bluuebunny/crossref_metadata_2025 huggingface dataset:
A cross‐sectional study on HPV testing with type 16/18 genotyping for cervical cancer screening in 11,064 Chinese women
Authors: Wu Qiongyan , Zhao Xiumin , Fu Yunfeng , Wang Xinyu , Zhang Xiaofei , Tian Xun , Cheng Bei , Lu Bingjian , Yu Xiao , Lan Suqiu , Lu Weiguo , Ma Ding , Cheng Xiaodong , Xie Xing
Published: April 2017

Cytology‐based cervical cancer screening is restricted because of a lack of cytologists. Thus, HPV‐based instead of cytology‐based screening may be a more suitable strategy in China. Here, we assessed the effectiveness of HPV testing (Cobas® 4800 Test, Roche) and HPV‐based programs to detect high‐grade cervical intraepithelial neoplasia (CIN) or cancer compared with cytology (Thinprep, Hologic) and cytology‐based programs through a cross‐sectional study in 11,064 Chinese women aged 21–65 years who were enrolled from Longyou County in Zhejiang Province, China. The rates of HPV positivity and cytology abnormality were 9.8% and 6.1%, respectively. The HPV positivity rate had two age peaks, 21–24 (15.4%) and 60–65 (14.4%) years. According to adjusted data, HPV testing demonstrated significantly higher sensitivity and negative predictive value (NPV) than cytology for detecting CIN2 or worse (90.0% vs. 66.7%, 99.9% vs. 99.5%), and there was an acceptable specificity (91.3%) and positive predictive value (PPV, 12.5%). Furthermore, primary HPV testing with type 16/18 genotyping showed the highest sensitivity (78.6%) and NPV (99.7%) among four screening strategies, and there was similar specificity (96.8%) and PPV (23.9%) compared with co‐testing screening to detect CIN2+, while there were fewer colposcopies (4.2) and tests (106.3) performed than with co‐testing and primary cytology screening to detect a case of high‐grade CIN. The differences in effectiveness were approximately similar when CIN3+ was the identifying target. Our findings suggest that primary HPV testing with type 16/18 genotyping has a higher sensitivity and NPV, possesses optimal cost/effectiveness in the first round of screening and is a feasible strategy of cervical cancer screening for Chinese women.
A rare cause of mechanical bowel obstruction: ingested vinyl glove. Unexpected diagnosis at laparoscopy
Authors: Smerieri Nazareno , Barbieri Italo , Fumagalli Matteo , Luppi Davide , Lanaia Andrea , Bonilauri Stefano
Published: April 2017

Key Clinical Message

The report suggests that, when the patient's history, clinical examination, and findings do not lead to a clear diagnosis in case of an acute abdomen, a laparoscopic approach, that has both, diagnostic and therapeutic value, is advised.
Interstitial lung disease of infancy caused by a new NKX2‐1 mutation
Authors: Safi Khalid H. , Bernat John A. , Keegan Catherine E , Ahmad Ayesha , Hershenson Marc B. , Arteta Manuel
Published: April 2017

Key Clinical Message

Patients with personal or family history of congenital hypothyroidism, and/or neurological findings that also have chronic respiratory symptoms may have a mutation in the NKX2.1 gene as the unifying cause of their disease. Brain–lung–thyroid disease is the ensuing condition, which although rare, needs to be part of the differential diagnosis.
Syndrome of progressive bone marrow failure and pancreatic insufficiency remains cryptic despite whole exome sequencing: variant of Shwachman‐Diamond syndrome or new condition?
Authors: Fadus Matthew C. , Rush Eric T. , Lettieri Christina K.
Published: April 2017

Key Clinical Message

This case underscores the difficulty in diagnosis of bone marrow failure disorders, as the presentation of disease can be inconsistent, complicated by complex and ever‐expanding genetic etiologies. A patient who presents with bone marrow failure and pancreatic insufficiency raises the question of Shwachman‐Diamond syndrome (SDS) or a new condition which resembles SDS.
Peripartum cardiomyopathy, what if your patient plans to reconceive?
Authors: Al Bannay Rashed , Husain Aysha , AlJufairi Zainab
Published: April 2017

Key Clinical Message

Patients with peripartum cardiomyopathy (PPCM) often express a desire to conceive again, and the risk of relapse in future pregnancies should be disclosed. No consensus is available that can determine that risk. Adequate contractile reserve, evidenced by a stress echocardiogram (exercise or dobutamine), can identify those with lower relapse risk.
“Chronic myelogenous leukemia in primary blast crisis” rather than “de novo BCR‐ABL1‐positive acute myeloid leukemia”
Authors: Pastoret Cedric , Houot Roch
Published: April 2017

Key Clinical Message

Differentiating chronic myelogenous leukemia in primary blast crisis (CML‐BC) from de novo BCR‐ABL1‐positive acute myeloid leukemia (AML) is a diagnostic challenge with therapeutic consequences. In our case, a basophilia, the presence of the Philadelphia chromosome in all metaphases and the strict exclusion of molecular hallmarks of AML lead us to retain the diagnosis of CML‐BC rather than BCR‐ABL1+ AML.
Highly Efficient Atom‐Economic Synthesis of Chiral Bis(indolyl)methanes Bearing Quaternary Stereogenic Carbon Centers
Authors: Zhang Yan , Zhang Si‐Xiang , Fu Li‐Na , Guo Qi‐Xiang
Published: April 2017

