bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma
Authors: Mitchell Deanna , Bergendahl Genevieve , Ferguson William , Roberts William , Higgins Timothy , Ashikaga Takamaru , DeSarno Mike , Kaplan Joel , Kraveka Jacqueline , Eslin Don , Werff Alyssa Vander , Hanna Gina K. , Sholler Giselle L. Saulnier
Published: July 2015

Background

The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses.

Procedure

Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28‐day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters Cmax, AUC0‐24, t1/2, CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma.

Results

We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m2. The non‐dose‐limiting toxicities at this dose were mainly anorexia and pain. The dose‐limiting toxicities (DLTs) of two patients at 135 mg/m2 were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy.

Conclusions

Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Pediatr Blood Cancer 2015; 9999:1–8 © 2015 Wiley Periodicals, Inc.
Frequency of Paroxysmal Nocturnal Hemoglobinuria Clones by Multiparametric Flow Cytometry in Pediatric Aplastic Anemia Patients of Indian Ethnic Origin
Authors: Sreedharanunni Sreejesh , Sachdeva Man Updesh Singh , Bose Parveen , Varma Neelam , Bansal Deepak , Trehan Amita
Published: July 2015

Background

The literature on paroxysmal nocturnal hemoglobinuria (PNH) in aplastic anemia (AA) is largely focused on adults with few studies in children. Moreover, large studies are conspicuously absent from developing countries. Knowledge of the prevalence and utility of their detection is required before widespread use of PNH screening in pediatric AA in resource‐limited settings.

Methods

We performed a retrospective audit over a period of 9 years to study the prevalence of PNH clones by flow cytometry (FCM) in children ≤12 years of age presenting with AA, and analyzed their response to immunosuppressant therapy.

Results

Nine (12.9%) out of 70 patients had PNH clones comprising >1% of the target cell population, including five patients (7.14%) with PNH clone size >10%. The clone size in monocytes ranged from 3.7% to 95.2% (median 21.1%) and in neutrophils from 1.6% to 87.6% (median 19.5%). Fluorescent aerolysin (FLAER)‐based FCM screening significantly improved the detection of PNH clones compared to non‐FLAER based screening techniques (18.4% vs. 6.25%). One child showed chronic intravascular hemolysis and another developed arterial stroke during the course of illness. None of our PNH‐positive AA patients tested for chromosome breakage studies (n = 8) showed increased clastrogen‐induced breakage.

Conclusions

A lower frequency but moderate/large‐sized PNH clones were seen in our pediatric AA population, compared to western data. FLAER‐based FCM screening significantly improved the detection of PNH clones. We recommend routine FLAER‐based screening of PNH in pediatric AA patients. Pediatr Blood Cancer 2015; 9999:XX–XX © 2015 Wiley Periodicals, Inc.
Synthesis and characterizations of magnetite nanocomposite films for radiation shielding
Authors: Badawy Sayed M. , Abd El‐Latif A.A.
Published: July 2015

Polyvinyl alcohol (PVA) films containing magnetite Fe3O4 nanoparticles have been prepared by co‐precipitation method for use in gamma ray shielding and protection. Characterizations of the magnetite/PVA nanocomposite films were investigated by X‐ray diffraction (XRD), transmission electron microscopy (TEM), UV–vis spectroscopy, and magnetization measurements. TEM images showed that the synthesized magnetite particles had about 6–11 nm dimensions. Optical study's results revealed that the optical energy band gaps of thin films range between 1.82 and 2.81 eV at room temperature using UV–visible absorption spectroscopy. The saturation magnetization (MS) value measured by vibrating sample magnetometer VSM was found to be 8.1 emu/g with superparamagnetic nature. The radiation shielding properties such as linear attenuation coefficients (μ) and half‐value thickness (HVT) for the magnetite nanocomposite films have been obtained experimentally for different photon energies. The results imply that these nanocomposites films are promising radiation shielding materials. POLYM. COMPOS., 38:974–980, 2017. © 2015 Society of Plastics Engineers
Power of positive thinking in quantitative proteomics
Authors: Armengaud Jean
Published: July 2015

Derivatization of proteins with specific isotope reagents has been widely explored for quantitative proteomics where the relative abundances of proteins present in different complex samples are compared by MS. This represents an interesting arena for innovation, where protein chemistry and MS are associated for the best of both worlds. Among the numerous reagents developed, those that introduce a permanent positive charge, such as (N‐succinimidyloxycarbonylmethyl)‐tris(2,4,6‐trimethoxyphenyl)phosphonium bromide (TMPP), increase the ionizability of their targets and thus improve the sensitivity of the approach. TMPP labeling also modifies the hydrophobicity and changes the peptide fragmentation pattern. Because TMPP reacts preferably with the N‐termini of proteins and peptides, its use has been explored for proteogenomics and de novo protein sequencing. In this issue of Proteomics, Shen et al. (Proteomics 2015, 15, 2903–2909) show that accurate quantitation of proteins can be obtained with light/heavy TMPP‐labeling of peptides, which can be easily prepared and desalted in a homemade C8‐SCX‐C8 stagetip, and then monitored by nano‐LC‐MS/MS analysis. Their results demonstrate enhanced sequence coverage compared with other approaches. Combined with an efficient enrichment procedure, the higher sensitivity of this “positive attitude” reagent may facilitate much deeper investigations into the quantitative proteomics of complex samples.
A facile synthesis of catechol‐functionalized poly(ethylene oxide) block and random copolymers
Authors: Mattson Kaila M. , Latimer Allegra A. , McGrath Alaina J. , Lynd Nathaniel A. , Lundberg Pontus , Hudson Zachary M. , Hawker Craig J.
Published: July 2015

