bluuebunny/crossref_metadata_2025 huggingface dataset:
Cells encapsulated in alginate: a potential system for delivery of recombinant proteins to malignant brain tumours
Authors: Read Tracy‐Ann , Stensvaag Vidar , Vindenes Harald , Ulvestad Elling , Bjerkvig Rolf , Thorsen Frits
Published: July 2002

Growth and progression of malignant brain tumours occurs in a micromilieu consisting of both tumour and normal cells. Several proteins have been identified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continuous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therapeutic importance. In this study we have investigated the growth characteristics of cells encapsulated in alginate, which represents a potential delivery system for recombinant proteins that may have antitumour effects. Three different cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, which is an immuno‐isolating substance extracted from brown seaweed. The encapsulated cells were observed at specific intervals during a 4‐month period after in vitro propagation and as transplants into the cortex of BD‐IX rats. Morphological studies showed that encapsulated cells proliferated and formed spheroids within the alginate in the in vitro cultures and after implantation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltration of mononuclear cells was observed in the brain bordering the alginate beads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation. The majority of inflammatory cells were reactive microglia and invading monocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N2 and will retain their viability and proliferative capacity.
Can cannabis trigger recurrent panic attacks in susceptible patients?
Authors: Langs G , Fabisch H , Fabisch K , Zapotoczky HG
Published: July 2002

Cannabis has been reported to produce acute psychiatric reactions, among these panic anxiety and derealization, which are self-limited. We report on three patients who experienced an initial panic attack during cannabis intake. Anxiety attacks reoccurred after the cessation of intake. Two of these patients had a current depressive disorder, one of them had a single Grand Mal seizure before the onset. We suggest that cannabis may trigger the emergence of recurrent panic attacks and uncover latent panic disorders in vulnerable persons.
Sildenafil citrate (Viagra) treatment of sexual dysfunction in a schizophrenic patient
Authors: Benatov R. , Reznik I. , Zemishlany Z.
Published: July 2002

A high frequency of sexual dysfunction occurs in treated and untreated patients with schizophrenia. Unfortunately, no effective therapy for this problem is currently available. We present a case of a 26-year-old patient with paranoid schizophrenia, who suffered from lack of desire and erection, and was successfully treated with sildenafil citrate (Viagra). This case illustrates the complex character of sexual dysfunction in male schizophrenic patients.
Geographical analysis of the risk of psychiatric hospitalization in Hamburg from 1988 – 1994
Authors: Maylath E. , Seidel J. , Werner B. , Schlattmann P.
Published: July 2002

The analysis of the geographical distribution of hospital cases is obviously important for the purpose of planning hospital services, but it is of even greater significance in the planning of psychiatric services. This concern motivated our seven-year-long study, which examined hospitalization risks among various categories of psychiatric disorders in the major German city of Hamburg. Our database encompassed 77% (n = 64,000) of all psychiatric admissions in a total of 41 hospitals, most of which are general hospitals. In order to carry out the geographical analysis we employed a new statistical method based on a mixture distribution model. According to our findings, the strongest indications of an increased frequency were among male cases of schizophrenia, drug abuse and organic psychoses, and female cases of neurotic disorders, personality disorders, drug abuse and schizophrenia. We found that some areas are exposed to a risk of hospitalization for these diagnostic categories which is more than 50% above the reference. Contrary to other authors we did not identify an increased frequency of admission concentrated in the inner-city area for any of the diagnostic groups. The risk of hospitalization for schizophrenics was almost entirely associated with the close proximity of psychiatric units, while the risks for neuroses and personality disorders, as well as alcohol and drug abuse, appeared to be concentrated in areas of low social status. However, a statistically relevant correlation between an increased risk of hospitalization and low social status could be determined only for drug abuse and alcoholism. In the end, we did identify two areas in which there was an increased risk of hospitalization for several diagnostic groups, and this information will undoubtedly facilitate the planning of hospital and psychiatric services. The fact that our findings deviate to some extent from other authors – especially with respect to neuroses and personality disorders, but also to addiction – can be attributed to the inclusion of psychiatric cases from general hospitals in our geographic analysis.
Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure
Authors: Tyni‐Lenné Raija , Dencker Kerstin , Gordon Allan , Jansson Eva , Sylvén Christer
Published: July 2002

Background:

Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF.

Methods:

Twenty‐four men and women [age 63 ± 9 years (mean ± S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30 ± 10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks.

Results:

Patient groups did not differ at baseline. Peak oxygen uptake (8%, P < 0.03), the distance walked in a 6‐min walking test (11%, P < 0.002), the health‐related quality of life (P < 0.001) and plasma norepinephrine levels at rest (32%, P < 0.003) and at submaximal intensities (P < 0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P < 0.02) and quality of life scores (P < 0.03).

