bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-Onset Complete Ovarian Failure and Lack of Puberty in a Woman With Mutated Estrogen Receptor β (ESR2)
Authors: Lang-Muritano Mariarosaria , Sproll Patrick , Wyss Sascha , Kolly Anne , Hürlimann Renate , Konrad Daniel , Biason-Lauber Anna 
Published: August 2018

AbstractContextEstrogen resistance due to mutations in the estrogen receptor α gene (ESR1) has been described in men and women and is characterized by osteoporosis, delayed bone age and continuous growth in adulthood, and delayed puberty and multiple ovarian cysts in women. Although mutations in the estrogen receptor β gene ESR2 were found in 46, XY patients with differences of sex development, no genetic variants of ESR2 were linked to gonadal defects in women.Settings and PatientHere we describe a 16-year-old female patient who came to our tertiary care hospital with complete lack of estrogen action, as demonstrated by absent breast development, primary amenorrhea, and osteoporosis, resembling patients with ESR1 mutation. However, her gonads were clearly abnormal (streak), a finding not observed in ESR1-deficient patients.DesignTo gain insights into the molecular consequences of the ESR2 defect, whole exome sequencing and extensive functional transactivation studies in ovarian, bone, and breast cells were conducted, with or without the natural activator of estrogen receptors, 17β-estradiol.ResultsWe identified a loss-of-function heterozygous mutation of a highly conserved residue in ESR2 that disrupts estradiol-dependent signaling and has a dominant negative effect, most likely due to failure to interact with its coactivator, nuclear coactivator 1.ConclusionsThis is a report of a loss-of-function mutation in the estrogen receptor β in a young woman with complete ovarian failure, suggesting that ESR2 is necessary for human ovarian determination and/or maintenance and that ESR1 is not sufficient to sustain ovarian function in humans.
Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward Improved Personalized Prognostication
Authors: Lippert Juliane , Appenzeller Silke , Liang Raimunde , Sbiera Silviu , Kircher Stefan , Altieri Barbara , Nanda Indrajit , Weigand Isabel , Gehrig Andrea , Steinhauer Sonja , Riemens Renzo J M , Rosenwald Andreas , Müller Clemens R , Kroiss Matthias , Rost Simone , Fassnacht Martin , Ronchi Cristina L 
Published: August 2018

Abstract

Context
Adrenocortical carcinoma (ACC) has a heterogeneous prognosis, and current medical therapies have limited efficacy in its advanced stages. Genome-wide multiomics studies identified molecular patterns associated with clinical outcome.

Objective
Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine.

Design
In total, 117 tumor samples from 107 patients with ACC were analyzed. Targeted next-generation sequencing of 160 genes and pyrosequencing of 4 genes were applied to formalin-fixed, paraffin-embedded (FFPE) specimens to detect point mutations, copy number alterations, and promoter region methylation. Molecular results were combined with clinical/histopathological parameters (tumor stage, age, symptoms, resection status, and Ki-67) to predict progression-free survival (PFS).

Results
In addition to known driver mutations, we detected recurrent alterations in genes not previously associated with ACC (e.g., NOTCH1, CIC, KDM6A, BRCA1, BRCA2). Best prediction of PFS was obtained integrating molecular results (more than one somatic mutation, alterations in Wnt/β-catenin and p53 pathways, high methylation pattern) and clinical/histopathological parameters into a combined score (P &lt; 0.0001, χ2 = 68.6). Accuracy of prediction for early disease progress was 83.3% (area under the receiver operating characteristic curve: 0.872, 95% confidence interval 0.80 to 0.94). Furthermore, 17 potentially targetable alterations were found in 64 patients (e.g., in CDK4, NOTCH1, NF1, MDM2, and EGFR and in DNA repair system).

