bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
Authors: Gholap Vinit V. , Heyder Rodrigo S. , Kosmider Leon , Halquist Matthew S.
Published: March 2020

In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids.
A BRAF V600E Mutation in RET-Negative Medullary Thyroid Cancer
Authors: Robbins Richard J. , Thomas Jessica S. , Osuna Patricia Mejia , Shakil Jawairia
Published: March 2020

We report the case of a woman with a sporadic medullary thyroid carcinoma. Genomic analysis found that her tumor did not contain any common RET mutations but did harbor a BRAF V600E mutation. Only one other well-confirmed example of the BRAF V600E mutation has been reported in an MTC patient. We conclude that this common BRAF mutation may independently drive neoplastic transformation of human parafollicular C cells.
Neisseria meningitidis as a Cause of Septic Arthritis: An Unusual Case of Periprosthetic Joint Infection
Authors: Mc Carthy A. , Broderick J. M. , Molloy A. P.
Published: March 2020

One of the most feared complications after arthroplasty is infection due to its significant impact on patient morbidity. Infection may transfer to the joint at the time of surgery or be seeded, haematologically, to the prosthetic joint from another infection source. In this case, a 72-year-old female presented with symptoms of septic arthritis seven years after her original arthroplasty surgery. At presentation, she denied trauma and any comorbidity which would predispose her to infection. Culturing of samples taken revealed the patient was infected with Neisseria meningitidis, and the patient underwent a DAIR procedure. She continued postoperative long-term antimicrobial therapy with resolution of her infection. Follow-up at one year showed complete resolution of the patient’s illness with a return to premorbid baseline. To our knowledge, this is the third reported case of septic arthritis caused by Neisseria meningitidis in a prosthetic joint in the literature.
USPF: Underwater Shrewd Packet Flooding Mechanism through Surrogate Holding Time
Authors: Ashraf Shahzad , Gao Mingsheng , Mingchen Zheng , Ahmed Tauqeer , Raza Asif , Naeem Hamad
Published: March 2020

The selection of optimal relay node ever remains a stern challenge for underwater routing. Due to a rigid and uncouth underwater environment, the acoustic channel faces inevitable masses that tarnish the transmission cycle. None of the protocols can cover all routing issues; therefore, designing underwater routing protocol demands a cognitive coverage that cannot be accomplished without meticulous research. An angle-based shrewd technique is being adopted to improve the data packet delivery, as well as revitalize the network lifespan. From source to destination, one complete cycle comprises three phases indeed; in the first phase, the eligibility of data packet belonging to the same transmission zone is litigated by Forwarder Hop Angle (FHA) and Counterpart Hop Angle (CHA). If FHA value is equal or greater than CHA, it presages that the generated packet belongs to the same transmission zone; otherwise, it portends that packet is maverick from other sectors. The second phase picks out the best relay node by computing a three-state link quality with prefix values using the Additive-Rise and Additive-Fall method. Finally, the third phase renders a decisive solution regarding exorbitant overhead fistula; a packet holding time is contemplated to prevent the packet loss probability. Simulation results using NS2 have been analyzed, regarding packet delivery ratio, packet error rate, communication overhead, and end-to-end delay. Comparing to HHVBF and GEDAR, USPF indeed has outperformed, leading into the evidence of applicability’s favor.
TAp63-Regulated miRNAs Suppress Cutaneous Squamous Cell Carcinoma through Inhibition of a Network of Cell-Cycle Genes
Authors: Davis Andrew John , Tsinkevich Maksym , Rodencal Jason , Abbas Hussein A. , Su Xiao-hua , Gi Young-Jin , Fang Bin , Rajapakshe Kimal , Coarfa Cristian , Gunaratne Preethi H. , Koomen John M. , Tsai Kenneth Y. , Flores Elsa R.
Published: March 2020

TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63−/− mice exhibit an increased susceptibility to ultraviolet radiation–induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these miRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either miRNA showed downregulation of cell-cycle progression and mitosis-associated proteins. A mouse to human and cross-platform comparison of RNA-sequencing and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Knockdown of these factors in cuSCC cell lines suppressed tumor cell proliferation and induced apoptosis. In addition, selective inhibition of AURKA suppressed cuSCC cell proliferation, induced apoptosis, and showed antitumor effects in vivo. Finally, treatment with miR-30c-2* or miR-497 miRNA mimics was highly effective in suppressing cuSCC growth in vivo. Our data establish TAp63 as an essential regulator of novel miRNAs that can be therapeutically targeted for potent suppression of cuSCC.

Significance:

This study provides preclinical evidence for the use of miR-30c-2*/miR-497 delivery and AURKA inhibition in the treatment of cuSCC, which currently has no FDA-approved targeted therapies.

