bluuebunny/crossref_metadata_2025 huggingface dataset:
Supramolecular Nanogel‐Based Universal Drug Carriers Formed by “Soft–Hard” Co‐Assembly: Accurate Cancer Diagnosis and Hypoxia‐Activated Cancer Therapy
Authors: Zhang Xiaodong , Chen Xiaokai , Wang Hong‐Yin , Jia Hao‐Ran , Wu Fu‐Gen
Published: February 2019

The development of multifunctional drug delivery systems (DDSs) capable of carrying various drugs for diverse disease treatments is highly desirable yet remains challenging. Taking advantage of the excellent properties of silicon‐containing nanodots (SiNDs), a self‐traceable nanogel‐based DDS formed by the co‐assembly of a “soft” copolymer and a “hard” fluorescent SiND is developed, which has tunable size/fluorescence, high encapsulation efficiencies (60–92%) for various small molecule drugs, and pH‐responsive drug release capability. As a proof of concept, 5‐aminolevulinic acid, a hydrophilic prodrug of protoporphyrin IX (PpIX), and tirapazamine (TPZ), a water‐soluble hypoxia‐responsive drug, are successfully and stably encapsulated into the nanogels. The drug‐loaded green‐emissive nanogels achieve the selective biosynthesis of red‐fluorescent PpIX in tumors and can serve as a ratiometric probe for accurate cancer diagnosis. Moreover, the in situ synthesized PpIX can consume oxygen to produce toxic singlet oxygen in the tumor microenvironment under light irradiation, thus activating the hypoxia‐dependent cytotoxicity of TPZ. Thanks to the less PpIX production and the neutral/normoxic environment in normal tissues, the nanoagents elicit negligible toxicity to normal cells even under light irradiation. Overall, this work develops a novel strategy for constructing a series of smart nanogels as universal DDSs and realizes precision cancer theranostics.
Cowpea Mosaic Virus Promotes Anti‐Tumor Activity and Immune Memory in a Mouse Ovarian Tumor Model
Authors: Wang Chao , Fiering Steven N. , Steinmetz Nicole F.
Published: February 2019

Cowpea mosaic virus (CPMV) is a promising platform nanotechnology with applications as a cancer therapeutic. To understand the therapeutic potential of CPMV in more detail, its antitumor mechanisms are investigated using a syngeneic immunocompetent murine orthotopic ovarian cancer model (ID8‐Defb29/Vegf‐A). CPMV treatment in situ promotes tumor regression and prevents tumor recurrence. Although CPMV does not kill tumor cells directly, it promotes an intra‐tumoral cytokine response which induces pre‐existing myeloid cells to break immunotolerance and initiate antitumor responses. The upregulation of interleukin‐6 and interferon‐γ as well as the downregulation of IL‐10 and transforming growth factor β are observed, associated with activation and repolarization of tumor‐associated macrophages and neutrophils to an anti‐tumor phenotype. Furthermore, the in situ administration of CPMV recruits dendritic cells and natural killer cells to the tumor site, and induces the expression of costimulatory molecules on CD11b– myeloid cells. By converting immunosuppressive myeloid cells into potent antigen‐presenting cells, in situ CPMV treatment significantly improves effector and memory CD4+ and CD8+ T cell responses and promoted systemic tumor‐specific cytotoxic CD8+ T cell activity. CPMV in situ immunotherapy induces significant tumor control in an aggressive ovarian tumor model by coordinating innate and adaptive immune responses involving neutrophils, macrophages, and T cells.
Thermal Fluctuations and Dynamic Modeling of a dAFM Cantilever
Authors: Pierro Elena , Bottiglione Francesco , Carbone Giuseppe
Published: February 2019

The Brownian thermal noise which affects the cantilever dynamics of a dynamic atomic force microscope (dAFM) is discussed, both when it works in air and in presence of water. The relationship between the cantilever thermal fluctuations and its interactions with the surrounding liquid is investigated, and an analytical model to describe the interaction forces is presented. The novelty of this approach is that a very simple integral expression to describe fluid–cantilever interactions is found. More specifically, besides including fluid inertia and viscosity, an additional diffusivity term needs to be considered, whose crucial influence for the correct evaluation of the cantilever response to the thermal excitation is shown. The coefficients of the model are obtained by using numerical results for a 2D fluid flow around a vibrating rectangular cross section, so that the dynamics of a dAFM cantilever can be characterized when it also operates in tilted conditions. The analytical model is validated by comparison with numerical and experimental data previously presented in literature, and with experiments carried out by the authors. It is shown that the present model can provide an extremely accurate prediction of the beam response up and beyond the second resonant peak.
Label‐Free Multiphoton Endomicroscopy for Minimally Invasive In Vivo Imaging
Authors: Dilipkumar Ashwathama , Al‐Shemmary Alaa , Kreiß Lucas , Cvecek Kristian , Carlé Birgitta , Knieling Ferdinand , Gonzales Menezes Jean , Thoma Oana‐Maria , Schmidt Michael , Neurath Markus F. , Waldner Maximilian , Friedrich Oliver , Schürmann Sebastian
Published: February 2019