Conclusions:

Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.
Aromatic Phosphonates: A Novel Group of Emitters Showing Blue Ultralong Room Temperature Phosphorescence
Authors: Thomas Heidi , Pastoetter Dominik L. , Gmelch Max , Achenbach Tim , Schlögl Annika , Louis Marine , Feng Xinliang , Reineke Sebastian
Published: April 2020

In recent years, there has been a growing interest in purely organic materials showing ultralong room‐temperature phosphorescence with lifetimes in the range of seconds. Still, the longest known phosphorescence lifetimes are only achieved with crystalline systems so far. Here, a rational design of a completely new family of halogen‐free organic luminescent derivatives in amorphous matrices, displaying both conventional fluorescence and phosphorescence is reported. Hydrogen bonding between the newly developed emitters and an ethylene‐vinyl alcohol copolymer (Exceval) matrix, which efficiently suppresses vibrational dissipation, enables bright long‐lived phosphorescence with lifetimes up to 2.6 s at around 480 nm. The importance of the chosen matrix is shown as well as the implementation in an organic programmable luminescent tag.
Valorization of pineapple peel waste and sisal fiber: Study of cellulose nanocrystals on polypropylene nanocomposites
Authors: Agarwal Jyoti , Mohanty Smita , Nayak Sanjay K.
Published: April 2020

The present study focuses on the isolation and characterization of the cellulose nanocrystals (CNCs) from the pineapple peel waste (PPW) (agro‐waste) and sisal fiber (SiF) (natural fiber) employing the acid hydrolysis method, and its comparison with the commercially available CNCs (CNC‐C). Furthermore, the CNCs from PPW, SiF, and CNC‐C were subjected to transmission electron microscopy (TEM), Fourier transform electron microscopy, X‐ray diffraction, particle size distribution, and zeta potential analysis. The studied properties of the isolated CNCs are considerably different from the PPW and SiF. The CNCs so formed have been estimated by TEM to be around 10–40 nm wide and length of several micrometers. Fourier transform electron microscopy studies described the removal of the noncellulosic components like lignin, hemicellulose, and pectin substances from the base materials in both the cases by employing acid hydrolysis method. Additionally, nanocomposites of CNC isolated from PPW along with polypropylene (PP) matrix were fabricated using melt blending method followed by injection molding. Maleic anhydride grafted PP (MAPP) acts as a compatibilizer for improving the dispersibility of hydrophilic CNC within the nonpolar PP matrix. The addition of CNC (3 wt%) along with MAPP at 5 wt% showed optimum tensile strength and modulus to the tune of 10.39 and 25.53%, respectively, when compared to their counterparts without MAPP. Dynamic mechanical analysis revealed an increased stiffness of PP in its nanocomposite system due to the addition of CNC. Scanning electron microscopy studies revealed uniform distribution of CNC within the nonpolar PP matrix in the presence of MAPP.
Microanatomical considerations for safe uncinate removal during anterior cervical discectomy and fusion: 10‐year experience
Authors: Clifton William , Valero‐Moreno Fidel , Vlasak Alexander , Damon Aaron , Tubbs R. Shane , Merrill Sarah , Pichelmann Mark
Published: April 2020

Cervical radiculopathy from uncovertebral joint (UVJ) hypertrophy and nerve root compression often occurs anterior and lateral within the cervical intervertebral foramen, presenting a challenge for complete decompression through anterior cervical approaches owing to the intimate association with the vertebral artery and associated venous plexus. Complete uncinatectomy during anterior cervical discectomy and fusion (ACDF) is a controversial topic, many surgeons relying on indirect nerve root decompression from restoration of disc space height. However, in cases of severe UVJ hypertrophy, indirect decompression does not adequately address the underlying pathophysiology of anterolateral foraminal stenosis. Previous reports in the literature have described techniques involving extensive dissection of the cervical transverse process and lateral uncinate process (UP) in order to identify the vertebral artery for safe removal of the UP. Recent anatomical investigations have detailed the microanatomical organization of the fibroligamentous complex surrounding the UP and neurovascular structures. The use of the natural planes formed from the encapsulation of these connective tissue layers provides a safe passage for lateral UP dissection during anterior cervical approaches. This can be performed from within the disc space during ACDF to avoid extensive lateral dissection. In this article, we present our 10‐year experience using an anatomy‐based microsurgical technique for safe and complete removal of the UP during ACDF for cervical radiculopathy caused by UVJ hypertrophy.
Assessing Reproducibility in Amyloid β Research: Impact of Aβ Sources on Experimental Outcomes
Authors: Foley Alejandro R. , Raskatov Jevgenij A.
Published: April 2020

The difficulty of synthesizing and purifying the amyloid β (Aβ) peptide, combined with its high aggregation propensity and low solubility under physiological conditions, leads to a wide variety of experimental results from kinetic assays to biological activity. Thus, it becomes challenging to reproduce outcomes, and this limits our ability to rely on reported results as the foundation for new research. This article examines variability of the Aβ peptide from different sources, comparing purity, and oligomer and fibril formation propensity side by side. The results highlight the importance of performing rigorous controls so that meaningful biophysical, biochemical, and neurobiological results can be obtained to improve our understanding on Aβ.
On the Stability of Solitary Water Waves with a Point Vortex
Authors: Varholm Kristoffer , Wahlén Erik , Walsh Samuel
Published: April 2020

This paper investigates the stability of traveling wave solutions to the free boundary Euler equations with a submerged point vortex. We prove that sufficiently small‐amplitude waves with small enough vortex strength are conditionally orbitally stable. In the process of obtaining this result, we develop a quite general stability/instability theory for bound state solutions of a large class of infinite‐dimensional Hamiltonian systems in the presence of symmetry. This is in the spirit of the seminal work of Grillakis, Shatah, and Strauss (GSS) , but with hypotheses that are relaxed in a number of ways necessary for the point vortex system, and for other hydrodynamical applications more broadly. In particular, we are able to allow the Poisson map to have merely dense range, as opposed to being surjective, and to be state‐dependent.

