bluuebunny/crossref_metadata_2025 huggingface dataset:
The Individual as System
Authors: Kislev Shachar Freddy ,   Philosophy Documentation Center
Published: January 2020

In British Hegelianism we find, forgotten, a weighty theory of individuality. This theory remains one of the most sustained attempts in the history of philosophy to analyze the individual, not in the social or psychological sense, but as a logical-metaphysical category. The Idealist conceptualization of the individual is bound with their unconventional theory of universals, for they argued that any individual is a “concrete universal,” and vice versa. This article reconstructs the British Idealist theory of individuality, highlighting its key insights: (a) the individual is not a simple unit, but a small system with interrelated parts; (b) the individual is not simply given, but is mediated by thought; (c) the individual is the conceptual glue holding the parts together and assigning them their respective places; (d) the conceptualization of the individual lies at the intersection of logic, aesthetics and systems theory.
Ki-67 Labeling Index in Pulmonary Carcinoid Tumors: Comparison Between Small Biopsy and Resection Using Tumor Tracing and Hot Spot Methods
Authors: Boland Jennifer M. , Kroneman Trynda N. , Jenkins Sarah M. , Terra Simone B.S.P. , Xie Hao , Molina Julian , Mounajjed Taofic , Roden Anja C.
Published: January 2020

Context.—

Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied.

Objective.—

To compare Ki-67 labeling obtained on small biopsies to subsequent resection.

Design.—

Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods.

Results.—

The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki-67 labeling index was greater in resection compared with biopsy by 0.7% (P = .02). Median tumor tracing Ki-67 was lower in resection compared with biopsy by 0.5% (P < .001). Receiver-operating characteristic analysis showed similar hot spot Ki-67 cutoffs to predict atypical histology (3.5% for biopsy, 3.6% for resection; area under the curve [AUC], 0.75 and 0.74, respectively). Different optimal cutoffs were needed for tracing method based on biopsy (2.1%; AUC, 0.75) compared with resection (1.0%; AUC, 0.67).

Conclusions.—

Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult.
Interference From High-Dose Biotin Intake in Immunoassays for Potentially Time-Critical Analytes by Roche
Authors: Mrosewski Ingo , Urbank Matthias , Stauch Thomas , Switkowski Rafael
Published: January 2020

Context.—

Immunoassays using the interaction between streptavidin and biotin are used for clinical chemical analytes on platforms by many different manufacturers. The design can be susceptible to interference from high-dose biotin intake in patients, which remains an often-overlooked confounder despite recently increased awareness.

Objective.—

To evaluate an easily implementable method of in vitro biotin depletion for the removal of biotin interference in immunoassays for potentially time-critical analytes.

Design.—

A biotin stock solution was made and de-identified patient samples were spiked to reach a biotin concentration of 1.126 × 106 pg/mL, the maximum reported biotin concentration 1 to 2 hours after a single oral dose of 300 mg biotin. Then, the resulting interference in Elecsys immunoassays for cortisol, cyclosporine A, tacrolimus, digitoxin, thyroid-stimulating hormone, free triiodothyronine, free thyroxine, C-peptide, insulin, N-terminal pro-B–type natriuretic peptide, troponin T high sensitive, human immunodeficiency virus, procalcitonin, β human chorionic gonadotropin, toxoplasma immunoglobulin M, and toxoplasma immunoglobulin G was evaluated before and after biotin depletion using streptavidin particles.

Results.—

All tested immunoassays, with the exception of toxoplasma immunoglobulin M and toxoplasma immunoglobulin G, suffered from significant biotin interference. The depletion protocol removed assay interference due to biotin and produced results that were close or identical to initial prespike measurements.

Conclusions.—

Despite an increase in turnaround times, biotin adsorption is a feasible countermeasure for biotin interference in Elecsys immunoassays. Until test kits with an increased resistance to the interference from high-dose biotin intake are distributed, the evaluated protocol can provide results properly reflecting the patient's clinical condition.
Survey on Om meditation: Its effects on the human body and Om meditation as a tool for stress management
Authors: Harne Bhavna P. , Tahseen Azra A. , Hiwale Anil S. , Dhekekar Ram S.
Published: January 2020

Meditation and yoga both have positive effects on physical, as well as mental health. Om mantra chanting, a simple and easy to practice, also comes under the aspect of meditation. The “Om” mantra is also considered as the very name of the absolute. Om meditation not only affects the various parts of the brain, such as pre-frontal cortex, vagus nerve, amygdala and others but also affects the heart rate and respiratory rate. Considering the healing effects of Om meditation, through this paper, we are trying to explore all the relevant work done in the field of Om meditation. The survey includes a large number of papers covering the research previously conducted by many researchers, their results and different techniques adopted to study the effect of Om meditation on human beings. Studies on Om meditation are categorized under four different heads: Neuroimaging studies, EEG studies, evoked potentials studies and other methods studies. Even though the existing research evidenced capability of Om meditation in curing anxiety and depression, more rigorous studies with better design, with larger sample size and with different control groups are required. Especially the need to explore untouched research areas of Loud Om meditation using EEG is suggested in the paper. Furthermore, future research directions are also suggested.
El sujeto en transición, una nueva subalternidad en el teatro chileno: análisis de "Flores de papel" y "El loco y la triste"
Authors: Aylwin Cristóbal , Pizarro Granada Maite
Published: January 2020