Herein we develop a facile synthetic strategy for the functionalization of well‐defined polyether copolymers with control over the number and location of catechol groups. Previously, the functionalization of polyethylene oxide (PEO)‐based polymers with catechols has been limited to functionalization of the chain ends only, hampering the synthesis of adhesive and antifouling materials based on this platform. To address this challenge, we describe an efficient and high‐yielding route to catechol‐functionalized polyethers, which could allow the effects of polymer architecture, molecular weight, and catechol incorporation on the adhesive properties of surface‐anchored PEO to be studied. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2685–2692
An effective combination of sanger and next generation sequencing in diagnostics of primary ciliary dyskinesia
Authors: Djakow Jana , Kramná Lenka , Dušátková Lenka , Uhlík Jiří , Pursiheimo Juha‐Pekka , Svobodová Tamara , Pohunek Petr , Cinek Ondřej
Published: July 2015

Background

Primary ciliary dyskinesia (PCD) is a multigenic autosomal recessive condition affecting respiratory tract and other organs where ciliary motility is required. The extent of its genetic heterogeneity is remarkable. The aim of the study was to develop a cost‐effective pipeline for genetic diagnostics using a combination of Sanger and next generation sequencing (NGS).

Materials and Methods

Data and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation.

Results

The causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi‐allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre‐screening step, being followed by an NGS panel for other, much larger, PCD genes.

Conclusions

We present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate‐size national collection of patients. This strategy has proven to be cost‐effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients. Pediatr Pulmonol. 2016;51:498–509. © 2015 Wiley Periodicals, Inc.
Practical tips on diagnosing and managing tremor
Authors: Kaski Diego
Published: July 2015

Tremor is a common complaint but making a definitive diagnosis can be difficult. This review offers practical tips on how to differentiate different tremor types and reviews current treatment options.
Surface damage and mechanical strength of silicon wafers
Authors: Würzner Sindy , Buchwald Rajko , Möller Hans Joachim
Published: July 2015

The fracture strength of silicon wafers used for photovoltaic and microelectronic applications mainly depends on the damage structure, which is introduced on the surface during processing of the wafers. The present paper investigates the formation and development of the damage structure by scratching, which occurs during grinding processes or when sawing with diamond coated wires. The basic scratching process has been studied with a newly developed scratch technique, where test parameters comparable to a real process could be used. Single scratch tests have been performed with diamond particles on monocrystalline silicon wafers with a defined surface orientation and under different applied forces. The resulting microcrack structure, which develops under the surface, has been investigated by confocal laser scanning microscopy, scanning electron microscope and Raman spectroscopy. Details of the shape, depth and distance of the cracks have been obtained by high quality sample cross sections. The orientations of the main microcrack planes are determined. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fragmentation pathways of synthetic and naturally occurring coumarin derivatives by ion trap and quadrupole time‐of‐flight mass spectrometry
Authors: Liang Xianrui , Han Xiaomei
Published: July 2015

Rationale

Synthetic and natural coumarin derivatives possess a wide range of biological activities. Fragmentation pathway studies are important in identifying both naturally occurring coumarins and synthetic coumarins with novel structures and properties.

Methods

The fragmentation pathways of eleven coumarin derivatives are investigated by electrospray ionization (ESI) ion‐trap mass spectrometry (ESI‐ITMSn) and ESI quadrupole time‐of‐flight mass spectrometry (QTOFMS) in positive mode. Compounds 1–9 in this study were newly synthesized in our laboratory. Compounds 10 and 11 were isolated from the root of Zanthoxylum armatum.

Results

The major fragmentation pathways for 11 coumarin derivatives are greatly affected by the heterocyclic ring structures and the side‐chain substituents. Typical losses of small neutral molecules, such as CH3CH2OH, CH2=CH2, CO, and H2O, are observed for compounds 1–5. Compounds 6–9 share similar fragmentation pathways through losses of CO, aromatic rings, and the coumarin skeleton. The main product ions at m/z 205, 219, and 220 observed for compounds 10 and 11 are produced by the loss of C5H12O2, C4H10O2, and the C4H9O2 radical, respectively.

Conclusions

The fragmentation pathways of 11 coumarin derivatives are elucidated based on ITMSn and QTOFMS spectral data. Differences in the structures of the heterocyclic rings and side‐chain substituents strongly affect the fragmentation pathways of the coumarins. The present results will facilitate further research into the fragmentation pathways and structural characterization of these classes of compounds with diverse structures. Copyright © 2015 John Wiley & Sons, Ltd.
Protonated N‐benzyl‐ and N‐(1‐phenylethyl)tyrosine amides dissociate via ion/neutral complexes
Authors: Paulose Justin , Achuthan Revi P. , Linsha Maria P. L. , Mathai George , Prasanth B. , Kumar Talluri M. V. N. , Srinivas Ragampeta
Published: July 2015

Rationale

The collisional‐induced dissociations (CID) of the [M+H]+ ions of molecules having benzyl groups attached to N‐atoms have been proposed to involve migration of the benzyl group through the intermediacy of ion/neutral complexes (INCs). We report the investigation of the mechanism of dissociation of protonated N‐benzyl‐ and N‐(1‐phenylethyl)tyrosine amides by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and density functional theory (DFT) calculations.