Conclusions
This study demonstrates that molecular profiling of FFPE tumor samples improves prognostication of ACC beyond clinical/histopathological parameters and identifies new potential drug targets. These findings pave the way to precision medicine in this rare disease.
Cell injury triggers actin polymerization to initiate epithelial restitution
Authors: Aihara Eitaro , Medina-Candelaria Neisha M. , Hanyu Hikaru , Matthis Andrea L. , Engevik Kristen A. , Gurniak Christine B. , Witke Walter , Turner Jerrold R. , Zhang Tongli , Montrose Marshall H. 
Published: August 2018

ABSTRACT
The role of the actin cytoskeleton in the sequence of physiological epithelial repair in the intact epithelium has yet to be elucidated. Here, we explore the role of actin in gastric repair in vivo and in vitro gastric organoids (gastroids). In response to two-photon-induced cellular damage of either an in vivo gastric or in vitro gastroid epithelium, actin redistribution specifically occurred in the lateral membranes of cells neighboring the damaged cell. This was followed by their migration inward to close the gap at the basal pole of the dead cell, in parallel with exfoliation of the dead cell into the lumen. The repair and focal increase of actin was significantly blocked by treatment with EDTA or the inhibition of actin polymerization. Treatment with inhibitors of myosin light chain kinase, myosin II, trefoil factor 2 signaling or phospholipase C slowed both the initial actin redistribution and the repair. While Rac1 inhibition facilitated repair, inhibition of RhoA/Rho-associated protein kinase inhibited it. Inhibitors of focal adhesion kinase and Cdc42 had negligible effects. Hence, initial actin polymerization occurs in the lateral membrane, and is primarily important to initiate dead cell exfoliation and cell migration to close the gap.
Involvement of the septation initiation network in events during cytokinesis in fission yeast
Authors: Dey Sumit K. , Pollard Thomas D. 
Published: August 2018

ABSTRACT
The septation initiation network (SIN), comprising a GTPase and a cascade of three protein kinases, regulates cell division in fission yeast Schizosaccharomyces pombe, but questions remain about its influence on cytokinesis. Here, we made quantitative measurements of the numbers of Cdc7p kinase molecules (a marker for SIN activity) on spindle pole bodies (SPBs), and on the timing of assembly, maturation and constriction of contractile rings via six different proteins tagged with fluorescent proteins. When SIN activity is low in spg1-106 mutant cells at 32°C, cytokinetic nodes formed contractile rings ∼3 min slower than wild-type cells. During the maturation period, these rings maintained normal levels of the myosin-II mEGFP–Myo2p but accumulated less of the F-BAR protein Cdc15p–GFP than in wild-type cells. The Cdc15p–GFP fluorescence then disintegrated into spots as mEGFP–Myo2p dissociated slowly. Some rings started to constrict at the normal time, but most failed to complete constriction. When high SIN activity persists far longer than normal on both SPBs in cdc16-116 mutant cells at 32°C, contractile rings assembled and constricted normally, but disassembled slowly, delaying cell separation.
The putative ceramide-conjugation protein Cwh43 regulates G0 quiescence, nutrient metabolism and lipid homeostasis in fission yeast
Authors: Nakazawa Norihiko , Teruya Takayuki , Sajiki Kenichi , Kumada Kazuki , Villar-Briones Alejandro , Arakawa Orie , Takada Junko , Saitoh Shigeaki , Yanagida Mitsuhiro 
Published: August 2018

ABSTRACT
Cellular nutrient states control whether cells proliferate, or whether they enter or exit quiescence. Here, we report characterizations of fission yeast temperature-sensitive (ts) mutants of the evolutionarily conserved transmembrane protein Cwh43, and explore its relevance to utilization of glucose, nitrogen source and lipids. GFP-tagged Cwh43 localizes at ER associated with the nuclear envelope and the plasma membrane, as in budding yeast. We found that cwh43 mutants failed to divide in low glucose and lost viability during quiescence under nitrogen starvation. In cwh43 mutants, comprehensive metabolome analysis demonstrated dramatic changes in marker metabolites that altered under low glucose and/or nitrogen starvation, although cwh43 cells apparently consumed glucose in the culture medium. Furthermore, we found that cwh43 mutant cells had elevated levels of triacylglycerols (TGs) and coenzyme A, and that they accumulated lipid droplets. Notably, TG biosynthesis was required to maintain cell division in the cwh43 mutant. Thus, Cwh43 affects utilization of glucose and nitrogen sources, as well as storage lipid metabolism. These results may fit a notion developed in budding yeast stating that Cwh43 conjugates ceramide to glycosylphosphatidylinositol (GPI)-anchored proteins and maintains integrity of membrane organization.
Regulation of global translation during the cell cycle
Authors: Stonyte Vilte , Boye Erik , Grallert Beáta 
Published: August 2018

