bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosis of hepatitis B virus reactivation in newly diagnosed multiple myeloma in modern era therapy: a retrospective study
Authors: Lv Weiran , Li Xiaojin , Xu Jingbo , Wang Yun , Huang Hanying , Hu Fang , Cui Yingying , Song Yuanbin , Chen Lezong , Wu Bingyi , Liang Yang
Published: November 2024

Studies on the prognosis of hepatitis B virus (HBV) reactivation following modern therapies for newly diagnosed MM (NDMM) are lacking. In this retrospective study, we aimed to assess the incidence, risk factors and prognosis of HBV reactivation in NDMM. A total of 33 of 355 patients with NDMM and HBV reactivation were included in this study. Multivariable analysis showed that hepatitis B surface antigen-positivity, hepatitis B core antibody-positivity, bortezomib-containing regimens, autologous stem cell transplantation, and gain of 1q21 were identified as independent risk factors of HBV reactivation in NDMM patients. The NDMM patients with HBV reactivation had poorer 3-year overall survival (OS) and progression-free survival (PFS) than did those without HBV reactivation, as confirmed by multivariate analysis. In conclusion, HBV reactivation in patients with NDMM constitutes a significant complication, correlating with reduced OS and PFS, and emerges as a potential adverse prognostic factor in the contemporary era of treatment.
The Effectiveness of the Itik Land Pop Up Store Advertising Message to Instagram Followers @myyellowduckling
Authors: Saraswati Ajeng Lintang , Hadi Ido Prijana , Yogatama Astri
Published: November 2024

My Yellow Duckling is a local brand that sells duck-themed merchandise. This brand started its business in 2019 and comes from the city of Surabaya. Starting with a drawing hobby from the owner of My Yellow Duckling, it led her to start transforming her draw into a product with selling value. She sells duck-themed merchandise, such as dolls, sticker, keychain, enamel pin, pouch, headband, and so on. My Yellow Duckling sells their product online via Shopee marketplace and offline by open a pop-up store in collaboration with the event market in Surabaya. In January 2024, My Yellow Duckling for the first time opened a pop-up store independently in Malang under the name Itik Land. To advertise their event, they use Instagram for share the message to consumer. This study uses SOR theory to determine the effectiveness of advertising messages to the audience. Advertising messages delivered will be measured effectively using AISAS models with 5 indicator, Attention, Interest, Search, Action, and Share. This type of research is descriptive with a quantitative approach. The study took data using an online questionnaire against 100 respondents using non-probability sampling techniques. The results of this study showed that messages of pop-up ads on Instagram followers @myyellowduckling proved effective with the highest average score at the attention level.
Fashion as Communication: Costume Dasiyah at Film Series Gadis Kretek
Authors: Triantoro Thessalonica Dwi Setya Angestuti , Budiana Daniel , Aritonang Agusly Irawan
Published: November 2024

Film as an audio-visual medium can convey messages verbally and non-verbally. In the filmseries 'Gadis Kretek', the message is communicated through dialogue and visual displays,namely fashion. Dasiyah, as one of the main characters, has iconic fashion compared to othercharacters. Dasiyah Fashion consists of the entire fashion, hair, make-up, and accessories usedby the actress as a costume used as a medium for character communication. Therefore, theauthor is interested in researching the meaning of denotation, connotation, and myths relatedto fashion from each Dasiyah fashion unit using Roland Barthes' semiotic analysis. So thisresearch can find out the full meaning of how fashion can communicate your character. It wasfound that fashion can express Dasiyah's life journey and her ideals regarding kretek amidstthe patriarchy are still strong in Javanese culture. Apart from that, through her fashion, Dasiyahcan position herself in society with her socio-economic status as an elite Javanese woman withher trading activities. The fashion worn by Dasiyah is not always stagnant, there is aprogressiveness of character that causes fashion alterations not by Javanese standards.
The Meaning of Political Messages in Carousel Posts on @ganjar_pranowo’s Instagram Account during the 2024 Electoral Campaign Period
Authors: Chandra Sentanu , Hadi Ido , Aritonang Agusly Irawan
Published: November 2024

This research is motivated by the phenomenon of the 2024 elections, focusing on the digital political campaigns based on social media. The study focused on examining the meanings of political messages constructed by the 2024 presidential candidate, Ganjar Pranowo, by relating them to the philosophy of Javanese cultural leadership. This is due to the contrast between the results of the party’s legislative elections and its vote acquisition in the presidential election contest. The type of research used is descriptive qualitative with the semiotic analysis method of Roland Barthes. The research subject consists of carousel posts on the Instagram account @ganjar_pranowo, while the research object is the meaning of Political Messages. The study found that the meaning of political messages is derived from the visible verbal and non-verbal messages. It also discovered the correlation between the meanings of ‘Penguin’ and ‘Swastika’ which were capitalized as campaign messages. Furthermore, the researcher interprets the message meanings as Javanese-centric leadership in Indonesia presidential, redefinition of the meaning ‘Merakyat’, the paternalistic side in ‘wong cilik’ politics, and the implementation of Hastabrata philosophy rooted in Ganjar Pranowo.
Impression Management Strategy of Khofifah Indar Parawansa on Instagram Account @khofifah.ip
Authors: Sitorus Emanuela , Priyowidodo Gatut , Aritonang Agusly Irawan
Published: November 2024

