bluuebunny/crossref_metadata_2025 huggingface dataset:
Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases
Authors: Leone Francesco , Artale Salvatore , Marino Donatella , Cagnazzo Celeste , Cascinu Stefano , Pinto Carmine , Fornarini Giuseppe , Tampellini Marco , Di Fabio Francesca , Sartore‐Bianchi Andrea , De Carlis Luciano , Pugliese Raffaele , Capussotti Lorenzo , Gioeni Luisa , Siena Salvatore , Aglietta Massimo
Published: July 2013

BACKGROUND

Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver‐only, metastatic colon cancer.

METHODS

Chemotherapy‐naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P‐XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression‐free survival, the percentage of patients whose disease became radically resectable, and the safety of the P‐XELOX combination.

RESULTS

A total of 49 patients were recruited, 35 of whom had wild‐type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty‐six patients were evaluable for response. After conversion P‐XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression‐free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P < .001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities.

CONCLUSIONS

Conversion P‐XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement. Cancer 2013;119:3429–3435.. © 2013 American Cancer Society.
A Spirobifluorene Derivative as a Single‐Emitting Component for a Highly Efficient White Organic Electroluminescent Device
Authors: Wen Hsin‐Yi , Chao Chun‐Ming , Chang Mei‐Ying , Hsieh Chiung‐Wen , Hsieh Shu‐Chen
Published: July 2013

We describe how the morphology, photoluminescence (PL), and electroluminescence properties of 2,2′,7,7′‐tetrakis(pyren‐1‐yl)‐9,9′‐spirobifluorene (TPSBF) are related to its film thickness and how, under optimized conditions, the three main PL emissions constitute a form of white light. We fabricated high‐brightness, broad‐spectrum, white‐light organic light‐emitting diodes, incorporating a single emission layer of the blue‐light‐emitting material TPSBF, which comprises four pyrene units linked to a spirobifluorene core. An organic light‐emitting device with the configuration indium tin oxide (170 nm)/4,4′,4′′‐tris[N‐(2‐naphthyl)‐N‐phenylamino]triphenylamine (15 nm)/4,4′‐bis[N‐(1‐naphthyl)‐N‐phenylamino]biphenyl (65 nm)/TPSBF (50 nm)/tris(8‐hydroxyquinoline)aluminum (30 nm)/LiF (0.8 nm)/Al (200 nm) exhibited a broad‐spectrum white emission with a maximum luminescence and current efficiency of 57 680 cd m−2 and 6.51 cd A−1, respectively, and Commission International De l’Eclairage coordinates of (0.29,0.36).
Structure–Property Relationships of Fe4S4 Clusters
Authors: Bergeler Maike , Stiebritz Martin T. , Reiher Markus
Published: July 2013

In this theoretical study, the sensitivity of Fe4S4 cluster properties, such as potential energy, spin coupling, adiabatic detachment energy, inner‐sphere reorganization energy, and reactivity, to structural distortions is investigated. [Fe4S4(SH)4]3−/2−/1− model clusters anchored by fixed hydrogen atoms are compared with Fe4S4 clusters coordinated by ethyl thiolates with fixations according to cysteine residues in crystal structures. For the model system, a dependence of the ground‐state spin‐coupling scheme on the hydrogen–hydrogen distances is observed. The minima of the potential energy surface of [Fe4S4(SH)4]2−/1− clusters are located at slightly smaller hydrogen–hydrogen distances than those of the [Fe4S4(SH)4]3− cluster. For inner‐sphere reorganization energies the spin‐coupling scheme adopted by the broken‐symmetry wave function plays an important role, since it can change the reorganization energies by up to 13 kcal mol−1. For most structures, [Fe4S4(SR)4]2− and [Fe4S4(SR)4]1− (R=H or ethyl, derived from cysteine) favor the same coupling scheme. Therefore, the reorganization energies for this redox couple are relatively low (6–12 kcal mol−1) compared with the 2−/3− redox couple favoring different spin‐coupling schemes before and after electron transfer (14–18 kcal mol−1). However, one may argue that more reliable reorganization energies are obtained if always the same spin‐coupling pattern is enforced. All theoretical observations and insights are discussed in the light of experimental results distilled from the literature.
Analytical modeling of Transmission Control Protocol NewReno using Generalized Stochastic Petri Nets
Authors: Vinayak Resham , Krishnaswamy Dilip , Dharmaraja Selvamuthu
Published: July 2013