El presente ensayo plantea mediante un análisis comparado una entrada de lectura para los textos Flores de papel, de Egon Wolff, y El loco y la triste, de Juan Radrigán. Con esto se pretende establecer una relación de equivalencia en tanto que en ambas obras la resistencia del subalterno se manifiesta a través de la configuración del espacio y del discurso marginal. Para el desarrollo de la propuesta se utilizarán algunas nociones de Mijail Bajtín, Gayatri Spivak, Enrique Luengo, Zygmunt Bauman y Georg Simmel, todas enfocadas a los poderes del discurso y a las circunstancias en que se produce la enunciación. Por encima de caracterizaciones abstractas, la idea es confirmar la presencia de un sujeto en transición que no se identifica plenamente con el bloque dominante ni con el dominado.

This essay proposes, through a comparative análisis, a reading entry for the texts Flores de papel, by Egon Wolff, and El loco y la triste, by Juan Radrigán. The idea is establishing an equivalence relationship in that in both works the resistance of the subaltern is manifested through the configuration of space and marginal discourse. For the development of the proposal will be used some notions of Mikhail Bakhtin, Gayatri Spivak, Enrique Luengo, Zygmunt Bauman and Georg Simmel, all focused on the powers of discourse and the circumstances in which the enunciation occurs. Above abstract characterizations, the idea is to confirm the presence of a subject in transition who does not fully identify with the dominant block or the dominated one.
Faverón Salvaje: Influencias de Roberto Bolaño en "Vivir abajo" de Gustavo Faverón Patriau
Authors: Pujante Cascales Basilio
Published: January 2020

Veinte años después de la publicación de Los detectives salvajes (1998) de Roberto Bolaño, el escritor peruano Gustavo Faverón Patriau publicó Vivir abajo (2018). En este artículo pretendemos, en primer lugar, analizar las características que hacen de Vivir abajo una novela ambiciosa y original dentro de la narrativa hispánica actual y, en segundo lugar, señalar las coincidencias con Los detectives salvajes y con el resto de la obra narrativa de Roberto Bolaño. Con este análisis queremos mostrar la importancia que posee, dos décadas después de su publicación, la obra cumbre del narrador chileno en la literatura latinoamericana actual. Asimismo, queremos llamar la atención sobre Vivir abajo, una obra que debe ocupar por derecho propio un puesto importante dentro del canon de la literatura hispánica.

Twenty years after the publication of Los detectives salvajes (1998) by Roberto Bolaño, the Peruvian writer Gustavo Faverón Patriau published Vivir abajo (2018). In this article, we will try, firstly, to analyze the characteristics that make Vivir abajo an ambitious and original novel within the current Hispanic fiction and, secondly, to indicate the coincidences with Los detectives salvajes and with the rest of Roberto Bolaño’s fiction. With this analysis, we want to show the influence that, two decades after its publication, the main book of the Chilean narrator still has nowadays in Latin American literature. Furthermore, we want to draw attention to Vivir abajo, a book that must occupy, in its own right, an important position within the canon of Hispanic literature.
'Felina é insinuante, embriagada y fuera de si'. La recepción de la ópera "Salomé" en Barcelona
Authors: Daufi Muñoz Alicia , Clos Soler Jordi
Published: January 2020

El presente trabajo tiene como objetivo dar a conocer cuál fue la recepción que tuvo la ópera Salomé en su estreno en la ciudad de Barcelona en 1910. Teniendo en cuenta el tipo de música de Richard Strauss y los gustos estéticos de la sociedad barcelonesa del momento, se comprende, fácilmente, que la ópera del compositor alemán tuvo un gran éxito, sobrepasando las otras obras que se estrenaron en ese mismo año. Para la realización de este estudio, se han analizado diferentes fuentes hemerográficas, con posiciones políticas distintas, y, a partir de éstas, se han podido conocer cuáles fueron las críticas que recibió la ópera Salomé, clasificándolas en diferentes categorías.

The aim of this paper is to explain how the opera Salomé was received in its premier in Barcelona in 1910. Concerning the style of Richard Strauss’s music and the aesthetic tastes shown by the Catalan society of the time, it is easy to understand the great success that the opera by the German composer attained. Such success surpassed, indeed, that of other works premiered on that same year in Barcelona. Different hemerographic sources, with different political tendencies, have been considered in the present study. All those newspapers published a variety of reviews on the opera Salomé, which will tell us how the work had been received in Barcelona.
Optical Quantum Memory and its Applications in Quantum Communication
Systems
Authors: Ma Lijun , Slattery Oliver , Tang Xiao
Published: January 2020