Impression management refers to an individual's need to present themselves acceptably to others, crucial for maintaining their image and achieving goals. This is particularly important for political actors in Indonesia as a democratic country. One political actor used impression management is Khofifah Indar Parawansa who needed to effectively manage her public image to secure a second term as Governor of East Java, particularly before the 2024 regional elections. This research analyzed Khofifah’s strategies on her Instagram account @khofifah.ip using descriptive quantitative content analysis methods. It examined verbal messages from 222 posts, including photos, videos, and text captions, between February 12, 2024, when Khofifah announced her candidacy, and May 9, 2024, when political dynamics changed. The strategies analyzed were ingratiation, self-promotion, intimidation, exemplification, and supplication. The research found that the most frequently used strategy by Khofifah was Ingratiation particularly the Other Enhancement tactic with the sub-indicator of Sympathy, emphasizing her efforts to gain public favor through various practices of sympathy tactics.
Opinions of Gen Z Surabaya Regarding the Effectiveness of the Spokes Character Ronald Mcdonald in Communicating McDonalds' Brand Image.
Authors: Isjwara Amadea Daphne , Indrayani Inri , Wijayanti Chory Angela
Published: November 2024

This research was conducted to determine the opinion of Gen Z in Surabaya regarding the effectiveness of Ronald McDonald's Spokes Character in communicating the McDonald's brand image. McDonalds as a fast-food restaurant uses a mascot to communicate its brand image, namely Ronald McDonald. The elements that determine the effectiveness of spokes character include Relevance to product, Expertise and Nostalgia. To measure the effectiveness of the spokes character, opinions were measured among Gen Z Surabaya, which is the dominant population and is interested in McDonalds. Gen Z Surabaya's opinion will be based on three progressive stages, namely Awareness, Acceptance and Action. So, to find out the opinion of Gen Z Surabaya regarding Ronald McDonald's spokes character, researchers conducted descriptive research with a quantitative approach. The method used was a survey of 100 Gen Z McDonald's Surabaya customers. The results of the research show that the Opinion of Gen Z Surabaya regarding the Effectiveness of Ronald McDonald's Spokes Character in Communicating the McDonalds Brand Image is positive and Expertise as the favourable element.
Persuasive Key Message Factors in Marjan Syrup Advertisements from 2021 - 2024
Authors: Maureen Kezia , Luik Jandy , Yogatama Astri
Published: November 2024

Marketing Public Relations (MPR) emphasises not on selling (as in advertising activities) but on providing information, education, and efforts to increase understanding through the addition of knowledge about a product brand. This approach has a stronger impact, and the message conveyed is more memorable to consumers. With a more intensive and comprehensive level of communication compared to advertising, MPR represents a higher concept than regular advertising. MPR emphasises the management aspect of marketing by highlighting consumer welfare. The Marjan Syrup advertisement is one of the most unique and interesting advertisements, which certainly does not escape the attention of the Indonesian public. Since 2019, Marjan has begun to step out of its "ordinary advertisement" comfort zone by using various editing techniques while still incorporating elements of Indonesian folklore. This study provides an overview of the persuasive key message factors contained in the Marjan Syrup advertisements from 2021 to 2024. Using quantitative content analysis, this study is able to examine the message structure, message content, framing, language, and emotional appeals present in each scene of the Marjan Syrup advertisements.The results of the study indicate that the advertisements from 2021 to 2024 contain persuasive key message factors. The most prominent indicators are Message Structure and Language. Additionally, the researchers found that the persuasive key message factors in these four years are suitable for further attracting viewers to the advertisements by conveying messages that contain persuasive elements
N‐glycan signatures identified in tumor interstitial fluid and serum of breast cancer patients: association with tumor biology and clinical outcome
Authors: Terkelsen Thilde , Haakensen Vilde D. , Saldova Radka , Gromov Pavel , Hansen Merete Kjær , Stöckmann Henning , Lingjærde Ole Christian , Børresen‐Dale Anne‐Lise , Papaleo Elena , Helland Åslaug , Rudd Pauline M. , Gromova Irina
Published: April 2018

Particular N‐glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N‐glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N‐glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N‐glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids (TIF, n = 85), paired normal interstitial fluids (NIF, n = 54) and serum samples (n = 28) followed by independent evaluation, with the ultimate goal of identifying tumor‐related N‐glycan patterns in blood of patients with breast cancer. The segregation of N‐linked oligosaccharides revealed 33 compositions, which exhibited differential abundances between TIF and NIF. TIFs were depleted of bisecting N‐glycans, which are known to play essential roles in tumor suppression. An increased level of simple high mannose N‐glycans in TIF strongly correlated with the presence of tumor infiltrating lymphocytes within tumor. At the same time, a low level of highly complex N‐glycans in TIF inversely correlated with the presence of infiltrating lymphocytes within tumor. Survival analysis showed that patients exhibiting increased TIF abundance of GP24 had better outcomes, whereas low levels of GP10, GP23, GP38, and coreF were associated with poor prognosis. Levels of GP1, GP8, GP9, GP14, GP23, GP28, GP37, GP38, and coreF were significantly correlated between TIF and paired serum samples. Cross‐validation analysis using an independent serum dataset supported the observed correlation between TIF and serum, for five of nine N‐glycan groups: GP8, GP9, GP14, GP23, and coreF. Collectively, our results imply that profiling of N‐glycans from proximal breast tumor fluids is a promising strategy for determining tumor‐derived glyco‐signature(s) in the blood. N‐glycans structures validated in our study may serve as novel biomarkers to improve the diagnostic and prognostic stratification of patients with breast cancer.
Selective induction of cancer cell death by VDAC1‐based peptides and their potential use in cancer therapy
Authors: Shteinfer‐Kuzmine Anna , Amsalem Zohar , Arif Tasleem , Zooravlov Alexandra , Shoshan‐Barmatz Varda
Published: April 2018