See related commentary by Parrales and Iwakuma, p. 2439
Zebrin Expression in the Cerebellum of Two Crocodilian Species
Authors: Gutiérrez-Ibáñez  Cristián  , Dannish Max R. , Kohl Tobias , Kettler Lutz  , Carr Catherine E. , Tisdale Ryan K. , Iwaniuk Andrew N. , Luksch Harald , Wylie Douglas R.
Published: March 2020

While in birds and mammals the cerebellum is a highly convoluted structure that consists of numerous transverse lobules, in most amphibians and reptiles it consists of only a single unfolded sheet. Orthogonal to the lobules, the cerebellum is comprised of sagittal zones that are revealed in the pattern of afferent inputs, the projection patterns of Purkinje cells, and Purkinje cell response properties, among other features. The expression of several molecular markers, such as aldolase C, is also parasagittally organized. Aldolase C, also known as zebrin II (ZII), is a glycolytic enzyme expressed in the cerebellar Purkinje cells of the vertebrate cerebellum. In birds, mammals, and some lizards (Ctenophoresspp.), ZII is expressed in a heterogenous fashion of alternating sagittal bands of high (ZII+) and low (ZII–) expression Purkinje cells. In contrast, turtles and snakes express ZII homogenously (ZII+) in their cerebella, but the pattern in crocodilians is unknown. Here, we examined the expression of ZII in two crocodilian species (Crocodylus niloticus and Alligator mississippiensis) to help determine the evolutionary origin of striped ZII expression in vertebrates. We expected crocodilians to express ZII in a striped (ZII+/ZII–) manner because of their close phylogenetic relationship to birds and their larger and more folded cerebellum compared to that of snakes and turtles. Contrary to our prediction, all Purkinje cells in the crocodilian cerebellum had a generally homogenous expression of ZII (ZII+) rather than clear ZII+/– stripes. Our results suggest that either ZII stripes were lost in three groups (snakes, turtles, and crocodilians) or ZII stripes evolved independently three times (lizards, birds, and mammals).
Causes of Chest Compression Interruptions During Out‐of‐Hospital Cardiac Arrest Resuscitation
Authors: Hanisch Jonathan R. , Counts Catherine R. , Latimer Andrew J. , Rea Thomas D. , Yin Lihua , Sayre Michael R.
Published: March 2020

Background

Interruptions in chest compressions contribute to poor outcomes in out‐of‐hospital cardiac arrest. The objective of this retrospective observational cohort study was to characterize the frequency, reasons, and duration of interruptions in chest compressions and to determine if interruptions changed over time.

Methods and Results

All out‐of‐hospital cardiac arrests treated by the Seattle Fire Department (Seattle, WA, United States) from 2007 to 2016 with capture of recordings from automated external defibrillators and manual defibrillators were included. Compression interruptions >1 second were classified into categories using audio recordings. Among the 3601 eligible out‐of‐hospital cardiac arrests, we analyzed 74 584 minutes, identifying 30 043 pauses that accounted for 6621 minutes (8.9% of total resuscitation duration). The median total interruption duration per case decreased from 115 seconds in 2007 to 72 seconds in 2016 (
P
<0.0001). Median individual interruption duration decreased from 14 seconds in 2007 to 7 seconds in 2016 (
P
<0.0001). Among interruptions >10 seconds, median interruption duration decreased from 20 seconds in 2007 to 16 seconds in 2016 (
P
<0.0001). Cardiac rhythm analysis accounted for most compression interruptions. Manual
ECG
rhythm analysis and pulse checks accounted for 41.6% of all interruption time (median individual interruption, 8 seconds), automated external defibrillator rhythm analysis for 13.7% (median, 17 seconds), and manual rhythm analysis and shock delivery for 8.0% (median, 9 seconds).

Conclusions

Median duration of chest compression interruptions decreased by half from 2007 to 2016, indicating that care teams can significantly improve performance. Reducing compression interruptions is an evidence‐based benchmark that provides a modifiable process quality improvement goal.
The “Cinema Remarks”: Wittgenstein on Moving-Image Media and the Ethics of Re-viewing
Authors: Rennebohm Kate
Published: March 2020

This essay uncovers and analyzes philosopher Ludwig Wittgenstein's little-known writings on film and related media, revealing their importance for film and media studies, the field of film philosophy, and for understanding Wittgenstein's later ethical thought. Through an explication of Wittgenstein's idiosyncratic ordinary-language philosophy, the author argues that these cinema remarks speak to Wittgenstein's sense that cinematic media offered new conceptualizations for thought on a variety of subjects. These include the nature of time, visual and phenomenological experience, and subjectivity. The remarks make clear, among other discoveries, that Wittgenstein was thinking about the relation of cinema and “the skeptical mindset” decades before Stanley Cavell made his influential arguments for such a connection. While the first half of the essay draws out the ethical stakes behind Wittgenstein's film remarks, the latter half turns explicitly to the philosopher's later, complex thought about ethics itself. Showing the importance of aesthetics, visuality, and sight to Wittgenstein's understanding of the field, this section addresses his notions of “aspect-seeing” and “aspect-change.” From this, the final section of contends that Wittgenstein's ethics want to work in the way he feels film can—by enabling one to “see anew” one's way of seeing as a way of seeing, thus opening new ethical-existential possibilities for one's way of being in the world.
Arabic Literature of the North Caucasian Naqshbandiyya in the 19th Century
Authors: Alıcı Gülfem
Published: March 2020