A highly efficient atom‐economic method for the preparation of chiral 3,3′‐bis(indolyl)methanes (3,3′‐BIMs) was developed. A chiral phosphoric acid (1 mol %) was found to promote the formation of structurally divers BIMs with quaternary stereogenic carbon centers in excellent yields with excellent enantioselectivities. Control experiments indicated that the simultaneous formation of two hydrogen bonds between the catalyst and the substrate was the key factor to obtain a good stereoselective outcome.
A Ratiometric Near‐Infrared Fluorogen for the Real Time Visualization of Intracellular Redox Status during Apoptosis
Authors: Saranya Giridharan , Anees Palapuravan , Joseph Manu M. , Maiti Kaustabh K. , Ajayaghosh Ayyappanpillai
Published: April 2017

Direct monitoring of apoptotic progression is a major step forward for the early assessment of therapeutic efficacy of certain treatments and the accurate evaluation of the spread of a disease. Here, the regulatory role of glutathione (GSH) is explored as a potential biomarker for tracking apoptosis. For this purpose, a near‐ infrared (NIR) squaraine dye is introduced that is capable of sensing GSH in a ratiometric manner by switching its emission from NIR (690 nm) to visible region (560 nm). The favorable biocompatible attributes of the probe facilitated the real‐time monitoring of apoptotic process in line with the conventional apoptotic assay. Furthermore, the robust nature of the probe was utilized for the quantitative estimation of GSH during different stages of apoptosis. Through this study, an easy and reliable method of assaying apoptosis is demonstrated, which can provide valuable insights in translational clinical research.
A Blueprint for Software Architectures in Process Optimization
Authors: Fricke Armin , Schöneberger Jan Christian
Published: April 2017

How to use software effectively and efficiently in the chemical, pharmaceutical and life science industries is one of the central questions in Process Optimization. The paper shows in five examples from chemical engineering how various programs connect to a first principle process simulator through the existing interfaces. It also shows how the functionality of a process simulator can be enhanced. Through the application programming interface (CC‐API), the objects are re‐used beyond the boundaries of the flow sheeting program CHEMCAD.
Optimization‐Based Process Synthesis Based on a Commercial Flowsheet Simulator
Authors: Janus Tim , Foussette Christophe , Urselmann Maren , Tlatlik Stephen , Gottschalk Axel , Emmerich Michael , Bäck Thomas , Engell Sebastian
Published: April 2017

Anhand von Simulationen mit einem kommerziellen Fließbildsimulator werden optimierte Fließbilder generiert. Da der Simulator keine expliziten Gleichungen und keine Ableitungen zur Verfügung stellt, wird ein memetischer Algorithmus eingesetzt. Dieser kombiniert einen evolutionären Algorithmus mit einer lokalen ableitungsfreien Suche. Es werden diskrete Designvariablen und kontinuierliche Parameter optimiert. Anhand eines Fallbeispiels wird das Verhalten des Optimierers demonstriert. Von Experten vorgeschlagene Startlösungen können deutlich verbessert werden, allerdings ist der Rechenzeitbedarf für komplexere Fließbilder noch relativ hoch.
Synthesis of Qinghaosu Analogues from Dihydroqinghao Aldehyde: A Dark Singlet Oxygen Approach
Authors: Liu Xunshen , Chen Huijun , Xu Zejun , Wu Yikang , Liu Bo
Published: April 2017

A range of qinghaosu (artemisinin) analogues were synthesized from modified dihydroqinghao acid/aldehyde using dark singlet oxygen to trigger off the key step of the trioxane formation. The newly accessed 1,2,4‐trioxanes featured a side chain extended from the carbon corresponding to the lactone carbonyl group of qinghaosu through a stable carbon‐carbon single bond instead of an acetal oxygen‐carbon bond in most similar analogues in the literature. Biotin and various amines were also connected to the qinghaosu core, respectively, through such a linear tether in efforts to develop hybrids and potentially useful probes in search of the in vivo targets.
A Time‐Resolved FRET Cell‐Based Binding Assay for the Apelin Receptor
Authors: Valencia Christel , Dujet Céline , Margathe Jean‐François , Iturrioz Xavier , Roux Thomas , Trinquet Eric , Villa Pascal , Hibert Marcel , Dupuis Elodie , Llorens‐Cortes Catherine , Bonnet Dominique
Published: April 2017

Analogues of apelin‐13 carrying diverse spacers and an ad hoc DY647‐derived fluorophore were designed and synthesized by chemoselective acylation of α‐hydrazinopeptides. The resulting probes retain very high affinity and efficacy for both the wild‐type and SNAP‐tagged apelin receptor (ApelinR). They give a time‐resolved FRET (TR‐FRET) signal with rare‐earth lanthanides used as donor fluorophores grafted onto the SNAP‐tagged receptor. This specific signal allowed the validation of a binding assay with a high signal‐to‐noise ratio. In such an assay, the most potent sub‐nanomolar fluorescent probe was found to be competitively displaced by the endogenous apelin peptides with binding constants similar to those obtained in a classical radioligand assay. We have thus validated the first TR‐FRET cell‐based binding assay for ApelinR with potential high‐throughput screening applications.
Cytologic features and clinical implications of undifferentiated carcinoma with osteoclastic giant cells of the pancreas: An analysis of 15 cases
Authors: Reid Michelle D. , Muraki Takashi , HooKim Kim , Memis Bahar , Graham Rondell P. , Allende Daniela , Shi Jiaqi , Schaeffer David F. , Singh Remmi , Basturk Olca , Adsay Volkan
Published: April 2017

BACKGROUND

The cytologic features of undifferentiated pancreatic carcinoma with osteoclastic giant cells (UOC) are rarely described.