Mitochondrial VDAC1 mediates cross talk between the mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2+, and metabolites and serves as a key player in apoptosis. As such, VDAC1 is involved in two important hallmarks of cancer development, namely energy and metabolic reprograming and apoptotic cell death evasion. We previously developed cell‐penetrating VDAC1‐derived peptides that interact with hexokinase (HK), Bcl‐2, and Bcl‐xL to prevent the anti‐apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma. In this study, we demonstrated the sensitivity of a panel of genetically characterized cancer cell lines, differing in origin and carried mutations, to VDAC1‐based peptide‐induced apoptosis. Noncancerous cell lines were less affected by the peptides. Furthermore, we constructed additional VDAC1‐based peptides with the aim of improving targeting, selectivity, and cellular stability, including R‐Tf‐D‐LP4, containing the transferrin receptor internalization sequence (Tf) that allows targeting of the peptide to cancer cells, known to overexpress the transferrin receptor. The mode of action of the VDAC1‐based peptides involves HK detachment, interfering with the action of anti‐apoptotic proteins, and thus activating multiple routes leading to an impairment of cell energy and metabolism homeostasis and the induction of apoptosis. Finally, in xenograft glioblastoma, lung, and breast cancer mouse models, R‐Tf‐D‐LP4 inhibited tumor growth while inducing massive cancer cell death, including of cancer stem cells. Thus, VDAC1‐based peptides offer an innovative new conceptual framework for cancer therapy.
Haem Structure and Function
Authors: Kim Hyung J
Published: April 2018

Haem is an iron‐containing cofactor that is universally utilised from single‐cell microbes to vertebrates. The porphyrin ring is the organic framework that coordinates the iron ion, and nature modifies the structure of this functionally versatile ring to create haems with different chemical properties. In addition, the type and the number of iron‐binding ligands from the haem protein's scaffold, which includes histidine, methionine and cysteine residues, also modulate the chemistry of haem. These interactions afford haem to function in dioxygen (O
2
) transport, as in myoglobin and haemoglobin; in electron transport, as in mono‐ and multihaem cytochromes and in enzymic reactions as in oxidases. Furthermore, the structural interactions between the haem and the proteinaceous ligands fine‐tune reduction potentials and give rise to distinct electronic absorption spectra that are useful for biochemical studies of haem proteins. As studies of haem and haem proteins continue, new functions are being discovered, including in the regulation of key cellular processes.

Key Concepts

Haem is an iron ion coordinated to a substituted porphyrin ring, called protoporphyrin IX (PPIX) and serves as a cofactor for a functionally diverse group of proteins.

The porphyrin ring can be structurally modified to produce haem types
b, c, a, o
or
d
.

The haem iron ion can coordinate five or six ligands where the five‐coordinate complexes can bind small ligands such as O
2
and/or participate in catalysis.

The highly conjugated π‐electron system of haem's porphyrin provides characteristic electronic absorbance spectrum for different types of haems and haem proteins.

Factors such as the type and the number of axial ligands to the haem iron, the nature of substituents to the porphyrin ring and charges near the haem centre contribute to modulating the reduction potential of haems.

Both the O
2
‐carrier haemoglobin and the enzyme peroxidase possess five‐coordinate His ligation systems, yet vastly different functions, illustrating the broad functional range of haem proteins by use of different protein environments.
Haemostasis: General Pathways
Authors: Balduini Alessandra , Balduini Cesare
Published: April 2018

Haemostasis protects the organism from bleeding due to tissue and vascular injury. It is a complex system of interconnected mechanisms that have the purpose of halting blood loss and reconstituting the integrity of the damaged tissue. The haemostatic process begins with a vascular damage that results in the exposure of the subendothelial collagen; this component is recognised by platelet receptors that initiate a series of events resulting in platelet aggregation with the formation of the primary unstable thrombus. Tissue damage also sets off the activation cascade of the coagulation factors, which results in the transformation of fibrinogen into fibrin, stabilising the thrombus. The final phase of haemostasis is the removal of the fibrin clot by plasmin, followed by wound healing of the damaged tissue. In normal conditions, haemostasis is controlled by sophisticated mechanisms that trigger the activation of the coagulation process to block blood loss, preventing unnecessary thrombus formation.

Key Concepts

Haemostasis is a system of highly interconnected mechanisms aimed at protecting the organism from blood loss.

Four phases occur in haemostasis: (1) tissue and vessel wall damage, (2) platelet activation, (3) blood clotting and (4) fibrinolysis and wound healing.

Injury of the vessel wall initiates the mechanisms responsible for platelet activation and coagulation factor activation.