ABSTRACT
It is generally accepted that global translation varies during the cell cycle and is low during mitosis. However, addressing this issue is challenging because it involves cell synchronization, which evokes stress responses that, in turn, affect translation rates. Here, we have used two approaches to measure global translation rates in different cell-cycle phases. First, synchrony in different cell-cycle phases was obtained involving the same stress, by using temperature-sensitive mutants. Second, translation and DNA content were measured by flow cytometry in exponentially growing, single cells. We found no major variation in global translation rates through the cell cycle in either fission yeast or mammalian cells. We also measured phosphorylation of eukaryotic initiation factor-2α, an event that is thought to downregulate global translation in mitosis. In contrast with the prevailing view, eIF2α phosphorylation correlated poorly with downregulation of global translation and ectopically induced eIF2α phosphorylation inhibited global translation only at high levels.
STRUCTURAL STYLE AND DEPOSITIONAL HISTORY OF THE SEMANGKO PULL APART BASIN IN THE SOUTHEASTERN SEGMENT OF SUMATRA FAULT ZONE
Authors: Mukti Maruf M 
Published: August 2018

Re-examination of published seismic data in the southeasternmost segment of the active Sumatra Fault zone (SFZ) reveals the characteristics of structural style and depositional history of Semangko pull apart basin (SPB). The SPB have been developed as a transtensional pull apart basin resulted from stepping over of the Semangko to Ujung Kulon segments of the SFZ. The geometry of SPB is of rhomboidal shape characterized by dual depocenters separated by a discrete structural high in the center of SPB. Based on the determination of pre- and syn-kinematic strata related to the formation of SPB, sedimentary units prior to deposition of Unit 3 can be regarded as pre-kinematic strata, whereas the syn-kinematic strata is represented by Unit 3. The basin sidewall faults of the SPB are likely to have been developed as en-echelon side wall faults and identified as the East Semangko Fault (ESF) and Kota Agung – South Panaitan Faults (KAF-SPF) in the western and eastern margin of the SPB, respectively. The development of discrete highs along the center of the SPB may relate to the formation of en-echelon cross-basin faults that are now overprinted by volcanic activity or magmatic intrusion.Analisa ulang data seismik yang telah dipublikasikan di daerah segmen paling tenggara dari zona sesar aktif Sumatra (SFZ) mengungkapkan karakteristik struktur dan sejarah pengendapan dari cekungan pull-apart Semangko (SPB). SPB terbentuk sebagai cekungan transtensional pull-apart yang dihasilkan dari step over segmen Semangko dan segmen Ujung Kulon. Geometri SPB adalah bentuk rhomboidal yang dicirikan oleh dua depocenter yang dipisahkan oleh struktur tinggian yang tidak menerus di bagian tengah SPB. Berdasarkan penentuan unit pre- dan syn-kinematic strata yang terkait dengan pembentukan SPB, unit sedimen yang terbentuk sebelum pengendapan Unit 3 dapat dianggap sebagai pre-kinematic strata, sedangkan syn-kinematic strata diwakili oleh Unit 3. Sesar side-wall dari SPB kemungkinan telah berkembang sebagai sesar yang bersifat en-echelon dan diidentifikasi sebagai Sesar Semangko Timur (ESF) dan Sesar Kota Agung - Panaitan Selatan (KAF-SPF) di tepian barat dan timur SPB. Pembentukan tinggian yang tidak menerus di sepanjang bagian tengah SPB berhubungan dengan pembentukan sesar-sesar cross-basin yang bersifat en-echelon yang sekarang telah tertutupi jejaknya oleh aktivitas gunung api atau intrusi magmatik.
Employment in Long-Term Care: The Role of Macroeconomic Conditions
Authors: Baughman Reagan 
Published: August 2018