METHODS

Cytologic and clinicopathologic characteristics in 15 UOC fine‐needle aspiration (FNA) specimens were analyzed.

RESULTS

FNA specimens were obtained from 6 men and 8 women with a mean age of 65 years who had UOCs (head, n = 7; body, n = 3; and tail, n = 4) with a mean radiologic size 7.3 cm, and some had a cystic component (n = 9). Three cell types (osteoclastic giant cells, pleomorphic tumor giant cells, and spindled/histiocytoid cells) were observed in 12 of 15 specimens (80%); and pancreatic ductal adenocarcinoma (PDAC) was present in 11 specimens. FNA diagnoses were UOC (n = 6), PDAC (n = 5), poorly differentiated carcinoma (n = 2), “suspicious for neoplasm” (n = 1), and “negative” (n = 1). Five of 5 specimens with osteoclastic giant cells were positive for cluster of differentiation 68 (CD68) (a glycoprotein that binds to low‐density lipoprotein). Pleomorphic tumor giant cells and spindled/histiocytoid cells were positive for pancytokeratin (6 of 7 specimens), CAM5.2 (2 of 3 specimens), and epithelial membrane antigen (2 of 2 specimens). INI‐1 protein expression was retained in 3 of 3 specimens. The Ki‐67 labeling index was assessed in 3 specimens and was 12%, 18%, and 40%; 4 of 12 resected UOCs were pure, and 8 were mixed with PDAC. One resection specimen had intraductal papillary mucinous neoplasm, and 2 had mucinous cystic neoplasms. The median overall survival (OS) of patients who had UOCs identified on FNA was 8 months (6 died [OS, 8 months; range, 2‐22 months], and 8 remained alive [OS, 3 months; range, 1‐27 months]), which was similar to the survival of 74 patients who had PDACs identified on FNA (OS, 15 months; P = .279) but worse than that of the 27 patients with UOCs who did not undergo FNA (OS, 92 months; P = .0135).

CONCLUSIONS

The 3 classical UOC cell types are identifiable on FNA, making cytologic diagnosis possible if considered in the differential. A PDAC component is often also observed. The survival advantage of UOC over pure PDAC appears to be negated by FNA and requires further investigation. Cancer Cytopathol 2017;125:563–75. © 2017 American Cancer Society.
Columnar cell variant of papillary thyroid carcinoma: Cytomorphological characteristics of 11 cases with histological correlation and literature review
Authors: Bongiovanni Massimo , Mermod Maxime , Canberk Sule , Saglietti Chiara , Sykiotis Gerasimos P. , Pusztaszeri Marc , Ragazzi Moira , Mazzucchelli Luca , Giovanella Luca , Piana Simonetta
Published: April 2017

BACKGROUND

The columnar cell variant of papillary thyroid carcinoma (PTC‐CCV) is a rare entity that demonstrates a more aggressive clinical course compared with the more common subtypes of PTC. On histology, it is defined by papillae or gland‐like structures lined by columnar cells displaying prominent nuclear stratification. Because to the authors' knowledge no characteristic cytomorphological features have been identified to date and typical features of PTC often are absent on cytology, the diagnosis of PTC‐CCV by fine‐needle aspiration (FNA) is challenging. This prompted the authors to evaluate a series of PTC‐CCV cases to identify features that could facilitate its diagnosis by FNA.

METHODS

A total of 11 surgical specimens of PTC‐CCV with corresponding preoperative cytology were identified over a 21‐year period. The cytological features of the aspirated specimens, consisting mostly of Papanicolaou and Diff‐Quick smears, were evaluated retrospectively.

RESULTS

All cases demonstrated the presence of papillary structures. The most important features observed in PTC‐CCV FNA specimens were hypercellularity with nuclear superposition and a paucity of nuclear pseudoinclusions and grooves.

CONCLUSIONS

Although PTC‐CCV may demonstrate features that overlap with those of the classic variant of PTC, hypercellular smears with papillary structures covered by cells with pseudostratified nuclei that show a paucity of nuclear pseudoinclusions and grooves should alert the cytopathologist to the possibility of this diagnosis. Cancer Cytopathol 2017;125:389–97. © 2017 American Cancer Society.
Ligand‐Controlled Formation and Photoluminescence Properties of CH3NH3PbBr3 Nanocubes and Nanowires
Authors: Zhang Feng , Chen Cheng , Kershaw Stephen V. , Xiao Changtao , Han Junbo , Zou Bingsuo , Wu Xing , Chang Shuai , Dong Yuping , Rogach Andrey L. , Zhong Haizheng
Published: April 2017

Light‐emitting halide perovskites are currently emerging as promising solution‐processed materials for optoelectronic applications, and correlations between their physical properties and morphologies are important drivers to guide material and device optimization. There is still a lack of precise control of the morphology in colloidal perovskite materials, and in the related studies of their shape‐dependent optical properties. Capitalizing on our previous works on the ligand‐assisted reprecipitation synthesis of colloidal perovskite nanocrystals, we have addressed the role of key experimental parameters in determining the degree of supersaturation that drives the crystallization of CH3NH3PbBr3 precursors. By adjusting the amount of ligands, we fabricated single crystalline CH3NH3PbBr3 nanocubes (size: ≈500 nm) and nanowires (length: 2–4.5 μm, width: ≈100 nm), and conducted steady‐state, time‐resolved, excitation power and temperature‐dependent photoluminescence measurements to investigate their shape‐dependent photoluminescence properties.
Enhanced Photocatalytic Water Splitting in a C2N Monolayer by C‐Site Isoelectronic Substitution
Authors: Kishore M.R. Ashwin , Ravindran P.
Published: April 2017