As a second application of the general theory, we consider a family of nonlinear dispersive PDEs that includes the generalized Korteweg–de Vries (KdV) and Benjamin‐Ono equations. The stability or instability of solitary waves for these systems has been studied extensively, notably by Bona, Souganidis, and Strauss , who used a modification of the GSS method. We provide a new, more direct proof of these results, as a straightforward consequence of our abstract theory. At the same time, we allow fractional dispersion and obtain a new instability result for fractional KdV. © 2020 Wiley Periodicals, Inc.
What prevents young adults from seeking help? Barriers toward help‐seeking for eating disorder symptomatology
Authors: Ali Kathina , Fassnacht Daniel B. , Farrer Louise , Rieger Elizabeth , Feldhege Johannes , Moessner Markus , Griffiths Kathleen M. , Bauer Stephanie
Published: April 2020

Objectives

The aim of this study was to investigate help‐seeking attitudes, intentions, and behaviors, and to systematically explore perceived barriers to help‐seeking for eating, weight, or shape concerns among young adults. Differences in perceived barriers as a function of type of eating disorder symptomatology were also examined.

Method

Data were collected using an online survey among individuals (aged 18‐25 years) in Australia. Overall, 291 young adults with varying levels of eating disorder symptoms completed measures of disordered eating, weight or shape concerns, help‐seeking barriers, attitudes, intentions, and behaviors. According to their self‐reported symptoms, participants were classified into four subgroups (i.e., anorexia nervosa [AN] symptoms, bulimia nervosa [BN] symptoms, binge‐eating disorder [BED] symptoms, and other eating disorder symptoms).

Results

Despite the belief that help‐seeking is useful, only a minority of participants with elevated symptoms, namely those with AN, BN, and BED symptoms, believed they needed help. Across the sample, the most frequently cited barriers to seeking help for eating disorder symptoms were: concern for others, self‐sufficiency, fear of losing control, denial and failure to perceive the severity of the illness, and stigma and shame.

Discussion

The findings highlight the need to educate young adults about the severity of eating disorders and the importance of seeking help, and to increase the awareness of help‐seeking barriers among those designing public health interventions as well as clinicians. Our findings suggest that help‐seeking barriers may differ depending on the type of eating disorder symptomology.
Design of a thermal management system for a battery pack in an electric vehicle using Dymola
Authors: Shet Veeraj V. , Ponangi Babu R. , Jacob Kiran
Published: April 2020

As the world moves toward more green and efficient means of modes of transport, electric vehicles are the most suitable and ideal choice to fulfill this requirement. Rapid developments in the field of battery technology are the main reason for their progress, but thermal management in such systems has been an area of concern for a long time. The work undertaken is to design and develop a battery management system (BMS) with a specific focus on the thermal behavior of the battery pack with varying vehicle loads as well as environmental conditions. To design an efficient BMS, one needs to model the battery behavior covering the thermal as well as electrical aspects of the battery. Apart from the battery model, a mathematical model of the electrical vehicle to mimic the various road load conditions for battery also needs to be modeled. Depending on the need for cooling based on battery behavior, the cooling circuit is modeled for the battery pack used. The entire study has been carried out using Dymola, a mathematical modeling software.
Carbon Nanomaterials Promote M1/M2 Macrophage Activation
Authors: Kinaret Pia Anneli Sofia , Scala Giovanni , Federico Antonio , Sund Jukka , Greco Dario
Published: April 2020

Toxic effects of certain carbon nanomaterials (CNM) have been observed in several exposure scenarios both in vivo and in vitro. However, most of the data currently available has been generated in a high‐dose/acute exposure setup, limiting the understanding of their immunomodulatory mechanisms. Here, macrophage‐like THP‐1 cells, exposed to ten different CNM for 48 h in low‐cytotoxic concentration of 10 µg mL−1, are characterized by secretion of different cytokines and global transcriptional changes. Subsequently, the relationships between cytokine secretion and transcriptional patterns are modeled, highlighting specific pathways related to alternative macrophage activation. Finally, time‐ and dose‐dependent activation of transcription and secretion of M1 marker genes IL‐1β and tumor necrosis factor, and M2 marker genes IL‐10 and CSF1 is confirmed among the three most responsive CNM, with concentrations of 5, 10, and 20 µg mL−1 at 24, 48, and 72 h of exposure. These results underline CNM effects on the formation of cell microenvironment and gene expression leading to specific patterns of macrophage polarization. Taken together, these findings imply that, instead of a high and toxic CNM dose, a sub‐lethal dose in controlled exposure setup can be utilized to alter the cell microenvironment and program antigen presenting cells, with fascinating implications for novel therapeutic strategies.
A review of agent‐based modeling of climate‐energy policy
Authors: Castro Juana , Drews Stefan , Exadaktylos Filippos , Foramitti Joël , Klein Franziska , Konc Théo , Savin Ivan , van den Bergh Jeroen
Published: April 2020