This paper presents a novel analytical model of Transmission Control Protocol (TCP) using a generalized stochastic Petri net (GSPN). Extensive simulation work has been done for the performance evaluation of TCP NewReno protocol. In view of the limitations of the simulation technique, we present an analytical approach using GSPN. A GSPN is a useful mathematical tool that solves continuous time Markov chains for complex systems and evaluates the stationary behavior. In this paper, we analyze the slow‐but‐steady variant of TCP NewReno. The model captures the behavioral aspects of the slow start and the congestion avoidance phase together with the fast retransmit and recovery capabilities of TCP NewReno. Performance metrics such as throughput, goodput, and task completion time of the system are obtained. The effect of variation in the model parameters on the performance is studied. The results are validated using the network simulator, and their accuracy is verified by evaluating the confidence interval. The performance of the proposed model is compared with that of TCP Reno. The performance of the proposed model is also compared with one of the previous models. The numerical illustrations and comparison of the proposed technique with simulation validates the accuracy, efficiency, and competence of the GSPN technique. While GSPN modeling for TCP is investigated in depth for the TCP NewReno and TCP Reno variant in this paper, other protocols could be also analyzed similarly. Copyright © 2013 John Wiley & Sons, Ltd.
Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to treatment implications
Authors: Moreira Rodrigo O. , Campos Stella C. , Soldera Ana L.
Published: July 2013

Alzheimer's Disease (AD) is the most common cause of dementia worldwide. Type 2 Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance (IR) and progressive β cell failure, and affected individuals are at increased risk to develop several forms of cognitive dysfunction, including AD. Different mechanisms have already been identified linking visceral obesity, IR and AD. Insulin resistance is associated with a decrease in glucose uptake by neurons, an increase in Amyloid β production and secretion, in the formation of senile plaques, and also in tau protein phosphorylation. Other mechanisms also include a decrease in Insulin Degrading Enzyme (IDE) activity and an increase in oxidative stress secondary to hyperglycemia. Taken together, these mechanisms suggest that drugs used to ameliorate hyperglycemia and IR may also have beneficial effects in diabetic patients with AD. Indeed, manuscripts investigating the effects of metformin, thiazolinediones, leptin, GLP‐1 therapies, insulin and bariatric surgery in cognition and AD have been published with very promising results, and may indicate an alternative approach for these patients. This article is protected by copyright. All rights reserved.
Restrictive eating behaviors are a nonweight‐based marker of severity in anorexia nervosa
Authors: De Young Kyle P. , Lavender Jason M. , Steffen Kristine , Wonderlich Stephen A. , Engel Scott G. , Mitchell James E. , Crow Scott J. , Peterson Carol B. , Le Grange Daniel , Wonderlich Joseph , Crosby Ross D.
Published: July 2013

Objective

The purpose of this study was to compare the type and frequency of restrictive eating behaviors across the two subtypes of anorexia nervosa (AN; restricting [ANr] and binge eating/purging [ANbp]) using ecological momentary assessment (EMA) and to determine whether subtype differences in restrictive eating behaviors were attributable to severity of the disorder or the frequency of binge eating.

Method

Participants (N = 118) were women at least 18 years of age with full (n = 59) or subthreshold (n = 59) AN who participated in a two week (EMA) protocol.

Results

General estimating equations revealed that individuals with ANbp generally reported more frequent restrictive eating behaviors than individuals with ANr. These differences were mostly accounted for by greater severity of eating psychopathology, indicating that the presence and frequency of restrictive eating behaviors in AN may be nonweight‐based markers of severity. Binge eating frequency did not account for these findings.

Discussion

The present findings are especially interesting in light of the weight‐based severity rating in the DSM‐5. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2013; 46:849–854)
Synthesis and Photophysical Properties of Push–Pull Structures Incorporating Diazines as Attracting Part with a Fluorene Core
Authors: Denneval Charline , Moldovan Oana , Baudequin Christine , Achelle Sylvain , Baldeck Patrice , Plé Nelly , Darabantu Mircea , Ramondenc Yvan
Published: July 2013

We report, herein, the synthesis of new push–pull chromophores that incorporate a diazine ring as the electron‐withdrawing part and an N,N‐dimethylaniline moiety as the electron‐donating part. Both of which are connected to a fluorene core. The length of the conjugated backbone was increased by incorporating ethynyl linkers and triazole rings on the both sides of the fluorene. The optical and two‐photon absorption (TPA) properties were investigated, which exhibitied high quantum yields (up to 70 %), significant Stokes shifts, and good TPA cross‐sections.
Total Synthesis of Carbazomycin G
Authors: Chakraborty Suchandra , Saha Chandan
Published: July 2013

A concise total synthesis of carbazomycin G has been completed in five steps. Cerium(IV) ammonium nitrate (CAN)–SiO2‐mediated oxidation of 2‐methyl‐2,3,4,9‐tetrahydro‐1H‐ carbazol‐1‐one afforded a carbazole‐1,4‐quinone derivative, 2‐methyl‐1H‐carbazole‐1,4(9H)‐dione, the synthetic precusor, which on, which, on Thiele acetylation under newly developed HBF4 catalysis conditions, yielded 4‐hydroxy‐2‐methyl‐9H‐carbazole‐1,3‐diyl diacetate. Finally, CAN‐SiO2‐mediated oxidative hydrolysis of the acetylation product and O‐methylation using a stoichiometric amount of diazomethane and subsequent regioselective nucleophilic addition of methyllithium led to carbazomycin G.
Double Asymmetric Induction in Organocatalyzed Aldol Reactions: Total Synthesis of (+)‐2‐epi‐Hyacinthacine A2and (–)‐3‐epi‐Hyacinthacine A1
Authors: Marjanovic Jasna , Divjakovic Vladimir , Matovic Radomir , Ferjancic Zorana , Saicic Radomir N.
Published: July 2013