Two‐dimensional (2D) semiconductors have shown great promise as efficient photocatalysts for water splitting. Tailoring the band gap and band edge positions are the most crucial steps to further improve the photocatalytic activity of 2D materials. Here, we report an improved photocatalytic water splitting activity in a C2N monolayer by isoelectronic substitutions at the C‐site, based on density functional calculations. Our optical calculations show that the isoelectronic substitutions significantly reduce the band gap of the C2N monolayer and thus strongly enhance the absorption of visible light, which is consistent with the observed redshift in the optical absorption spectra. Based on the HSE06 functional, the calculated band edge positions of C2−xSixN and C2−xGexN monolayers are even more favorable than the pristine C2N monolayer for the overall photocatalytic activity. On the other hand, for the C2−xSnxN monolayer, the conduction band minima is more positive than the oxygen reduction potential and, hence, Sn substitution in C2N is unfavorable for the water decomposition reaction. In addition, the isoelectronic substitutions improve the separation of e−–h+ pairs, which, in turn, suppress the recombination rate, thereby leading to enhanced photocatalytic activity in this material. Our results imply that Si‐, and Ge‐substituted C2N monolayers will be a promising visible‐light photocatalysts for water splitting.
Immunoblotting and Immunodetection
Authors: Ni Duojiao , Xu Peng , Gallagher Sean
Published: April 2017

Immunoblotting (western blotting) is used to identify specific antigens recognized by polyclonal or monoclonal antibodies. This unit provides protocols for all steps, starting with solubilization of the protein samples, usually by means of SDS and reducing agents. Following solubilization, the material is separated by SDS‐PAGE and the antigens are electrophoretically transferred to a membrane, a process that can be monitored by reversible staining with Ponceau S. The transferred proteins are bound to the surface of the membrane, providing access to immunodetection reagents. After nonspecific binding sites are blocked, the membrane is probed with the primary antibody and washed. The antibody‐antigen complexes are tagged with fluorophores, horseradish peroxidase, or alkaline phosphatase coupled to a secondary anti‐IgG antibody, and detected using appropriate fluorescent imaging technologies or with chromogenic or luminescent substrates. Finally, membranes may be stripped and reprobed. © 2017 by John Wiley & Sons, Inc.
Ethnic Difference in the Pharmacodynamics‐efficacy Relationship of Dipeptidyl Peptidase‐4 Inhibitors Between Japanese and non‐Japanese Patients: A Systematic Review
Authors: Ito Y , Ambe K , Kobayashi M , Tohkin M
Published: April 2017

A systematic review of the differences in the efficacy of dipeptidyl peptidase‐4 (DPP‐4) inhibitors between Japanese and non‐Japanese subjects was conducted. We searched for randomized controlled trials in patients with type 2 diabetes mellitus (T2DM) that studied the intervention of a DPP‐4 inhibitor once‐daily vs. placebo, as monotherapy or as add‐on therapy. Data regarding placebo‐corrected HbA1c reduction and trough DPP‐4 inhibition rate after ≥12 weeks' treatment were extracted. In the 12 eligible studies, linear regression analysis revealed that the hemoglobin A1c (HbA1c) reduction at each DPP‐4 inhibition level was larger in studies involving Japanese patients than in studies involving non‐Japanese patients, with statistical significance between the two groups (P < 0.0001). Sensitivity analysis excluding studies of add‐on therapies supported the robustness of the result. Our study indicated that DPP‐4 inhibitors show greater efficacy in Japanese patients than in non‐Japanese patients, which may be an important consideration in the global development strategy of new diabetic medications.
Dendrite Suppression by Synergistic Combination of Solid Polymer Electrolyte Crosslinked with Natural Terpenes and Lithium‐Powder Anode for Lithium‐Metal Batteries
Authors: Shim Jimin , Lee Jae Won , Bae Ki Yoon , Kim Hee Joong , Yoon Woo Young , Lee Jong‐Chan
Published: April 2017

Lithium‐metal anode has fundamental problems concerning formation and growth of lithium dendrites, which prevents practical applications of next generation of high‐capacity lithium‐metal batteries. The synergistic combination of solid polymer electrolyte (SPE) crosslinked with naturally occurring terpenes and lithium‐powder anode is promising solution to resolve the dendrite issues by substituting conventional liquid electrolyte/separator and lithium‐foil anode system. A series of SPEs based on polysiloxane crosslinked with natural terpenes are prepared by facile thiol–ene click reaction under mild condition and the structural effect of terpene crosslinkers on electrochemical properties is studied. Lithium powder with large surface area is prepared by droplet emulsion technique (DET) and used as anode material. The effect of the physical state of electrolyte (solid/liquid) and morphology of lithium‐metal anode (powder/foil) on dendrite growth behavior is systematically studied. The synergistic combination of SPE and lithium‐powder anode suggests an effective solution to suppress the dendrite growth owing to the formation of a stable solid–electrolyte interface (SEI) layer and delocalized current density.
A comprehensive assessment of immunophenotyping performed in cryopreserved peripheral whole blood
Authors: Verschoor Chris P. , Kohli Vikas , Balion Cynthia
Published: April 2017

Background

Monitoring the frequency and phenotype of white blood cell subsets using flow cytometry (immunophenotyping) has proven to be an incredibly powerful tool in the assessment of health. Although improved technologies have aided in the practical implementation of immunophenotyping in clinical and epidemiological studies, the transportation of blood from the site of collection to a central laboratory for analysis within a reasonable timeframe may not be feasible. Hence, the purpose of the following study was to investigate the validity of cryopreserved whole blood as a simple to prepare and cost‐effective biospecimen for multi‐colour immunophenotyping in a large epidemiological study—namely, The Canadian Longitudinal Study on Aging (CLSA).