Coagulation factors are plasma proteins that in the absence of tissue damage circulate in blood in an inactive form. Tissue lesion provokes a proteolytic cascade that sequentially activates all the factors, resulting in the formation of the stable fibrin clot.

The haemostatic mechanisms are limited to the area in which tissue injury and platelet adhesion occurred.

Upon definitive arrest of bleeding, the fibrin network is dissolved by plasmin deriving from proteolytic activation of plasminogen.

Plasminogen activation is strongly stimulated by fibrin, and therefore plasmin is active only in the areas in which fibrin is present.

Alterations of the different haemostatic mechanisms result in severe pathologic conditions that represent one of the main causes of death in modern society.

The haemostatic process is controlled by sophisticated mechanisms aimed at maintaining a functionally correct balance between prothrombotic and antithrombotic pathways.
HAPPY
Mapping
Authors: Dear Paul H
Published: April 2018

For large genomes, such as most eukaryotes, it is difficult or impossible to produce a complete, gap‐free genome sequence. Genome mapping entails finding the relative positions of different deoxyribonucleic acid (DNA) sequences in such an incompletely sequenced genome, often across large distances (kb or Mb). An accurate genome map arranges sequence fragments in context, and can also be used to guide directed sequencing efforts to close the remaining gaps. HAPPY mapping is a versatile
in vitro
method for making such genome maps. Genomic DNA is broken randomly and diluted to the point where samples contain only a few molecules. Many such samples are analysed and, if two sequences (markers) are often found together in the same sample, this implies that they are often on the same DNA fragment and therefore adjacent in the genome.

Key Concepts

A genome map shows the positions of different DNA sequences in a genome, even if the genome has not been fully sequenced.

Genome maps show the large‐scale organisation of the genome, across many kilobases or megabases.

Genome maps can help to guide efforts to close in a full genome sequence, by showing the size and position of remaining gaps.

HAPPY mapping relies only on
in vitro
steps, and is less prone to artefacts than some other mapping methods

HAPPY mapping can be used to make maps with resolutions from kilobases to hundreds of kilobases.
Dominance and Recessivity
Authors: Wilkie Andrew OM
Published: April 2018

The terms dominance and recessivity, originally codified by Gregor Mendel, are not strictly speaking intrinsic properties of genes or alleles but describe, in diploid organisms, the pattern of occurrence of a phenotypic trait with respect to the possible combinations of two alleles. If the trait is present in the heterozygote, it is said to be dominant or semidominant, and if it is present only in one of the homozygotes, it is recessive. In contemporary genetics, these terms are frequently used in a different but useful way to describe a property of the variant or mutant allele itself in relation to the normal, wild‐type state; this context is very helpful for understanding the molecular mechanisms by which mutations lead to disease. Practical applications include elucidation of genotype–phenotype relationships, structure–function studies of proteins and prediction of patterns of segregation of phenotypes to offspring in contexts such as selective breeding and genetic counselling.

Key Concepts

In comparing the traits (phenotypes) associated with alleles
A
and
B
in a diploid organism, the dominant phenotype is that observed in association with genotypes
AA
and
AB
, whereas the recessive phenotype is that observed in association with the
BB
genotype.

Semidominance of the phenotypes occurs when that associated with
AB
is intermediate between
AA
and
BB
.

A less formally correct, but operationally useful allele‐centric definition occurs when comparing the phenotypes associated with a rare variant allele to the normal (wild‐type) state. When heterozygotes appear phenotypically normal, the variant allele is described as recessive, but if they are abnormal, it is described as dominant.

Most (∼90%) variants of large phenotypic effect result in loss‐of‐function and the associated phenotype only manifests in the homozygous state (recessive to the wild‐type), because in heterozygotes, the function of the remaining wild‐type allele is sufficient for homeostasis.

Fewer than 10% of variants of large effect are associated with a phenotype in heterozygosity with wild type (i.e. dominant genetics). The reasons why the remaining wild‐type allele is unable to buffer the phenotype fall into distinct categories, depending on whether the functional consequence of the variant allele is to lose, gain or alter function.

Haploinsufficiency refers to the situation in which the remaining wild‐type allele (
A
) is unable to compensate fully for loss‐of‐function of the variant allele
B
, so that the phenotype in
AB
heterozygotes differs from normal.

Nonhaploinsuffciency or altered‐function mechanisms of dominance are diverse and specific to the context of the gene/protein involved. Common consequences include dominant‐negative activity and gain‐of‐function, which can include structural disruption and toxic cellular effects.
Nitrification
Authors: Stein Lisa Y , Nicol Graeme W
Published: April 2018

The global nitrogen cycle is initiated by the fixation of atmospheric N
2
, by either natural or chemical processes, to bioavailable ammonium (NH
4
+
). Nitrification is the oxidative process that transforms this ammonium to nitrate, via a nitrite intermediate. Nitrification is performed solely by microorganisms: ammonia‐oxidising bacteria and archaea oxidise ammonia to nitrite, nitrite‐oxidising bacteria oxidise nitrite to nitrate and comammox bacteria oxidise ammonia to nitrate. Nitrifiers (and anammox) are distinguished from other microorganisms as they can grow solely from the oxidation of inorganic nitrogenous molecules and fix carbon dioxide as their sole carbon source, although many can also grow using alternative catabolic processes, by cross‐feeding, and/or by mixotrophy. Key enzymes to the nitrification process include ammonia monooxygenase, hydroxylamine dehydrogenase and nitrite oxidoreductase. A putative enzyme catalysing nitric oxide oxidation to nitrite is currently uncharacterised. Essential intermediates to nitrification include hydroxylamine, nitric oxide and nitrite. As well as performing a required component of the global nitrogen cycle, nitrifying microorganisms are also responsible for the loss of nitrogen‐based fertilisers in soil and play a critical role in emission of the potent greenhouse gas, nitrous oxide, as mediated by production and consumption of nitric oxide in their metabolism.

