bluuebunny/crossref_metadata_2025_split huggingface dataset:
Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study
Authors: Reiss Kim A. , Yu Shun , Mamtani Ronac , Mehta Rajni , D’Addeo Kathryn , Wileyto E. Paul , Taddei Tamar H. , Kaplan David E. 
Published: September 2017

Purpose Sorafenib is currently the only Food and Drug Administration–approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.
Loss of OCRL increases ciliary PI(4,5)P2 in Lowe oculocerebrorenal syndrome
Authors: Prosseda Philipp P. , Luo Na , Wang Biao , Alvarado Jorge A. , Hu Yang , Sun Yang 
Published: September 2017

ABSTRACT
Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood. Here, we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P. In particular, subcellular distribution of PI(4,5)P2 build-up was observed at the transition zone. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from Lowe syndrome mouse model as well as in Ocrl-null MEFs, which was reversed by reintroduction of OCRL. Similarly, expression of wild-type OCRL reversed the elevated PI(4,5)P2 in Lowe patient cells. Accumulation of sonic hedgehog protein in response to hedgehog agonist was decreased in MEFs derived from a Lowe syndrome mouse model. Together, our findings show for the first time an abnormality in ciliary phosphoinositides of both human and mouse cell models of Lowe syndrome.
An Equilibrium Analysis of a Multiclass Queue with Endogenous Abandonments in Heavy Traffic
Authors: Ata Baris , Peng Xiaoshan 
Published: September 2017

This paper studies a multiclass queueing system with endogenous abandonments where congestion affects customers’ abandonment behavior, and vice versa. Our model captures this interaction by developing two closely related models: an abandonment model and a queueing model. In the abandonment model, customers take the virtual waiting time distribution as given. Class k customers receive a reward rk from service and incur a cost ck per period of waiting. Customers are forward looking and make wait or abandon decisions dynamically to maximize their expected discounted utilities. The queueing model takes the customers’ abandonment time distribution as an input and studies the resulting virtual waiting time distribution. Because the multiclass queueing system is not amenable to exact analysis, we resort to an approximate analysis in the conventional heavy traffic limit (under the hazard rate scaling). Leveraging the so-called state-space collapse property, we provide a characterization of the system performance. Combining the results for the two models, we show that there exists a unique equilibrium in which the customers’ abandonment time and the virtual waiting time for the various classes are consistent in the two models. Finally, we provide a computational scheme to calculate the equilibrium numerically and apply that using data from an Israeli bank call center. The online appendix is available at https://doi.org/10.1287/opre.2017.1638 .
Bewertung von Unternehmen im Lebensmittelsektor
Authors: Schader Christian , Jawtusch Julia , Stolze Matthias 
Published: September 2017

Die Welternährungsorganisation FAO hat nun erstmals eine umfassende Definition von Nachhaltigkeit für den Lebensmittelsektor vorgelegt. Auf dieser Basis wurde mit SMART eine Methode entwickelt, anhand derer Unternehmen aus dem Lebensmittelbereich ihre Nachhaltigkeitsleistungen darstellen können.
Equivalent Circuit Parametrization Utilizing FE Model Order Reduction and its Application to Piezoelectric Generators and Actuators
Authors: Wurpts Wiebold , Twiefel Jens , Brouet Francois 
Published: September 2017

Abstract
Equivalent circuits are often the first choice for the modeling of piezoelectric systems, as they allow for the consideration of the complete electro-mechanical system with one or even more modes. The parameters of the equivalent circuit model are identified by a measured or simulated frequency response. In this contribution a method for a direct modal condensation of the equivalent parameters for arbitrary FE structures and loads is described and discussed. First the proposed method is demonstrated for a continuous piezoelectric rod and then applied to discrete finite element models. The derived equivalent circuit has an identical appearance to the classical solution, but additionally allows arbitrarily load conditions. Furthermore, the structure of the derived equivalent circuit depends on whether short- or open-circuited modes are used for the modal expansion. The influence of truncated modes is discussed utilizing residual terms, leading to a better understanding of the circuit parameters. Additionally the model based approaches in the third part an experimental parameter identification procedure for many modes is presented as well. The influence of the load and the quality of the model order reduction are discussed for piezoelectric rods. The methods are demonstrated for a base excited energy harvesting system an ultrasonic grubber.
Sulfates of Sorghum vinegar residue waste as potential catalysts
Authors: Qiao Yuanbiao , Qin Wenhao , Li Qingshan 
Published: September 2017