This article analyses the Sufi treatise al-Ādāb al-marḍiyya fī l-ṭarīqa al-naqshbandiyya written by the Daghestanian Naqshbandī shaykh Jamāl al-Dīn al-Ghāzīghumūqī (d. 1866/67), the Sufi master, companion and father-in-law of Imām Shāmil (d. 1871). After providing an outline of the life and activities of Shaykh Jamāl al-Dīn I will examine the concepts, persons, and practices treated in his Ādāb which not only provide valuable insights regarding the mystical orientation of the Sufi shaykh, but the North Caucasian Naqshbandiyya during the anti-Russian jihād movement in the 19th century. My aim is to illustrate that this document indicates no or in a minor degree references to the Khālidiyya branch of the Naqshbandiyya. This leads me to the assumption that in the case of the Daghestanian Naqshbandiyya in the 19th century, we have a premature, i.e. not developed form of the Khālidiyya.
Sanctity, Orality and Questions about Cultural and Religious Identity in North Morocco
Authors: El Hour Rachid
Published: March 2020

This study presents some results from my fieldwork dealing with the female saints of the north Moroccan city of Alcazarquivir, which has been carried out between 2012 and 2014 in that village. The connections between orality and writing are more frequent as the educational level of the interviewee is higher; some of these informants raised roader issues regarding the evolution of the customs or the cult of saints. At the same time, it has been possible to observe the dissemination of oral traditions existing in other Moroccan regions that were not gathered in the hagiographical literature. In this study, I will offer some reflections concerning the data collected about a concrete example, that of Lallā ʿĀʾisha al-Khaḍrāʾ, one of the most important saints of Alcazarquivir and main character of a large part of the information compiled about the female saints of this city. Both the oral and written sources used in this study will be provided. Narrations related to Lallā ʿĀʾisha will be analyzed together with additional stories from ethnographic and anthropological sources on Moroccan female saints. The studied narrations highlight the problematic and complex character of Lallā ʿĀʾisha’s historicity, among other things. Finally, the symbolism of color green will be studied since al-Khaḍrāʾ (the Green) is the denomination by which Lallā ʿĀʾisha is known.
Notes on the genus Pseudoliparis (Orchidaceae, Malaxidinae), with description of a new species from New Guinea and a new synonymous name

Authors: MARGOŃSKA HANNA B.
Published: March 2020

At present, Pseudoliparis Finet (1907: 536) includes about 44 species, but nearly a quarter of these have been described relatively recently. The species of Pseudoliparis are generally poorly known and represented in herbaria and liquid collections. Many species are still known from only a few specimens or just the type-collection/protologue (e.g. especially some of Schlechter’s species). Their distribution also contributes to making them poorly known: tropical regions of Southeast Asia through Micronesia, especially New Guinea and the surrounding islands. Knowledge of their ecology, phenology and occurrence is limited as well. However, recent research clearly shows that their floral morphology and coloration and records about their olfactory characteristics are adaptations to specific pollinators, probably small Diptera or Hymenoptera, which promote reproductive their isolation.
Bothynus entellus (LePeletier & Serville) (Coleoptera: Scarabaeidae: Dynastinae) species group: taxonomic revision and description of two new species
Authors: DUARTE PAULO R.M. , GROSSI PASCHOAL C.
Published: March 2020

The Bothynus entellus (LePeletier & Serville) (Coleoptera: Scarabaeidae: Dynastinae: Pentodontini) species group is reviewed with redescriptions, diagnoses, illustrations, and separate identification keys to males and females. Distribution maps for all species in this species group are presented for the first time. Furthermore, two new species, Bothynus araya Duarte & Grossi new species and Bothynus condacki Duarte & Grossi new species, are described.
Taiwan's perilous futures: Chinese Nationalism, the 2020 Presidential Elections, and U.S.‐China Tensions Spell Trouble for Cross‐strait Relations
Authors: Gries Peter , Wang Tao
Published: March 2020

The Taiwan Strait is heating up, as Mainland Chinese netizens, generals, and politicians increasingly talk about ‘forceful’ rather than ‘peaceful’ reunification. While Xi Jinping and Chinese nationalists desperately desire Taiwan's reunification, Trump's isolationist “America First” rhetoric has only encouraged reckless Chinese thinking about forcing reunification, and the Taiwanese remain largely passive, unable to confront an overwhelming threat. Wishful thinking in Beijing, Taipei, and Washington is increasing the odds of miscalculation. The 2020 presidential elections in Taiwan and the United States, and the ongoing U.S.‐China trade war, furthermore, bode ill for peace in the Taiwan Strait.
Application of Attachable Magnetic Nerve Stimulator in Intraoperative Facial Nerve Monitoring during Ear Surgery
Authors: Oh Se‐Joon , Choi Sung‐Won , Lee Seokhwan , Na Han‐Seul , Sung Eui‐Suk , Shin Sung‐Chan , Lee Byung‐Joo
Published: March 2020