Key Concepts

Nitrification is an oxidative process that transforms reduced nitrogen, primarily ammonia, to nitrate.

Fluxes in nitrogen transformations associated with nitrification activity have accelerated greatly over the past century owing to the production and application of inorganic ammonium‐based fertilisers.

Microorganisms involved in nitrification are ubiquitously distributed in nature and found virtually everywhere that ammonia and oxygen are present.

Nitrification is mediated by bacteria and archaea and is performed by either two (ammonia and nitrite oxidisers) or one (comammox) canonical functional group.

Autotrophic pathways of ammonia‐ and nitrite‐oxidising bacteria are the Calvin cycle or reverse TCA cycle; ammonia‐oxidising archaea assimilate carbon dioxide via the 3‐hydroxypropionate/4‐hydroxybutyrate pathway.

Key enzymes of nitrification are ammonia monooxygenase, hydroxylamine dehydrogenase, nitric oxide oxidase (putative) and nitrite oxidoreductase.

Methanotrophic and heterotrophic microorganisms can carry out parts of nitrification but cannot grow from oxidising reduced nitrogen compounds.

Mechanisms for the production of nitric oxide and nitrous oxide are distinct among nitrifying microorganisms.

Comparative genome analysis and the use of differential inhibitors can assist in determining differences in physiology and niche preference among nitrifying microorganisms.

There is substantial physiological diversity within individual functional groups (e.g. ammonia oxidisers) which results in niche differentiation both within and between taxonomic groups of nitrifiers.
Family‐Based Association Test (
FBAT
)
Authors: Laird Nan M , Lange Christoph
Published: April 2018

Statistical tests of association are commonly used to confirm or exclude a relationship between disease and selected genetic variants. Tests based on data from unrelated individuals are popular, but can be invalid in the presence of genetic confounding, for example the sample contains individuals with different genetic ancestries. Family designs that use affected individuals and their relatives can limit the problem of validity using within‐family comparisons. The transmission disequilibrium test (TDT) is the original family test for association proposed for affected offspring and their parents. The test is simple and intuitive, is totally robust and the most powerful against an alternative that assumes an additive mode of inheritance. The family‐based association test (FBAT) is a generalisation of the TDT suitable for other family designs; other modes of inheritance; dichotomous, measured and time‐to‐onset phenotypes and haplotypes of tightly linked markers. FBATs are generally less powerful than tests based on a sample of equivalent size of unrelated individuals, but special settings exist, for example testing for rare variants with affected offspring and their parents, where the family design has a power advantage.

Key Concepts

Genetic tests based on population or cohort samples can be invalid owing to differing genetic ancestries.

Association designs using family members can reduce or avoid bias using within‐family comparison.

The simplest family test is the TDT which uses affected offspring and their parents.

FBAT refers to a class of tests for family designs that can accommodate any type of genetic model, any phenotype and any family configuration, for example parents and their offspring, sibships or even general pedigrees.

FBATs are based on the distribution of Mendelian transmissions from parents to offspring and thus only require that Mendel's Laws hold under the null hypothesis of no linkage and no association.

FBAT tests can accommodate missing parents or founders by conditioning on the observed genotype configuration in the family, or technically, on the sufficient statistics for the missing parents/founders.

Other methods for testing with family designs that are based on the distribution of genotypes, rather than transmissions, are not completely robust to population substructure in the presence of admixture.

In general, FBATs are less powerful than their population‐based counterparts, given the same amount of genotyping required, but in some circumstances, for example for rare variants, and in testing for gene–environment interactions, they can be more powerful.

With rare variants, it is generally considered desirable to consider jointly all rare variants in a specific region. This may require dealing with transmissions of multiple correlated variants that leads to using a number of different approximations.
Regulation of Mitochondrial Energy Metabolism
Authors: Lalou Claude , Bellance Nadège
Published: April 2018

Mitochondria are organelles that play various roles in the physiology processes such as energy production, calcium signalling and apoptosis. Mitochondria are continually solicited to reply to the cell's energy demand. Thus, impairments in mitochondrial function can lead to diseases, because of its implication into cells homeostasis and its essential role in ATP (adenosine triphosphate) production. The energy metabolism is regulated by mTOR (mechanistic target of rapamycin) and AMPK (AMP‐activated protein kinase) signalling pathways. In addition, the mitochondrial biogenesis is controlled by a triad of transcription factors, PGC1α (PPARγ coactivator 1 alpha)–NRF1 (nuclear respiratory factor 1)–TFAM (mitochondrial transcription factor A). Once the regulations behind the energy synthesis are altered, the organelle will adapt accordingly. Overall, the deficiencies that characterised mitochondria in pathologies are not just about structural defaults. Impairments can target regulation processes. In other words, the energy remodelling or worse, the mitochondrial energy crisis, results from upstream factors. Then, the mechanisms behind regulations of mitochondrial energy metabolism appear to impact cell physiology, as can be deduced from remodelling reported in neurodegenerative diseases or even cancer.