AbstractA sealed wet curing design on sulfatingSorghumvinegar residue waste is drilled with sulfo/sulfoalkyl chemicals. Sulfation degrees in the case of reactions with sulfuric acid, sodium sulfite, sulfamic acid, benzenesulfonic acid,p-toluenesulfonic acid and sodium laurilsulfate range from 14.7 to 36.9 mg sulfo per gram waste. The C–O–S formation gives rise to accessional noncrystallinity and mesoporosity of morphology, a character for potential alternatives in catalysis. Waste sulfates are employed as candidates in catalyzing the condensation of α-glycolic acid and urea substitutes for yielding imidazolidine-2,4-dione derivatives. Catalytic and specific activities in terms of derivative productions are 2.6–34.3 (×103U) and 0.8–5.4 U/mg sulfo, together with the maximal yields of 49.4%–97.6%. Chemical linkage of sulfo/sulfoalkyl groups manifests synergism with intrinsic acidity of waste with respect to catalysis. A rational design of green chemistry is guaranteed by no excess of chemicals and easy recyclability of catalysts.
Influence of Thermal Ageing on Microstructure and Tensile Properties of P92 Steel
Authors: Sakthivel T. , Selvi S. Panneer , Parameswaran P. , Laha K. 
Published: September 2017

AbstractMicrostructure and tensile properties of P92 steel in the normalized and tempered, and thermal aged at 923 K for 5000 h and 10,000 h conditions have been investigated. Laves phase precipitate was observed in the thermal-aged steels. The size of Laves phase precipitate increased with increase in thermal exposure. This was also confirmed from the observation that the area fraction of Laves phase precipitate was higher in the 5000 h aged condition which decreased with further increase in thermal exposure. On the other hand, the size and area fraction of M23C6 precipitate were found increased in the 5000 h aged steel, further continued to enhanced precipitation of fine M23C6 in the 10,000 h aged steel. This resulted in significant increase in area fraction and comparable size with the steel aged for 5000 h. Hardness of the steel was decreased with increase in the duration of ageing. Thermal-aged steels exhibited lower yield stress, ultimate tensile strength and relatively higher ductility in comparison with steel in the normalized and tempered condition. The increase in lath width and recovery of dislocation structure under thermal-aged condition resulted in lower tensile strength and hardness. An extensive Laves phase formation and coarsening by loss of tungsten in the matrix led to decrease in the tensile strength predominantly in the 5000 h aged steel. The tensile strength of 10,000 h aged steel was comparable with that of 5000 h aged steel due to enhanced precipitation of fine M23C6 in the steel due to enhanced mobility of carbon in the absence of tungsten in the matrix.
The organization of flint processing in the Bronze Age and Early Iron Age: the example of the workshops at Nieborowa in central-eastern Poland
Authors: Boroń Tomasz 
Published: September 2017

Zusammenfassung:Die Fundstelle Nieborowa – im zentral-östlichen Polen an der Grenze zu der Łęczyńsko-Włodawskie Seenplatte und den Chełm Hügeln gelegen – wurde von Halina Mackiewicz (Institut für die Geschichte der Materiellen Kultur [seit 1992 Institut für Archäologie und Ethnologie der Polnischen Akademie der Wissenschaften]) in den Jahren 1964–1977 untersucht. Auf einem Gebiet von über 3500 mDer Lagerplatz bestand aus vier Werkstätten – zwei planigraphisch abgegrenzte (A, B) und zwei auf Basis der zusammengefügten Elemente rekonstruierte Werkstätten (C, D). Alle Werkstätten wiesen einen Durchmesser von etwa 1 m auf, die Entfernung zwischen ihnen betrug zwischen 1 und 3 m. Übereinstimmende Beobachtungen wie die Verwendung gleicher Feuersteinmaterialien und die Anwendung identischer Techniken zur Kernbearbeitung erlauben die Annahme gleichzeitig arbeitender Werkstätten. Die Distribution der Artefakte, die Struktur der Zusammenlegungen, die Homogenität des Feuersteininventars und die Separierung der Werkplätze zur Kernbearbeitung innerhalb jeder Werkstatt sprechen für eine singulär erfolgte Ansiedlung.Im Fall der besprochenen Werkstätten konnte erkannt werden, dass die Organisation der Bearbeitung des lokalen Feuersteinrohstoffes nach einem wiederkehrenden Schema erfolgte.
Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior
Authors: Pérez-Domínguez Martha , Tovar-y-Romo Luis B. , Zepeda Angélica 
Published: September 2017

AbstractThe dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.
KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS
Authors: Apara Akintomide , Galvao Joana , Wang Yan , Blackmore Murray , Trillo Allison , Iwao Keiichiro , Brown Dale P. , Fernandes Kimberly A. , Huang Abigail , Nguyen Tu , Ashouri Masoumeh , Zhang Xiong , Shaw Peter X. , Kunzevitzky Noelia J. , Moore Darcie L. , Libby Richard T. , Goldberg Jeffrey L. 
Published: September 2017

