0°C and b) calcination. Silica sol dried into xerogels were prepared and calcined at 200°C and 250°C. Characterization of xerogels showed the infrared band areas of the organic groups to evaluate the thermal stability. For xerogel employed single (pH 5.5) and dual (pH 7.65) catalyst, infrared spectra showed mostly look similar Si-C area at similar wavelength. Silica xerogel is more effectively prepared from TEOS with one-step single acid catalyst including calcination.
Organoïdes dérivés des adénocarcinomes pancréatiques
Authors: Dusetti Nelson , Iovanna Juan
Published: February 2020

L’adénocarcinome canalaire pancréatique (PDAC) est une maladie à évolution rapide le plus souvent mortelle. Malgré les énormes progrès dans la compréhension des mécanismes reliés à la pathogenèse du PDAC, l’impact de ces avancées sur la prise en charge des patients se fait encore attendre. L’une des applications les plus prometteuses des organoïdes est qu’ils peuvent servir de plate-forme pour la sélection de drogues mieux adaptées à chaque patient. Les organoïdes pancréatiques peuvent être générés à partir de petites quantités de tissu. Cette approche a ainsi le potentiel d’identifier les vulnérabilités thérapeutiques individuelles en permettant de personnaliser les traitements. Ces analyses nécessitent néanmoins plusieurs semaines avant d’obtenir suffisamment d’organoïdes d’un même individu, de pouvoir réaliser les tests de plusieurs drogues et d’analyser les résultats, ce qui limite l’utilisation de cette méthodologie en pratique clinique courante pour les patients, dont il faut se rappeler que la moitié décède dans les 6 mois qui suivent le diagnostic. Pour surmonter cet obstacle, nous avons évalué la capacité d’identification de patients présentant un profil particulier de sensibilité à un traitement donné, de signatures moléculaires transcriptomiques. Les approches fondées sur ce type de profilage transcriptomique ont l’énorme avantage d’utiliser très peu de matériel biologique. Elles permettent également de réduire sensiblement le temps pour la sélection des drogues qui se révèlent plus efficaces pour un patient défini.
mTOR-Inhibitor-induzierte Pneumonitis bei einem 72-jährigen Patienten nach Herztransplantation
Authors: Kasper Philipp , Göbel Heike , Michels Guido
Published: February 2020

Anamnese Ein 72-jähriger herztransplantierter Patient stellte sich mit progredienter Belastungsdyspnoe in der Klinik vor. Zuvor war infolge einer zunehmenden Nierenfunktionseinschränkung die Umstellung seiner immunsuppressiven Therapie auf den mTOR-Inhibitor Everolimus erfolgt. Bei initialem Verdacht einer ambulant erworbenen Pneumonie erfolgte zunächst die Einleitung einer empirischen antiinfektiven Therapie, worunter es jedoch zu einer weiteren Verschlechterung mit Ausbildung eines akuten Lungenversagens und Beatmungspflichtigkeit kam.

Untersuchungen Im Rahmen der erweiterten Diagnostik erfolgte eine transbronchiale Lungenbiopsie, wobei sich das Bild einer medikamentös-toxischen Lungenparenchymschädigung zeigte.

Diagnose Klinisch und pathologisch wurde die Arbeitsdiagnose einer mTOR-Inhibitor-induzierten Pneumonitis gestellt.

Therapie und Verlauf Die bestehende Everolimus-Therapie wurde umgehend beendet und eine hochdosierte Glukokortikoid-Therapie initiiert, woraufhin zunächst eine rasche respiratorische Stabilisierung eintrat.

Folgerung Die Everolimus-induzierte Pneumonitis repräsentiert eine seltene, jedoch schwerwiegende Komplikation, welche bei allen Patienten unter Therapie mit mTOR-Inhibitoren und neu aufgetretener Belastungsdyspnoe differenzialdiagnostisch in Erwägung gezogen werden sollte.
Solving the chaotic source separation problem
Authors: Kim Meeri
Published: February 2020

A new article describes a novel framework to disentangle a mixed signal from two independent chaotic systems using a tank of water as an intermediate system.
Loneliness as a mediator of the impact of social isolation on cognitive functioning of Chinese older adults
Authors: Yang Rumei , Wang Haocen , Edelman Linda S , Tracy Eunjin L , Demiris George , Sward Katherine A , Donaldson Gary W
Published: February 2020

Background and Objective

older adults have increased risk of social isolation, loneliness and cognitive functioning impairment, but the relationships among these factors are not conclusive. We investigated the potential mediation mechanism of loneliness on the association between social isolation and cognitive functioning among Chinese older adults within their cultural context.