Optical quantum memory is a device that can store the quantum state of photons and
retrieve it on demand and with high fidelity. It is emerging as an essential device to
enhance security, speed, scalability, and performance of many quantum systems used in
communications, computing, metrology, and more. In this paper, we will specifically
consider the impact of optical quantum memory on quantum communications systems.
Following a general overview of the theoretical and experimental research progress in
optical quantum memory, we will outline its role in quantum communications, including as
a photon source, photon interference, quantum key distribution (QKD), quantum
teleportation, quantum repeater, and quantum networks.
Les pratiques d’enseignement de futures enseignantes et futurs enseignants d’histoire-géographie du secondaire au Québec : épistémologie pratique et agentivité
Authors: Boutonnet Vincent
Published: January 2020

Cette étude de cas présente les résultats de pratiques d’enseignement déclarées de quatre futurs enseignantes et enseignants d’histoire au secondaire durant un stage en blocs étalés au Québec. À la suite de la réussite de leur stage, nous avons collecté plusieurs documents et nous avons conduit une entrevue d’explicitation afin de décrire leur épistémologie pratique, ainsi que leurs dispositifs d’enseignement durant leur stage. Cette recherche se concentre sur les données issues de l’entrevue et des cartes conceptuelles réalisées dans le cadre de leur cours de didactique. Les données révèlent une tension entre le milieu de formation universitaire et le milieu de pratique durant le stage. Nous utilisons le concept d’agentivité pour explorer en quoi ces futurs enseignants et enseignantes réussissent à concilier différentes contraintes, dont l’usage du cahier d’exercices ou la pression de l’examen ministériel. En outre, nous illustrons l’évolution de leur épistémologie pratique par l’analyse de cartes conceptuelles réalisées à différents moments de la session. Ces cartes montrent que les stagiaires intègrent autant des savoirs pratiques issus du milieu que des savoirs théoriques issus de leurs cours théoriques. Nous discutons de cette épistémologie pratique au regard de l’accomplissement de leur agentivité durant le stage.
Créer une carte narrative sur Google Maps : étude du raisonnement géographique et de la cohérence textuelle chez les élèves de la 9e année secondaire
Authors: Benimmas Aïcha , Blain Sylvie
Published: January 2020

Les objectifs du présent article visent à examiner le raisonnement géographique manifesté chez des élèves de 9e année grâce à la création de cartes narratives sur Google Maps; à explorer les habiletés de ces élèves en ce qui a trait à l’utilisation de Google Maps; à estimer leur appréciation quant à l’intégration des cartes narratives au cours de géographie et à évaluer la qualité des textes qu’ils ont produits dans ces cartes narratives. Grâce à une méthode de recherche à la fois exploratoire et développementale, les cartes narratives sont examinées à l’aide de grilles d’analyse (raisonnement géographique et cohérence textuelle). Les résultats obtenus indiquent que les textes écrits sont essentiellement descriptifs et démontrent un certain raisonnement géographique relationnel avec des tentatives d’interprétation et d’explication limitées au site visuel. Si les élèves adaptent leur vocabulaire à la situation de communication, leurs textes descriptifs semblent manquer de cohérence macrostructurelle. Cependant, les élèves participants à l’étude semblent développer de nouvelles habiletés techniques sur Google Maps et apprécier l’intégration de la carte narrative au cours de géographie.
L’intervention éducative en sciences humaines et sociales au primaire à travers les zones d’ombre des discours sur les pratiques d’enseignement
Authors: Araújo-Oliveira Anderson
Published: January 2020

L’article présente une analyse du discours officiel relatif à l’enseignement des sciences humaines et sociales (SHS) au primaire. Pour ce faire, l’analyse descriptive des orientations gouvernementales sera accompagnée de l’identification d’un certain nombre de zones d’ombre (incohérences, ambiguïtés, contradictions, etc.) qui y sont sous-jacentes. Des apprentissages considérés comme étant importants à construire, mais qui ne font pas l’objet d’une évaluation, une compétence à développer considérée comme fondamentale alors qu’aucune plage horaire n’est prévue au régime pédagogique à son enseignement, des compétences centrées sur la capacité à raisonner et à argumenter alors que l’évaluation se centre davantage sur la description de connaissances factuelles n’en sont que quelques exemples. N’étant pas toujours univoques, ces orientations sont susceptibles de laisser place à des lectures et des interprétations variées sur le plan des paramètres devant présider à l’intervention éducative de l’enseignant, notamment en ce qui a trait à l’apport des SHS à la triple mission de l’école québécoise, au statut et à la place des savoirs scolaires au sein d’une approche par compétences, ainsi qu’au rôle de la démarche d’enseignement-apprentissage dans l’intervention éducative.
Effects of Flood on Food Security, Livelihood and Socio-economic Characteristics in the Flood-prone Areas of the Core Niger Delta, Nigeria
Authors: Week D. A. , Wizor C. H.
Published: January 2020