Methods

In fresh and cryopreserved blood and cryopreserved peripheral blood mononuclear cells (PBMCs) we measured cellular viability and the quantities (absolute counts and relative frequencies) of total leukocytes, neutrophils, monocytes, CD4/CD8 T‐lymphocytes, B‐lymphocytes, natural killer (NK) cells, NKT cells, plasmacytoid dendritic cells (pDCs), and basophils.

Results

Estimates obtained from immunophenotyping in cryopreserved blood were comparable to fresh blood (Avg. rho: absolute cell counts = 0.71, frequency relative to CD45 leukocytes = 0.84, frequency relative to PBMCs = 0.86), cryopreserved PBMCs (0.86), and complete blood counts by hematological analyzer (0.71) and exhibited good intra‐ and inter‐assay precision (Avg. CV = 4% and 3%, respectively).

Conclusions

Given this, cryopreserved blood should be considered a feasible biospecimen in clinical and epidemiological studies requiring leukocyte immunophenotyping. © 2017 International Clinical Cytometry Society
Isobolographic Analyses of Proglumide–Celecoxib Interaction in Rats with Painful Diabetic Neuropathy
Authors: Suarez‐Mendez Samuel , Tovilla‐Zarate Carlos A. , Ortega‐Varela Luis F. , Bermudez‐Ocaña Deysi Y. , Blé‐Castillo Jorge L. , González‐Castro Thelma B. , Zetina‐Esquivel Alma M. , Diaz‐Zagoya Juan C. , Esther Juárez‐Rojop Isela
Published: April 2017

Preclinical Research

The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non‐selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase‐2 inhibitor, celecoxib in streptozotocin (STZ)‐induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20–160 mg/kg) and celecoxib (0.3–30 mg/kg) in these fixed dose ratio combinations induced dose‐dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED40 values were calculated for the treatments and an isobologram was constructed. Theoretical ED40 values for combination proglumide–celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED40 values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide–celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116–123, 2017. ©2017 Wiley Periodicals, Inc.
Maternal rearing environment impacts autonomic nervous system activity
Authors: Bliss‐Moreau Eliza , Moadab Gilda , Capitanio John P.
Published: April 2017

While it is now well known that social deprivation during early development permanently perturbs affective responding, accumulating evidence suggests that less severe restriction of the early social environment may also have deleterious effects. In the present report, we evaluate the affective responding of rhesus macaque (Macaca mulatta) infants raised by their mothers in restricted social environments or by their mothers in large social groups by indexing autonomic nervous system activity. Following a 25‐hr evaluation of biobehavioral organization, electrocardiogram, and an index of respiration were recorded for 10 min. This allowed for an evaluation of both heart rate and respiratory sinus arrhythmia (RSA), an index of parasympathetic activity, during a challenging situation. Three‐ to four‐month‐old infants raised in restricted social environments had significantly higher heart rates and lower RSA as compared to infants raised in unrestricted social environments, consistent with a more potent stress response to the procedure. These results are consistent with mounting evidence that the environment in which individuals are raised has important consequences for affective processing.
lmplementation of the prolyl hydroxylase inhibitor Roxadustat (FG‐4592) and its main metabolites into routine doping controls
Authors: Eichner Daniel , Van Wagoner Ryan M. , Brenner Mitch , Chou James , Leigh Scott , Wright Lee R. , Flippin Lee A. , Martinelli Michael , Krug Oliver , Schänzer Wilhelm , Thevis Mario
Published: April 2017

The utility of hypoxia‐inducible factor (HIF) prolyl hydroxylase inhibitors as a therapeutic means of treating patients suffering from anaemia has been demonstrated for various clinical settings. However, besides this intended use, HIF stabilizers can be the subject of misuse in amateur and elite sports due to their erythropoietic properties, as recently proven by several cases of adverse analytical findings in doping control testing. Consequently, to allow for adequate and comprehensive test methods, knowledge of the drug candidates' metabolism and analytical options enabling appropriate detection windows in sports drug testing samples (i.e., blood and urine) is essential to doping control laboratories. In the present study, a novel HIF prolyl hydroxylase inhibitor referred to as Roxadustat (FG‐4592) and main plasma‐ and urine‐derived metabolites were investigated in the context of routine doping control analytical approaches. Liquid chromatography‐mass spectrometry‐based test methods were used to study the target analytes' dissociation pathways following electrospray ionization and collision‐induced dissociation. Diagnostic precursor‐product ion pairs were selected to enable the implementation of the intact drug Roxadustat and selected metabolites into multi‐analyte initial testing procedures for plasma and urine specimens. The assays were validated in accordance to guidelines of the World Anti‐Doping Agency (WADA) and results demonstrated the suitability (fitness‐for‐purpose) of the employed analytical methods with detection limits ranging from 0.05 to 1 ng/mL and 1 to 5 ng/mL for urine and plasma, respectively. Subsequently, elimination study plasma and urine samples collected up to 167 h post‐administration were analyzed using the validated methods, which suggested the use of different target analytes for blood and urine analyses with FG‐4592 and its glucuronide, respectively, for optimal detection windows. Additionally, a light‐induced rearrangement product (photoisomer) of Roxadustat resulted in the formation of an additional compound of identical mass. Copyright © 2017 John Wiley & Sons, Ltd.
Inland waters and their role in the carbon cycle of Alaska
Authors: Stackpoole Sarah M. , Butman David E. , Clow David W. , Verdin Kristine L. , Gaglioti Benjamin V. , Genet Hélène , Striegl Robert G.
Published: April 2017