Agent‐based models (ABMs) have recently seen much application to the field of climate mitigation policies. They offer a more realistic description of micro behavior than traditional climate policy models by allowing for agent heterogeneity, bounded rationality and nonmarket interactions over social networks. This enables the analysis of a broader spectrum of policies. Here, we review 61 ABM studies addressing climate‐energy policy aimed at emissions reduction, product and technology diffusion, and energy conservation. This covers a broad set of instruments of climate policy, ranging from carbon taxation, and emissions trading through adoption subsidies to information provision tools such as smart meters and eco‐labels. Our treatment pays specific attention to behavioral assumptions and the structure of social networks. We offer suggestions for future research with ABMs to answer neglected policy questions.

This article is categorized under:

Climate Economics > Economics of Mitigation
Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells
Authors: Behr Anne-Cathrin , Kwiatkowski Anna , Ståhlman Marcus , Schmidt Felix Florian , Luckert Claudia , Braeuning Albert , Buhrke Thorsten
Published: April 2020

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are man-made chemicals that are used for the fabrication of many products with water- and dirt-repellent properties. The toxicological potential of both substances is currently under debate. In a recent Scientific Opinion, the European Food Safety Authority (EFSA) has identified increased serum total cholesterol levels in humans as one major critical effect being associated with exposure to PFOA or PFOS. In animal studies, both substances induced a decrease of serum cholesterol levels, and the underlying molecular mechanism(s) for these opposed effects are unclear so far. In the present study, we examined the impact of PFOA and PFOS on cholesterol homoeostasis in the human HepaRG cell line as a model for human hepatocytes. Cholesterol levels in HepaRG cells were not affected by PFOA or PFOS, but both substances strongly decreased synthesis of a number of bile acids. The expression of numerous genes whose products are involved in synthesis, metabolism and transport of cholesterol and bile acids was strongly affected by PFOA and PFOS at concentrations above 10 µM. Notably, both substances led to a strong decrease of CYP7A1, the key enzyme catalyzing the rate-limiting step in the synthesis of bile acids from cholesterol, both at the protein level and at the level of gene expression. Moreover, both substances led to a dilatation of bile canaliculi that are formed by differentiated HepaRG cells in vitro. Similar morphological changes are known to be induced by cholestatic agents in vivo. Thus, the strong impact of PFOA and PFOS on bile acid synthesis and bile canalicular morphology in our in vitro experiments may allow the notion that both substances have a cholestatic potential that is connected to the observed increased serum cholesterol levels in humans in epidemiological studies.
Separase activity distribution can be a marker of major molecular response and proliferation of CD34+ cells in TKI-treated chronic myeloid leukemia patients
Authors: Spiess Birgit , Kleiner Helga , Flach Johanna , Fabarius Alice , Saussele Susanne , Hofmann Wolf-Karsten , Seifarth Wolfgang
Published: April 2020

Separase, a cysteine endopeptidase, is a key player in mitotic sister chromatid separation, replication fork dynamics, and DNA repair. Aberrant expression and/or altered separase proteolytic activity are associated with aneuploidy, tumorigenesis, and disease progression. Since genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML), we have comparatively examined separase proteolytic activity in TKI-treated chronic phase CML. Separase proteolytic activity was analyzed on single cell level in 88 clinical samples and in 14 healthy controls by a flow cytometric assay. In parallel, BCR-ABL1 gene expression and replication fork velocity were measured by qRT-PCR and DNA fiber assays, respectively. The separase activity distribution (SAD) value indicating the occurrence of MNCs with elevated separase proteolytic activity within samples was found to positively correlate with BCR-ABL1 gene expression levels and loss of MMR (relapse) throughout routine BCR-ABL1 monitoring. Analyses of CD34+ cells and MNCs fractionized by flow cytometric cell sorting according to their separase activity levels (H- and L-fractions) revealed that CD34+ cells with elevated separase activity levels (H-fractions) displayed enhanced proliferation/viability when compared with cells with regular (L-fraction) separase activity (mean 3.3-fold, p = 0.0011). BCR-ABL1 gene expression positivity prevailed in MNC H-fractions over L-fractions (42% vs. 8%, respectively). Moreover, expanding CD34+ cells of H-fractions showed decreased replication fork velocity compared with cells of L-fractions (p < 0.0001). Our data suggests an association between high separase activity, residual BCR-ABL1 gene expression, and enhanced proliferative capacity in hematopoietic cells within the leukemic niche of TKI-treated chronic phase CML.
The Effectiveness of the KiVa Bullying Prevention Program in Wales, UK: Results from a Pragmatic Cluster Randomized Controlled Trial
Authors: Axford Nick , Bjornstad Gretchen , Clarkson Suzy , Ukoumunne Obioha C. , Wrigley Zoe , Matthews Justin , Berry Vashti , Hutchings Judy
Published: April 2020