The stereodivergent synthesis of two hyacinthacine analogues, which relies on an organocatalyzed aldol addition, is described. The aldol addition of dioxanone to an α‐N‐carbobenzyloxy‐substituted chiral aldehyde, promoted by both (R)‐ and (S)‐proline, proceeds in reasonable yields with acceptable diastereomeric ratios. The success of the reaction may be due to the use of an acyclic aldehyde acceptor, which allows reagent control of the stereochemical outcome of the key aldolization step in both the matched and mismatched cases.
Preparation of Peptide Thioesters through Fmoc‐Based Solid‐Phase Peptide Synthesis by Using Amino Thioesters
Authors: Stuhr‐Hansen Nicolai , Wilbek Theis S. , Strømgaard Kristian
Published: July 2013

An effective procedure for the synthesis of peptide alkyl thioesters by 9‐fluorenylmethoxycarbonyl (Fmoc) solid‐phase peptide synthesis was developed. The free C terminus of a fully protected peptide was coupled in solution with the free amino group of an amino thioester. This furnished the fully protected peptide thioester, which was globally deprotected to afford the desired unprotected peptide thioester. The method is compatible with labile groups such as phosphoryl and glycosyl moieties.
Selective and Simultaneous Voltammetric Determination of Glutathione, Uric Acid and Penicillamine by a Modified Carbon Nanotube Paste Electrode
Authors: Mazloum‐Ardakani Mohammad , Sheikh‐Mohseni Mohammad Ali , Mirjalili Bibi‐Fatemeh
Published: July 2013

In this paper, the use of a carbon paste electrode (CPE) modified by (E)‐3‐((2‐(2,4‐dinitrophenyl)hydrazono)methyl)benzene‐1,2‐diol (DHB) and carbon nanotubes (CNTs) for the determination of glutathione (GSH), uric acid (UA) and penicillamine (PA) is described. Initially, cyclic voltammetry was used to investigate the redox properties of the modified electrode in phosphate buffer. Next, the electrocatalytic oxidation of GSH via EC′ mechanism at the modified electrode was described. At the optimum pH of 7.0, the oxidation of GSH occurs at a potential that is 530 mV less positive than that of an unmodified carbon paste electrode. The values of the diffusion coefficient (D=2.5×10−6 cm2 s−1) and the catalytic rate constant (k=1.7×103 M−1 s−1) were calculated for GSH, using chronoamperometry. Based on differential pulse voltammetry, the oxidation of GSH exhibited a dynamic range between 0.4 and 700.0 µM and a detection limit (3σ) of 70.0 nM. Also, simultaneous determination of GSH, UA and PA was described at the modified electrode. Finally, this method was used for the determination of these substances in synthetic solutions and blood serum samples.
Nano‐Roughening a Pt Disk Microelectrode via Electrochemical Alloying‐Dealloying in Ionic Liquid Electrolyte
Authors: Jiang Junhua , Wang Xinying , Zhang Lei
Published: July 2013

A green chemistry method to nano‐roughen a Pt disk microelectrode has been successfully developed via electrochemical alloying‐dealloying in an ionic liquid bath comprising of ZnCl2 and 1‐ethyl‐3‐methylimidazolium chloride. The nano‐roughened Pt layer possesses bark‐like nanoporous structures characteristic of nano‐sized aggregates separated by nano‐cracks whose width ranging from around 50 to 200 nm. The nano‐roughened microelectrode possesses high surface area and diffusional properties typical of a microelectrode. Electrochemical oxidation and reduction of nitrite have been studied as an example for demonstrating that the nano‐roughened microelectrode is a promising technique for electroanalysis and electrocatalysis applications.
Tilted hexagonal post arrays: DNA electrophoresis in anisotropic media
Authors: Chen Zhen , Dorfman Kevin D.
Published: July 2013

Using Brownian dynamics simulations, we show that DNA electrophoresis in a hexagonal array of micron‐sized posts changes qualitatively when the applied electric field vector is not coincident with the lattice vectors of the array. DNA electrophoresis in such “tilted” post arrays is superior to the standard “un‐tilted” approach; while the time required to achieve a resolution of unity in a tilted post array is similar to an un‐tilted array at a low‐electric field strengths, this time (i) decreases exponentially with electric field strength in a tilted array and (ii) increases exponentially with electric field strength in an un‐tilted array. Although the DNA dynamics in a post array are complicated, the electrophoretic mobility results indicate that the “free path,” i.e. the average distance of ballistic trajectories of point‐sized particles launched from random positions in the unit cell until they intersect the next post, is a useful proxy for the detailed DNA trajectories. The analysis of the free path reveals a fundamental connection between anisotropy of the medium and DNA transport therein that goes beyond simply improving the separation device.
Environmental sustainability of emerging algal biofuels: A comparative life cycle evaluation of algal biodiesel and renewable diesel
Authors: Zaimes George G. , Khanna Vikas
Published: July 2013