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9's axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9's neurite growth suppressionin vitroand promoted axon regenerationin vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.SIGNIFICANCE STATEMENTInjured CNS nerves fail to regenerate spontaneously. Promoting intrinsic axon growth capacity has been a major challenge in the field. Here, we demonstrate that knocking down Krüppel-like transcription factor 9 (KLF9) via shRNA promotes long-distance axon regeneration after optic nerve injury and uncover a novel and important KLF9–JNK3 interaction that contributes to axon growth suppressionin vitroand regenerative failurein vivo. These studies suggest potential therapeutic approaches to promote axon regeneration in injury and other degenerative diseases in the adult CNS.
Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points
Authors: Cho In Ha , Panzera Lauren C. , Chin Morven , Hoppa Michael B. 
Published: September 2017

Neurotransmitter release depends on voltage-gated Na+channels (Navs) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na+channels. Using optical recordings of Ca2+and membrane voltage, we demonstrate here that Na+channel β2 subunits (Navβ2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Navβ2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca2+entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Navβ2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons.SIGNIFICANCE STATEMENTVoltage-gated Ca2+channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na+channel β2 subunits modulate AP-evoked Ca2+-influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the brain.
Odorant Receptor Sensitivity Modulation inDrosophila
Authors: Guo Hao , Kunwar Kishor , Smith Dean 
Published: September 2017

The ability to modulate sensitivity in sensory systems is essential for useful information to be extracted from fluctuating stimuli in a wide range of background conditions. The mechanisms underlying sensitivity regulation in insect primary olfactory neurons are poorly understood. Here we reveal that dephosphorylation of OrcoS289that occurs upon prolonged odor exposure is a mechanism underlying reduction in odorant sensitivity inDrosophilaprimary olfactory neurons in both sexes.OrcoS289Amutants, unable to phosphorylate this position, have low intrinsic odorant sensitivity that is independent of altered expression or localization. A phosphomimetic allele,OrcoS289D, has enhanced odorant sensitivity compared with wild-type controls. To explore the functional ramifications of this phosphorylationin vivo, we generated phospho-specific antiserum to OrcoS289and show that phosphorylation at this residue is dynamically regulated by odorant exposure with concomitant modulation of odorant sensitivity. OrcoS289is phosphorylated in the sensitized state, and odorant exposure triggers dephosphorylation and desensitization without altering receptor localization. We further show that dephosphorylation of OrcoS289is triggered by neuronal activity, and not conformational changes in the receptor occurring upon ligand binding. Mutant flies unable to regulate Orco function through phosphorylation at S289 are defective for odor-guided behavior. These findings provide insight into the mechanisms underlying regulation of insect odorant receptorsin vivo.SIGNIFICANCE STATEMENTWe have uncovered a mechanism underlying olfactory receptor sensitivity regulation inDrosophila. The phosphorylation state of OrcoS289is altered in an odorant-dependent manner and changes in phosphorylation affect receptor sensitivity without changing subcellular localization. We show that neuronal activity triggers the phosphorylation changes and that this phenomenon is important for odorant-guided behaviors inDrosophila. This phosphorylation site is conserved in other insects, including mosquitoes, indicating this mechanism may be a target for manipulation of insect behaviors in the future.
Mendelism: New Insights from Gregor Mendel’s Lectures in Brno
Authors: Zhang Hui , Chen Wen , Sun Kun 
Published: September 2017

AbstractAfter dissolving misinterpretation and prejudice of the newspaper report of Mendel’s lectures, we found the lecture content can be recovered...Interpretation of Gregor Mendel’s work has previously been based on study of his published paper “Experiments in Plant Hybridization.” In contrast, the lectures that he gave preceding publication of this work have been largely neglected for more than 150 years. Here, we report on and interpret the content of Mendel’s previous two lectures, as they were reported in a local newspaper. We comprehensively reference both the text of his paper and the historical background of his experiments. Our analysis shows that while Mendel had inherited the traditional research program on interspecific hybridization in plants, he introduced the novel method of ratio analysis for representing the variation of unit-characters among offspring of hybrids. His aim was to characterize and explain the developmental features of the distributional pattern of unit-characters in two series of hybrid experiments, using self-crosses and backcrosses with parents. In doing so, he not only answered the question of what the unit-characters were and the nature of their hierarchical classification, but also successfully inferred the numerical principle of unit-character transmission from generation to generation. He also established the nature of the composition and behaviors of reproductive cells from one generation to the next. Here we highlight the evidence from Mendel’s lectures, clearly announcing that he had discovered the general law of cross-generation transmission of unit-characters through reproductive cells containing unit-factors. The recovered content of these previous lectures more accurately describes the work he performed with his garden peas than his published paper and shows how he first presented it in Brno. It is thus an invaluable resource for understanding the origin of the science of genetics.