Methods

The amides were synthesized from the corresponding amino acids and amines. The ESI‐MS/MS spectra were recorded using an Agilent QTOF 6540 mass spectrometer. The DFT calculations were performed by using Gaussian 09 software. The structures of the [M+H]+ ions, intermediates, products and transition states (TS) were optimized at the B3LYP/6‐31G(d,p) level of theory.

Results

CID of the [M+H]+ ions of N‐benzyltyrosine amide yields two product ions due to rearrangements: (i) the [M+H–74]+ ion (m/z 197) due to benzyl migration to the hydroxyphenyl ring and (ii) the [M+H–45]+ ion (m/z 226) due to benzyl migration to the NH2 group. DFT calculations suggest that the rearrangements occur through an INC in which the benzyl cation is the cation partner. The [M+H]+ion of N‐(1‐phenylethyl)tyrosine amide rearranges to an INC of the 1‐phenylethyl cation. Subsequent elimination of styrene occurs by transfer of a proton from the 1‐phenylethyl cation to the neutral partner.

Conclusions

The [M+H]+ ions of both N‐benzyl (1) and N‐(1‐phenylethyl) (2) tyrosine amide rearrange into INCs. The dissociation of [M+H]+ ion of 1 yields the benzyl cation and [M+H–74]+ and [M+H–45]+ due to benzyl migration to the hydroxyphenyl ring and NH2 group, respectively. However, the formation of the [M+H–74]+ ion is not observed when the aromatic ring is deactivated. The [M+H]+ ion of 2 either dissociates to form the 1‐phenylethyl cation or [M+H–styrene]+. Copyright © 2015 John Wiley & Sons, Ltd.
Application of a multivariate normal distribution methodology to the dissociation of doubly ionized molecules: The DMDS (CH3‐SS‐CH3) case
Authors: Varas Lautaro R. , Pontes F. C. , Santos A. C. F. , Coutinho L. H. , de Souza G. G. B.
Published: July 2015

Rationale

The ion‐ion‐coincidence mass spectroscopy technique brings useful information about the fragmentation dynamics of doubly and multiply charged ionic species. We advocate the use of a matrix‐parameter methodology in order to represent and interpret the entire ion‐ion spectra associated with the ionic dissociation of doubly charged molecules. This method makes it possible, among other things, to infer fragmentation processes and to extract information about overlapped ion‐ion coincidences. This important piece of information is difficult to obtain from other previously described methodologies.

Methods

A Wiley‐McLaren time‐of‐flight mass spectrometer was used to discriminate the positively charged fragment ions resulting from the sample ionization by a pulsed 800 eV electron beam. We exemplify the application of this methodology by analyzing the fragmentation and ionic dissociation of the dimethyl disulfide (DMDS) molecule as induced by fast electrons. The doubly charged dissociation was analyzed using the Multivariate Normal Distribution.

Results

The ion‐ion spectrum of the DMDS molecule was obtained at an incident electron energy of 800 eV and was matrix represented using the Multivariate Distribution theory. The proposed methodology allows us to distinguish information among [CHnSHn]+/[CH3]+ (n = 1–3) fragment ions in the ion‐ion coincidence spectra using ion‐ion coincidence data. Using the momenta balance methodology for the inferred parameters, a secondary decay mechanism is proposed for the [CHS]+ ion formation. As an additional check on the methodology, previously published data on the SiF4 molecule was re‐analyzed with the present methodology and the results were shown to be statistically equivalent.

Conclusions

The use of a Multivariate Normal Distribution allows for the representation of the whole ion‐ion mass spectrum of doubly or multiply ionized molecules as a combination of parameters and the extraction of information among overlapped data. We have successfully applied this methodology to the analysis of the fragmentation of the DMDS molecule. Copyright © 2015 John Wiley & Sons, Ltd.
Clinical factors affecting the accuracy of a CT‐based active infrared navigation system
Authors: Liu Yajun , Zhao Jingwei , Fan Mingxing , Lv Yanwei , Liu Wenyong , Tian Wei
Published: July 2015

Background

Computer‐assisted navigation technology has been widely used during spine surgery; however, the desired accuracy cannot be easily obtained and sustained. Our goal was to determine whether and how clinical factors affect the accuracy of a CT‐based active infrared navigation system.

Methods

Using the Sawbone model, we recorded the clinical accuracy of the navigation system, based on several clinical statuses.

Results

Clinical accuracy may change when the height or angle of the bed is changed. Within the visible area of the camera, the nearer the distance between the camera and the model, the better the clinical accuracy. The clinical accuracy of the CT‐based active infrared navigation system may decrease due to exposure to shadowless lamps.