Holistic evaluation via a life cycle based approach is critical for guiding the environmentally conscious development of emerging microalgal biofuel pathways. This study models the energy return on investment (EROI) and life cycle greenhouse gas (GHG) emissions for producing algal derived biodiesel and renewable diesel under different production pathways—consisting of a combination of algal cultivation, harvesting, extraction, and coproduct utilization scenarios. The results indicate that in the base‐case scenario(s) the EROI for microalgae fuels range from 0.26 to 1.20 with GHG emissions ranging from 50 to 240 gCO2 equivalent/MJ‐fuel depending on the choice of cultivation variables, coproduct utilization options, and processing technologies. In the improved scenario(s), algal fuels have an EROI ranging from 0.81 to 2.01 and GHG emissions ranging from 30 to 90 gCO2 eq./MJ‐fuel. Furthermore, improved scenarios with favorable EROI and GHG emissions profile for microalgal biofuels are plagued with high technological uncertainty. This suggests that broad advances in algal technologies are required if algal fuels are to be competitive with other leading second generation and advanced biofuels. The choice of fuel conversion technology was found to have a comparatively small impact on overall life‐cycle energy use and GHG emissions. Therefore, the choice of fuel product may be based on other criteria such as fuel storage stability and compatibility with transportation fuel infrastructure. © 2013 American Institute of Chemical Engineers Environ Prog, 32: 926–936, 2013
Tree root mounds and their role in transporting soil on forested landscapes
Authors: Hoffman Benjamin S. S. , Anderson Robert S.
Published: July 2013

The growth and decay of tree roots can stir and transport soil. This is one process that contributes to the mass‐movement of soil on hillslope. To explore the efficiency of this process, we document the mounding of soil beside Ponderosa and Lodgepole pine trees in the forests that dominate the mid‐elevations of Colorado's Boulder Creek watershed. Mounds are best expressed around Ponderosa pines, reaching vertical displacements above the far‐field slopes of order 10–20 cm, fading into the slope by roughly 100 cm distance from the trunks with common diameters of 30 cm. Positive mounding occurs on all sides of trees on slopes, indicating that the mounding is not attributable to deflection of a creeping flow of soil around the tree, but rather to the insertion of root volume on all sides in the subsurface. Mounding is commonly asymmetric even on cross‐slope profiles. Significant variation in the mound sizes results in no clear relationship between tree diameter and root volume displaced. These observations motivated the development of a discrete element model of tree root growth using the LIGGGHTS model, in which grains we specified to be ‘root cells’ were allowed to enlarge within the simulated granular matrix. Mounding could be reproduced, with the majority of the vertical displacement of the surface being attributable to reduction of the bulk density due to dilation of the granular matrix during root enlargement. Finally, we develop a previous analysis of the role of roots in transporting soil during growth and decay cycles. We find that even in shallow soils, the root‐cycle can drive significant soil transport down forested montane slopes. Copyright © 2013 John Wiley & Sons, Ltd.
Comparative Performance Analysis of Anode‐Supported Micro‐Tubular SOFCs with Different Current‐Collection Architectures
Authors: De la Torre R. , Avila‐Paredes H. J. , Sglavo V. M.
Published: July 2013

In this study, the performances of single micro‐tubular solid oxide fuel cells based on the NiO–YSZ/YSZ/LSM system with two different current‐collection architectures were compared. In the first case, a straight Ni wire was inserted within the hole of the cell before the electrochemical testing, and in the second case, a coil integrated‐current collector within the anode layer was already arranged for electrical connections during cell processing. The current produced in each case was collected from double terminal and the performance of the cells was estimated by electrochemical I–V characterization. The maximum power outputs generated in the cells with the integrated‐current collector and the common current‐collection architectures were of ∼200 and ∼55 mW cm–2, respectively at 800 °C under a wet H2 fuel flow.
Localized refractory dissolved organic carbon sinks in the deep ocean
Authors: Hansell Dennis A. , Carlson Craig A.
Published: July 2013

The global ocean holds one of Earth's major carbon reservoirs as dissolved organic matter (662 ± 32 PgC). Most of this material (>95%) is termed refractory dissolved organic carbon (RDOC) as Williams and Druffel (1987) found it to be old relative to the circulation time of the ocean. While RDOC within the modern ocean is thus perceived as vast and only slowly renewed, its mobilization has been implicated by Sexton et al. (2011) to explain Earth's transient warming events (i.e., hyperthermals) of the Paleocene and Eocene epochs (65–34 million years ago). Assessing this proposed function of RDOC as a rapidly (~5–10 kyr) exchangeable carbon reservoir is presently limited by insufficient knowledge of the responsible processes. Here we investigate the dynamics of RDOC in the deep Pacific Ocean, previously characterized by concentration gradients thought to be established by slow but systematic RDOC removal with circulation and aging of the water masses. We demonstrate that RDOC is instead conserved during much of its circulation, but that there exist localized sinks in the deep, far North Pacific and at mid depth in the subtropical South Pacific. Water mass mixing into these sink regions creates the observed RDOC gradients. Together, the Pacific sinks remove 7–29% of the 43 Tg RDOC added to the deep global ocean each year with overturning circulation, and point to an important but still unidentified control on the RDOC inventory of deep marine systems.
Global assessment of limitation to symbiotic nitrogen fixation by phosphorus availability in terrestrial ecosystems using a meta‐analysis approach
Authors: Augusto Laurent , Delerue Florian , Gallet‐Budynek Anne , Achat David L.
Published: July 2013