The study evaluated the implementation fidelity and effectiveness of KiVa, an evidence-based program that aims to prevent and address bullying in schools, with a particular emphasis on changing the role of bystanders. The study was a two-arm waitlist control cluster randomized controlled trial in which 22 primary schools (clusters) (N = 3214 students aged 7–11) were allocated using a 1:1 ratio to intervention (KiVa; 11 clusters,n = 1588 students) and a waitlist control (usual school provision; 11 clusters,n = 1892 children)). The trial statistician (but not schools or researchers) remained blind to allocation status. The outcomes were as follows: student-reported victimization (primary outcome) and bullying perpetration; teacher-reported child behavior and emotional well-being; and school absenteeism (administrative records). Implementation fidelity was measured using teacher-completed online records (for class lessons) and independent researcher observations (for school-wide elements). Outcome analyses involved 11 intervention schools (n = 1578 children) and 10 control schools (n = 1636 children). There was no statistically significant effect on the primary outcome of child-reported victimization (adjusted intervention/control OR 0.76; 95% CI 0.55 to 1.06;p = 0.11) or on the secondary outcomes. The impact on victimization was not moderated by child gender, age, or victimization status at baseline. Lesson adherence was good but exposure (lesson length) was lower than the recommended amount, and there was considerable variability in the implementation of whole school elements. The trial found insufficient evidence to conclude that KiVa had an effect on the primary outcome. A larger trial of KiVa in the UK is warranted, however, with attention to issues regarding implementation fidelity. Trial registration: Current Controlled Trials ISRCTN23999021 Date 10-6-13
Directed discrete midpoint convexity
Authors: Tamura Akihisa , Tsurumi Kazuya
Published: April 2020

For continuous functions, midpoint convexity characterizes convex functions. By considering discrete versions of midpoint convexity, several types of discrete convexities of functions, including integral convexity, L$$^\natural$$

♮

-convexity and global/local discrete midpoint convexity, have been studied. We propose a new type of discrete midpoint convexity that lies between L$$^\natural$$

♮

-convexity and integral convexity and is independent of global/local discrete midpoint convexity. The new convexity, named DDM-convexity, has nice properties satisfied by L$$^\natural$$

♮

-convexity and global/local discrete midpoint convexity. DDM-convex functions are stable under scaling, satisfy the so-called parallelogram inequality and a proximity theorem with the same small proximity bound as that for L$$^{\natural }$$

♮

-convex functions. Several characterizations of DDM-convexity are given and algorithms for DDM-convex function minimization are developed. We also propose DDM-convexity in continuous variables and give proximity theorems on these functions.
How Unitary is the EU Trade Mark? Territorial Aspects of Acquired Distinctiveness
Authors: Żelechowski Łukasz
Published: April 2020

The geographical scope of the acquired distinctiveness of EU trade marks (EUTMs) is the subject of recurring dilemmas in case law and among scholars. The development of case law in this area is driven by the endeavour to reconcile the requirement that the acquired distinctiveness of such marks ought to be present throughout all Member States while simultaneously allowing certain evidentiary relaxation in that regard. Ultimately, however, the content of the requirements of establishing acquired distinctiveness in such instances remains, in the light of case law, uncertain. This paper argues that the principle of the unitary character of EUTMs should lead to adopting a more unitary approach towards the assessment of acquired distinctiveness, instead of the country-by-country approach dominant in case law. More specifically, whenever no territorially varying consumer perceptions are involved in establishing a lack of inherent distinctiveness of an EUTM, the territory of the EU should be treated, for the sake of establishing acquired distinctiveness, as a monolith undivided by borders between the Member States. This is normally the case with non-word marks, such as shapes or colour marks, which are perceived in a uniform manner throughout the EU as either possessing or lacking inherent distinctiveness. Concessions from this unitary approach are justified whenever territorially varying perceptions are involved. This normally concerns the descriptiveness or otherwise non-distinctiveness of word marks due to linguistic differences that are tailored across borders between Member States. The posited unitary approach concerning non-word marks should, however, be a measured one. Not only should acquired distinctiveness be present in the majority of the EU territory, but it should also be located at a proper geographical spread (without, however, following the country-by-country method). In the light of this approach, a non-word EUTM could still be registered (and remain incontestable) based on acquired distinctiveness when EU territories where acquired distinctiveness has not been established would constitute “blank” areas sporadically scattered across the Union without, however, constituting a concentrated larger part of the EU. Such “blank” areas could correspond to territories of a specific Member State or Member States. Negative effects of overprotection in such “blank” areas could be subsequently prevented with additional mitigating tools available at the stage of infringement and enforcement of EUTMs.
A proof that rectified deep neural networks overcome the curse of dimensionality in the numerical approximation of semilinear heat equations
Authors: Hutzenthaler Martin , Jentzen Arnulf , Kruse Thomas , Nguyen Tuan Anh
Published: April 2020