The study examined the effects of flood risk levels on food security, livelihood and socio-economic characteristics in the flood-prone areas of the core Niger Delta, Nigeria using a descriptive survey design and 790 respondents were selected with the aid of a multistage stratified sampling technique in Bayelsa, Delta and Rivers States, representing the core Niger Delta. Descriptive statistics were used in the analysis and presentation of data. The findings of the study showed that 75.3% of the respondents agreed that basic food is scarce after all flood incident. However, 69.9% attested to the fact that growth and development of crops are affected when flood washes away farmlands. It can also be seen that flood increases food insecurity, unavailability of staple food and malnutrition as agreed by 78.3% of the total respondents. Furthermore, 77.1% of respondents agreed that flood increases the inability of plants to absorb essential nutrients necessary for proper growth while 71.4% agreed that flooding leads to the erosion or loss of the nutritional status of crops planted in the communities. Also, 69.9% agreed that the washing away of farmlands have led to chronic, long-lasting food insecurity in the communities. Further evidence from the study shows that 75.6% of respondents agreed that the incident of flood leads to acute food insecurity which affects the livelihood of the residents. It is also revealed that flood affects households or residents' investments (64.7%) and losing occupation and source of income from flooding leads to difficulty in caring for the children (60.9%). It is concluded that floods have reduced the efficiencies of farmland in terms of food production causing food insecurity, income reduction and poor livelihood among the residents of the core the Niger Delta States. The study, therefore, recommended that communities should advocate, promote and inculcate the spirit of the commitment of individuals and households towards the continued and holistic development (via social, economic, health, and infrastructural), food security, and increased livelihood in flood-prone communities. The Ministry of Agriculture should ensure that smart agriculture is adopted as a way out to resolve the issues of flood-induced food insecurity and structural measures like dams, culverts, drainages and ditches should be constructed by government and her intervention agencies to accommodate and reduce the runoff or overflow of floodwaters which causes severe social, economic and infrastructural damages or impacts during flooding.
Antioxidant and Anti Nutritional Composition of Germinated Quinoa (Chenopodium quinoa Willd)
Authors: Srujana M. Naga Sai , Kumari B. Anila , Maheswari K. Uma , Devi K. B. Suneetha , Suneetha W. Jessie
Published: January 2020

Aim: To analyse the antioxidant and antinutritional components of germinated quinoa.

Sample: Whole (HGQ) and dehulled (DGQ) quinoa grain (Chenopodium quinoa Willd) was procured from Department of Agronomy, College of Agriculture, PJTS Agricultural University, Rajendranagar, Hyderabad and commercially processed quinoa seed (CGQ) purchased from local market was germinated at 20ºC temperature for 4hrs and analyzed.

Study Design: Analysing antioxidants and antinutritional components.

Place and Duration of Study: Analysis was conducted in PGRC Laboratory, PJTSAU, Rajendranagar, Hyderabad.

Results: The total phenol content and flavonoid content increased upon germination and was high for HGQ and DGQ was high compared to CGQ. IC50 value for antioxidant value of CGQ in methanol and water extract was low compared to HGQ and DGQ. The oxalate content of germinated quinoa ranged from 6.17 ±0.01 to 9.45±0.02mg/100g. The saponin content of germinated quinoa was high for HGQ and DGQ compared to CGQ. When compared to the raw there was 104.16% reduction was seen in HGQ, whereas it reduced to 404.85% in DGQ. But when compared to the commercial variety the saponin contents were 23.07% (DGQ) and 69.35% (HGQ) more. This may be because of processing conditions of commercial variety.
Bone marrow stromal cell‐derived growth inhibitor serves as a stress sensor to induce autophagy
Authors: Zhang Jianbin , Wang Liming , Xu Jian , Tang Yancheng , Huang Bo , Chen Zhifeng , Zhang Ting , Shen Han‐Ming , Wu Yihua , Xia Dajing
Published: January 2020

Autophagy is an evolutionarily conserved stress response that promotes the lysosomal degradation of intracellular components. The bone marrow stromal cell‐derived growth inhibitor (BDGI) functions as a stress sensor which is upregulated by oxidative stress and DNA damage. However, the role of BDGI in autophagic response to certain stresses remains unknown. Here, our results demonstrate that BDGI defines the impact of autophagy induction under stresses. Overexpression of BDGI promotes, while knockdown of BDGI impairs, autophagy. Mechanistically, BDGI localizes to the nucleus and interacts with the transcription factor transcription factor EB to increase the expression of multiple autophagy‐ and lysosome‐related genes. In addition, BDGI regulates autophagy in a p53‐dependent manner. Furthermore, BDGI‐induced autophagy enables cell survival under stress conditions. Taken together, our study demonstrates that BDGI is a stress sensor that positively regulates autophagy.
Crystal structure of botulinum neurotoxin subtype A3 cell binding domain in complex with GD1a co‐receptor ganglioside
Authors: Gregory Kyle S. , Liu Sai Man , Acharya K. Ravi
Published: January 2020