Symbiotic nitrogen fixation (SNF) is the main natural source of nitrogen (N) in terrestrial ecosystems worldwide. Previous studies have shown that fixation of N by plants can be limited by the availability of phosphorus (P) in soils. We used global meta‐analysis to investigate how P availability controls SNF. In experiments in which plants were grown in an artificial medium, severe P deficiencies in the nutritive solution ([PO4] < 5–42 μM) depressed SNF flux through both a direct decrease in the plant fixation rate (i.e., decreased N fixed per unit of plant biomass) and an indirect effect (i.e., through plant biomass). In most experiments with plants grown in soils, SNF was proportional to plant biomass and was consequently only indirectly limited by P. Some cases using unfertilized and weathered soils (ultisols or oxisols), where plants were particularly P stressed, were an exception with both direct and indirect P limitations. Our global analysis of the P‐SNF relationship indicated that P bioavailability commonly limited SNF flux. We conclude that the main driver of in situ P limitation is indirect via limitation of plant growth, except in certain cases where both indirect and direct constraints may play a role. These cases of severe P deficiency may be mainly found in weathered tropical soils of Africa and South America, probably in unfertilized croplands which are depleted in P due to repeated biomass harvests.
Sill and lava geochemistry of the mid‐Norway and NE Greenland conjugate margins
Authors: Neumann Else‐Ragnhild , Svensen Henrik , Tegner Christian , Planke Sverre , Thirlwall Matthew , Jarvis Kym E.
Published: July 2013

This paper presents major, trace‐elements, and Sr‐Nd isotopes for two prominent sills formed during the opening of the North Atlantic, sampled by the Utgard borehole (6607/5‐2) in the Vøring Plateau. The Utgard sills are compared to opening‐related lavas recovered from ODP Leg 104 Hole 642E farther west on the Vøring Plateau and on the NE Greenland conjugate margin. The Utgard sills (3.6–5.9 wt % MgO) are enriched in strongly relative to moderately incompatible trace elements and have 87Sr/86Sr and 143Nd/144Nd ratios of 0.70380–70387 and 0.51292–0.51293, respectively, in the Upper Utgard Sill, and 0.70303–0.70306 and 0.51297–0.51299 in the Lower Sill. Alteration is minor. The Utgard melts originated by partial melting of an asthenospheric, depleted mantle source (DMM or Iceland Rift Zone, IRZ, type) with chemical characteristics similar to the source that gave rise to NE Greenland lavas. The Utgard magmas underwent extensive fractional crystallization in the lower crust (Upper Sill: >70%; Lower Sill: >55%) with removal mainly of olivine and pyroxenes, accompanied by ≤1% assimilation of crustal melts. This crystallization formed significant masses of dense cumulates (∼3.25 g/cm3) (underplating). Assuming an areal extent similar to that of the two sills, we estimate a composite layer of ultramafic cumulates mixed with less dense country rocks to be >320 m thick beneath the two Utgard sills and >8.8 km beneath the thickest part of the Vøring Plateau lavas. Opening‐related cumulates may thus account for a significant part of the lower crustal high‐velocity, high‐density bodies (average density 3.1 g/cm3) along the Norwegian margin.
Shifting seasonality and increasing frequency of precipitation in wet and dry seasons across the U.S.
Authors: Pal Indrani , Anderson Bruce T. , Salvucci Guido D. , Gianotti Daniel J.
Published: July 2013

Water management, agriculture, and ecological systems are sensitive to the frequency and timing of precipitation. Here we document historical trends in these characteristics for station‐specific wet and dry seasons over the U.S. from 1930 to 2009. Simulations based on Markovian precipitation occurrence models are used as a null against which to test observed trends without resorting to area averaging. Most regions display increases in precipitation frequency during both wet and dry seasons accompanied by a decrease in length of dry spells. Prominent increases (decreases) occur over the Central and Great Plains during the dry season. An exception is the Atlantic Plains, which experienced a decrease in frequency and an increase in dry spell length, especially during the wet season. Regionally consistent trends in the timing of wet and dry seasons are also evident, particularly over the Ohio (Missouri) River valleys where the dry season now arrives up to 2–3 weeks earlier (later).
Time‐varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: An EEG‐TMS study
Authors: Ferreri Florinda , Vecchio Fabrizio , Ponzo David , Pasqualetti Patrizio , Rossini Paolo Maria
Published: July 2013

Purpose

Motor evoked potentials (MEPs) elicited by a train of consecutive, individual transcranial magnetic stimuli demonstrate fluctuations in amplitude with respect to time when recorded from a relaxed muscle. The influence of time‐varying, instantaneous modifications of the electroencephalography (EEG) properties immediately preceding the transcranial magnetic stimulation (TMS) has rarely been explored. The aim of this study was to investigate the influence of the pre‐TMS motor cortex and related areas EEG profile on time variants of the MEPs amplitude.