Abstract
As populations age dramatically in developed economies, understanding the dynamics of employment in long-term care will help to ensure an adequate workforce and increase quality of care. Although downturns in the business cycle are associated with decreases in employment at the aggregate level and across most sectors of the economy, there are several reasons to believe that employment in the health and long-term care sectors increases during recessions. This is the first study of the relationship between changes in macroeconomic conditions and employment duration of direct care workers based upon analysis of detailed, monthly individual-level data. The results suggest that direct care workers have longer employment spells during recessionary periods, a countercyclical effect, but one that is confined to nursing home settings. However, the length of job spells in hospitals appears to be procyclical.
Evaluation in the predictive value of serum human epididymal protein 4 (HE4), cancer antigen 125 (CA 125) and a combination of both in detecting ovarian malignancy
Authors: Teh Beng Hock , Yong Soon Leong , Sim Wee Wee , Lau Kim Bee , Suharjono Haris Njoo 
Published: August 2018

Abstract

Background
This study was conducted to evaluate the performance of human epididymal protein 4 (HE4), cancer antigen 125 (CA 125) and a combination of both via the Risk of Ovarian Malignancy Algorithm (ROMA) in detecting ovarian malignancy.

Methods
This was a diagnostic study enrolling 129 patients with pelvic mass(es) suspected of originating in the ovary who had been scheduled for surgery or radiological-guided biopsy. Serum HE4 and CA 125 levels were measured. HE4, CA 125 and ROMA were evaluated for sensitivity, specificity, positive predictive value and negative predictive value. The receiver operating characteristic (ROC) plots were graphed and area under the curve (AUC) values were calculated to investigate the accuracy of each marker for predicting ovarian malignancy.

Results
Overall, CA 125 remained significantly more sensitive (88.9% vs. 51.9%, p = 0.006) but less specific (56.9% vs. 95.1%, p < 0.001) than HE4. HE4 was superior to CA 125 in specificity (97.7% vs. 54.5%, p < 0.001) for premenopausal women. ROMA was non-significantly more sensitive (100.0% vs. 92.3%, p = 1.000) than CA 125 but both were equally specific (71.4%) for the postmenopausal group. In the premenopausal group, the AUC of serum HE4 was higher than serum CA 125 (0.851 vs. 0.817) but was equivalent to ROMA (0.851 vs. 0.859). In the postmenopausal group, ROMA exhibited an excellent AUC value as compared to CA 125 and HE4 (AUC of 0.907 vs. 0.874 vs. 0.863, respectively).

Conclusion
HE4 is useful in ruling out ovarian malignancy among premenopausal women. For postmenopausal women, ROMA appears to be an all-rounder with overall good sensitivity and specificity.
Common illnesses in tropical Asia and significance of medical volunteering
Authors: Rim Chai Hong , Lee Chang Won , Heo Young Soo , Aieng Rinet , Jun Sung Yeon , Choi Sung Hun , Rim Jae Suk 
Published: August 2018