We developed an attachable magnetic nerve stimulator (AMNS) that connects the metallic instruments to a neurophysiological monitoring unit for monitoring the facial nerve (FN) during ear surgery and present our experiences with intraoperative neuromonitoring (IONM) of the FN using AMNS. The FN in 20 patients who underwent tympanomastoidectomy for chronic ear disease was examined. The electromyography (EMG) amplitudes of the FN using AMNS were assessed. The EMG amplitudes of the FN at 1.00‐mA stimulation during drilling were 265 ± 64 µV in the orbicularis oris and 288 ± 57 µV in the orbicularis oculi. The EMG amplitudes using AMNS attached to the surgical instruments under 0.35‐mA stimulus at the tympanic segment of the FN were 196 ± 43 µV in the orbicularis oris and 197 ± 41 µV in the orbicularis oculi. The application of continuous stimulation with burr and surgical instruments using the AMNS is feasible and effective for FN stimulation and identification.
Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells
Authors: Jin Lu , Yuan Feng , Dai Guangcheng , Yao Qiu , Xiang Han , Wang Lixia , Xue Boxin , Shan Yuxi , Liu Xiaolong
Published: March 2020

Background

High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms.

Methods

O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified.

Results

Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy.

Conclusion

We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK.

Graphical abstract

Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.
Unveiling the impact of glycerol phosphate (DOP) in the dinoflagellate Peridinium bipes by physiological and transcriptomic analysis
Authors: Yang Yanjun , Shi Junqiong , Jia Yunlu , Bai Fang , Yang Songqi , Mi Wenmei , He Shuhan , Wu Zhongxing
Published: March 2020

Background

The ability to use dissolved organic phosphorus (DOP) is important for survival and competition when phytoplankton are faced with scarcity of dissolved inorganic phosphorus (DIP). However, phosphorus availability to the freshwater dinoflagellate Peridinium bipes has received relatively little attention, the efficiency of glycerol phosphate use by phytoplankton has rarely been investigated, and the regulatory molecular mechanisms remain unclear.

Result

In the present study, cultures of the freshwater dinoflagellate Peridinium bipes were set up in 119 medium (+DIP), DIP-depleted 119 medium (P-free), and β-glycerol phosphate-replacing-DIP medium (+DOP). Gene expression was analyzed using transcriptomic sequencing. The growth rate of cells in DOP treatment group was similar to that in DIP group, but chlorophyll a fluorescence parameters RC/CS0, ABS/CS0, TR0/CS0, ET0/CS0 and RE0/CS0 markedly decreased in the DOP group. Transcriptomic analysis revealed that genes involved in photosynthesis, including psbA, psbB, psbC, psbD, psaA and psaB, were downregulated in the DOP group relative to the DIP group. Glycerol-3-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, rather than alkaline phosphatase, were responsible for β-glycerol phosphate use. Intercellular gluconeogenesis metabolism was markedly changed in the DOP group. In addition, genes involved in ATP synthases, the TCA cycle, oxidative phosphorylation, fatty acid metabolism and amino acid metabolism in P. bipes were significantly upregulated in the DOP group compared with the DIP treatment.

Conclusions

These findings suggested that β-glycerol phosphate could influence the photosynthesis and metabolism of P. bipes, which provided a comprehensive understanding of the phosphorus physiology of P. bipes. The mechanisms underlying the use of β-glycerol phosphate and other DOPs are different in different species of dinoflagellates and other phytoplankton. DIP reduction may be more effective in controlling the bloom of P. bipes than DOP reduction.
Combining morphological and metabarcoding approaches reveals the freshwater eukaryotic phytoplankton community
Authors: Huo Shouliang , Li Xiaochuang , Xi Beidou , Zhang Hanxiao , Ma Chunzi , He Zhuoshi
Published: March 2020

Background

Phytoplankton diversity can be difficult to ascertain from morphological analyses, because of the existence of cryptic species and pico- and concealed phytoplankton. In-depth sequencing and metabarcoding can reveal microbial diversity, and identify novel diversity. However, there has been little comparison of metabarcoding and morphological datasets derived from the same samples, and metabarcoding studies covering total eukaryotic phytoplankton diversity are rare. In this study, the variable V7 region of the 18S rDNA gene was employed to explore eukaryotic phytoplankton diversity in 11 Chinese freshwater environments, and further compared with the dataset obtained through morphological identification.