Design

secondary analysis of the baseline wave (2011–12) of the harmonised China Health and Retirement Longitudinal Study.

Setting and Subjects

community-dwelling older adults in China (N = 7,410 participants aged 60–101 years).

Methods

we applied a multiple indicator multiple cause approach to determine whether the construct of social isolation is well defined by four indicators (social activity engagement, weekly adult children contact, caregiving for grandchildren and living alone) and used structural equation modelling to examine the direct and indirect effects among variables of interest.

Results

the results demonstrated that social activity engagement, weekly adult children contact and caregiving for grandchildren were significantly related to social isolation (β = −0.26 to −0.28) (Living alone was fixed to 1 for model identification.) The indirect effect of social isolation on cognitive functioning through loneliness was significant (β = −0.15), indicating loneliness was an important mediator. However, the direct effect of social isolation on cognitive functioning also remained significant (β = −0.83), suggesting a partial mediation effect.

Conclusions

our study highlights the mediation role of loneliness in the relationship between social isolation and cognitive functioning among Chinese older adults. The findings support the beneficial effects of maintaining social relations and coping with feelings of loneliness on older adults’ cognitive functioning.
Positive and negative experiences and life satisfaction among spousal caregivers for frail older adults in urban China: a parallel process model
Authors: Jiang Nan , Lu Nan , Sun Qian , Lou Vivian W Q
Published: February 2020

Objectives

Previous literature has suggested that negative and positive aspects of spousal caregiving co-exist. However, positive and negative experiences were often examined independently. This study aimed to empirically test a parallel process model of spousal caregiving.

Methods

This cross-sectional survey of family caregiving involved 269 frail older adults living in Shanghai, China, in 2016. Quota sampling was conducted to find community-dwelling frail older adults with a primary caregiver. Path analysis was used to identify the relationship between negative and positive caregiving experiences and life satisfaction.

Results

We found two independent paths towards life satisfaction: (i) activities of daily living were negatively associated with burden, and burden was associated with lower life satisfaction; and (ii) spousal caregivers’ self-reported health and financial state were positively associated with positive appraisal, and positive appraisal was associated with higher life satisfaction. Caregiving time contributed to both aspects of caregiving experiences. The covariance between caregiving burden and positive appraisals was not statistically significant.

Conclusion

Spousal caregiving involves a parallel process. Negative and positive experiences are separate constructs and their associations with life satisfaction vary. We advocate for policy and interventions that promote positive views of caregiving that encourage caregivers to develop a high level of overall life satisfaction despite the hardships of their caregiving tasks.
GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A
Authors: Shimamoto Kazumi , Tanimoto Keiji , Fukazawa Takahiro , Nakamura Hideaki , Kanai Akinori , Bono Hidemasa , Ono Hiromasa , Eguchi Hidetaka , Hirohashi Nobuyuki
Published: February 2020

We previously demonstrated that expression of a Krüppel-like zinc finger transcription factor, GLIS1, dramatically increases under hypoxic conditions via a transcriptional mechanism induced by HIF-2α cooperating with AP-1 members. In this study, we focused on the functional roles of GLIS1 in breast cancer. To uncover its biological function, the effects of altered levels of GLIS1 in breast cancer cell lines on cellular growth, wound-healing and invasion capacities were assessed. Knockdown of GLIS1 using siRNA in BT-474 cells resulted in significant growth stimulation under normoxia, while attenuation was found in the cell invasion assay under hypoxic conditions. In MDA-MB-231 cells expressing exogenous 3xFLAG-tagged GLIS1, GLIS1 attenuated cell proliferation and enhanced cell mobility and invasion capacities under normoxia. In addition, breast cancer cells expressing GLIS1 acquired resistance to irradiation. Whole transcriptome analysis clearly demonstrated that downstream signals of GLIS1 are related to various cellular functions. Among the genes with increased expression, we focused on WNT5A. Knockdown of WNT5A indicated that enhancement of acquired cell motility in the MDA-MB-231 cells expressing GLIS1 was mediated, at least in part, by WNT5A. In an analysis of publicly available data, patients with estrogen receptor-negative breast cancer showing high levels of GLIS1 expression showed much worse prognosis than those with low levels. In summary, hypoxia-induced GLIS1 plays significant roles in breast cancer cells via regulation of gene expression related to cell migration and invasion capacities, resulting in poorer prognosis in patients with advanced breast cancer.
A Generalizable Multivariate Brain Pattern for Interpersonal Guilt
Authors: Yu Hongbo , Koban Leonie , Chang Luke J , Wagner Ullrich , Krishnan Anjali , Vuilleumier Patrik , Zhou Xiaolin , Wager Tor D
Published: February 2020