Multiphoton microscopy of cellular autofluorescence and second harmonic generation from collagen facilitates imaging of living cells and tissues without the need for additional fluorescent labels. Here, a compact multiphoton endomicroscope for label‐free in vivo imaging in small animals via side‐viewing needle objectives is presented. Minimal invasive imaging at cellular resolution is performed in colonoscopy of mice without surgical measures and without fluorescent dyes as a contrast agent. The colon mucosa is imaged repeatedly in the same animal in a mouse model of acute intestinal inflammation to study the process of inflammation at the tissue level within a time period of ten days, demonstrating the capabilities of label‐free endomicroscopy for longitudinal studies for the first time.
Highly Stable Oxygen Electrodes Enabled by Catalyst Redistribution through an In Situ Electrochemical Method
Authors: Liu Bin , Xu Wu , Luo Langli , Zheng Jianming , Ren Xiaodi , Wang Hui , Engelhard Mark H. , Wang Chongmin , Zhang Ji‐Guang
Published: February 2019

In this work, for the first time an in situ electrochemical pretreatment approach to fabricate a highly reversible oxygen electrode with redistributed ultrafine RuO2 catalysts on a carbon nanotube (CNT) matrix is reported. The optimally pretreated RuO2/CNT oxygen electrodes demonstrate an extremely stable cycling life, 800 times with non‐Li metal anode, under a capacity‐limited protocol of 800 mAh g−1 in an ether‐based electrolyte in an O2 environment. The highly stable activity of ultrafine RuO2 catalysts in oxygen reduction and evolution processes originates from the synergetic effect of greatly reduced size of catalyst (<2 nm) and uniform redistribution of catalyst particles after the in situ electrochemical pretreatment process. The pretreatment method discovered in this work can not only significantly enhance the activity/efficiency of the catalysts used for air electrodes but can also be widely applied to other electro‐catalysis systems.
Hydrous RuO2‐Decorated MXene Coordinating with Silver Nanowire Inks Enabling Fully Printed Micro‐Supercapacitors with Extraordinary Volumetric Performance
Authors: Li Hongpeng , Li Xiran , Liang Jiajie , Chen Yongsheng
Published: February 2019

The fabrication of fully printable, flexible micro‐supercapacitors (MSCs) with high energy and power density remains a significant technological hurdle. To overcome this grand challenge, the 2D material MXene has garnered significant attention for its application, among others, as a printable electrode material for high performing electrochemical energy storage devices. Herein, a facile and in situ process is proposed to homogeneously anchor hydrous ruthenium oxide (RuO2) nanoparticles on Ti3C2Tx MXene nanosheets. The resulting RuO2@MXene nanosheets can associate with silver nanowires (AgNWs) to serve as a printable electrode with micrometer‐scale resolution for high performing, fully printed MSCs. In this printed nanocomposite electrode, the RuO2 nanoparticles contribute high pseudocapacitance while preventing the MXene nanosheets from restacking, ensuring an effective ion highway for electrolyte ions. The AgNWs coordinate with the RuO2@MXene to guarantee the rheological property of the electrode ink, and provide a highly conductive network architecture for rapid charge transport. As a result, MSCs printed from the nanocomposite inks demonstrate volumetric capacitances of 864.2 F cm−3 at 1 mV s−1, long‐term cycling performance (90% retention after 10 000 cycles), good rate capability (304.0 F cm−3 at 2000 mV s−1), outstanding flexibility, remarkable energy (13.5 mWh cm−3) and power density (48.5 W cm−3).
Strategies for interfacial localization of graphene/polyethylene‐based cocontinuous blends for electrical percolation
Authors: Mun Sung Cik , Kim Min Jae , Cobos Mónica , Gu Liangliang , Macosko Christopher W.
Published: February 2019

We have investigated melt blending approaches to interfacial localization of few‐layer graphene in cocontinuous polymer blends with polyethylene as one of the components. When linear low‐density polyethylene (LLDPE)/polypropylene (PP) or high‐density polyethylene (HDPE)/polylactic acid (PLA) and graphene were mixed all together, graphene preferred polyethylene over PP or PLA. When PP and graphene were premixed and blended with polyethylene, some graphene was trapped at the blend interface but not enough to cover the large interfacial area. In contrast, an ultralow electrical percolation was achieved (< 0.1 vol%) in HDPE/PLA blend due to smaller interfacial area. In another approach, polystyrene was added as a tertiary minor component to HDPE/PLA blends. This continuous interfacial layer containing graphene led to a low electrical percolation threshold (< 0.2 vol%). From these investigations, we suggest general ways to reduce a percolation threshold by kinetic control of the morphology of cocontinuous polymer blends.
Gain scheduling PID control for directed self‐assembly of colloidal particles in microfluidic devices
Authors: Gao Yu , Lakerveld Richard
Published: February 2019

Directed self‐assembly provides a promising route to fabricate small‐scale structures for various engineering applications. The use of the external fields of variable strength and frequency allows for active controls to be implemented. For assembling specific structural features, precise control over a local particle density is often needed, which can be achieved using feedback control. However, the strong nonlinear behavior of directed self‐assembly complicates such control. In this work, a gain‐scheduling feedback control strategy for directed self‐assembly of colloidal particles is presented. The process gain is described by an empirical steady‐state model, which is used for scheduling a proportional‐integral feedback controller. The automated controller is implemented experimentally in a microfluidic device for directed self‐assembly of colloidal particles. The gain‐scheduled controller shows a significantly improved dynamic performance compared with a conventional proportional‐integral controller over a broad range of operating parameters.
Fitness benefits and costs of floral advertising traits: insights from rayed and rayless phenotypes ofAnacyclus(Asteraceae)
Authors: Cerca José , Agudo Alicia B. , Castro Sílvia , Afonso Ana , Alvarez Inés , Torices Rubén
Published: February 2019