Conclusions

The clinical accuracy of the CT‐based active infrared navigation system may be influenced by the clinical status of shadowless lamps, different distances between the camera and model and different postures of the surgical bed. Copyright © 2015 John Wiley & Sons, Ltd.
On generalized fixed sequence procedures for controlling the FWER
Authors: Qiu Zhiying , Guo Wenge , Lynch Gavin
Published: July 2015

Testing a sequence of pre‐ordered hypotheses to decide which of these can be rejected or accepted while controlling the familywise error rate (FWER) is of importance in many scientific studies such as clinical trials. In this paper, we first introduce a generalized fixed sequence procedure whose critical values are defined by using a function of the numbers of rejections and acceptances, and which allows follow‐up hypotheses to be tested even if some earlier hypotheses are not rejected. We then construct the least favorable configuration for this generalized fixed sequence procedure and present a sufficient condition for the FWER control under arbitrary dependence. Based on the condition, we develop three new generalized fixed sequence procedures controlling the FWER under arbitrary dependence. We also prove that each generalized fixed sequence procedure can be described as a specific closed testing procedure. Through simulation studies and a clinical trial example, we compare the power performance of these proposed procedures with those of the existing FWER controlling procedures. Finally, when the pairwise joint distributions of the true null p‐values are known, we further improve these procedures by incorporating pairwise correlation information while maintaining the control of the FWER. Copyright © 2015 John Wiley & Sons, Ltd.
A robust direct current control of DFIG wind turbine with low current THD based predictive approach
Authors: Zarei Mohammad Ebrahim , Asaei Behzad
Published: July 2015

This paper presents a simple and robust direct current control based predictive approach for rotor side converter (RSC) of the doubly fed induction generator (DFIG), which operates at a constant switching frequency and has a fast dynamic response. First, sector of required rotor voltage vector is predicted in this strategy, and according to this predicted sector, two active vectors and two zero vectors are elected in each switching period. Derivatives of rotor current in the synchronous frame are determined for each predicted voltage vector in every period. These derivatives are used to compute the duration of the vectors in such a way that the current error at the end of the switching period gets minimized. The accuracy of the proposed control strategy under variation of rotor speed is evaluated in Matlab/Simulink environment for a 2 MW DFIG. Moreover, the impact of parameter variations on the system is examined for this suggested technique. Furthermore, the dynamic response and stator current total harmonic distortion (THD) of proposed strategy is compared with traditional vector control (VC), direct power control (DPC) and predictive direct power control (PDPC) methods. Finally, the performance of the proposed method is evaluated under disturbance voltage. The results demonstrate that suggested control technique has the lowest stator current THD and operates perfectly near the synchronous speed and under grid voltage dip. Copyright © 2015 John Wiley & Sons, Ltd.
The influence of ocean variations on the climate of Ireland
Authors: McCarthy G. D. , Gleeson E. , Walsh S.
Published: July 2015

The influence of the ocean circulation on the climate of Ireland is more subtle than it first appears. Temperatures in Ireland are warmer than similar Pacific maritime climates. It is heat ‐ carried primarily in the Atlantic overturning circulation ‐ released over the Atlantic that provides this additional warmth. We investigate variations in Irish climate using long‐term station‐based time series. The Atlantic multidecadal oscillation (AMO) explains over 90% of the pronounced decadal temperature and summer precipitation variation. Understanding the impact of these ocean variations when interpreting long climate records, particularly in the context of a changing climate, is crucial.
Perception of available space during chimpanzee introductions: Number of accessible areas is more important than enclosure size
Authors: Herrelko Elizabeth S. , Buchanan‐Smith Hannah M. , Vick Sarah‐Jane
Published: July 2015

Restricting animals to different areas of their enclosure, for both brief and extended durations, is a key element of animal management practices. With such restrictions, available space decreases and the choices the animals can make are more limited, particularly in relation to social dynamics. When unfamiliar individuals are introduced to each other, group dynamics can be unpredictable and understanding space usage is important to facilitate successful introductions. We studied the behavioral, welfare‐related responses of two groups of zoo‐housed chimpanzees (n = 22) as they were introduced to each other and experienced a variety of enclosure restrictions and group composition changes. Our analysis of available space while controlling for chimpanzee density, found that arousal‐related scratching and yawning decreased as the number of enclosure areas (separate rooms) available increased, whereas only yawning decreased as the amount of available space (m2) increased. Allogrooming, rubbing, and regurgitation/reingestion rates remained constant as both the number of enclosure areas and amount of space changed. Enclosure space is important to zoo‐housed chimpanzees, but during introductions, a decrease in arousal‐related scratching indicates that the number of accessible areas is more important than the total amount of space available, suggesting that it is important to provide modular enclosures that provide choice and flexible usage, to minimize the welfare impact of short‐ and long‐term husbandry needs. Zoo Biol. 34:397–405, 2015. © 2015 Wiley Periodicals, Inc.
Capitellum Fracture Fragment Excision: A Case Series
Authors: Garner Matthew R. , Schottel Patrick C. , Hotchkiss Robert N. , Daluiski Aaron , Lorich Dean G.
Published: July 2015

Background

Fractures of the capitellum are rare injuries, and few studies have reported the results of fragment excision.