Method

MRI‐navigated TMS and multichannel TMS‐compatible EEG devices were used. For each experimental subject, post‐hoc analysis of the MEPs amplitude that was based on the 50th percentile of the MEPs amplitude distribution provided two subgroups corresponding to “high” (large amplitude) and “low” (small amplitude). The pre‐stimulus EEG characteristics (coherence and spectral profile) from the motor cortex and related areas were analyzed separately for the “high” and “low” MEPs and were then compared.

Results

On the stimulated hemisphere, EEG coupling was observed more often in the high compared to the low MEP trials. Moreover, a paradigmatic pattern in which TMS was able to lead to significantly larger MEPs was found when the EEG of the stimulated motor cortex was coupled in the beta 2 band with the ipsilateral prefrontal cortex and in the delta band with the bilateral centro‐parietal‐occipital cortices.

Conclusion

This data provide evidence for a statistically significant influence of time‐varying and spatially patterned synchronization of EEG rhythms in determining cortical excitability, namely motor cortex excitability in response to TMS. Hum Brain Mapp 35:1969–1980, 2014. © 2013 Wiley Periodicals, Inc.
Punishing unfairness: Rewarding or the organization of a reactively aggressive response?
Authors: White Stuart F. , Brislin Sarah J. , Sinclair Stephen , Blair James R.
Published: July 2013

Objectives

The neural correlates of human cooperative behavior remain poorly understood. Previous work has suggested that increases in striatal activation while punishing unfair offers represents reward signaling. However, other regions are also implicated when punishing others, for example dorsomedial frontal cortex (dmFC), anterior insula cortex (AIC), and periaqueductal gray (PAG). Moreover, the response of other regions implicated in signaling reward, for example ventromedial prefrontal cortex (vmPFC) or posterior cingulate cortex (PCC), has not been systematically examined.Experimental Design:Functional magnetic resonance imaging utilizing parametric modulation was conducted on 21 healthy adults participating in a social exchange paradigm.Principal Observations:Participants showed significant positive modulation of activity as a function of delivered punishment in caudate, dmFC, AIC, and PAG; that is, higher punishments by participants of unsatisfactory offers were associated with increasing activity within these regions. However, participants showed significantnegativemodulation of activity as a function of delivered punishment in vmPFC and PCC; increases in punishment level by participants were associated withdecreasesin activity within these regions.Conclusions:The current data question whether caudate activity when punishing unfair offers should be considered to indicate the reward value of this punishment. Instead, this activity, in conjunction with activity within dmFC, AIC, and PAG, may represent the organization of an untypical, punishing response that represents a reactive aggressive response to provocation. Notably, an inverse, regulatory relationship between vmPFC and PAG activity has been previously implicated in the context of another stimulus for reactive aggression; looming threat (Mobbs et al. [2007]: Science 317:1079–1083).Hum Brain Mapp 35:2137–2147, 2014. ©2013 Wiley Periodicals, Inc.
Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo
Authors: Fallowfield Jonathan A. , Hayden Annette L. , Snowdon Victoria K. , Aucott Rebecca L. , Stutchfield Ben M. , Mole Damian J. , Pellicoro Antonella , Gordon-Walker Timothy T. , Henke Alexander , Schrader Joerg , Trivedi Palak J. , Princivalle Marc , Forbes Stuart J. , Collins Jane E. , Iredale John P.
Published: July 2013

Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting of the dynamic component of PHT and markers of MF activation using short-term administration of the peptide hormone relaxin (RLN). We defined the portal hypotensive effect in rat models of sinusoidal PHT and the expression, activity, and function of the RLN-receptor signaling axis in human liver MFs. The effects of RLN were studied after 8 and 16 weeks carbon tetrachloride intoxication, following bile duct ligation, and in tissue culture models. Hemodynamic changes were analyzed by direct cannulation, perivascular flowprobe, indocyanine green imaging, and functional magnetic resonance imaging. Serum and hepatic nitric oxide (NO) levels were determined by immunoassay. Hepatic inflammation was assessed by histology and serum markers and fibrosis by collagen proportionate area. Gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting and hepatic stellate cell (HSC)-MF contractility by gel contraction assay. Increased expression of RLN receptor (RXFP1) was shown in HSC-MFs and fibrotic liver diseases in both rats and humans. RLN induced a selective and significant reduction in portal pressure in pathologically distinct PHT models, through augmentation of intrahepatic NO signaling and a dramatic reduction in contractile filament expression in HSC-MFs. Critical for translation, RLN did not induce systemic hypotension even in advanced cirrhosis models. Portal blood flow and hepatic oxygenation were increased by RLN in early cirrhosis. Treatment of human HSC-MFs with RLN inhibited contractility and induced an antifibrogenic phenotype in an RXFP1-dependent manner. Conclusion: We identified RXFP1 as a potential new therapeutic target for PHT and MF activation status. (HEPATOLOGY 2014;59:1492-1504)
Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early‐stage breast cancer
Authors: Wang‐Johanning Feng , Li Ming , Esteva Francisco J. , Hess Kenneth R. , Yin Bingnan , Rycaj Kiera , Plummer Joshua B. , Garza Jeremy G. , Ambs Stefan , Johanning Gary L.
Published: July 2013