Feeling guilty when we have wronged another is a crucial aspect of prosociality, but its neurobiological bases are elusive. Although multivariate patterns of brain activity show promise for developing brain measures linked to specific emotions, it is less clear whether brain activity can be trained to detect more complex social emotional states such as guilt. Here, we identified a distributed guilt-related brain signature (GRBS) across two independent neuroimaging datasets that used interpersonal interactions to evoke guilt. This signature discriminated conditions associated with interpersonal guilt from closely matched control conditions in a cross-validated training sample (N = 24; Chinese population) and in an independent test sample (N = 19; Swiss population). However, it did not respond to observed or experienced pain, or recalled guilt. Moreover, the GRBS only exhibited weak spatial similarity with other brain signatures of social-affective processes, further indicating the specificity of the brain state it represents. These findings provide a step toward developing biological markers of social emotions, which could serve as important tools to investigate guilt-related brain processes in both healthy and clinical populations.
Markets for data
Authors: Koutroumpis Pantelis , Leiponen Aija , Thomas Llewellyn D W
Published: February 2020

Although datasets are abundant and assumed to be immensely valuable, they are not being shared or traded openly and transparently on a large scale. We investigate the nature of data trading with a conceptual market design approach and demonstrate the importance of provenance to overcome appropriability and quality concerns. We consider the requirements for efficient data exchange, comparing existing trading arrangements against efficient market models and show that it is possible to achieve either large markets with little control or small markets with greater control. We describe some future research directions.
Pointwise Convergence of the Schrödinger Flow
Authors: Compaan Erin , Lucà Renato , Staffilani Gigliola
Published: February 2020

In this paper we address the question of the pointwise almost everywhere limit of nonlinear Schrödinger flows to the initial data, in both the continuous and the periodic settings. Then we show how, in some cases, certain smoothing effects for the non-homogeneous part of the solution can be used to upgrade to a uniform convergence to zero of this part, and we discuss the sharpness of the results obtained. We also use randomization techniques to prove that with much less regularity of the initial data, both in continuous and the periodic settings, almost surely one obtains uniform convergence of the nonlinear solution to the initial data, hence showing how more generic results can be obtained.
A Really Big Button That Doesn’t Do Anything? The Anti-NME Clause in US Trade Agreements Between Law and Geoeconomics
Authors: Vidigal Geraldo
Published: February 2020

The United States-Mexico-Canada Agreement (USMCA) features a clause, dubbed ‘anti-China’, which sets out legal consequences in case one of the parties negotiates or enters into a free trade agreement (FTA) with a nonmarket economy (NME). A similarly worded objective appears among the negotiating objectives of the US for FTAs with the European Union, Japan, and the United Kingdom. This article examines the anti-NME clause, arguing that its concrete legal consequences are less relevant than its symbolic effects. The USMCA clause itself is difficult to replicate in bilateral agreements, since it depends on cooperation between the two nonsigning parties. Its operation is nonetheless similar to that of two unilateral remedies available under the law of treaties, permitting a reasonable assessment that the clause, if it follows its original design, will aim to permit termination of bilateral US FTAs in response to the other party entering into an NME FTA. While such a clause would offer little in terms of concrete effects if added to agreements that already permit unilateral withdrawal, its greatest value may not be in its legal effects but in its legitimating and signaling properties, which push USMCA parties to establish a common front in the ‘geoeconomic’ dispute between the United States and China.