Questions/Purposes

The purpose of this study was to determine range of motion and short-term clinical outcomes for patients treated with capitellum excision.

Methods

A retrospective review was performed to identify all patients with an isolated capitellum fracture who underwent excision as definitive treatment at our institutions. Mechanism of injury, associated elbow injuries, type of capitellum fracture, complications, and postoperative outcomes including final elbow range of motion (ROM), elbow instability, and Disabilities of the Arm, Shoulder and Hand (DASH) score were recorded.

Results

Four patients met the inclusion and exclusion criteria of this study. All patients were female with an average age of 69 years (range 42–85). Based on the Bryan and Morrey classification system, three (75%) fractures were classified as type I and one (25%) fracture as type III. The average clinical follow-up was 11 months. Final examination demonstrated a mean elbow range of motion from 14° (range 0–30) of extension to 143° (range 130–160) of flexion. All patients had full forearm rotation, and there was no clinical evidence of elbow instability. The average DASH score was 18.3 (12.5–24.2) at final follow-up.

Conclusion

Excision of the capitellum, much like excision of the radial head, results in acceptable short-term outcome scores and elbow range of motion in patients with fractures that are not amenable to open reduction and internal fixation.
Die Innere Stadt als Wohnstandort der „jungen Alten“?
Authors: Rabe A. , Hohn U.
Published: July 2015

Is the inner city an attractive place for the “young elderly” to live? During decades suburbanization was the dominant pattern of city development in Germany. However, since the 2000s an increasing attraction of urban living and the trend of re-urbanization are discussed in research as well as in public. Due to an increasing average age and life expectancy of the population as a main sub-process of demographic change in Germany, the question arises whether the inner city as a residential area also becomes more attractive for the elderly. Especially “young elderly” people (ca. 50–70 years old) are getting into focus. Because of a transitional phase of their lives, they might show a greater willingness to change the residential location to adapt to their new needs.

In order to analyze the attractiveness of the inner city as a residential area for the “young elderly”, residential location decisions, which were realized between 2010 and 2012, were investigated using the city of Bonn as an example. The results of a survey and in-depth interviews show that the inner city cannot be considered as a homogeneous space, but that small-scale differences in the attractiveness as a residential area exist. In summary, the “young elderly” prefer the fringe of the inner city while the city center is important for their shopping and leisure activities, but not as attractive for them to live. However, also within the fringe of the inner city more and less attractive residential areas can be identified corresponding to lifestyle and income of the “young elderly”.
Mutational analysis of the Notch2 negative regulatory region identifies key structural elements for mechanical stability
Authors: Stephenson Natalie L. , Avis Johanna M.
Published: July 2015

The Notch signalling pathway is fundamental to cell differentiation in developing and self‐renewing tissues. Notch is activated upon ligand‐induced conformational change of the Notch negative regulatory region (NRR), unmasking a key proteolytic site (S2) and facilitating downstream events. The favoured model requires endocytosis of a tightly bound ligand to transmit force to the NRR region, sufficient to cause a structural change that exposes the S2 site. We have previously shown, using atomic force microscopy and molecular dynamics simulations, that application of force to the N‐terminus of the Notch2 NRR facilitates metalloprotease cleavage at an early stage in the unfolding process. Here, mutations are made within the heterodimerization (HD) domain of the NRR that are known to cause constitutive activation of Notch1 whilst having no effect on the chemical stability of Notch2. Comparison of the mechanical stability and simulated forced unfolding of recombinant Notch2 NRR proteins demonstrates a reduced stability following mutation and identifies two critical structural elements of the NRR in its response to force – the linker region between Lin12‐Notch repeats LNRA and LNRB and the α3 helix within the HD domain – both of which mask the S2 cleavage site prior to Notch activation. In two mutated proteins, the LNRC:HD domain interaction is also reduced in stability. The observed changes to mechanical stability following these HD domain mutations highlight key regions of the Notch2 NRR that are important for mechanical, but not chemical, stability. This research could also help determine the fundamental differences in the NRRs of Notch1 and Notch2.
National survey of emergency physicians for transient ischemic attack (TIA) risk stratification consensus and appropriate treatment for a given level of risk
Authors: Perry Jeffrey J. , Losier Justin H. , Stiell Ian G. , Sharma Mukul , Abdulaziz Kasim
Published: July 2015

Introduction

Five percent of transient ischemic attack (TIA) patients have a subsequent stroke within 7 days. The Canadian TIA Score uses clinical findings to calculate the subsequent stroke risk within 7 days. Our objectives were to assess 1) anticipated use; 2) component face validity; 3) risk strata for stroke within 7 days; and 4) actions required, for a given risk for subsequent stroke.

Methods

After a rigorous development process, a survey questionnaire was administered to a random sample of 300 emergency physicians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique.

Results

From a total of 271 eligible surveys, we received 131 (48.3%) completed surveys; 96.2% of emergency physicians would use a validated Canadian TIA Score; 8 of 13 components comprising the Canadian TIA Score were rated as Very Important or Important by survey respondents. Risk categories for subsequent stroke were defined as minimal-risk: <1%; low-risk: 1%–4.9%; high-risk 5%–10%; critical-risk: > 10% risk of subsequent stroke within 7 days.