A simple and accurate test to detect early‐stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV‐K(HML‐2)) transcription may be increased in human breast tumors. We hypothesized that HERV‐K(HML‐2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were used to detect serum anti‐HERV‐K(HML‐2) antibody titers. RNA was extracted from sera and analyzed by real‐time RT‐PCR to quantitate the level of HERV‐K(HML‐2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV‐K(HML‐2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval 0.77–1.00) for DCIS and of 0.95 (95% confidence interval 0.89–1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV‐K(HML‐2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV‐K(HML‐2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease.
IMPROVING FARMERS’ ACCESS TO IRRIGATION IN THE BUFFER ZONE: AN EFFECTIVE WAY TO CONSERVE BIODIVERISTY IN THE CHITWAN NATIONAL PARK
Authors: Adhikari K.R. , Tan Y.C. , Lai J.S. , Chen Z.S. , Mishra V.S.
Published: July 2013

Drawing results from multi‐scale studies, this paper addresses the important coexistence between the Chitwan National Park and buffer‐zone farmers’ communities in the East Rapti River basin of Nepal. The relationship between the two is discussed using results of land use change (1978–2010) and water availability analysis (1976–2010). At basin level, though there are indications of losses of the government forest, the utilizable outflow of water in the river is still abundant because the process of depletion of water is very low. Scaling down to local level, irrigation systems originating in the river were evaluated and farmers interviewed across locations. There were statistical differences in irrigation system performance affecting water availability for crop production in the buffer zone. Because irrigation plays a disproportionately greater role in farm income and economic water scarcity could be removed, improvement in access to irrigation could effectively help improve food sufficiency and reduce income disparity in this basin. In the forest of the national park, encroachment seems to be low but frequencies of rhino poaching and timber pilferage have remained relatively high. As the buffer zone is the gateway to the park, and subsistence farm families live on the fringes of the park, helping irrigation development would strengthen farmers’ cooperation in enhancing resource conservation of the park. Copyright © 2013 John Wiley & Sons, Ltd.
Variation of ostracod communities in a lowland river channel as exemplified by the lower course of the Oder (N‐W Poland)
Authors: Szlauer‐Łukaszewska Agnieszka
Published: July 2013

The study has investigated the variation in the ostracod communities of the lower course of the Oder River in relation to different substrates in two habitat types: river bed and littoral. Mineral sediment prevailed in the littoral, whereas organic sediment prevailed in the river bed. Physocypria kraepelini and Darwinula stevensoni were typical taxa of the river bed, while juvenile Candoninae, Cypria ophtalmica, and Cypridopsis vidua were typical of the littoral. Eutrophic waters of the lower course of the river provided favorable conditions for the development of ostracods, confirmed by high population density: 1200 ind. m−2 for the littoral and 39 100 ind. m−2 for the river bed. Insufficient amount of organic matter, turbulences, and water level fluctuations in the littoral resulted in the population density there being 30 times lower than in the river bed. In the littoral the number of Ostracoda taxa was higher than in the river bed. The species composition of the Ostracoda in the littoral and river bed was analogous to the littoral and profundal zone of lakes.
Novel molecular correlates of endocannabinoid‐mediated fear‐conditioned analgesia in rats
Authors: Olango W.M. , Géranton S.M. , Roche M. , Hunt S.P. , Finn D.P.
Published: July 2013

Background

Fear‐conditioned analgesia (FCA) is the profound suppression of pain during exposure to conditioned aversive stimuli and is mediated at spinal and supraspinal levels. The endocannabinoid system plays a key role in FCA. This study investigated brain and spinal cord expression of genes implicated in pain‐ and fear‐related plasticity (Zif268 and Sgk1), following expression of formalin‐evoked nociception, contextual fear or endocannabinoid‐mediated FCA.

Methods

Adult male Lister‐Hooded rats received intra‐plantar injection of formalin or saline, with or without administration of the CB1 receptor antagonist AM251 (3 mg/kg, i.p.) or vehicle, 30 min prior to re‐exposure to an arena paired 24 h previously with footshock. Real time quantitative polymerase chain reaction was used to measure expression of Zif268 and Sgk1 mRNA in the dorsal horn of the spinal cord (DHSC) and rostral ventromedial medulla (RVM) 30 min following arena re‐exposure.

Results

Intra‐plantar injection of formalin resulted in an increase in Zif268 and Sgk1 mRNA expression in the ipsilateral DHSC of non–fear‐conditioned rats, effects not observed in rats expressing FCA. Systemic administration of the CB1 receptor antagonist/inverse agonist AM251 attenuated both FCA and the FCA‐associated suppression of Zif268 expression in the ipsilateral DHSC without affecting expression of Sgk1. Conditioned fear was associated with an increase in Zif268 mRNA expression in the RVM of saline‐, but not formalin‐treated rats.