Results

Annotation by the evolutionary placement algorithm (EPA) rather than alignment with the SILVA database improved the taxonomic resolution, with 346 of 524 phytoplankton operational taxonomic units (OTUs) being assigned to the genus or species level. The number of unassigned OTUs was greatly reduced from 259 to 178 OTUs by using the EPA in place of the SILVA database. Metabarcoding detected 3.5 times more OTUs than the number of morphospecies revealed by morphological identification; furthermore, the number of species and the Shannon–Wiener index inferred from the two methods were correlated. A total of 34 genera were identified via both methods, while 31 and 123 genera were detected solely in the morphological or metabarcoding dataset, respectively.

Conclusion

The dbRDA plot showed distinct separation of the phytoplankton communities between lakes and reservoirs according to the metabarcoding dataset. The same pattern was obtained on the basis of 10 environmental variables in the PCO ordination plot, while the separation of the populations based on morphological data was poor. However, 30 morphospecies contributed 70% of the community difference between lakes and reservoirs in the morphological dataset, while 11 morphospecies were not found by metabarcoding. Considering the limitations of each of the two methods, their combination could substantially improve phytoplankton community assessment.
Development of a test method for transformation of veterinary pharmaceuticals and biocides in anaerobic liquid manure
Authors: Junker Thomas , Atorf Cornelia , Berkner Silvia , Düring Rolf-Alexander , Hennecke Dieter , Herrchen Monika , Konradi Sabine , Merrettig-Bruns Ute , Römbke Jörg , Wagner Julia , Weinfurtner Karlheinz
Published: March 2020

Background

Spreading of manure on agricultural soils represents an important pathway by which veterinary medicinal and biocidal products enter the environment. To assess their environmental impact in the context of authorization processes, experimental testing of transformation of these compounds in manure is considered in regulatory guidance documents. However, there is no standardized experimental test method available so far. To fill this gap, an experimental test method was developed to examine transformation in liquid cattle and pig manure.

Results

To account for manure specifics and for a possible influence of manure parameters on transformation rates, a comprehensive data acquisition and statistical analysis were performed. To address the variability of liquid manure of different type and origin, 30 manures were sampled and characterized. Thereof, three cattle and three pig manures were selected to perform anaerobic transformation studies with two radiolabeled veterinary medicinal active substances (14C-salicylic acid and 14C-paracetamol) and a confidential radiolabeled “14C-biocide B” serving as test compounds. Spatial and seasonal variability of manure parameters was quantified, and a sampling technique to obtain homogenous manure samples was developed. Transformation studies with six replicates per sampling point were conducted to examine the influence of test setup, of manure storage conditions, and of parameter variations between manure of the same species and of different species on half-lives, formation of extractable and non-extractable residues and mineralization rates. Finally, a test design was established that yields reproducible results for transformation studies in liquid cattle and pig manure under anaerobic conditions.

Conclusions

Results give a reliable basis for an experimental test method to perform anaerobic transformation studies in liquid cattle and pig manure. The developed test method comprises detailed guidance on selection of sampling date and site, collection from manure tank, storage duration and temperature in the laboratory, duration of manure acclimation period, and the incubation system design. It proved to give reproducible results in a validation ring test performed in a follow-up project and is planned to be submitted as draft test guideline for approval by the OECD.
Identification of key differentially expressed genes and gene mutations in breast ductal carcinoma in situ using RNA-seq analysis
Authors: Zhu Congyuan , Hu Hao , Li Jianping , Wang Jingli , Wang Ke , Sun Jingqiu
Published: March 2020

Background

The aim of this study was to identify the key differentially expressed genes (DEGs) and high-risk gene mutations in breast ductal carcinoma in situ (DCIS).

Methods

Raw data (GSE36863) were downloaded from the database of Gene Expression Omnibus (GEO), including three DCIS samples (DCIS cell lines MCF10.DCIS, Sum102, and Sum225) and one normal control sample (normal mammary epithelial cell line MCF10A). The DEGs were analyzed using NOIseq and annotated via DAVID. Motif scanning in the promoter region of DEGs was performed via SeqPos. Additionally, single nucleotide variations (SNVs) were identified via GenomeAnalysisTK and SNV risk was assessed via VarioWatch. Mutant genes with a high frequency and risk were validated by RT-PCR analyses.

Results

Finally, 5391, 7073, and 7944 DEGs were identified in DCIS, Sum102, and Sum22 cell lines, respectively, when compared with MCF10A. VENN analysis of the three cell lines revealed 603 upregulated and 1043 downregulated DEGs, including 16 upregulated and 36 downregulated transcription factor (TF) genes. In addition, six TFs each (e.g.,E2F1andCREB1) were found to regulate the core up- and downregulated DEGs, respectively. Furthermore, SNV detection results revealed 1104 (MCF10.DCIS), 2833 (Sum102), and 1132 (Sum22) mutation sites. Four mutant genes (RWDD4,SDHC,SEPT7, andSFN) with high frequency and risk were identified. The results of RT-PCR analysis as well as bioinformatics analysis consistently demonstrated that the expression ofRWDD4,SDHC,SEPT7, andSFNwas downregulated in the tumor tissues as compared with that in adjacent non-tumor tissues.