Conclusion

A validated Canadian TIA Score will likely be used by emergency physicians. Most components of the TIA Score have high face validity. Risk strata are definable, which may allow physicians to determine immediate actions, based on subsequent stroke risk, in the emergency department.
Decomposition of the temporal growth rate in linear instability of compressible gas flows
Authors: Weder Mario , Gloor Michael , Kleiser Leonhard
Published: July 2015

We present a decomposition of the temporal growth rate ${\it\omega}_{i}$ which characterises the evolution of wave-like disturbances in linear stability theory for compressible flows. The decomposition is based on the disturbance energy balance by Chu (Acta Mech., vol. 1 (3), 1965, pp. 215–234) and provides terms for production, dissipation and flux of energy as components of ${\it\omega}_{i}$. The inclusion of flux terms makes our formulation applicable to unconfined flows and flows with permeable or vibrating boundaries. The decomposition sheds light on the fundamental mechanisms determining temporal growth or decay of disturbances. The additional insights gained by the proposed approach are demonstrated by an investigation of two model flows, namely compressible Couette flow and a plane compressible jet.
‘WHERE WATER WELLS UP FROM THE EARTH’: EXCAVATIONS AT THE FINDSPOT OF THE LATE BRONZE AGE HOARD FROM BROADWARD, SHROPSHIRE
Authors: Bradley Richard , Lewis Jodie , Mullin David , Branch Nicholas
Published: July 2015

The paper begins by considering the importance of springs as a focus for votive deposits in Bronze Age Britain. This is not a new idea, but nowhere has this association been examined through the excavation of one of these features. The point is illustrated by excavation at the findspot of a famous group of Late Bronze Age weapons, the Broadward hoard, discovered in 1867. Little was known about the site, where it was found or the character of the original deposit, but a study of contemporary accounts of the hoard, combined with geophysical and topographical surveys, led to small-scale excavation in 2010, which showed that the deposit had most probably been buried in a pit on the edge of a spring. Other finds associated with the spring included an Early Bronze Age macehead, a Roman pot and various Saxon and medieval animal bones. The latest deposit, with a post-medieval carbon date, included a wooden knife or dagger. An adjacent palaeochannel provided an important environmental sequence for this part of the English–Welsh borderland and suggests that the Late Bronze Age hoard had been deposited not far from a settlement. A nearby earthwork enclosure was associated with a clay weight, which may be of similar date. Despite the limited scale of the fieldwork, it illustrates the potential for treating springs associated with artefact finds on the same terms as other archaeological deposits.
The ammonitesKarakaschicerasandNeohoploceras(Valanginian Neocomitidae) from the Neuquen Basin, West-Central Argentina
Authors: Aguirre-Urreta María B.
Published: July 2015

Three species ofKarakaschiceras, K. attenuatus(Behrendsen, 1892),K. neumayri(Behrendsen, 1892), andK. lycoris(Leanza and Giovine, 1949), and one species ofNeohoploceras, N. arnoldi(Pictet and Campiche, 1860), are described and figured from the Valanginian strata of the Neuquén basin in west-central Argentina. The large collection of fossils available for study shows wide intraspecific variation regarding ornament and whorl section inKarakaschiceras neumayriandNeohoploceras arnoldi, casting some doubts on the current systematics applied to species of these genera. The biostratigraphic position of the four species in the Neuquén basin corresponds to theKarakaschiceras attenuatusSubzone of theOlcostephanus atherstoniZone. This subzone is correlated with the MediterraneanKarakaschiceras inostranzewiandSaynoceras verrucosumzones of Europe at the base of upper Valanginian sections.
Apparatus composition and structure of the Pennsylvanian conodont genus Gondolella based on assemblages from the Desmoinesian of northwestern Illinois, U.S.A.
Authors: von Bitter Peter H. , Merrill Glen K.
Published: July 2015

Gondolella pohli new species assemblages, from the Desmoinesian of Illinois, confirm that the initial apparatus reconstruction of the conodont genus Gondolella was incomplete and support later reconstructions based on discrete elements.

Gondolella pohli is the first species of a biostratigraphically important conodont genus to be based primarily on assemblages and to be placed within a known phylogeny. The 43 assemblages confirm the presence of seven distinct element types in the Gondolella apparatus and permit the reconstruction of each of these to a greater degree than previously possible. Because the assemblages are probably all fecal, the apparatus of the closely related Neogondolella is used to interpret the apparatus plan—the position and identity of the 15 elements—single pairs of Pa, Pb, M, Sb1, and Sb2 elements, two pairs of Sc elements, and an unpaired bilaterally symmetrical Sa element in the Gondolella apparatus. Using the similarity of the latter to the apparatuses of the better known ozarkodinids, we infer a three-dimensional fanlike apparatus architecture for the prioniodinid Gondolella. Gondolella is apparently restricted to the Pennsylvanian and probably evolved in the Early Pennsylvanian from the Idioprioniodus-Embsaygnathus lineage by loss of the Pa element posterior process and by remodelling of the other apparatus elements. Some species in the Idioprioniodus-Gondolella lineage are atypical among prioniodinids in having developed a Pa element platform; the lineage is also noteworthy because both ancestor and descendant inhabited low-energy, low pH environments during the Pennsylvanian.
Late Miocene three-toed horse Protohippus (Mammalia, Equidae) from southern Alabama
Authors: Macfadden Bruce J. , Dobie James L.
Published: July 2015