Botulinum neurotoxins (BoNTs) are one of the most toxic proteins known to humans. Their molecular structure is comprised of three essential domains—a cell binding domain (HC), translocation domain and catalytic domain (light chain) . The HC domain facilitates the highly specific binding of BoNTs to the neuronal membrane via a dual‐receptor complex involving a protein receptor and a ganglioside. Variation in activity/toxicity across subtypes of serotype A has been attributed to changes in protein and ganglioside interactions, and their implications are important in the design of novel BoNT‐based therapeutics. Here, we present the structure of BoNT/A3 cell binding domain (HC/A3) in complex with the ganglioside GD1a at 1.75 Å resolution. The structure revealed that six residues interact with the three outermost monosaccharides of GD1a through several key hydrogen bonding interactions. A detailed comparison of structures of HC/A3 with HC/A1 revealed subtle conformational differences at the ganglioside binding site upon carbohydrate binding.
Sister Chromatid Cohesion, Chromosome Instability (CIN) and Diseases
Authors: Zhang Wei , Yuen Karen Wing Yee
Published: January 2020

To pass on the complete set of genetic information from mother to daughter cells in mitosis, or from parental germ cells to gametes in meiosis, chromosomal deoxyribonucleic acid (DNA) must be accurately replicated and sister chromatids must be held together before they separate in anaphase. Sister chromatid cohesion is a dynamic process that is regulated by the cohesin complex, cell cycle regulation of cohesin ring loading, cohesion establishment, maintenance and dissolution. Cohesion‐related proteins also play additional roles in DNA replication, DNA repair, and gene regulation. Defects in sister chromatid cohesion or cohesion dissolution will lead to aneuploidy and chromosome instability (CIN). Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing. Understanding of the pathology of these diseases enables recent development of cohesion genes as biomarkers in prognosis and therapies that target cohesion defects or CIN.

Key Concepts

Sister chromatid cohesion is an important cell cycle‐regulated process that maintains chromosome stability.

Sister chromatid cohesion is established in S phase coupled with DNA replication, maintained in G2/M phase until anaphase onset.

Many cohesion‐related proteins also play roles in DNA replication, DNA repair and gene regulation.

Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing.

Cohesion genes can be used as biomarkers in cancer prognosis, and cancer therapies can target tumours with cohesion defects or CIN.
Cryptochromes: How Blue Light Perception Influences Plant Physiology
Authors: Fantini Elio , Facella Paolo
Published: January 2020

Light plays a pivotal role in several physiological processes during plant growth, development and adaptation. Plants sense and respond to fluctuating light conditions using various photoreceptors such as phytochromes, cryptochromes and phototropins. In particular, cryptochromes are able to monitor, capture and transmit the stimuli of UVA/blue light in order to promote photomorphogenesis and regulate many aspects of plant development and growth including seed germination and seedling de‐etiolation, flowering induction, circadian rhythms and stress responses. Cryptochromes influence all these processes by modulating the expression pattern of several genes; such massive regulation is fundamental for optimising all physiological properties of plants throughout their life cycle.

Key Concepts

Light is essential for plant life.

Plants use photoreceptors to sense and monitor quality, direction, intensity and length of light stimulus.

Cryptochromes play fundamental roles in plant development.

Cryptochromes are highly conserved among plant species.

Cryptochromes regulate many light‐dependent physiological processes.
B‐Cell Antigen Receptor: Assembly and Diversification
Authors: Mohammad Mahwish M , Guillou Morwenna Le , Ghamlouch Hussein , Aoufouchi Said
Published: January 2020

Immunoglobulin (Ig) genes of mammalian B cells undergo two processes that diversify their genomic sequence and structure. The first one concerns the BCR assembly that is achieved through a combinatorial rearrangement of a large number of V, D and J gene segments. This process is essential for B‐cell development and occurs during early B‐cell differentiation in the bone marrow without antigenic challenge. The second process includes somatic hypermutation (SHM), and class switch recombination (CSR), start when the B cell encounters an antigen at the periphery. While the two processes share the action of ubiquitous DNA repair factors to carry out all the steps necessary for creating recombination and mutations in genomic DNA, they are initiated by different lymphoid‐specific factors. On one hand, the action of recombination activating genes 1 and 2 (RAG1 and RAG2) is required for the V(D) J rearrangements and, on the other hand, the action of activation‐induced cytidine deaminase (AID) for both SHM and CSR. The ultimate goal of these diversification mechanisms is to create a dynamic and robust immune response.

Key Concepts

V(D)J recombination is a programmed that generates B‐ and T‐cell receptors in vertebrates (BCR and TCR).

V(D)J recombination requires precise cutting of the DNA at recombination signal sequences (RSS) followed by rejoining of the resulting termini. Imprecisions during the ends‐joining reaction contribute significantly to increasing the variability of the resulting functional BCR and TCR.

RAG1, RAG2 and TdT are the three lymphoid‐specific factors needed for V(D)J recombination and for the junctional diversity observed during lymphoid development.

B‐cells provide the antibody‐mediated immune response (humoral immunity). It can generate antibodies to an immense variety of pathogenic antigens.

Somatic hypermutation (SHM) and class switch recombination (CSR) occur only in germinal centre B cells.

During SHM, DNA repair mechanisms are diverted from their canonical role in preserving genomic integrity to permit high rate of mutations.

SHM and CSR both occur in germinal centre in secondary lymphoid tissues and require activation‐induced cytidine deaminase (AID).

AID deaminates deoxy‐cytosine on single‐stranded DNA.