Abstract
This study was conducted to provide practical information for actual preparation of medical volunteering in tropical Asia, mainly the distribution of common illnesses encountered during mission. From 2012 to 2017, we visited two rural areas of Eastern Cambodia for medical volunteering missions, Cham Lak and Khsoem. Neither area has electricity or public water. We classified the common cases encountered during missions into six groups (upper respiratory infection, gastroenteritis, vaginitis and/or cystitis, dermatitis, work-related pain and parasite prevention) and assessed the distribution. In Cham Lak and Khsoem, 558 and 371 people were treated, respectively. The most commonly encountered cases in children under age of 18 were upper respiratory infection, followed by parasite control and dermatitis, in both areas. There was no significant difference in distribution between the two areas. For adults, the most common illnesses in Cham Lak area were vaginitis and/or cystitis, followed by gastroenteritis and work-related pain. In Khsoem area, the common illnesses were work-related pain followed by gastroenteritis, and upper respiratory infection. The distribution between the two areas differed significantly (p <0.001). The difference might be due to the water source and main crops of agriculture. Successful preparation of a medical volunteering needs deep understanding of the destination community.
Intervention effects in grammar and language acquisition
Authors: Rizzi Luigi 
Published: August 2018

AbstractIntervention effects have been thoroughly studied in formal syntax in the domain of weak islands. They also have recently been appealed to in the study of language acquisition, to capture certain difficulties that young children manifest in the mastery of some object A’-bar dependencies (relatives, questions, topicalizations). Can one unify such distinct utilizations of the concept of intervention under a single formal locality principle? This paper explores the possibility of a unitary approach by proposing solutions for observed discrepancies between the effects in adults and children, and more generally between the different utilizations of the concept of intervention in recent work on adult grammar and language acquisition. Relativized Minimality (RM) is seen as a formal principle penalizing configurations as a function of the distinctness between target and intervener in local relations, where distinctness is precisely expressed as a grammar-based notion. A unitary system consisting of RM and an explicit distinctness hierarchy is argued to be operative in intervention effects in grammar and language acquisition.
The Diagonalizable Nonnegative Inverse Eigenvalue Problem
Authors: Cronin Anthony G , Laffey Thomas J. 
Published: August 2018

Abstract
In this articlewe provide some lists of real numberswhich can be realized as the spectra of nonnegative diagonalizable matrices but which are not the spectra of nonnegative symmetric matrices. In particular, we examine the classical list σ = (3 + t, 3 − t, −2, −2, −2) with t ≥ 0, and show that 0 is realizable by a nonnegative diagonalizable matrix only for t ≥ 1. We also provide examples of lists which are realizable as the spectra of nonnegative matrices, but not as the spectra of nonnegative diagonalizable matrices by examining the Jordan Normal Form
The Free Energy for Rotating and Charged Black Holes and Banados, Teitelboim and Zanelli Black Holes
Authors: Hussein N.A. , Eisa D.A. , Ibrahim T.A.S. 
Published: August 2018

Abstract
This paper aims to obtain the thermodynamic variables (temperature, thermodynamic volume, angular velocity, electrostatic potential, and heat capacity) corresponding to the Schwarzschild black hole, Reissner-Nordstrom black hole, Kerr black hole and Kerr-Newman-Anti-de Sitter black hole. We also obtained the free energy for black holes by using three different methods. We obtained the equation of state for rotating Banados, Teitelboim and Zanelli black holes. Finally, we used the quantum correction of the partition function to obtain the heat capacity and entropy in the quantum sense.
Über Zwischenprodukte der Riboflavin-Biosynthese bei Saccharomyces cerevisiae
Authors: Lingens F. , Oltmanns O. , Bacher A. 
Published: August 2018

Using various riboflavin deficient mutants of S. cerevisiae, we have found two intermediates of the riboflavin biosynthesis. 6.7-Dimethyl-8-ribityl-lumazine was isolated from the culture fluid of two mutants. The formation of 4-ribitylamino-5-amino-uracil by two other mutants was proved by trapping the product with glyoxal or diacetyl, leading to the formation of 8-ribityl-lumazine or 6,7-dimethyl-8-ribityl-lumazine and riboflavin respectively. These mutants were able to grow in riboflavin free medium supplemented with diacetyl.
6,7-Dimethyl-8-ribityl-lumazine promoted the growth of adequately blocked mutants.
Der Einfluß der Solvatation auf die thermische cis→trans-Isomerisierung quartärer Stilbazolium-Salze / The Effect of Solvation on the Thermal cis→trans Isomerization of Quarternary Stilbazolium Salts
Authors: Güsten Hans , Schulte-Frohlinde Dietrich 
Published: August 2018