Dental and postcranial remains of a donkey-sized, three-toed, primitive horse were collected from the “Undifferentiated Miocene” Ecor Rouge Sand (which underlies the widespread Citronelle Formation) from the Mauvilla site in southern Alabama. These fossils probably pertain to a single individual of Protohippus gidleyi Hulbert, 1988. This represents an exceedingly rare occurrence of a late Tertiary land mammal from the central Gulf Coastal Plain and allows comparisons with better-known, contemporaneous land-mammal assemblages from Florida. Based on the known biochronology of Protohippus gidleyi from other localities, and the stratigraphic position of the Mauvilla record, the age of: 1) the Ecor Rouge Sand is late Miocene (latest Clarendonian to early Hemphillian landmammal “age”), between 9.0 to 6.5 Ma; and 2) the overlying Citronelle Formation near its type locality in southern Alabama is therefore late Miocene or younger.
Bryozoan growth habits: Classification and analysis
Authors: Hageman Steven J. , Bock Philip E. , Bone Yvonne , Mcgowran Brian
Published: July 2015

Bryozoans are an important part of the benthic marine fauna in a wide variety of modern environments and are found in rock forming abundance in a number of settings throughout much of the Phanerozoic. Bryozoologists and nonspecialists have grouped taxa into colonial growth forms (e.g., erect fenestrates or encrusting sheets), both to simplify analyses and because correlations exist between some colony growth forms and the environmental conditions in which the organism lived. These correlations allow for the possibility of paleoenvironmental analyses based on skeletons alone. Existing bryozoan colonial growth form classifications do not, however, fully exploit the ecological information present in colony form.

A new scheme is proposed here (Analytical Bryozoan Growth Habit Classification), which provides a list of colony-level morphological characteristics for bryozoan growth habits. This differs from previous approaches to bryozoan growth form analysis in that it is a classification of growth habit characteristics rather than a classification of morphological groups as such. The classification is based on eleven character classes, which describe the orientation of the colony and its occupation of, and placement in space. The overall colony shape is described based on the arrangement of modules in colonial growth. This classification provides a common ground for systematic comparison of character states among varied bryozoan growth habits. This approach allows for the evaluation of correlations among observed morphological character states and specific environmental conditions in which they develop. In addition, these growth habit characters can be used to recognize, characterize, evaluate, and apply more traditional growth form groups in broader studies.
Kulumbella and Microcardinalia (Chiastodoca) new subgenus, Early Silurian divaricate stricklandiid brachiopods from Anticosti Island, eastern Canada
Authors: Jin Jisuo , Copper Paul
Published: July 2015

Ribbing became an increasingly common feature of pentamerid shells, especially the family Stricklandiidae, during the later Llandovery (Early Silurian). The thin shells of stricklandiids from the Llandovery (Aeronian-Telychian) equatorial carbonate rampshelf of Anticosti Island reveal at least three ribbing designs in various genera; 1) radially arranged ribs, e.g., Costistricklandia; 2) divergent, chevron-like ribs, e.g., Ehlersella; and 3) diagonally criss-cross, mutually intersecting divaricate ribs, as in Kulumbella and Microcardinalia (Chiastodoca) new subgenus. Weakly divaricate species previously assigned to Kulumbella, Stricklandia or Microcardinalia from Anticosti Island, South China and the Baltic region, are assigned to the new subgenus Chiastodoca (type Stricklandinia salterii Billings, 1868), and they are suggested to have evolved their divaricate ribbing from smooth forms, independently from the earlier genus Kulumbella, in the same sense that radial or divergent ribbing was developed separately in a number of pentamerid and stricklandiid lineages in the late Llandovery and Wenlock. In Anticosti, the divaricate genus Kulumbella, originally described from Siberia, appeared, without a known ancestral form, in the Anticosti Basin (as K. xacta n.sp.), and became extinct equally suddenly in the upper part of the Gun River Formation (mid-Aeronian). This sudden arrival of immigrant taxa, originally appearing earlier in other areas, is matched in other brachiopod groups and corals in the Anticosti section. Weakly divaricate ribbing in Chiastodoca is characteristic of the early Telychian (Ferrum Member, Jupiter Formation), and radial ribbing is typical of the late Telychian genus Costistricklandia (Pavillon Member, Jupiter Formation).
A global review of the Virgianidae (Ashgillian-Llandovery, Brachiopoda, Pentameroidea)
Authors: Jia-Yu Rong , Boucot A. J.
Published: July 2015

A review of the Late Ordovician, chiefly mid-Ashgillian, to Early Silurian, Llandoverian, pentameroidean brachiopods, the Virgianidae, permits them to be assigned to three subfamilies (Virgianinae [10 genera assigned], Mariannaellinae [5 genera assigned], Pleurodiinae [2 genera assigned]). Diagnoses are presented for each subfamily, with comments on diagnostic characters for each genus and species. All the genera occur in what are interpreted to have been relatively low latitude, warm water environments in Arctic North America, northern Europe, northern Asia, central Asia and South China; the presence of Australian Ordovician virgianids is uncertain at this time. The mid-Ashgillian pentameroid adaptive radiation was followed by latest Ordovician mass extinction, subsequently surviving recovery and radiation in the middle-Late Llandovery. Silurian radiations convergently mimicked the Ordovician event in many respects.
Scolecodont systematics exemplified by the polychaeteHadoprion cervicornis(Hinde, 1879)
Authors: Eriksson Mats , Bergman Claes F.
Published: July 2015