Ten–eleven translocation (TET) proteins (mainly TET2et TET3) are key regulators of immunoglobulin light chain rearrangement, class switch recombination and plasma cell differentiation.
Clinical Utility of Molecular Genetic Cancer Profiling
Authors: Joseph Loren
Published: January 2020

The ability to sequence entire genomes and transcriptomes is revolutionising cancer biology and, more slowly, cancer medicine. The evidence that large‐scale sequencing has clinical utility, that it improves outcomes, is slowly accumulating. A major controversy has centred on whether or not all tumours refractory to standard therapy should undergo therapy selection by molecular genetic cancer profiling (MGCP). Despite several completed or ongoing clinical trials, this issue is not settled; however, other forces now ensure that MGCP will become a routine diagnostic tool. Biopsies are becoming smaller, providing greater safety for patients, but yielding less DNA/RNA while there are now sufficiently many molecularly targeted agents approved in major cancers that testing by single‐gene assays is no longer practical or economical.

Key Concepts

A clinical test does not have inherent clinical utility.

The clinical utility of molecule genetic cancer profiling varies with the intended clinical use: diagnosis, prognosis, treatment selection, and cancer risk assessment.

Assessment of clinical utility does NOT include consideration of cost.

There is incomplete consensus on which genes should be in a molecular genetic cancer profile but in practice panels cover at most several hundred genes (ie much smaller than an exome).

Most molecular genetic cancer profiling has used tumor genomic DNA but assays are increasingly including analysis of RNA for translocation detection and gene expression.

The traditional method for determining clinical utility, the randomized clinical trial, is evolving to facilitate screening of many genes and many molecularly targeted agents rapidly.

Large‐scale clinical trials are underway to assess the clinical utility of applying molecular genetic panels to all cancers in a histology‐agnostic fashion.

Clinical trials for molecularly targeted agents predicted to be beneficial by molecular genetic cancer profiling are always conducted on patients with advanced disease who have already failed several established ‘lines of therapy’.

Likelihood of response to a new class of therapy, immune checkpoint inhibitors, might be predicted by microsatellite instability and, possibly, by the Tumor Mutation Burden.

Response to another new class of therapy, CAR‐T cells, might be mutation agnostic.
Emerging Role of Adrenomedullin as Sepsis Prognostic Marker
Authors: Lia Maria Stella , Angeletti Silvia , Bernardini Sergio , Minieri Marilena
Published: January 2020

Sepsis represents an important and global health problem. It affects 27–30 million people every year, 7–9 million of these die. Sepsis occurs when the body uncontrolled response to an infection injures its own tissues and organs. If it is not quickly recognised and treated, it may led to septic shock, multiorgan failure and death. Together with clinical signs, a series of biomarkers can be very useful in the early diagnosis of sepsis. Adrenomedullin (ADM) is one of these biomarkers, not only important for sepsis diagnosis but also particularly useful for prognosis. ADM is a hormone secreted by endothelial cells, involved in regulation of the endothelium barrier and vascular tone, so playing a decisive role in the inflammation process. The mid regional‐proadrenomedullin (MR‐proADM) is the molecule detected in septic patients because it is more stable than ADM and is released in an equimolar ratio of the active portion. MR‐proADM is capable to identify disease severity and progression, more accurately than other biomarkers and clinical scores. Inclusion of MR‐proADM assay in clinical routine could help the clinicians to manage septic patients especially by identifying their mortality risk.

Key Concepts

Sepsis is considered one of the most important public health concern with high rates of morbidity, mortality and resource consuming worldwide;

Sepsis is defined as uncontrolled immune response against infections;

A fast diagnosis of sepsis is necessary to promptly initiate the appropriate treatment;

Several biomarkers are adopted in clinical settings for sepsis diagnosis and prognosis, but the ‘gold standard’ has not found yet;

Mid Regional‐proAdrenomedullin (MR‐proADM) is a novel promising biomarker of prognosis associated to sepsis severity playing an important role in the initial evaluation and clinical management of septic patient.
Ramularia collo‐cygni
– An Enemy in Waiting
Authors: Dussart Francois , Creissen Henry E , Havis Neil D
Published: January 2020

Ramularia collo‐cygni
, the agent responsible for Ramularia leaf spot disease of barley, possesses many mechanisms for avoiding detection by the host, which enables it to survive as an endophyte for much of the plant's life cycle before eventually turning pathogenic. The fungus has also eluded farmers and scientists for decades as it is a late season disease that often displays symptoms after the last possible fungicide intervention when crop scouting for disease has been completed. Visual symptoms are also hard to distinguish from other pathogens, which has resulted in misdiagnoses. The ability of the fungus to spread not only via infected seed but also on infected straw and wind dispersal, coupled with its ability to rapidly evolve resistance to fungicides, has resulted in an escalation in the perceived threat it presents to barley production worldwide. A greater understanding of the plant–fungus interaction is required if future control strategies are to be successful.

Key Concepts

Plant–fungi interactions can be complex and highly variable, including mutualism, parasitism and commensalism.

Global movement of seed can significantly influence the spread of seed‐borne diseases.

Plant breeding for disease control requires identification of a suitable breeding target, which may be challenging.