Conclusions

The differentially expressed TFs, TFs regulating DEGs (e.g.,E2F1andCREB1), and high-frequency mutant genes (RWDD4,SDHC,SEPT7, andSFN) might play key roles in the pathogenesis of DCIS.
Implementation of opioid maintenance treatment in prisons in North Rhine-Westphalia, Germany – a top down approach
Authors: Böhmer Kathrin , Schecke Henrike , Render Irmgard , Scherbaum Norbert
Published: March 2020

Background

Opioid Maintenance Treatment (OMT) is a well-evaluated treatment of opioid use disorder (OUD). Especially, under the condition of imprisonment, OMT is a preventive measure regarding infectious diseases such as hepatitis C. However, only a minority of prisoners with OUD are currently in OMT in numerous countries. In 2009, the Ministry of Justice of the federal state of North Rhine-Westphalia (NRW), Germany, launched the process of implementing OMT in prisons with various elements (e.g. development of recommendations regarding the treatment of prisoners with OUD, monitoring the number of prisoners in OMT, education of prison doctors). In the recommendations OMT was defined as the gold standard of treatment of OUD.

Methods

To assess the effectiveness of the implementation strategy a survey on the prevalence of OMT in prisons in NRW was carried out twice a year by the Ministry of Justice between 2008 and 2016. Participants were prisoners in NRW, Germany. The diagnosis of OUD at admission to prison and the treatment state on survey dates was measured.

Results

The number of prisoners in NRW dropped from 17,301 in 2008 to 16,432 in 2016. In the same period, the number of prisoners with OUD (mainly males) dropped from 4201 persons to 3650 persons and the number of prisoners in OMT increased from 139 persons (3.3%) to 1415 (38.7%) persons.

Discussion

Currently, the percentage of prisoners with OUD in OMT in NRW is almost reaching the treatment rate outside prisons in Germany (45–50%). However, after release from prison there is still a high risk for a discontinuation of OMT.

Conclusions

Overall, the top-down approach of implementing OMT in prisons in the federal state of NRW was effective.
Effects of fasting on the expression pattern of FGFs in different skeletal muscle fibre types and sexes in mice
Authors: Jia Wei-hua , Wang Nuo-qi , Yin Lin , Chen Xi , Hou Bi-yu , Wang Jin-hua , Qiang Gui-fen , Chan Chi Bun , Yang Xiu-ying , Du Guan-hua
Published: March 2020

Fibroblast growth factors (FGFs) belong to a large family comprising 22 FGF polypeptides that are widely expressed in tissues. Most of the FGFs can be secreted and involved in the regulation of skeletal muscle function and structure. However, the role of fasting on FGF expression pattern in skeletal muscles remains unknown. In this study, we combined bioinformatics analysis and in vivo studies to explore the effect of 24-h fasting on the expression of Fgfs in slow-twitch soleus and fast-twitch tibialis anterior (TA) muscle from male and female C57BL/6 mice. We found that fasting significantly affected the expression of many Fgfs in mouse skeletal muscle. Furthermore, skeletal muscle fibre type and sex also influenced Fgf expression and response to fasting. We observed that in both male and female mice fasting reduced Fgf6 and Fgf11 in the TA muscle rather than the soleus. Moreover, fasting reduced Fgf8 expression in the soleus and TA muscles in female mice rather than in male mice. Fasting also increased Fgf21 expression in female soleus muscle and female and male plasma. Fasting reduced Fgf2 and Fgf18 expression levels without fibre-type and sex-dependent effects in mice. We further found that fasting decreased the expression of an FGF activation marker gene—Flrt2 in the TA muscle but not in the soleus muscle in both male and female mice. This study revealed the expression profile of Fgfs in different skeletal muscle fibre types and different sexes and provides clues to the interaction between the skeletal muscle and other organs, which deserves future investigations.
Recombinant expression and characterization of two glycoside hydrolases from extreme alklinphilic bacterium Cellulomonas bogoriensis 69B4T
Authors: Li Fan , Dong Jiaying , Lv Xue , Wen Yanqiu , Chen Shan
Published: March 2020