Hadoprion cervicornis(Hinde, 1879) from the Upper Ordovician and Lower Silurian (Cincinnatian to Medinian) replaces four generic and eight specific names:Arabellites cervicornis, A. aciculatus, Oenonites acinaces, Ildraites horridus, I. laeohorridus, I. cervicornis, Nereidavus hamus, andN. alatus.This example illustrates the advantages of a nomenclature in accordance with the ICZN. The authors reject the use of parataxonomy for fossil jawed polychaetes.
Chaoborus Lichtenstein (Diptera: Chaoboridae) pupae from the middle Eocene of Mississippi
Authors: Johnston John E. , Borkent Art
Published: July 2015

Pupae of the nonbiting midge Chaoborus are reported from the middle Eocene (Claibornian) Tallahatta Formation in Benton County, Mississippi. These pupae are placed within the genus Chaoborus because the shape of the respiratory organs, length of the abdomen, and shape of the anal paddles closely resemble other species of this extant genus. This occurrence represents the oldest record of Chaoborus pupae and the first record of fossil Chaoborus from North America. The flora and fauna found associated with the fossil pupae along with the known habitats of extant Chaoborus pupae indicate a lentic environment. This interpretation corresponds to the depositional environment of similar Eocene-aged clay deposits in western Tennessee.
Nacocrinus elliotti, a new pachylocrinid from the Naco Formation (Pennsylvanian, Desmoinesian) of central Arizona
Authors: Webster Gary D. , Olson Thomas J.
Published: July 2015

Nacocrinus elliotti new genus, new species, is reported from the beta member of the Naco Formation (Pennsylvanian, Desmoinesian) at the Kohl Ranch locality in central Arizona. This is the first pachylocrinid reported from the Naco Formation.
Some Albian (Cretaceous) asteroids (Echinodermata) from Texas and their paleobiological implications
Authors: Blake Daniel B. , Reid Robert
Published: July 2015

An asteroid fauna is described from the Albian (Cretaceous) interval of the Washita Group of central Texas. New genera and species areAlkaidia sumralli, (Benthopectinidae),Capellia mauricei(Goniasteridae), andBetelgeusia reidi(Radiasteridae). Additional new genera areFomalhautia(Goniasteridae), andDenebiaandAltairia(Ophidiasteridae).Crateraster texensis(Goniasteridae), new combination, is similar to the European type species,C. quinqueloba.An unnamed species ofCraterasterand an unassigned goniasterid are also present. All Washita genera are extinct, but all belong to extant families. The fauna is largely distinct from that of the somewhat younger European Cretaceous chalk.

The Radiasteridae (e.g.,Betelgeusia) is inferred to hold a basal position in the Paxillosida;Betelgeusiaextends the range of the family back to the Cretaceous, closer to the diversification of the living asteroid orders. Asteroids capable of burying themselves in sediment (and only self-buriers) share some form of channelization for the passage of water currents between the primary ossicles of the body surface. Channels inBetelgeusiaindicate semi-infaunal habits similar to those of livingAstropectenandLuidia. Betelgeusiarepresents the third semi-infaunal paxillosidan family now known from the Cretaceous, although none are known from older rocks, suggesting a broadening of the asteroid adaptive zone during the Cretaceous. The Goniasteridae, Radiasteridae, and Benthopectinidae are less important in shelf settings today than they appear to have been during Washita deposition, whereas the Astropectinidae, Luidiidae, and the Echinasteridae are absent from the Washita although they are common today in similar settings.
Discovery of fish mortality horizon at the K-T Boundary on Seymour Island: Re-evaluation of events at the end of the Cretaceous
Authors: Zinsmeister William J.
Published: July 2015

The discovery of a fish bone layer immediately overlying the K-T iridium anomaly on Seymour Island, Antarctic Peninsula, which may represent the first documented mass kill associated with the impact event, together with new faunal data across the boundary has provided new insight into events at the end of the Cretaceous. The utilization of a geographical approach and a new graphical representation of range data has revealed that events at the end of the Cretaceous were not instantaneous, but occurred over a finite period of time. Although the fish bone layer may contain victims of the impact event, the absence of ammonites in either the iridiumbearing layer or the overlying fish layer suggests that the extinction event at the end of the Cretaceous was the culmination of several processes beginning in the late Campanian. The impact was the proverbial “straw that broke the camel's back,” leading to the extinction of many others forms of life that might have survived the period of global biotic stress during the waning stages of the Mesozoic if there had not been an impact. The absence of mass extinction following catastrophic geologic events in a biotic robust world, such as the Middle Ordovician Millbrig-Big Bentonite volcanic event suggests that the biosphere is remarkably resilient to major geologic catastrophes with mass extinction events occurring only when there is a conjunction of geologic events none of which might be capable of producing a global mass extinction by itself.