Breeding for resistance to one pathogen may lead to control issues for another pathogen.

Integrated pest management practices must consider nonchemical control measures and, when using pesticides, antiresistance strategies.

Single‐site fungicides are vulnerable to losses in efficacy due to the evolution of resistance in the pathogen population.
A Highly Stretchable, Real‐Time Self‐Healable Hydrogel Adhesive Matrix for Tissue Patches and Flexible Electronics
Authors: Luo Jun , Yang Jiaojiao , Zheng Xiaoran , Ke Xiang , Chen Yantao , Tan Hong , Li Jianshu
Published: January 2020

The development of biocompatible self‐healable hydrogel adhesives for skin or wet, stretchable surfaces in air or under water is highly desirable for various biomedical applications ranging from skin patches to bioelectronics. However, it has been proven to be very challenging because most existing hydrogel adhesives are cytotoxic, or poorly adhere to dynamic or stretchable surfaces in wet environments. In this study, multifunctional hydrogel adhesives derived from silk fibroin (SF) and tannic acid (TA) are effectively constructed with high extensibility (i.e., up to 32 000%), real‐time self‐healing capability, underwater adhesivity, water‐sealing ability, biocompatibility, and antibiotic properties. According to all‐atom molecular dynamics simulation studies, the properties of the hydrogel adhesives, especially high extensibility, are mainly attributed to the hydrogen bonds between TA and the SF chains in water, and water and TA molecules can result in loose assemblies with fewer β‐sheets, and more random coils in the SF. Conductivity can also be easily introduced to the adhesive matrix and adjusted when the strain of the adhesives occurs. Considering that it has multiple functions and can be efficiently prepared, the proposed hydrogel adhesives have the potential for future medical applications, such as tissue adhesives and integrated bioelectronics.
Recent Advances in the Transdermal Delivery of Protein Therapeutics with a Combinatorial System of Chemical Adjuvants and Physical Penetration Enhancements
Authors: An Young‐Hyeon , Park Mihn Jeong , Lee Joon , Ko Junghyeon , Kim Su‐Hwan , Kang Dong Hyeon , Hwang Nathaniel S.
Published: January 2020

Since the development of protein‐based therapeutics, research has been underway to deliver protein therapeutics into the systemic circulation and target sites have been actively conducted. Most protein‐based therapeutics require parenteral administration, due to their intrinsic vulnerability and susceptibility to enzyme‐mediated degradation. Among the routes of administration, the transdermal delivery system has been regarded as a promising technique to deliver protein therapeutics, offering the advantages of painless administration, ease of termination, and avoidance of first‐pass metabolism. However, unlike small molecular drugs, protein therapeutics have limited skin penetration, due to their macromolecular and hydrophilic properties. Both cheimcal adjuvants (CAs)‐treatment methods and physical penetration enhancer methods (PPEs) have been utilized to increase skin permeability for protein therapeutics. The CAs, which include chemical penetration enhancers and nanocarriers, permit the protein therapeutics to transport easily into the skin, by modifying the stratum corneum (SC) or fabricating their stable formulation. The PPEs, including iontophoresis, electroporation, and ultrasound, can improve the skin permeability of the therapeutic agent through disrupting the SC. In this review, the techniques of both chemical and physical enhancement methods are introduced and an overview of the latest approaches to the transdermal delivery of protein therapeutics is provided.
Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment
Authors: Peng Yang , Bariwal Jitender , Kumar Virender , Tan Chalet , Mahato Ram I.
Published: January 2020

Nanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.
Extreme soil surface temperatures reflect need to rethink agronomic management
Authors: O'Brien Peter L. , Hatfield Jerry L.
Published: January 2020

The soil surface exists at the soil–atmosphere interface and is critical in regulating transfers of water, energy, and nutrients in agroecosystems. Soil surface temperature plays an important role in the rate and quantity at which these resources cross the interface, as temperature regulates numerous physical, chemical, and biological processes. Many current management practices manipulate soil surface temperatures, especially through tillage or residue management, to create conditions suitable for early‐season crop growth. However, these conditions persist beyond plant establishment and have the potential to develop extremely high temperatures, even in historically mild climates. We show the potential for extreme maximum soil surface temperatures in Iowa after crop establishment but before canopy closure and discuss possible consequences of those temperatures. Given the conditions required to develop extreme maximum temperatures, we contend that soil surface temperatures may be an indicator of conditions that are inconsistent with highly productive, sustainable, efficient agroecosystems.
Doping High‐Mobility Donor–Acceptor Copolymer Semiconductors with an Organic Salt for High‐Performance Thermoelectric Materials
Authors: Guo Jing , Li Guodong , Reith Heiko , Jiang Lang , Wang Ming , Li Yuhao , Wang Xinhao , Zeng Zebing , Zhao Huaizhou , Lu Xinhui , Schierning Gabi , Nielsch Kornelius , Liao Lei , Hu Yuanyuan
Published: January 2020