The magnitude of Alaska (AK) inland waters carbon (C) fluxes is likely to change in the future due to amplified climate warming impacts on the hydrology and biogeochemical processes in high latitude regions. Although current estimates of major aquatic C fluxes represent an essential baseline against which future change can be compared, a comprehensive assessment for AK has not yet been completed. To address this gap, we combined available data sets and applied consistent methodologies to estimate river lateral C export to the coast, river and lake carbon dioxide (CO2) and methane (CH4) emissions, and C burial in lakes for the six major hydrologic regions in the state. Estimated total aquatic C flux for AK was 41 Tg C/yr. Major components of this total flux, in Tg C/yr, were 18 for river lateral export, 17 for river CO2 emissions, and 8 for lake CO2 emissions. Lake C burial offset these fluxes by 2 Tg C/yr. River and lake CH4 emissions were 0.03 and 0.10 Tg C/yr, respectively. The Southeast and South central regions had the highest temperature, precipitation, terrestrial net primary productivity (NPP), and C yields (fluxes normalized to land area) were 77 and 42 g C·m−2·yr−1, respectively. Lake CO2 emissions represented over half of the total aquatic flux from the Southwest (37 g C·m−2·yr−1). The North Slope, Northwest, and Yukon regions had lesser yields (11, 15, and 17 g C·m2·yr−1), but these estimates may be the most vulnerable to future climate change, because of the heightened sensitivity of arctic and boreal ecosystems to intensified warming. Total aquatic C yield for AK was 27 g C·m−2·yr−1, which represented 16% of the estimated terrestrial NPP. Freshwater ecosystems represent a significant conduit for C loss, and a more comprehensive view of land‐water‐atmosphere interactions is necessary to predict future climate change impacts on the Alaskan ecosystem C balance.
Long‐term continental changes in wing length, but not bill length, of a long‐distance migratory shorebird
Authors: Lank David B. , Xu Cailin , Harrington Brian A. , Morrison Richard I. Guy , Gratto‐Trevor Cheri L. , Hicklin Peter W. , Sandercock Brett K. , Smith Paul Allen , Kwon Eunbi , Rausch Jennie , Pirie Dominix Lisa D. , Hamilton Diana J. , Paquet Julie , Bliss Sydney E. , Neima Sarah G. , Friis Christian , Flemming Scott A. , Anderson Alexandra M. , Ydenberg Ronald C.
Published: April 2017

We compiled a >50‐year record of morphometrics for semipalmated sandpipers (Calidris pusilla), a shorebird species with a Nearctic breeding distribution and intercontinental migration to South America. Our data included >57,000 individuals captured 1972–2015 at five breeding locations and three major stopover sites, plus 139 museum specimens collected in earlier decades. Wing length increased by ca. 1.5 mm (>1%) prior to 1980, followed by a decrease of 3.85 mm (nearly 4%) over the subsequent 35 years. This can account for previously reported changes in metrics at a migratory stopover site from 1985 to 2006. Wing length decreased at a rate of 1,098 darwins, or 0.176 haldanes, within the ranges of other field studies of phenotypic change. Bill length, in contrast, showed no consistent change over the full period of our study. Decreased body size as a universal response of animal populations to climate warming, and several other potential mechanisms, are unable to account for the increasing and decreasing wing length pattern observed. We propose that the post‐WWII near‐extirpation of falcon populations and their post‐1973 recovery driven by the widespread use and subsequent limitation on DDT in North America selected initially for greater flight efficiency and latterly for greater agility. This predation danger hypothesis accounts for many features of the morphometric data and deserves further investigation in this and other species.
Universal expressions of population change by the Price equation: Natural selection, information, and maximum entropy production
Authors: Frank Steven A.
Published: April 2017

The Price equation shows the unity between the fundamental expressions of change in biology, in information and entropy descriptions of populations, and in aspects of thermodynamics. The Price equation partitions the change in the average value of a metric between two populations. A population may be composed of organisms or particles or any members of a set to which we can assign probabilities. A metric may be biological fitness or physical energy or the output of an arbitrarily complicated function that assigns quantitative values to members of the population. The first part of the Price equation describes how directly applied forces change the probabilities assigned to members of the population when holding constant the metrical values of the members—a fixed metrical frame of reference. The second part describes how the metrical values change, altering the metrical frame of reference. In canonical examples, the direct forces balance the changing metrical frame of reference, leaving the average or total metrical values unchanged. In biology, relative reproductive success (fitness) remains invariant as a simple consequence of the conservation of total probability. In physics, systems often conserve total energy. Nonconservative metrics can be described by starting with conserved metrics, and then studying how coordinate transformations between conserved and nonconserved metrics alter the geometry of the dynamics and the aggregate values of populations. From this abstract perspective, key results from different subjects appear more simply as universal geometric principles for the dynamics of populations subject to the constraints of particular conserved quantities.
Population genomics reveals a candidate gene involved in bumble bee pigmentation
Authors: Pimsler Meaghan L. , Jackson Jason M. , Lozier Jeffrey D.
Published: April 2017