Premise of the Study

Ray flowers commonly observed in daisies’ flowering heads are a well‐known example of advertising structures for enhancing pollinator attraction. Despite this, ray loss has occurred in multiple lineages, which still rely on pollinators, suggesting that rayless phenotypes could also be adaptive for animal‐pollination. Here, we investigate the benefits and costs of these specialized floral advertising structures by comparing rayed and rayless phenotypes in two hybridizing closely related species.

Methods

We assessed the advantages and costs of ray production in terms of floral visitor's attraction, pollen limitation, and female reproductive success using the broad natural variation on ray size and number at the contact zone ofA. clavatus(rayed) andA. valentinus(rayless). In addition, we experimentally explored the effect of rays under controlled neighborhoods and the effect of ray removal on fruit production.

Key Results

In sympatry, rayed phenotypes attracted significantly more visitors than rayless plants, in which seed production was pollen limited. However, rayed phenotypes did not show higher fruit set or seed production than rayless phenotypes. Fruit set and seed production benefited from denser neighborhood displays and larger individual floral displays, respectively. The removal of ray florets did not appear to enable resource reallocation to fruit production.

Conclusions

Rayless heads compensated their lower visitation rate by means of a higher number of flowers per head achieving similar fecundity levels to rayed plants. The larger size of rayless heads might thus indicate an inflorescence‐level trade‐off between attraction and fertility.
A 2q24.2 microdeletion containing TANK as novel candidate gene for intellectual disability
Authors: Karoglan Ante , Schanze Denny , Bär Claudia , Muschke Petra , Zenker Martin , Schanze Ina
Published: February 2019

Interstitial deletions within the chromosomal region 2q24.2 have already been linked to intellectual disability (ID) in the past. In most cases the described patients showed a syndromic form of ID associated with large deletions containing multiple genes. Here we describe a family with two siblings with mild non‐syndromic ID. They shared the same 564 kb deletion in the chromosomal region 2q24.2 containing only the TANK gene, which was inherited from the similarly affected father, thus suggesting haploinsufficiency of TANK as a novel cause of non‐syndromic ID. TANK encodes the TRAF family member‐associated NF‐kappa‐B activator (OMIM #603893), which is expressed in many tissues. It functions as an adapter protein that interacts with the NF‐kappa‐B pathway and SOX11, an essential transcription factor in regeneration, survival and differentiation of the neuronal system. TANK has not been linked to ID or other human diseases before. To further elucidate the role of TANK in non‐syndromic ID, we screened a cohort of 288 TANK deletion negative non‐syndromic mental retardation patients for TANK mutations without identifying any pathogenic variant.
Achieving the targets of sustainable development goals (2030 agenda) for congenital disorders in Asia: Bottlenecks and interventions
Authors: Thong Meow‐Keong
Published: February 2019

The United Nations General Assembly adopted the 2030 Agenda for Sustainable Development in November 2015 which included a set of 17 measurable “sustainable development goals” (SDGs). The SDGs included targets to end preventable deaths of newborns and children under 5 years of age by 2030, universal health care coverage, reduction of premature mortality from noncommunicable diseases (NCDs) by 33% as well as support the development and research for medicines for both communicable and NCDs. Although some successes were achieved in combating communicable diseases and improved childhood mortality rates, health systems in Asia are generally characterized by lack of accurate epidemiological information on congenital disorders, lack of human and financial resources, and inadequate focus on public health strategies to ensure targeted interventions, low level knowledge on congenital disorders amongst the community and healthcare providers and the ethical dilemma of managing rare congenital disorders in an environment of low national health expenditures. These bottlenecks must be addressed systematically and interventions such as the use of innovative epidemiological tools to overcome lack of data, increased efforts to standardize rare disease nomenclature and classification and renewed interest in birth defects registries by countries in the region must be considered. Targeted curative and public health approaches currently used in thalassaemia and neural tube defects may be used for other congenital disorders in Asian countries. The implementation of congenital disorders‐related research, prevention, care, and treatment delivery services must be integrated into existing health systems in order to be effective to achieve the targets of SDG2030.
Investigating the effect of endocranial volume on cranial shape in platyrrhines and the relevance of this relationship to interpretations of the fossil record
Authors: Halenar‐Price Lauren , Tallman Melissa
Published: February 2019

Objectives

Fossils have been linked to Alouatta based on shared cranial morphology and small brain size. However, the relationship between endocranial volume and cranial shape is unclear; it is possible that any platyrrhine with a small brain may exhibit “Alouatta‐like” features due to being “de‐encephalized.” We test two hypotheses: (a) there are aspects of cranial shape related to encephalization common to all platyrrhines; (b) it is these cranial traits that unite the small‐brained “Alouatta‐like” fossils.