Key Concepts

ROS are involved in energy homeostasis by activating AMPK.

PGC1á is not only related to mitochondrial biogenesis. It stimulates gluconeogenesis.

MFN2 may have opposite functions in neurodegenerative disease and cancer.

Mitochondrial deficiencies that induce impairments in energy production, lead to neurodegeneration.

Bioenergetics characterization of tumours is essential for specific targeting in chemotherapy treatment.

LONP1, involved in mitochondrial quality control and energy metabolism, may be consider as a bioenergetic biomarker in cancer.

AMPK induces mitochondrial biogenesis and catabolism; while mTORC1 induces anabolism.
Plant Lipid Droplets
Authors: McLachlan Deirdre H
Published: April 2018

Plant lipid droplets are small, lipid‐rich organelles found in most cell types. Their function as an energy store for postgerminative seedling establishment has been well documented in seeds; however, their function in other tissue types is not so obvious. There is now a growing body of evidence to suggest that lipid droplets are important for biotic and abiotic stress responses in vegetative tissues, and recent work has shown that they are also used as energy stores in those tissues. Biogenesis and degradation of these organelles is currently of great interest to the biotechnology sector, as engineering of these processes can be used to enhance and alter lipid production for applications such as human and animal nutrition, drug delivery and recombinant protein production.

Key Concepts

Lipid droplets are found in all plant organs.

Lipid droplet coat proteins are involved in the biogenesis, degradation and function of plant lipid droplets.

Both seed and nonseed tissues use lipid droplets as an energy store.

Lipid droplets are important for plant stress signalling in vegetative tissues.

Plant lipid metabolism is of key interest to the biotechnology industry.
Heat Shock Protein 47 (
HSP47
)
Authors: Ibrahim Fatin Hazwani , Abd Latip Normala , Abdul‐Wahab Mohd Firdaus
Published: April 2018

Heat shock protein 47 (HSP47), a noninhibitory serine protease inhibitor (SERPIN, clade H1) family member, is a unique collagen‐specific molecular chaperone. The binding of HSP47 to collagen has been the subject of intense investigation, as it binds to and only to collagen. This binding specificity presents a relatively unexplored potential of using HSP47 as a target for treatment of collagen‐related diseases and abnormalities. Homology model studies and structural determination have revealed the important amino acid residues for HSP47‐collagen binding interaction. HSP47‐knockout experiment in mice proved the importance of HSP47 for correct folding of collagen triple helices, thus critical for normal development. Various diagnostic and treatment strategies based on the unique HSP47 functions are now being investigated and proposed.

Key Concepts

Many heat shock proteins (HSPs) act as molecular chaperones to counter the damaging effects of heat, for example unfolding, aggregation and degradation.

HSP47 is a collagen‐specific chaperone, essential for collagen biosynthesis.

HSP47 binding and release is pH‐dependent, with the involvement of His residues that governs the release.

HSP47 has the potential to be used as diagnostic and therapeutic targets in various diseases and abnormalities.

HSP47 modulators and inhibitors are under extensive investigation due to its therapeutic potential in many types of diseases.
Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis
Authors: Capellari Sabina , Baiardi Simone , Rinaldi Rita , Bartoletti‐Stella Anna , Graziano Claudio , Piras Silvia , Calandra‐Buonaura Giovanna , D'Angelo Roberto , Terziotti Camilla , Lodi Raffaele , Donadio Vincenzo , Pironi Loris , Cortelli Pietro , Parchi Piero
Published: April 2018

Truncating mutations in PRNP have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel PRNP stop‐codon mutations (p.Y163X, p.Y169X) in two Italian kindreds. Disease typically presented in the third or fourth decade with progressive autonomic failure and diarrhea. Moreover, one proband (p.Y163X) developed late cognitive decline, whereas some of his relatives presented with isolated cognitive and psychiatric symptoms. Our results strengthen the link between PRNP truncating mutations and systemic abnormal PrP deposition and support a wider application of PRNP screening to include unsolved cases of familial autonomic neuropathy.
Adaptive formation control of autonomous underwater vehicles with model uncertainties
Authors: Gao Zhenyu , Guo Ge
Published: April 2018

This paper investigates the formation control problem of underactuated autonomous underwater vehicles (AUVs). What makes this problem different and challenging is that, in the AUV model, the mass and damping matrices are not diagonal with nonzero off‐diagonal terms and unknown hydrodynamic damping terms. To address the effect of nonzero off‐diagonal terms, we introduce a coordinate transformation, while the unknown hydrodynamic damping terms are approximated adaptively by a neural network. Then, a leader‐follower control strategy is presented, where each follower needs to track a virtual vehicle. This strategy translates the formation control problem into a set of position (including heading) tracking problems for the following AUVs. The position and heading tracking controller is designed based on Lyapunov direct method and backstepping technique, taking into account the effect of the nonzero off‐diagonal terms in the mass matrix and the unknown hydrodynamic damping terms. Simulations are given to demonstrate the effectiveness of the control method proposed.
Hydrogen‐Bonded Liquid Crystals in Confined Spaces—Toward Photonic Hybrid Materials
Authors: Spengler Matthias , Dong Ronald Y. , Michal Carl A. , Hamad Wadood Y. , MacLachlan Mark J. , Giese Michael
Published: April 2018