Abstract
The solvent, temperature, concentration, pH, substitution as well as anion dependency were measured of the reaction rate constants for thermal cis→trans isomerization of quarternary stilbazolium salts (1). From the ionic conductance of 1 in the different solvents used the dissociation constants as well as the degree of dissociation were calculated according to the method by Shedlovsky.
The rate of the cis→trans isomerization is extremely sensitive to the solvent. In protic solvents the reaction rate decreases linearly with increasing Z-values indicated by Kosower. In dipolar aprotic and non-polar solvents the reaction rate is independent of the solvent parameters. It is concluded that the thermal cis→trans isomerization of stilbazolium salts (1) in dilute solutions occurs within the cation independently of the anion. The enormous increase of the rate of isomerization from stilbenes and stilbazoles to stilbazolium salts as well as their strong dependency on the solvent is due to the positive charge in 1 and the associated specific solvation phenomena. A possible polar transition state is discussed.
Synthese und Kristallstruktur von Gd2 NCl3 / Synthesis and Crystal Structure of Gd2 NCl3
Authors: Schwanitz-Schüller Ulrich , Simon Arndt 
Published: August 2018

Abstract
The new compound Gd2NCl3 is formed from GdCl3 with Gd and N2 as well as from GdCl3 with GdN (at 1020 K). The crystal structure contains NGd4 tetrahedra, which are linked via opposite edges to form infinite chains (Orthorhombic, Pbcn; a = 1301.7(1), b = 673.10(6), c = 614.03(7) pm; R = 0.031 for 578 independent reflections). The formal analogy with structures containing condensed clusters, e.g. Gd2Cl3, is discussed.
Neue Gadoliniumcarbidbromide: Gd2C2 Br2 / New Gadolinium Carbide Bromides: Gd2C2 Br2 and Gd2CBr2
Authors: Schwanitz-Schüller Ulrich , Simon Arndt 
Published: August 2018

Abstract
The new compounds Gd2C2Br2, Gd2Br2 and Gd6C2Br7 are formed from GdBr3 with Gd and carbon at 1170 to 1320 K. The crystal structures contain condensed Gd octahedra, which are filled with either C2 -groups or carbon atoms. (Gd2C2Br2 : monoclinic, C2/m; a = 702.5(2), b = 383.61(9), c = 986.8(3) pm; β = 94.47(2)°; R = 0.063 for 330 independent reflections. Gd2CBr2 : trigonal, twinned, P3 ml; a = 382.09(7), c = 982.4(4) pm; R = 0.074 with 123 independent reflections.
Reaktion von Tetraschwefeltetranitrid mit Rhenium(VII)-chloronitrid Die Kristallstruktur von [Ph4As+ ]2 [Cl4 Re(NS)(NSCl) 2- ] · CH2 Cl2 / Reaction of Tetrasulfurtetranitride with Rhenium(VII)-chloronitride The Crystal Structure of [Ph4 As+ ]2 [Cl4 Re(NS)(NSCl)2- ] · CH2Cl2
Authors: Anhaus Jens , Siddiqi Zafar A. , Roesky Herbert W. , Bats Jan W. , Elerman Yalcin 
Published: August 2018

Abstract
The synthesis of [Ph4As+]2[Cl4Re(NS)(NSCl)2-] · CH2Cl2 (4) from the reaction of S4N4, Cl4ReN, and Ph4AsCl is reported. CH2Cl2 is used as solvent. The reaction of S4N4 with Re2Cl10 similarly leads to the salt [Ph4As+][Cl2ReNS-] (5) in a smaller yield. 4 crystallizes in the triclinic space group P1̅ with Z = 2, a - 10.434(2), b = 12.1454(6), c = 21.125(2) Å, a = 81.210(6), β = 86.70(1), γ = 76.624(8)°.