Materials and methods

Three‐dimensional cranial shape and endocranial volume (ECV) were measured on 350+ extant platyrrhine crania, Cartelles, Paralouatta, and Antillothrix. Encephalization quotient (EQ) was calculated using regressions of ECV on cranial centroid size. Multivariate regressions were performed using the shape coordinates and EQ and shape changes associated with EQ were visualized. Cranial shape was predicted for a hypothetical primate with an EQ matching the fossils and this shape was compared to the Alouatta mean.

Results

There is a significant proportion of cranial shape variation explained by EQ in some taxa. The aspects of shape that are correlated with EQ are shared by several taxa and some have parallel regression vectors, but there is no overall pattern of shape change common to all platyrrhines. However, all taxa look more similar to Alouatta when their EQ is decreased, particularly Pithecia.

Discussion

Given that a decrease in encephalization can cause a more Alouatta‐like cranial shape in many extant platyrrhines, it should not be automatically assumed that Alouatta‐like cranial traits in a small‐brained fossil are evidence of a phylogenetic link to the alouattin clade.
Accumulation of prion protein in the vagus nerve in creutzfeldt–jakob disease
Authors: Kresl Philip , Rahimi Jasmin , Gelpi Ellen , Aldecoa Iban , Ricken Gerda , Danics Krisztina , Keller Eva , Kovacs Gabor G.
Published: February 2019

Disease‐associated proteins are thought to propagate along neuronal processes in neurodegenerative diseases. To detect disease‐associated prion protein (PrPSc) in the vagus nerve in different forms and molecular subtypes of Creutzfeldt–Jakob disease (CJD), we applied 3 different anti‐PrP antibodies. We screened the vagus nerve in 162 sporadic and 30 genetic CJD cases. Four of 31 VV‐2 type sporadic CJD and 7 of 30 genetic CJD cases showed vagal PrPSc immunodeposits with distinct morphology. Thus, PrPSc in CJD affects the vagus nerve analogously to α‐synuclein in Parkinson disease. The morphologically diverse deposition of PrPSc in genetic and sporadic CJD argues against uniform mechanisms of propagation of PrPSc. Ann Neurol 2019;85:782–787
Rethinking interhemispheric imbalance as a target for stroke neurorehabilitation
Authors: Xu Jing , Branscheidt Meret , Schambra Heidi , Steiner Levke , Widmer Mario , Diedrichsen Jörn , Goldsmith Jeff , Lindquist Martin , Kitago Tomoko , Luft Andreas R. , Krakauer John W. , Celnik Pablo A. ,   the SMARTS Study Group
Published: February 2019

Objective

Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition (IHI) from the intact to the damaged hemisphere before movement execution (premovement IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal premovement IHI is causal to poor behavioral outcome and should therefore be present early after stroke when motor impairment is at its worst. To test this idea, in a longitudinal study, we investigated interhemispheric interactions by tracking patients’ premovement IHI for one year following stroke.

Methods

We assessed premovement IHI and motor behavior five times over a 1‐year period after ischemic stroke in 22 patients and 11 healthy participants.

Results

We found that premovement IHI was normal during the acute/subacute period and only became abnormal at the chronic stage; specifically, release of IHI in movement preparation worsened as motor behavior improved. In addition, premovement IHI did not correlate with behavioral measures cross‐sectionally, whereas the longitudinal emergence of abnormal premovement IHI from the acute to the chronic stage was inversely correlated with recovery of finger individuation.

Interpretation

These results suggest that interhemispheric imbalance is not a cause of poor motor recovery, but instead might be the consequence of underlying recovery processes. These findings call into question the rehabilitation strategy of attempting to rebalance interhemispheric interactions in order to improve motor recovery after stroke. Ann Neurol 2019;85:502–513
Derivation and Validation of a Major Toxicity Risk Score Among Nonsteroidal Antiinflammatory Drug Users Based on Data From a Randomized Controlled Trial
Authors: Solomon Daniel H. , Shao Ming , Wolski Kathy , Nissen Steven , Husni M. Elaine , Paynter Nina
Published: February 2019

Objective

While nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used in rheumatology, they can cause major toxicity. Improving the risk/benefit ratio requires a more precise understanding of risk. This study was undertaken to derive and validate a risk score for major toxicity among NSAID users enrolled in a randomized controlled trial.

Methods

Patients enrolled in a randomized controlled trial who had known cardiovascular disease or risk factors as well as osteoarthritis or rheumatoid arthritis were divided into derivation and validation cohorts. Patients were randomized to receive celecoxib, naproxen, or ibuprofen at typical dosages. The risk score was designed to predict the 1‐year occurrence of major toxicity among NSAID users, including major adverse cardiovascular events, acute kidney injury, significant gastrointestinal events, and mortality. Variables significantly associated with major toxicity were candidates for inclusion in the final regression model. After derived models were found to have a similar model fit in the validation set, the cohorts were combined, allowing calculation of a risk score.

Results

In the derivation cohort, significant variables included age, male sex, history of cardiovascular disease, hypertension, diabetes mellitus, tobacco use, statin use, elevated serum creatinine level, hematocrit level, and type of arthritis. The C‐index was 0.73 in the validation cohort and 0.71 in the total cohort; the model was well calibrated. Of the total population with complete data (n = 23,735), 1,080 participants (4.6%) had a predicted 1‐year risk of major toxicity of <1%, 16,273 (68.6%) had a predicted risk of 1–4%, and 6,382 (26.9%) had a predicted risk of >4%.