Variation in bumble bee color patterns is well‐documented within and between species. Identifying the genetic mechanisms underlying such variation may be useful in revealing evolutionary forces shaping rapid phenotypic diversification. The widespread North American species Bombus bifarius exhibits regional variation in abdominal color forms, ranging from red‐banded to black‐banded phenotypes and including geographically and phenotypically intermediate forms. Identifying genomic regions linked to this variation has been complicated by strong, near species level, genome‐wide differentiation between red‐ and black‐banded forms. Here, we instead focus on the closely related black‐banded and intermediate forms that both belong to the subspecies B. bifarius nearcticus. We analyze an RNA sequencing (RNAseq) data set and identify a cluster of single nucleotide polymorphisms (SNPs) within one gene, Xanthine dehydrogenase/oxidase‐like, that exhibit highly unusual differentiation compared to the rest of the sequenced genome. Homologs of this gene contribute to pigmentation in other insects, and results thus represent a strong candidate for investigating the genetic basis of pigment variation in B. bifarius and other bumble bee mimicry complexes.
Sex‐specific repeatabilities and effects of relatedness and mating status on copulation duration in an acridid grasshopper
Authors: Haneke‐Reinders Michael , Reinhold Klaus , Schmoll Tim
Published: April 2017

In species with direct sperm transfer, copulation duration is a crucial trait that may affect male and female reproductive success and that may vary with the quality of the mating partner. Furthermore, traits such as copulation duration represent the outcome of behavioral interactions between the sexes, for which it is important—but often difficult—to determine which sex is in phenotypic control. Using a double‐mating protocol, we compared copulation durations between (1) virgin and nonvirgin and (2) sibling and nonsibling mating pairs in rufous grasshoppers Gomphocerippus rufus. Nonvirgin copulations took on average approximately 30% longer than virgin copulations, whereas relatedness of mating partners was not a significant predictor of copulation duration. Longer nonvirgin copulations may represent a male adaptation to sperm competition if longer copulations allow more sperm to be transferred or function as postinsemination mate guarding. The absence of differences between pairs with different degrees of relatedness suggests no precopulatory or preinsemination inbreeding avoidance mechanism has evolved in this species, perhaps because there is no inbreeding depression in this species, or because inbreeding avoidance occurs after copulation. Controlling for the effects of male and female mating status (virgin vs. nonvirgin) and relatedness (sibling vs. nonsibling), we found significant repeatabilities (R) in copulation duration for males (R = 0.33; 95% CI: 0.09–0.55) but not for females (R = 0.09; 95% CI: 0.00–0.30). Thus, copulation durations of males more strongly represent a nontransient trait expressed in a consistent manner with different mating partners, suggesting that some aspect of the male phenotype may determine copulation duration in this species. However, overlapping confidence intervals for our sex‐specific repeatability estimates indicate that higher sampling effort is required for conclusive evidence.
How spatial scale shapes the generation and management of multiple ecosystem services
Authors: Lindborg Regina , Gordon Line J. , Malinga Rebecka , Bengtsson Jan , Peterson Garry , Bommarco Riccardo , Deutsch Lisa , Gren Åsa , Rundlöf Maj , Smith Henrik G.
Published: April 2017

The spatial extent of ecological processes has consequences for the generation of ecosystem services related to them. However, management often fails to consider issues of scale when targeting ecological processes underpinning ecosystem services generation. Here, we present a framework for conceptualizing how the amount and spatial scale (here discussed in terms of extent) of management interventions alter interactions among multiple ecosystem services. First, we identify four types of responses of ecosystem service generation: linear, exponential, saturating, and sigmoid, and how these are related to the amount of management intervention at a particular spatial scale. Second, using examples from multiple ecosystem services in agricultural landscapes, we examine how the shape of these relationships can vary with the spatial scale at which the management interventions are implemented. Third, we examine the resulting scale‐dependent consequences for trade‐offs and synergies between ecosystem services as a consequence of interventions. Finally, to inform guidelines for management of multiple ecosystem services in real landscapes, we end with a discussion linking the theoretical relationships with how landscape configurations and placement of interventions can alter the scale at which synergies and trade‐offs among services occur.
Design for ground beetle abundance and diversity sampling within the National Ecological Observatory Network
Authors: Hoekman David , LeVan Katherine E. , Gibson Cara , Ball George E. , Browne Robert A. , Davidson Robert L. , Erwin Terry L. , Knisley C. Barry , LaBonte James R. , Lundgren Jonathan , Maddison David R. , Moore Wendy , Niemelä Jari , Ober Karen A. , Pearson David L. , Spence John R. , Will Kipling , Work Timothy
Published: April 2017

The National Ecological Observatory Network (NEON) will monitor ground beetle populations across a network of broadly distributed sites because beetles are prevalent in food webs, are sensitive to abiotic factors, and have an established role as indicator species of habitat and climatic shifts. We describe the design of ground beetle population sampling in the context ofNEON's long‐term, continental‐scale monitoring program, emphasizing the sampling design, priorities, and collection methods. Freely availableNEONground beetle data and associated field and laboratory samples will increase scientific understanding of how biological communities are responding to land‐use and climate change.
Scatter‐hoarding rodents select different caching habitats for seeds with different traits
Authors: Wang Bo , Corlett Richard T.
Published: April 2017