Deep neural networks and other deep learning methods have very successfully been applied to the numerical approximation of high-dimensional nonlinear parabolic partial differential equations (PDEs), which are widely used in finance, engineering, and natural sciences. In particular, simulations indicate that algorithms based on deep learning overcome the curse of dimensionality in the numerical approximation of solutions of semilinear PDEs. For certain linear PDEs it has also been proved mathematically that deep neural networks overcome the curse of dimensionality in the numerical approximation of solutions of such linear PDEs. The key contribution of this article is to rigorously prove this for the first time for a class of nonlinear PDEs. More precisely, we prove in the case of semilinear heat equations with gradient-independent nonlinearities that the numbers of parameters of the employed deep neural networks grow at most polynomially in both the PDE dimension and the reciprocal of the prescribed approximation accuracy. Our proof relies on recently introduced full history recursive multilevel Picard approximations for semilinear PDEs.
Biological Activities of Two Major Copaiba Diterpenoids and Their Semi-synthetic Derivatives
Authors: Çiçek Serhat Sezai , Wenzel-Storjohann Arlette , Girreser Ulrich , Tasdemir Deniz
Published: April 2020

The oleoresin of Copaifera reticulata Ducke, Fabaceae, is a traditional Brazilian remedy used for a wide range of applications. Commonly named copaiba, the oleoresin has been found to exhibit strong antimicrobial effects in our previous study, which could be attributed to some of its diterpenoid constituents. In order to find new biological activities and to eventually enhance the before observed effects, (−)-polyalthic acid (1) and kaurenoic acid (2), together with eight prepared semi-synthetic derivatives (1a–1c and 2a–2e) were evaluated for their cytotoxic, antibacterial and antifungal properties. Regarding the gram-positive bacteria Enterococcus faecium and methicillin-resistant Staphylococcus aureus, we found that both the exocylic methylene group and the carboxyl group were crucial for the activity against these two clinically relevant bacterial strains. Investigation of the antifungal activity, in contrast, showed that the carboxyl group is unnecessary for the effect against the dermatophytes Trichophyton rubrum and Cryptococcus neoformans, indicated by low micromolar IC50 values for both (−)-polyalthic acid diethylamide (1a) as well as (−)-polyalthic acid methyl ester (1b). Apart from studying the biological activity, the structure of one semi-synthetic derivative, compound 1c, is being reported for the first time. During the course of the structure elucidation of the new compound, we discovered inconsistencies regarding the stereochemistry of polyalthic acid and its stereoisomers, which we clarified in the present work.
Effects of strawberry intervention on cardiovascular risk factors: a meta-analysis of randomised controlled trials
Authors: Gao Qi , Qin Li-Qiang , Arafa Ahmed , Eshak Ehab S. , Dong Jia-Yi
Published: April 2020

We conducted a meta-analysis of randomised controlled trials (RCT) to examine the effects of strawberry interventions on cardiovascular risk factors. We searched multiple databases including PubMed, Web of Science and Scopus to identify eligible studies published before 19 May 2019. The endpoints were blood pressure, total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, TAG, fasting blood glucose, endothelial function and inflammatory factors. Pooled analyses were performed using random- or fixed-effects models according to a heterogeneity test. We also conducted sub-group analyses by baseline endpoint levels. We included eleven RCT in this meta-analysis (six for blood pressure, seven for lipid profile, seven for fasting blood glucose and six for C-reactive protein (CRP)). Overall, the strawberry interventions significantly reduced CRP levels by 0·63 (95 % CI −1·04, −0·22) mg/l but did not affect blood pressure, lipid profile or fasting blood glucose in the main analyses. Our analysis stratified by baseline endpoint levels showed the strawberry interventions significantly reduced TC among people with baseline levels >5 mmol/l (−0·52 (95 % CI −0·88, −0·15) mmol/l) and reduced LDL-cholesterol among people with baseline levels >3 mmol/l (−0·31 (95 % CI −0·60, −0·02) mmol/l). There was little evidence of heterogeneity in the analysis and no evidence of publication bias. In summary, strawberry interventions significantly reduced CRP levels and may improve TC and LDL-cholesterol in individuals with high baseline levels.
Red–green–blue analysis of nasal mucosa discolouration in allergic rhinitis
Authors: Degirmenci N , Dogan R , Tugrul S , Senturk E , Toprak A , Ozturan O
Published: April 2020

Objective

To evaluate the colour values of nasal mucosa for the purpose of presenting an objective parameter of allergic rhinitis.

Methods

Seventy-three patients with allergic rhinitis (allergy group) and 73 normal healthy individuals (control group) were included in the study. Endoscopic examinations were conducted, and endoscopic photographs of the septum and both inferior turbinates were taken. The Adobe Photoshop Elements 7.0 software program was used to measure the numerical values of red–green–blue (RGB) colour components in the endoscopic photographs of nasal mucosa.

Results

The G and B values were significantly higher in the allergy group compared to the control group (both p < 0.05). Cumulative R, G and B values of all measurement points were significantly higher in the allergy group compared to the control group (p < 0.05).