Conclusion

The risk score accurately categorizes the 1‐year risk of major toxicity among NSAID users and may be useful in identifying patients who can safely use these agents.
Rainwater harvesting potential in a semiarid Southern California city
Authors: Summerville Nathaniel , Sultana Rebeka
Published: February 2019

To determine the rainwater capture potential in a small residential city located in semiarid Southern California, a model of the city's existing storm drainage system was developed using a watershed management model based on the U.S. Environmental Protection Agency's storm water management model. The model analyzes the effect of (1) 2‐ and 10‐year 24‐h storms and (2) dry, average, and wet climatic conditions under five different scenarios, considering (1) single rain barrel, (2) 5 rain barrels, (3) 7 rain barrels, (4) 10 rain barrels, and (5) a storage tank in each residential lot. Results show that, due to its fixed capacity, rain barrel(s) can only save a limited amount of water. A storage tank per lot increases rainwater capture efficiency, which can collect 19% of city's annual reclaimed water volume in an average climatic year. However, storage tanks can only be cost‐effective to residents through financial supports from local agencies.
Birth prevalence of orofacial clefts among perinatal infants: A register‐based study in Bao'an district, Shenzhen, China
Authors: Luo Ya Li , Wang Wei , Gao Xiao Hui , Huang Yue Hua , Xu Quan , Cheng Yu Li
Published: February 2019

Background

The birth prevalence of orofacial clefts (OFCs) has been widely studied, but results are considerable varied, and epidemiological studies in southern China are few in numbers. To address this gap, we carried out a register‐based study to estimate the birth prevalence of OFCs in Bao'an district, Shenzhen, China.

Methods

Data of perinatal infants born between 2003 and 2017 were extracted from Shenzhen Maternal and Child Health Management System. The overall OFCs birth prevalence with 95% confidence interval (CI) as well as subgroup analysis based on selected demographic factors was conducted. Cochran–Armitage trend tests were applied to evaluate the time trend by 5‐year intervals.

Results

The overall birth prevalence of OFCs, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) was 1.30 (95% CI 1.21–1.39), 1.00 (95% CI 0.92–1.08), and 0.30 (95% CI 0.25–0.34) per 1,000 births, respectively. An overall declining tendency was observed in the OFCs (from 1.83 to 1.04 per 1,000 births), specifically CL/P (from 1.53 to 0.69 per 1,000 births) birth prevalence over 5‐year intervals, with statistical significance (p < 0.01). Subgroup analysis revealed that the CL/P and CPO birth prevalence was differed by infant gender, household registration, maternal age, and parity.

Conclusion

Our findings had firstly reported the birth prevalence of OFCs in Bao'an district, and might help other researchers to plan more comprehensive public health strategies to reduce the occurrence of OFCs in further generation.
Die Wiener Hirnforschung und die Entstehung des österreichischen Positivismus
Authors: Hlade Josef
Published: February 2019

Viennese Brain Research and the Formation of Austrian Positivism. In this paper, I want to argue that the Vienna School of Medicine and especially the Viennese Brain Anatomy had an impact on the formation of the Austrian positivism. I argue that Carl von Rokitansky's (1804–1878) doctrine that psychological phenomena must be translated into anatomical facts and Theodor Meynert's (1833–1892) theory of brain functions served as one basis for the formation of the Austrian positivism. In this sense, two of the main early positivistic thinkers, Ernst Mach (1838–1916) and Richard Wahle (1857–1935), used Meynert's brain theory to argue for a bundle view of the Self. Friedrich Jodl (1849–1914) also thought about his theory, and even Moritz Schlick (1882–1936) who demanded a ‘reduction of the psychology to the brain physiology’ grappled with this approach. Meynert, a scholar of Rokitansky, the founder of the Vienna School of Medicine, was a leading figure in the history of neurology and has made several significant contributions to this discipline. He argues that the Self does not exist from an anatomical point of view. As Richard Wahle tells us, Meynert's theory of the brain functions was widely accepted under the brain researchers by the end of the nineteenth century and at the beginning of the twentieth century. He makes clear that brain researchers did in common refer to Meynert's theory to explain psychical functions as brain functions. He says from their point of view there was no doubt about it. Mach talks about Meynert's theory in Erkenntnis und Irrtum. There he says that Meynert's brain theory explains the nature and conditions of the consciousness. Michael Hagner argues that Mach's “Das Ich ist unrettbar” is hardly imaginable without the cerebral embedding of the mental functions.
Afrika im Blick der akademischen Welt der DDR. Ein wissenschaftsgeschichtlicher Überblick der afrikabezogenen Ethnographie
Authors: van der Heyden Ulrich
Published: February 2019

Africa in the View of the Academic World of the GDR: An Overview of the History of African Ethnography. Ethnography – also referred to as ethnology by the GDR – was a “minor subject” in which typical big science problems such as mass‐study and large‐scale research played no role. It was therefore not the focus of science policy interventions by the state and/or its ruling party. Nevertheless, ethnographic research, exemplified by the sub‐discipline related to Africa, remained within the limits set by the state and ruling party. Despite of these relative restrictions, the two East German universities in Berlin and Leipzig, as well as the ethnological museums in Leipzig and Dresden, have succeeded in presenting research results that are relevant and remain valid to the present day.
Ein Haus für Pettenkofer. Wissenschaftliche Traditionspflege in München 1902–1962
Authors: Schütz Mathias
Published: February 2019