Two novel glycoside hydrolases were cloned from the genomic DNA of alklinphilic bacterium Cellulomonas bogoriensis 69B4T and functionally expressed in Escherichia coli. The two enzymes shared less than 73% of identities with other known glycosidases and belonged to glycoside hydrolase families 5 and 9. Recombinant Cel5A exhibited optimum activity at pH 5.0 and at a temperature of 70 °C, and Cel9A showed optimum activity at pH 7.0 and at a temperature of 60 °C. The two enzymes exhibited activity at alkaline pH 11 and were stable over a wide range of pH. The maximum activities of Cel5A and Cel9A were observed in 0.5 M NaCl and 1 M KCl, respectively. In addition, these two enzymes exhibited excellent halostability with residual activities of more than 70% after pre-incubation for 6 days in 5 M NaCl or 4 M KCl. Substrate specificity analysis revealed that Cel5A and Cel9A specifically cleaved the β-1,4-glycosidic linkage in cellulose with the highest activity on carboxymethyl cellulose sodium (78.3 and 145.3 U/mg, respectively). Cel5A is an endoglucanase, whereas Cel9A exhibits endo and exo activities. As alkali-activated, thermo-tolerant, and salt-tolerant cellulases, Cel5A and Cel9A are promising candidates for further research and industrial applications.
Alternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks
Authors: Zhang Jia-Min , Zou Lee
Published: March 2020

To escape replicative senescence, cancer cells have to overcome telomere attrition during DNA replication. Most of cancers rely on telomerase to extend and maintain telomeres, but 4–11% of cancers use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). ALT is prevalent in cancers from the mesenchymal origin and usually associates with poor clinical outcome. Given its critical role in protecting telomeres and genomic integrity in tumor cells, ALT is an Achilles heel of tumors and an attractive target for cancer therapy. Here, we review the recent progress in the mechanistic studies of ALT, and discuss the emerging therapeutic strategies to target ALT-positive cancers.
mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges
Authors: Zou Zhilin , Tao Tao , Li Hongmei , Zhu Xiao
Published: March 2020

Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.
Alternative splicing signatures in preimplantation embryo development
Authors: Tian Geng G. , Li Jing , Wu Ji
Published: March 2020

Background

Preimplantation embryo development is a highly ordered sequence of processes and it requires a precise temporal and spatial control of gene expression. Alternative splicing (AS) is a crucial process that changes the genomic instructions into functional proteins, playing a critical role in the regulation of gene expression. Therefore, studies of AS can significantly improve our understanding of transcription and splicing events in preimplantation embryo development.

Results

To study signatures of AS in embryo development, we firstly identified the critical stage for gene transcription during the preimplantation embryo development. By analyzing single cells RNA-seq (scRNA-seq) data, we found that the two-cell stage is a critical stage for gene transcription in preimplantation embryo development. Further study showed that AS was widespread in preimplantation embryo development, especially at the two-cell stage. In combination with high-throughput chromosome conformation (Hi-C) data, we demonstrated that AS genes were highly enriched in TAD boundaries, while they had no relationship with the A/B compartment and TAD.

Conclusion

Our results provide new insight into the relationship among AS, gene transcription and chromatin structure in preimplantation embryo development.
Matrix transformations of Norlund–Orlicz difference sequence spaces of nonabsolute type and their Toeplitz duals
Authors: Kılıçman Adem , Raj Kuldip
Published: March 2020

In this paper, the Nörlund–Orlicz difference sequence space$\mathcal{N}^{t}(\mathcal{F},\Delta^{m}_{n},u,q)$Nt(F,Δnm,u,q)of nonabsolute type is introduced as a domain of Nörlund means which is isomorphic to the space$\ell(p)$ℓ(p)and the basis of the space is constructed. Additionally, theα−,β−, andγ-duals of the spaces are computed and their matrix transformations are given. Finally, the properties like rotundity, modularity of the newly formed spaces are established.
Flexural Capacity and Behaviour of Geopolymer Concrete Beams Reinforced with Glass Fibre-Reinforced Polymer Bars
Authors: Ahmed Hemn Qader , Jaf Dilshad Kakasor , Yaseen Sinan Abdulkhaleq
Published: March 2020

Geopolymer concrete (GPC) with Glass fibre-reinforced polymer (GFRP) bars can provide a better construction system with high sustainability, high durability, and adequate strength. Few studies deal with the combination of these materials. The present investigation obtains the flexural capacity and behaviour of GPC and ordinary Portland concrete beams reinforced with GFRP bars (GFRP-RGPC and GFRP-ROPC, respectively). Twelve beams consisting of nine GFRP-RGPC and three GFRP-ROPC beams were cast and tested by using the four-point bending test over an active span of 2000 mm. Rebar ratio, compressive strength, and concrete types were taken as the variables. Initial cracking load, ultimate load capacity, load–deflection behaviour, Load–strain curves, crack width, the number of cracks and failure modes, were studied. Experimental results of beams were compared with the proposed equations provided by ACI 440.1R-15, CSA S806-12, and parabolic stress block method. The Results showed the decrease of deflection and increase of first cracking load by increasing the compressive strength. A slight increase in the deflection of GFRP-RGPC beams and approximately the same value of ultimate load were observed. GFRP-RGPC beams also recorded a higher value of crack width compared with GFRP-ROPC beams. The parabolic stress block method predicted the flexural capacity of the beams close to the experimental results rather than ACI 440.1R-15 and CSA S806-12.
Biometric and genetic differences in kelabau (Osteochilus spp.) as revealed using cytochrome c oxidase subunit 1
Authors: Asiah Nur , Junianto Junianto , Yustiati Ayi , Sukendi Sukendi , Fahmi Melta Rini , Muchlisin Zainal A. , Kadapi Muhamad , Windarti Windarti
Published: March 2020