Conclusions

The present findings suggest that Zif268 in the DHSC is an important molecular correlate of endocannabinoid‐mediated FCA, and that fear‐related expression of Zif268 in the RVM is influenced by the presence of nociceptive tone.
Forcing and feedback in the MPI‐ESM‐LR coupled model under abruptly quadrupled CO2
Authors: Block K. , Mauritsen T.
Published: July 2013

Radiative feedback mechanisms associated with temperature, water vapor, cloud, and surface albedo change determine climate sensitivity to radiative forcing. Here we use the linearized radiative kernel‐technique in combination with a Gregory analysis to determine the strength and structure of feedbacks, as well as direct and adjusted CO2 forcings in the coupled Max Planck Institute Earth System Model at base resolution (MPI‐ESM‐LR). We show that the combined Kernel‐Gregory approach yields an elegant separation of surface temperature‐dependent feedbacks from contributions to radiative forcing by fast adjustments. MPI‐ESM‐LR exhibits a relatively large cloud adjustment of nearly 2 W m−2 in direct response to quadrupled CO2, with positive cloud adjustment evident throughout the tropics, subtropics and over most landmasses whereas midlatitude storm tracks contribute negatively. The model features a nonlinear regression of radiation imbalance to global mean surface temperature change, resulting in a significantly increasing effective climate sensitivity after about 20 years which is approximately at temperatures 4–5 K above preindustrial. This feature is not uncommon among climate models and is relevant for future climate projections. We analyze the contribution of the individual feedback processes to this behavior and discuss possible origins such as differential ocean warming patterns associated with deep‐ocean heat uptake or state dependencies of the feedback processes.
Novel biomimetic thermosensitive β‐tricalcium phosphate/chitosan‐based hydrogels for bone tissue engineering
Authors: Dessì M. , Borzacchiello A. , Mohamed Tawheed H. A. , Abdel‐Fattah Wafa I. , Ambrosio L.
Published: July 2013

Among the less invasive surgical procedures for tissue engineering application, injectable in situ gelling systems have gained great attention. In this contest, this article is aimed to realize thermosensitive chitosan‐based hydrogels, crosslinked with β‐glycerophosphate and reinforced via physical interactions with β‐tricalcium phosphate. The kinetics of sol–gel transition and the composite hydrogel properties were investigated by rheological analysis. The hydrogels were also characterized by Fourier transform infrared study, X‐ray diffraction, scanning electron microscopy, transmission electron microscopy analysis, and thermal and biological studies. The hydrogels exhibit a gel‐phase transition at body temperature, and a three‐dimensional network with typical rheological properties of a strong gel. The presence of the inorganic phase, made up of nanocrystals, provides a structure with chemico‐physical composition that mimics natural bone tissue, favoring cellular activity. These findings suggest the potential of the materials as promising candidates for hard tissue regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2984–2993, 2013.
The Asymptotic Existence of Group Divisible ‐Designs of Large Order with Index One
Authors: Mohácsy Hedvig
Published: July 2013

The following result gives the answer to the question of whether for a fixed number of groups u and fixed block size k a group divisible t‐design of group type with block size k and index one exists for sufficiently large m if the necessary arithmetic conditions are satisfied. Let k and u be positive integers, . Then there exists an integer such that there exists a group divisible t‐design of group type with block size k and index one for any integer satisfying the necessary arithmetic conditions

urn:x-wiley:10638539:media:jcd21365:jcd21365-math-0007The case of this theorem gives an existence theorem for transversal t‐designs of large order, which was previously proved by J. L. Blanchard in an unpublished manuscript.
Transcription Factor Sp1 Regulates T‐Type Ca2+ Channel CaV3.1 Gene Expression
Authors: González‐Ramírez Ricardo , Martínez‐Hernández Elizabeth , Sandoval Alejandro , Felix Ricardo
Published: July 2013

Voltage‐gated T‐type Ca2+ (CaV3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T‐channel genes (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV3.1–CaV3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA‐less sequence containing several potential transcription factor‐binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ∼1.5 kb 5′‐upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E‐115 cell line. In silico analysis revealed that this region possesses a TATA‐less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over‐expression enhanced promoter activity while siRNA‐mediated Sp1 silencing significantly decreased the level of CaV3.1 protein and reduced the amplitude of whole‐cell T‐type Ca2+ currents expressed in the N1E‐115 cells. These results provide new insights into the molecular mechanisms that control CaV3.1 channel expression. J. Cell. Physiol. 229: 551–560, 2014. © 2013 Wiley Periodicals, Inc.
Doxylamine pharmacokinetics following single dose oral administration in children ages 2–17 years
Authors: Balan Guhan , Thompson Gary A. , Gibb Roger , Li Lijuan , Hull David , Seeck Molly
Published: July 2013

To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2–17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non‐compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P‐value = 0.0517). As expected due to increasing body size, CLo and Vz/F increased with age. Due to a similar increase with age for Clo and Vz/F, no age‐related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo; although Vz/F remained age‐dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax, whereas AUC increases only 60%.