A House for Pettenkofer. Cultivation of a Scientific Tradition in Munich, 1902–1962. The article deals with three attempts to preserve the memory as well as the scientific heritage of Max von Pettenkofer, made by his successors at the University of Munich's Institute of Hygiene, Max von Gruber, Karl Kisskalt, and Hermann Eyer. All of those scientific memorials were supposed to take the form of a building: an interdisciplinary center of science and education in the city of Munich, an outpost of the Institute of Hygiene in Pettenkofer's birthplace in rural Bavaria, and a new building for the institute itself. The effort to establish such a place of memory and emulation were driven, on the one hand, by Pettenkofer's downright mythical reputation as the man who not only had established a new scientific field but saved Munich from dirt and pestilence; on the other hand, it was motivated by his successors’ respective understanding of which aspects of Pettenkofer's legacy were worth preserving as well as helpful in order to advance their own scientific and institutional standing – a calculation which turned out to be still valid and compelling more than half a decennium after Pettenkofer's death.
Der Klassische Archäologe Hermann Thiersch (1874–1939) und der Erwerb der Basler Papyrussammlung im Jahr 1899/1900
Authors: Huebner Sabine R.
Published: February 2019

The Classical Archaeologist Hermann Thiersch (1874–1939) and the Acquisition of the Basel Papyrus Collection in 1899/1900. During the winter of 1899/1900, the young archaeologist Hermann Thiersch traveled to Cairo to purchase papyri for the universities in Basel, Strasbourg, and Munich. By this point, European and North American collectors and researchers were racing to discover the finest material either for their own archaeological excavations or by purchasing papyri from local antiquities dealers who were generally supplied with material by looters. This article examines the acquisition of the Basel papyrus collection in the context of the great ‘papyrus rush’ that was in full swing. It also offers an insight into the collaboration of European archaeologists and classicists working in Egypt at the turn of the twentieth century.
Gene‐Centric Metagenome Analysis Reveals Gene Clusters for Carbon Monoxide Conversion and Validates Isolation of a Clostridial Acetogen for C2 Chemical Production
Authors: Kang Hyunsoo , Park Byeonghyeok , Bolo Nicole R. , Pathiraja Duleepa , Park Shinyoung , Cha Minseok , Choi In‐G. , Chang In S.
Published: February 2019

Syngas fermentation is largely dependent on acetogens that occur in various anaerobic environmental samples including soil, sediment, and feces. Here the authors report the metagenomic isolation of acetogens for C2 chemical production from syngas. Screening acetogens for C2 chemical production typically involves detecting the presence of the Wood‐Ljungdahl Pathway for carbon monoxide conversion. The authors collect samples from river‐bed sediments potentially having conditions suitable for carbon monoxide‐converting anaerobes, and enrich the samples under carbon monoxide selection pressure. Changes in the microbial community during the experimental procedure are investigated using both amplicon and shotgun metagenome sequencing. Combined next‐generation sequencing techniques enabl in situ tracking of the major acetogenic bacterial group and lead to the discovery of a 16 kb of gene cluster for WLP. The authors isolat an acetogenic clostridial strain from the enrichment culture (strain H21‐9). The functional activity of H21‐9 is confirmed by its high level of production of C2 chemicals from carbon monoxide (77.4 mM acetate and 2.5 mM of ethanol). This approach of incorporating experimental enrichment with metagenomic analysis can facilitate the discovery of novel strains from environmental habitats by tracking target strains during the screening process, combined with validation of their functional activity.
CRISPR/Cas9‐Mediated Knockout of MicroRNA‐744 Improves Antibody Titer of CHO Production Cell Lines
Authors: Raab Nadja , Mathias Sven , Alt Kerstin , Handrick René , Fischer Simon , Schmieder Valerie , Jadhav Vaibhav , Borth Nicole , Otte Kerstin
Published: February 2019

MicroRNAs (miRNAs) are noncoding RNAs that serve as versatile molecular engineering tools to improve production cells by overexpression or knockdown of miRNAs showing beneficial or adverse effects on cell‐culture performance. The genomic knockout (KO) of noncoding RNAs in Chinese hamster ovary (CHO) production cells has not been reported. However, given the significant number of miRNAs showing negative effects on CHO‐bioprocess performance and the development of clustered regularly interspaced short palindromic repeats/CRISPR‐associated proteins (CRISPR/Cas9), genome editing tools facilitate precise optimization of CHO cells via modulation of noncoding RNAs. In a previous high‐content miRNA screen, miR‐744 was identified as a potential target associated with reduced productivity. Hence, the genomic miR‐744 precursor sequence is deleted by two single guide RNA (sgRNA)‐Cas9‐mediated DNA double‐strand breaks (DSB) flanking the miR‐744 locus. After fluorescence‐activated cell sorting (FACS), clonal miR‐744 KO cell lines are recovered and three of them are confirmed as miR‐744 KOs. Impacts of CRISPR/Cas9 editing are characterized at the genetic, transcript, and phenotypic levels. During batch cultivation, antibody titers of miR‐744 KOs are significantly increased to 190–311 mg L−1 compared to a nontargeting (NT) sgRNA transfected clonal control with 156 mg L−1, pointing towards the potential of miRNA KO for cell line engineering.
Design and preparation of organic nanomaterials using self‐assembled peptoids
Authors: Battigelli Alessia
Published: February 2019