Background: Kelabau (Osteochilus spp.) is a freshwater fish commonly found in the rivers of Riau, Indonesia. Researchers believe that these are Osteochilus kelabau; however, accurate taxonomic determination of these fish in Riau waters has not been made. The purpose of this study was to facilitate the identification of the kelabau based on its morphology and genetics using biometric and cytochrome c oxidase subunit 1 (CO1) analyses, respectively.

Methods: Fish samples were collected from the Siak, Kampar and Rokan rivers in Riau Province, Indonesia. The DNA of 90 fish was extracted from the caudal fins using a DNA extraction kit, after which it was amplified using primers Fish-F1 and Fish-R1. Sequencing was conducted by Applied Biosystems Macrogen Korea, and the DNA sequences were then edited and aligned using MEGA v. 7. All samples were BLAST-searched for identification using the National Center for Biotechnology Information and BOLD System. Phylogenetic trees were constructed, and the similarity index was calculated using accession numbers AP011385.1 and KC631202.1 in GenBank.

Results: Analysis of the consensus barcode sequence for 86 species revealed a high percentage of barcode matches (96%–97% in GenBank and 96.6%–96.76% in the BOLD System). The nucleotide distance between groups of kelabau from the different rivers based on the Kimura 2-parameter model gave the following results: 0.05% between groups from the Siak and Kampar rivers, 0.09% between those from the Siak and Rokan rivers and 0.05% between those from the Kampar and Rokan rivers. The nucleotide distance between the groups in the Siak (0.09%), Kampar (0.00%) and Rokan (0.10%) Rivers indicated that the kelabau in those rivers were related to each other.

Conclusions: Based on the results of the research data using CO1 and biometric analyses, the kelabau were confirmed to be O. melanopleurus.
A case of osteomalacia in human skeletal remains from St Hripsime Church (Horom, Armenia)
Authors: Khudaverdyan A. Yu. , Yengibaryan A. A. , Hovhanesyan A. A. , Khachatryan H. H. , Yeganyan L. G.
Published: March 2020

In this study, we investigated the remains of an individual that were recovered during cleansing work of the Church of St Hripsime. Macroscopic and X-Ray inspections yielded pathological criteria which indicated osteomalacic origin. The findings of the study suggest that the individual who lived in the Late Medieval period may have gone through multiple episodes of vitamin D deficiency. Vitamin D deficiency as an effect of deficient exposure to sunlight (in particular, in rural individuals who lived in underground houses) and nourishment deficiency could be described as the main causes leading to osteomalacia in Armenia.
Anthropology Section of the Estonian Naturalists Society 80
Authors: Veldre Gudrun
Published: March 2020

Anthropology Section of the Estonian Naturalists Society 80
Practice Summary: Improved Reliability via Optimization in Residential Microgrids
Authors: McIlvenna Amelia , Ostrowski Jim , Herron Andrew , King Daniel , Irminger Philip , Hambrick Joshua , Ollis Ben
Published: March 2020

Southern Company is an electric utility that is embracing residential microgrids as a platform for distributed energy. The first residential microgrid in the southeastern United States was constructed in Hoover, Alabama, as a testbed for development. To operate the microgrid, we developed an optimization model for unit commitment and economic dispatch. The optimization model was implemented in a microgrid central controller and tested under various operational scenarios. Challenges also include developing a pricing algorithm to deliver price forecasts to the residential homes in the microgrid and open-source software restrictions.
THE PRINCIPAL’S LEADERSHIP AS THE EFFORT TO BUILD STUDENTS’ CHARACTER
Authors: Dekawati Ipong
Published: March 2020

Education is an effort to change behavior as well as building the character of the students. The decisive character of students is the foundation for the realization of national dignity in the future. In the education institution, the principal has the responsibility for making an effort to build the students’ character. This research focused on investigating the principal’s leadership in building students’ character. The research method used is descriptive and verification methods—a quantitative method conducted in this research. The data collection, the direct observation within five junior high schools, interviews with five principals of junior high school, and questionnaire (closed and structured) distributed to 85 teachers. The samples determined by using Slovin formulas with a simple random sampling technique. The regression analysis technique used in the process of data analysis. The significant test was done by doing F-test. The result shows that principal leadership is one of the alternative ways to build students’ character. Based on the result, the author suggests that (1) the principal improves information disclosure through communication by maximizing digital communication facilities and holding flag ceremony to convey information optimally. (2) The principal builds solid teamwork and participates in social activities through cooperation with local communities in protecting the environment.