A series of hybrid materials based on chiral nematic mesoporous organosilica (CNMO) films infiltrated with liquid crystalline hydrogen‐bonded assemblies is prepared and characterized with respect to the mutual manipulation of the photonic properties of the host and the liquid‐crystalline behavior of the guest. Detailed differential scanning calorimetry studies reveal the impact of confinement on the mesomorphic behavior of the liquid crystalline assemblies in the pores of the CNMO films. The photonic properties of the chiral nematic mesoporous host can be controlled by changing the temperature or irradiating the films with UV light. These stimuli‐induced phase transitions are accompanied by changes in the orientational order of the mesogens as revealed by 19F NMR spectroscopy. The combination of confinement and changes in the molecular orientation in a unique hybrid material based on hydrogen‐bonded liquid crystals and a porous host with a chiral nematic mesostructure is an interesting concept for the design of optical sensors, reflectors, or filters.
Engineering Micropatterned Dry Adhesives: From Contact Theory to Handling Applications
Authors: Hensel René , Moh Karsten , Arzt Eduard
Published: April 2018

Reversible adhesion is the key functionality to grip, place, and release objects nondestructively. Inspired by nature, micropatterned dry adhesives are promising candidates for this purpose and have attracted the attention of research groups worldwide. Their enhanced adhesion compared to nonpatterned surfaces is frequently demonstrated. An important conclusion is that the contact mechanics involved is at least as important as the surface energy and chemistry. In this paper, the roles of the contact geometry and mechanical properties are reviewed. With a focus on applications, the effects of substrate roughness and of temperature variations, and the long‐term performance of micropatterned adhesives are discussed. The paper provides a link between the current, detailed understanding of micropatterned adhesives and emerging applications.
Cobalt Boron Imidazolate Framework Derived Cobalt Nanoparticles Encapsulated in B/N Codoped Nanocarbon as Efficient Bifunctional Electrocatalysts for Overall Water Splitting
Authors: Liu Mei‐Rong , Hong Qin‐Long , Li Qiao‐Hong , Du Yonghua , Zhang Hai‐Xia , Chen Shumei , Zhou Tianhua , Zhang Jian
Published: April 2018

The development of efficient and low‐cost bifunctional electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is highly desirable for electrochemical energy conversion. Herein, this study puts forward a new Co decorated N,B‐codoped interconnected graphitic carbon and carbon nanotube materials (Co/NBC) synthesized by direct carbonization of a cobalt‐based boron imidazolate framework. It is demonstrated that the carbonization temperature can tune the surface structure and component of the resultant materials and optimize the electrochemically active surface area to expose more accessible active sites, effectively boosting the electrocatalytic activity. As a result, the optimized Co/NBC shows superior bifunctional catalytic activity and stability toward OER and HER in 1.0 m KOH solution. Furthermore, the catalyst can serve as both the anode and cathode for water splitting to achieve a current density of 10 mA cm−2 at a cell voltage of 1.68 V. Experimental results and theoretical calculations indicate that the excellent activity of Co/NBC catalyst benefits from the synergistic effect of partial oxidation of metallic cobalt, conductive N,B‐codoped graphitic carbon and carbon nanotube, and the coupled interactions among these components. This work opens a promising avenue toward the exploration of boron imidazolate frameworks as efficient heteroatom‐doped catalysts for electrocatalysis.
Hydrophobic Patterning‐Based 3D Microfluidic Cell Culture Assay
Authors: Han Sewoon , Kim Junghyun , Li Rui , Ma Alice , Kwan Vincent , Luong Kevin , Sohn Lydia L.
Published: April 2018

Engineering physiologically relevant in vitro models of human organs remains a fundamental challenge. Despite significant strides made within the field, many promising organ‐on‐a‐chip models fall short in recapitulating cellular interactions with neighboring cell types, surrounding extracellular matrix (ECM), and exposure to soluble cues due, in part, to the formation of artificial structures that obstruct >50% of the surface area of the ECM. Here, a 3D cell culture platform based upon hydrophobic patterning of hydrogels that is capable of precisely generating a 3D ECM within a microfluidic channel with an interaction area >95% is reported. In this study, for demonstrative purposes, type I collagen (COL1), Matrigel (MAT), COL1/MAT mixture, hyaluronic acid, and cell‐laden MAT are formed in the device. Three potential applications are demonstrated, including creating a 3D endothelium model, studying the interstitial migration of cancer cells, and analyzing stem cell differentiation in a 3D environment. The hydrophobic patterned‐based 3D cell culture device provides the ease‐of‐fabrication and flexibility necessary for broad potential applications in organ‐on‐a‐chip platforms.
Contact Lenses for Color Blindness
Authors: Badawy Abdel‐Rahman , Hassan Muhammad Umair , Elsherif Mohamed , Ahmed Zubair , Yetisen Ali K. , Butt Haider
Published: April 2018