The self‐assembly and self‐organization of peptoids, peptidomimetic polymers composed of N‐substituted glycine monomers, can result in a plethora of well‐defined organic nanostructures. Such classes of nanomaterials represent highly interesting functional platforms for many applications, for example, drug delivery, sensing, and catalysis. The main advantages of using self‐assembling peptoids to engineer organic nanostructures include their chemical diversity, biocompatibility, enzymatic stability, and ease of synthesis. The goal of this review is to present a comprehensive summary of the most relevant studies regarding the self‐assembling process of peptoids into zero‐, one‐, and two‐dimensional nanostructures, with a focus on their mechanism of formation and their potential applications.
Autologous fat transplantation alters gene expression patterns related to inflammation and hypoxia in the irradiated human breast
Authors: Lindegren A , Schultz I , Sinha I , Cheung L , Khan A A , Tekle M , Wickman M , Halle M
Published: February 2019

Background

Radiation-induced fibrosis, an adverse effect of breast cancer treatment, is associated with functional and cosmetic impairment as well as surgical complications. Clinical reports suggest improvement following autologous fat transplantation, but the mechanisms underlying this effect are unknown. A global gene expression analysis was undertaken to identify genetic pathways dysregulated by radiation and evaluate the impact of autologous fat transplantation on gene expression.

Methods

Adipose tissue biopsies were taken synchronously from irradiated and contralateral non-irradiated breasts, before and 1 year after autologous fat transplantation. Whole-genome gene expression analyses were performed, and Hallmark gene set analysis used to explore the effect of radiotherapy and autologous fat transplantation on gene expression.

Results

Forty microarrays were analysed, using bilateral biopsies taken from ten patients before and after autologous fat transplantation. Forty-five pathways were identified among the 3000 most dysregulated transcripts after radiotherapy in irradiated compared with non-irradiated breast (P ≤ 0·023; false discovery rate (FDR) no higher than 0·026). After autologous fat transplantation, 575 of the 3000 genes were again altered. Thirteen pathways (P ≤ 0·013; FDR 0·050 or less) were identified; the top two canonical pathways were interferon-γ response and hypoxia. Correlative immunohistochemistry showed increased macrophage recruitment in irradiated tissues.

Conclusion

The present findings contribute to understanding of how autologous fat transplantation can ameliorate radiation-induced fibrosis. This further supports the use of autologous fat transplantation in the treatment of radiation-induced fibrosis.
Diagnostic performance of MRI for assessment of response to neoadjuvant chemoradiotherapy in oesophageal cancer
Authors: Vollenbrock S E , Voncken F E M , van Dieren J M , Lambregts D M J , Maas M , Meijer G J , Goense L , Mook S , Hartemink K J , Snaebjornsson P , ter Beek L C , Verheij M , Aleman B M P , Beets-Tan R G H , Bartels-Rutten A
Published: February 2019

Background

Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non-surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2-weighted (T2W) and diffusion-weighted (DW) MRI.

Methods

Patients with locally advanced oesophageal cancer who underwent T2W- and DW-MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five-point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW-MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated.

Results

Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W-MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW-MRI were 90–97 and 42–50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W-MRI, and 0·71, 0·70 and 0·70 on T2W + DW-MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24–0·55 on T2W-MRI to 0·55–0·71 with DW-MRI.

Conclusion

Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.
Chiral high‐performance liquid and supercritical fluid chromatographic enantioseparations of limonene‐based bicyclic aminoalcohols and aminodiols on polysaccharide‐based chiral stationary phases
Authors: Orosz Tímea , Bajtai Attila , Minh Le Tam , Tanács Dániel , Szakonyi Zsolt , Fülöp Ferenc , Péter Antal , Ilisz István
Published: February 2019

Enantioseparation of limonene‐based bicyclic 1,3‐aminoalcohols and 1,3,5‐ and 1,3,6‐aminodiols was performed by normal‐phase high‐performance liquid chromatographic and supercritical fluid chromatographic (SFC) methods on polysaccharide‐based chiral stationary phases. The effects of the composition of the mobile phase, the column temperature and the structures of the analytes and chiral selectors on retention and selectivity were investigated by normal‐phase LC and SFC technique. Thermodynamic parameters derived from selectivity–temperature‐dependence studies were found to be dependent on the chromatographic method applied, the nature of the chiral selector and the structural details of the analytes. Enantiorecognition in most cases was enthalpically driven but an unusual temperature behavior was also observed: decreased retention times were accompanied by improved separation factors with increasing temperature, i.e. some entropically driven separations were also observed. The elution sequence was determined in all cases. The separation of the stereoisomers was optimized in both chromatographic modalities.
A resting‐state study of volumetric and functional connectivity of the habenular nucleus in treatment‐resistant depression patients
Authors: Luan Shu‐xin , Zhang Lei , Wang Rui , Zhao Hua , Liu Chang
Published: February 2019

Objective

To investigate the volumetric and functional connectivity of the habenular nucleus in treatment‐resistant depression (TRD) patients using the resting‐state functional magnetic resonance imaging (rs‐fMRI) approach.