Seed caching by scatter‐hoarding rodents is an important dispersal mechanism for many plant species, and the microhabitat of the caching site influences the quality and effectiveness of this dispersal. Shrub vegetation is a major determinant of microhabitat heterogeneity in the forest understory and influences both rodent activity and foraging behavior, and seed germination and seedling establishment. However, very few studies have investigated how shrubs affect this important mutualistic plant–animal interaction and how this is influenced by seed traits. In this study, we monitored rodent choices of caching microhabitat for 3564 artificial seeds that varied in size, nutrient content, and tannin content. By analyzing 1333 primary caches and 209 secondary caches, we showed that rodents selected different caching microhabitats for seeds with different traits. Larger and more nutritious seeds were cached in shrubs more frequently than in the open, while tannin content had no effects on the probability of seeds being cached in shrubs. Furthermore, shrub cover significantly increased the distance which seeds were transported by rodents. If these caching differences apply to natural seeds and persist through seedling establishment and subsequent growth, they could play an important role in the spatial pattern of forest regeneration.
Flow Injection Amperometric Analysis of H2O2 at Platinum Nanoparticles Modified Pencil Graphite Electrode
Authors: Karakaya Serkan , Dilgin Yusuf
Published: April 2017

A Pt nanoparticle modified Pencil Graphite Electrode (PGE) was proposed for the electrocatalytic oxidation and non‐enzymatic determination of H2O2 in Flow Injection Analysis (FIA) system. Platinum nanoparticles (PtNPs) electrochemically deposited on pretreated PGE (p.PGE) surface by recording cyclic voltammograms of 1.0 mM of H2PtCl6 solution in 0.10 M KCl at scan rate of 50 mV s−1 for 30 cycles. Cyclic voltammograms show that the oxidation peak potential of H2O2 shifts from about +700 mV at bare PGE to +50 mV at PtNPs/p.PGE vs. Ag/AgCl /KCl (sat.). It can be concluded that PtNPs/p.PGE exhibits a good electrocatalytic activity towards oxidation of H2O2. Then, FI amperometric analysis of H2O2 was performed under optimized conditions using a new homemade electrochemical flow cell which was constructed for PGE. Linear range was found as 2.5 μM to 750.0 μM H2O2 with a detection limit of 0.73 μM (based on Sb/m of 3). As a result, this study shows the first study on the FI amperometric determination of H2O2 at PtNPs/p.PGE which exhibits a simple, low cost, commercially available, disposable sensor for H2O2 detection. The proposed electrode was successfully applied to determination of H2O2 in real sample.
Controls on sand ramp formation in southern Namibia
Authors: Rowell Alex , Thomas David , Bailey Richard , Stone Abi , Garzanti Eduardo , Padoan Marta
Published: April 2017

Sand ramps have the potential to provide rich palaeoenvironmental information in dryland regions where proxy records are typically scarce. However, current knowledge of the geomorphic controls and processes of sand ramp formation is limited. This study provides a data‐rich examination of the key factors controlling sand ramp formation. The location and morphology of 75 sand ramps in southern Namibia are examined. The sediments and chronologies of 10 sand ramps are studied in detail using 51 OSL dates and 83 grain‐size and LOI samples. Heavy mineral assemblages are used to determine the provenance of 10 samples and OSL sensitivity is used to explore geomorphic processes of eight samples.

Sand ramp morphology can be grouped into one of four classes of increasing size and complexity and is closely linked to the available accommodation space. Heavy mineral assemblages indicate local sediment sources and all 75 studied sand ramps are within 4 km of a large ephemeral river channel or within 5.5 km of a dune field. Therefore, accommodation space and sediment supply are identified as the primary controls of sand ramp formation. Sedimentology and OSL sensitivity suggest a complex interplay of aeolian, fluvial and colluvial processes contribute to sand ramp formation with large variability observed between ramps. Three of the ten dated sand ramps have been present in the Namibian landscape for >100 ka. Eight sand ramps show episodic deposition between >75–12 ka and five show evidence of surface reworking over the past 2 ka. Environmental sensitivity is probably linked to the size and availability of the accommodation space. Therefore, individual sand ramps are expected to reflect local environmental conditions, recording when an abundant sediment supply coincided with available accommodation space, while a regional analysis of multiple sand ramps with chronometric data offers the potential to identify larger scale palaeoenvironmental controls of sediment supply. © 2017 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Efficient message recovery proxy blind signature scheme from pairings
Authors: Verma Girraj Kumar , Singh B. B.
Published: April 2017

The recent applications of communication technology like e‐bookings, e‐shopping, e‐cash, etc. have inspired the need of delegation of signing capacity along with anonymity. A proxy blind signature scheme is a method of such delegation along with anonymity. In these signature schemes, a user can get a signature on a document of her/his choice from a proxy signer (who is signing the document on behalf of an original signer with delegated signing power) without revealing its contents. These signature schemes are mostly used by low bandwidth systems and thus small messages are signed. In this article, we introduce a proxy blind signature scheme with message recovery to shorten the message signature size. Through comparison with existing efficient proxy blind signature schemes, we show that the proposed scheme is the shortest in size and more efficient in computation cost.