Color vision deficiency (color blindness) is an inherited genetic ocular disorder. While no cure for this disorder currently exists, several methods can be used to increase the color perception of those affected. One such method is the use of color filtering glasses which are based on Bragg filters. While these glasses are effective, they are high cost, bulky, and incompatible with other vision correction eyeglasses. In this work, a rhodamine derivative is incorporated in commercial contact lenses to filter out the specific wavelength bands (≈545–575 nm) to correct color vision blindness. The biocompatibility assessment of the dyed contact lenses in human corneal fibroblasts and human corneal epithelial cells shows no toxicity and cell viability remains at 99% after 72 h. This study demonstrates the potential of the dyed contact lenses in wavelength filtering and color vision deficiency management.
Bioinspired Stimuli‐Responsive Color‐Changing Systems
Authors: Isapour Golnaz , Lattuada Marco
Published: April 2018

Stimuli‐responsive colors are a unique characteristic of certain animals, evolved as either a method to hide from enemies and prey or to communicate their presence to rivals or mates. From a material science perspective, the solutions developed by Mother Nature to achieve these effects are a source of inspiration to scientists for decades. Here, an updated overview of the literature on bioinspired stimuli‐responsive color‐changing systems is provided. Starting from natural systems, which are the source of inspiration, a classification of the different solutions proposed is given, based on the stimuli used to trigger the color‐changing effect.
Effect of Various Oxidants on Reaction Mechanisms, Self‐Limiting Natures and Structural Characteristics of Al2O3 Films Grown by Atomic Layer Deposition
Authors: Wang Haoran , Liu Yunfei , Liu Hui , Chen Zheng , Xiong Pengpeng , Xu Xiangchen , Chen Fangyi , Li Kun , Duan Yu
Published: April 2018

The present study investigates the Al2O3 films grown by low‐temperature atomic layer deposition (ALD) with water vapor (H2O), oxygen plasma (O2 plasma), and ozone gas (O3) serving as oxidants. The reaction processes with different oxidants are examined by in situ quadrupole mass spectrometry analysis of the gas phase species, which reveals a possible sequential reaction mechanism of trimethylaluminum and O2 plasma. The coefficient of standard deviation (CSD) of the oscillation frequency change of the in situ quartz crystal microbalance (Δf) to represent the self‐limiting nature of the films is used, and an obvious relationship is observed between the CSD of Δf values and the density of ALD films, which suggests the intrinsic relationship between the structural characteristics and the self‐limiting natures of the ALD processes outside the temperature window. Fourier transform infrared spectroscopy reveals a large number of OCO, CO, and CH bonds remaining in the H2O‐based Al2O3 films, and the smallest concentration of carbon species is found to remain in the O3‐based Al2O3 films, which explains the sources of the different self‐limiting natures and structural characteristics for the different oxidant‐based Al2O3 films.
Self‐Cleaning and Antibacterial Zeolitic Imidazolate Framework Coatings
Authors: Miao Weizhen , Wang Jing , Liu Jindun , Zhang Yatao
Published: April 2018

Superhydrophobic surface with self‐cleaning function like lotus leaf can inhibit bacterial adhesion to some extent; however, it cannot completely avoid bacterial contamination because it could not kill them. In this work, a facile modified sol–gel method to prepare self‐cleaning and antibacterial coating is proposed. Zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles with good hydrophobic and antibacterial properties are mixed with polyvinylidene fluoride (PVDF) colloidal particle suspension, then, the PVDF/ZIF‐8 nanocomposite is modified with 1H, 1H, 2H, 2H‐perfluorooctyltriethoxysilane (POTS) to prepare PVDF/ZIF‐8/POTS (PZP) coating solution. The resultant PZP nanocomposite coatings have a high contact angle (>160°) and a low sliding angle (<7°). Meanwhile, it is found that the dirt particles accumulated on the surface can be easily washed off by rolling water droplets, demonstrating its superb self‐cleaning function. Notably, the PZP nanocomposite coating shows excellent antibacterial activity against Gram‐negative Escherichia coli. These ZIF‐8‐based nanocomposite coatings with superb self‐cleaning function and high antibacterial activity denote their great potential in a wider range of practical applications.
Particle Transport–Based Triboelectric Nanogenerator for Self‐Powered Mass‐Flow Detection and Explosion Early Warning
Authors: Gu Guang Qin , Han Chang Bao , Bai Yu , Jiang Tao , He Chuan , Chen Bao Dong , Wang Zhong Lin
Published: April 2018

In the process of particle transport in pipes, particles get charged, and the discharge process can cause fire and explosion, which causes great harm to the safe production. In this paper, a particle transport triboelectric nanogenerator (PT‐TENG) based on particle transport in pipes is developed. The PT‐TENG can be utilized to monitor the mass‐flow of the particles and make explosion early warning without supplying the power. Under the condition of particles passing one by one, the moving speed of the particles can be obtained. When the particles transport continuously, the PT‐TENG can be used as a self‐powered detector to detect the mass flow of the particles in time. The mass flow detector can be installed both inside and outside the transport pipe. The PT‐TENG can be used as a power source to charge capacitors and light up light‐emitting diodes (LEDs). Moreover, a self‐powered explosion early warning device has been developed based on the PT‐TENG, which will have widespread application in the safety production.