Methods

A total of 15 TRD patients, who visited the Mental Health Institute of the First Hospital Affiliated with Jilin University between August 2014 and March 2015, along with 15 normal subjects, were enrolled into this study for structural and functional imaging. Functional connectivity analysis was performed using bilateral habenular nuclei as the region of interest in contrast to whole‐brain voxels.

Results

No significant difference of absolute volume was found in bilateral habenular nuclei between TRD patients and healthy controls, or after controlling for individual total intracranial volume. However, functional connectivity analysis showed increased connectivity between the right habenular nucleus with the medial superior frontal gyrus, anterior cingulate cortex and medial orbitofrontal gyrus, and decreased connectivity with the corpus callosum in the TRD group. For the left habenular nucleus seed, the brain region with increased functional connectivity in the inferior temporal gyrus and decreased functional connectivity in the insular was found in the TRD patients.

Conclusion

Abnormal functional connectivity was present between the habenular nucleus and the default mode network in TRD patients. Dysfunction in habenular nucleus‐related circuitry for processing negative emotion might form the pathological basis for TRD. Significant asymmetric functional connectivity was also found between bilateral habenular nuclei in TRD patients. Such asymmetry suggests potentially divergent strategy for intervention on bilateral habenular nucleus regions in the future management of depression.
Influence of Alkoxy Chain Length on the Properties of Two‐Dimensionally Expanded Azulene‐Core‐Based Hole‐Transporting Materials for Efficient Perovskite Solar Cells
Authors: Truong Minh Anh , Lee Jaehyun , Nakamura Tomoya , Seo Ji‐Youn , Jung Mina , Ozaki Masashi , Shimazaki Ai , Shioya Nobutaka , Hasegawa Takeshi , Murata Yasujiro , Zakeeruddin Shaik Mohammed , Grätzel Michael , Murdey Richard , Wakamiya Atsushi
Published: February 2019

A series of two‐dimensionally expanded azulene‐core‐based π systems have been synthesized with different alkyl chain lengths in the alkoxy moieties connected to the partially oxygen‐bridged triarylamine skeletons. The thermal, photophysical, and electronic properties of each compound were evaluated to determine the influence of the alkyl chain length on their effectiveness as hole‐transporting materials (HTMs) in perovskite solar cells (PSCs). All the synthesized molecules showed promising material properties, including high solubility, the formation of flat and amorphous films, and optimal alignment of energy levels with perovskites. In particular, the derivatives with methyl and n‐butyl in the side chains retained amorphous stability up to 233 and 159 °C, respectively. Such short alkoxy chains also resulted in improved electrical device properties. The PSC device fabricated with the HTM with n‐butyl side chains showed the best performance with a power conversion efficiency of 18.9 %, which compares favorably with that of spiro‐OMeTAD‐based PSCs (spiro‐OMeTAD=2,2′,7,7′‐tetrakis[N,N‐bis(p‐methoxyphenyl)amino]‐9,9′‐spirobifluorene).
Ionic‐Liquid‐Assisted Hydrothermal Synthesis of Ag/AgBr for Photodegradation of Imidacloprid under Visible Light
Authors: Guo Dandan , Zhu Xiaoqing , Chen Sheyun , Wang Cenling , Pi Mingli , Chen Xiaoxia , Shi Yuqing , Dai Jingtao
Published: February 2019

Ag/AgBr photocatalysts are prepared by a ionic‐liquid‐assisted hydrothermal method. The as‐prepared photocatalysts are characterized by scanning electron microscopy, X‐ray powder diffraction, X‐ray photoelectron spectroscopy, Brunauer–Emmett–Teller measurement, and diffuse reflectance spectroscopy. Ag/AgBr exhibits significant photocatalytic activity toward degradation of imidacloprid under visible light. After 9 h, the conversion percentage of imidacloprid reaches 90%. Besides, the cycle performances suggest a good stability of the catalyst. The photocatalytic kinetics indicate that the degradation processes follow pseudo‐first‐order kinetics. According to the fact that electron holes •OH and •O2− greatly promote the photodegradation process, the degradation mechanism is proposed.
Computational intelligence based design of implant for varying bone conditions
Authors: Chatterjee Subhomoy , Dey Swati , Majumder Santanu , RoyChowdhury Amit , Datta Shubhabrata
Published: February 2019

The objective is to make the strain deviation before and after implantation adjacent to the femoral implant as close as possible to zero. Genetic algorithm is applied for this optimization of strain deviation, measured in eight separate positions. The concept of composite desirability is introduced in such a way that if the microstrain deviation values for all eight cases are 0, then the composite desirability is 1. Artificial neural network (ANN) models are developed to capture the correlation of the microstrain in femur implants using the data generated through finite element simulation. Then, the ANN model is used as the surrogate model, which in combination with the desirability function serves as the objective function for optimization. The optimum achievable deviation was found to vary with the bone condition. The optimum implant geometry varied for different bone condition, and the findings act as guideline for designing patient‐specific implant.