Conclusion

Nasal mucosa discolouration can be measured objectively with RGB analysis to aid the diagnosis of allergic rhinitis.
SCFA: mechanisms and functional importance in the gut
Authors: Martin-Gallausiaux Camille , Marinelli Ludovica , Blottière Hervé M. , Larraufie Pierre , Lapaque Nicolas
Published: April 2020

In recent years, the importance of the gut microbiota in human health has been revealed and many publications have highlighted its role as a key component of human physiology. Owing to the use of modern sequencing approaches, the characterisation of the microbiome in healthy individuals and in disease has demonstrated a disturbance of the microbiota, or dysbiosis, associated with pathological conditions. The microbiota establishes a symbiotic crosstalk with their host: commensal microbes benefit from the nutrient-rich environment provided by the gut and the microbiota produces hundreds of proteins and metabolites that modulate key functions of the host, including nutrient processing, maintenance of energy homoeostasis and immune system development. Many bacteria-derived metabolites originate from dietary sources. Among them, an important role has been attributed to the metabolites derived from the bacterial fermentation of dietary fibres, namely SCFA linking host nutrition to intestinal homoeostasis maintenance. SCFA are important fuels for intestinal epithelial cells (IEC) and regulate IEC functions through different mechanisms to modulate their proliferation, differentiation as well as functions of subpopulations such as enteroendocrine cells, to impact gut motility and to strengthen the gut barrier functions as well as host metabolism. Recent findings show that SCFA, and in particular butyrate, also have important intestinal and immuno-modulatory functions. In this review, we discuss the mechanisms and the impact of SCFA on gut functions and host immunity and consequently on human health.
Conversion to psychosis in adolescents and adults: similar proportions, different predictors
Authors: Zhang TianHong , Xu LiHua , Chen Ying , Wei YanYan , Tang XiaoChen , Hu YeGang , Li ZhiXing , Gan RanPiao , Wu GuiSen , Cui HuiRu , Tang YingYing , Hui Li , Li ChunBo , Wang JiJun
Published: April 2020

Background

Age effects may be important for improving models for the prediction of conversion to psychosis for individuals in the clinical high risk (CHR) state. This study aimed to explore whether adolescent CHR individuals (ages 9–17 years) differ significantly from adult CHR individuals (ages 18–45 years) in terms of conversion rates and predictors.

Method

Consecutive CHR individuals (N = 517) were assessed for demographic and clinical characteristics and followed up for 3 years. Individuals with CHR were classified as adolescent (n = 244) or adult (n = 273) groups. Age-specific prediction models of psychosis were generated separately using Cox regression.

Results

Similar conversion rates were found between age groups; 52 out of 216 (24.1%) adolescent CHR individuals and 55 out of 219 (25.1%) CHR adults converted to psychosis. The conversion outcome was best predicted by negative symptoms compared to other clinical variables in CHR adolescents (χ2 = 7.410, p = 0.006). In contrast, positive symptoms better predicted conversion in CHR adults (χ2 = 6.585, p = 0.01).

Conclusions

Adolescent and adult CHR individuals may require a different approach to early identification and prediction. These results can inform the development of more precise prediction models based on age-specific approaches.
The potential role of dietary advanced glycation endproducts in the development of chronic non-infectious diseases: a narrative review
Authors: Garay-Sevilla M. E. , Beeri M. S. , de la Maza M. P. , Rojas A. , Salazar-Villanea S. , Uribarri J.
Published: April 2020

Increasing clinical and experimental evidence accumulated during the past few decades supports an important role for dietary advanced glycation endproducts (AGE) in the pathogenesis of many chronic non-infectious diseases, such as type 2 diabetes, CVD and others, that are reaching epidemic proportions in the Western world. Although AGE are compounds widely recognised as generated in excess in the body in diabetic patients, the potential importance of exogenous AGE, mostly of dietary origin, has been largely ignored in the general nutrition audience. In the present review we aim to describe dietary AGE, their mechanisms of formation and absorption into the body as well as their main mechanisms of action. We will present in detail current evidence of their potential role in the development of several chronic non-infectious clinical conditions, some general suggestions on how to restrict them in the diet and evidence regarding the potential benefits of lowering their consumption.
Coping and Suicide in College Students
Authors: Yi Shangwen , Chang Edward C. , Chang Olivia D. , Seward Noelle J. , McAvoy Leah B. , Krause Emmaleigh R. , Schaffer Miranda R. , Novak Claire J. , Ip Ka , Hirsch Jameson K.
Published: April 2020

Abstract. Background: Transitioning to college life in young adulthood can represent a challenging developmental period and college students are at heightened risk for engaging in suicidality. Aims: We aimed to investigate the roles dispositional optimism and coping strategies play in suicide risk (viz., suicidality) and suicide protection (viz., reasons for living) in college students. Method: A sample of 252 American college students were surveyed using anonymous questionnaires and hierarchical regression analyses were conducted to analyze the data. Results: Coping strategies, as a set, played an important role in both suicidality and reasons for living, after controlling for demographic factors (age and sex). When dispositional optimism was entered into the model, it was found to account for a significant amount of additional unique variance in both suicidality and reasons for living, even after accounting for coping. Limitations: It is unknown whether optimism remains meaningful in its association with suicide risk and protection beyond coping in other populations. Conclusion: Effective coping and optimism are associated with decreased suicide risk and increased suicide protection. Our findings point to the consistent role of dispositional optimism, over coping, in both suicide risk and protection.
Author Correction: The balance of metagenomic elements shapes the skin microbiome in acne and health
Authors: Barnard Emma , Shi Baochen , Kang Dezhi , Craft Noah , Li Huiying
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A carboxylate-assisted amination/unactivated C(sp2)–H arylation reaction via a palladium/norbornene cooperative catalysis
Authors: An Yang , Zhang Bo-Sheng , Zhang Zhe , Liu Ce , Gou Xue-Ya , Ding Ya-Nan , Liang Yong-Min
Published: April 2020