Organic semiconductors (OSCs) are attractive for fabrication of thermoelectric devices with low cost, large area, low toxicity, and high flexibility. In order to achieve high‐performance organic thermoelectric devices (OTEs), it is essential to develop OSCs with high conductivity (σ ), large Seebeck coefficient (S), and low thermal conductivity (κ ). It is equally important to explore efficient dopants matching the need of thermoelectric devices. The thermoelectric performance of a high‐mobility donor–acceptor (D–A) polymer semiconductor, which is doped by an organic salt, is studied. Both a high p‐type electrical conductivity approaching 4 S cm−1 and an excellent power factor (PF) of 7 µW K−2 m−1 are obtained, which are among the highest reported values for polymer semiconductors. Temperature‐dependent conductivity, Seebeck coefficient and power factor of the doped materials are systematically investigated. Detailed analysis on the results of thermoelectric measurements has revealed a hopping transport in the materials, which verifies the empirical relationship: S ∝ σ−1/4 and PF ∝ σ1/2. The results demonstrate that D–A copolymer semiconductors with proper combination of dopants have great potential for fabricating high‐performance thermoelectric devices.
The impact of tillage row orientation on physical and chemical sediment enrichment
Authors: Wacha Kenneth M. , Papanicolaou A. N. Thanos , Abban Benjamin K. , Wilson Christopher G. , Giannopoulos Christos P. , Hou Tingyu , Filley Timothy R. , Hatfield Jerry L.
Published: January 2020

This study aimed to better understand how tillage row orientation with respect to dominant flow‐pathway along hillslope impacts runoff and the transport of different sediment size fractions. Experimental plots were constructed in contour ridge till (CRT) and parallel ridge till (PRT) sites to monitor runoff and sediment fluxes. Particle size fractions of the sediment, along with organic C and N contents were measured to quantify physical and chemical enrichment ratios for the two tillage orientations. In the CRT plot, tillage produced large oriented roughness elements along the contours, which acted as little check dams, while in the PRT site, the roughness elements helped confine and concentrate the runoff. In the CRT, the “check dams” resulted in a runoff coefficient of .03, while in the PRT, the flow confinement between rows produced a runoff coefficient of .82. Moreover, the erosion rates at the CRT site were 97% less than those in the PRT plot. Large contours produced finer sediment fractions due to the selective sorting in ponded furrows. More aggregate sediment fractions were present in the PRT site, which was dominated by rill erosion. Physical enrichment revealed selective entrainment of finer sediment particles during erosion. Finer‐grain particles with higher specific surface areas, attached more organic C resulting in chemical enrichment. Physical and chemical enrichment methods were found to be in good agreement. These findings suggest transport models that can simulate size fraction updates to the soil active layer can be used to estimate SOC redistribution and hence more accurate C budgets.
The sorghum epicuticular wax locus Bloomless2 reduces plant damage in P898012 caused by the sugarcane aphid
Authors: Harris‐Shultz Karen , Punnuri Somashekhar , Knoll Joseph E. , Ni Xinzhi , Wang Hongliang
Published: January 2020

The sugarcane aphid [Melanaphis sacchari] has been rapidly spreading in the southern United States with devastating impacts on sorghum [Sorghum bicolor (L.) Moench]. Previous studies have shown the sorghum epicuticular wax mutants, in particular a bloomless2 (bm2) mutant and a sparse bloom mutant, were resistant to greenbugs [Schizaphis graminum], a type of aphid. In this study we sought to determine if five different genotypes, which all have mutations in the Bm2 locus, differ for sugarcane aphid resistance as compared to their respective wild‐type plants (P954035, P898012, and Tx7078). Two greenhouse studies with artificial infestation and one field study under natural infestation were conducted. Aphid numbers on the second leaf from the top and the lowest green leaf, plant damage, and plant growth stage were assessed at weekly intervals. The Greenhouse Test 2 and the Field test were the most effective at determining plant resistance and susceptibility to the sugarcane aphid. Bm2 mutants in the P898012 background had greater aphid damage than their wild type plants. These findings suggest that the Bm2 locus has a role in reducing aphid damage in the P898012 background yet has a limited role in the Tx7078 and P954035 backgrounds.
Nitrospira bacteria in paddy soil reduced by biochar application
Authors: Yin Xiaohong , Chen Jiana , Fan Long , Tao Zui , Huang Min , Zou Yingbin
Published: January 2020

Biochar application can depress nitrification in paddy soils, but the microbiological mechanisms involved in this process are not clearly understood. This study was conducted to test the hypothesis that biochar may affect nitrification bacteria in paddy soils. Bacterial communities in a paddy soil with and without applications of biochar were compared in a field experiment. Results indicated that the total number of operational taxonomic units (OTUs) of bacteria was not significantly affected by biochar application (20 Mg rice husk biochar ha–1). However, the application of biochar significantly changed the structure of the bacterial community. In particular, the number of OTUs affiliated with Nitrospirae, a key bacterial phylum in nitrification, was significantly reduced, by 25%, by biochar application. The biochar‐induced reduction in Nitrospirae could be explained in part by interspecific competition with Firmicutes and Bacteroidetes phyla, which were significantly increased by application of biochar. The results of this study suggest that biochar may affect nitrification by changing levels of nitrification bacteria in paddy soils.