A carboxylate-assisted palladium-catalysed Catellani reaction, which is compatible with ortho-amination and unactivated C(sp2)–H arylation, synthesized a series of 1-amino substituted dihydrophenanthridines, phenanthridines and 6H-benzo[c]chromenes.
Iron assisted formation of CO2 over condensed CO and its relevance to interstellar chemistry
Authors: Methikkalam Rabin Rajan J. , Ghosh Jyotirmoy , Bhuin Radha Gobinda , Bag Soumabha , Ragupathy Gopi , Pradeep Thalappil
Published: April 2020

Catalytic conversion of CO to CO2 assisted by neutral iron atoms has been investigated in ultrahigh vacuum (UHV) under cryogenic conditions (10 K).
A photothermal-hypoxia sequentially activatable phase-change nanoagent for mitochondria-targeting tumor synergistic therapy
Authors: Qu Jia , Teng Dengke , Sui Guoqing , Guan Shihui , Wang Yang , Wang Qimeihui , Lin Yuanqiang , Ran Haitao , Wang Zhigang , Wang Hui
Published: April 2020

The advantages of PCM@Lip/IT NPs include mitochondrial-targeting, on-demand drug release, and prodrug activation by hypoxia with guidance/monitoring by PA and FL imaging.
Development of new self-assembled cationic amino liposomes for efficient gene delivery
Authors: Wu Yihang , Xiong Yue , Wang Ling , Zhou Quanming , Li Linxian , Levkin Pavel A. , Davidson Gary , Gao Liqian , Deng Wenbin
Published: April 2020

A library of lipidoids self-assembling to liposomes exhibits excellent transfection efficiency in HEK 293T cells and mESCs with low cytotoxicity.
A general platinum-catalyzed alkoxycarbonylation of olefins
Authors: Yang Ji , Liu Jiawang , Ge Yao , Huang Weiheng , Schneider Carolin , Dühren Ricarda , Franke Robert , Neumann Helfried , Jackstell Ralf , Beller Matthias
Published: April 2020

Herein, we report the first efficient platinum-catalysed alkoxycarbonylations of olefins including sterically hindered and functionalized ones. This atom-efficient catalytic transformation provides straightforward access to a variety of valuable esters.
Co3O4 nanoparticles embedded in nitrogen-doped graphitic carbon fibers as a free-standing electrode for promotion of lithium ion storage with capacitive contribution
Authors: Chen Yangshen , Wu Tianyu , Chen Wanzheng , Zhang Wenhui , Zhang Lulu , Zhu Zeyu , Shao Meng , Zheng Bing , Li Sheng , Zhang Weina , Pei Wen-Bo , Wu Jiansheng , Huo Fengwei
Published: April 2020

Co3O4@NGFs can alleviate volumetric expansion, facilitate rapid electron transfer and achieve a high lithium storage capacity during the surface- and diffusion-controlled capacitive processes.
Beyond temperature: controlling collagen fibrillogenesis under physiological conditions via interaction with cucurbit[7]uril
Authors: Xie Qiuping , Hou Delong , Chang Jinming , Xu Zhou , Zeng Qi , Wang Zhonghui , Chen Yi
Published: April 2020

A supramolecular strategy as efficient as temperature that enabled facile control over collagen fibrillogenesis under physiological conditions was reported.
Microscope laser assisted photooxidative activation of bioorthogonal ClickOx probes
Authors: Kormos Attila , Kern Dóra , Egyed Alexandra , Söveges Bianka , Németh Krisztina , Kele Péter
Published: April 2020

A photoactivatable fluorogenic tetrazine-rhodaphenothiazine probe was synthesized and studied in light-assisted, bioorthogonal labeling schemes.
Reactivity of borohydride incorporated in coordination polymers toward carbon dioxide
Authors: Kadota Kentaro , Sivaniah Easan , Horike Satoshi
Published: April 2020

Borohydride-containing coordination polymers convert CO2 into formate or formylhydroborate depending on their crystal structures.
A competitive coordination-based immobilization-free electrochemical biosensor for highly sensitive detection of arsenic(v) using a CeO2–DNA nanoprobe
Authors: Yang Limin , An Bin , Yin Xuehan , Li Feng
Published: April 2020

A competitive coordination-based immobilization-free electrochemical biosensor was developed for highly sensitive detection of arsenic(v) using a CeO2–DNA nanoprobe.
A water-soluble pyrazino[2,3-g]quinoxaline photosensitizer for high-efficiency one- and two-photon excited bioimaging and photodynamic therapy
Authors: Zhang Li-Peng , Li Xianqiang , Liu Tianlong , Kang Lin , Huang Xing , Zhao Yuxia
Published: April 2020

A water-soluble pyrazino[2,3-g]quinoxaline photosensitizer was synthesized and exhibited excellent performance for both one- and two photon excited bioimaging and photodynamic therapy.
TheCSDand knowledge databases: from answers to questions
Authors: Shevchenko Alexander P. , Eremin Roman A. , Blatov Vladislav A.
Published: April 2020

We develop tools for extracting new information on crystal structures from crystallographic databases and show how to use these tools in the design of coordination compounds.