bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic dissolutions and unifications
Authors: Ellis Christopher J.
Published: February 2017

I reexamine the key results from the literature on the size and number of countries under different political institutions in a simple dynamic model. I find that the canonical static results that democracies lead to too many too‐small countries and that Leviathans lead to too few too‐large countries no longer necessarily hold. The key dynamic element that drives the new results is that public goods are modeled as public capital; this changes the incentives to unify or divide countries. I also show that there are hysteresis effects on the size and number of countries; that is, arbitrary initial configurations of national boundaries may tend to persist because of the initial public capital location decisions they promote.
The mineralogy, petrology, and composition of anomalous eucrite Emmaville
Authors: Barrett T. J. , Mittlefehldt D. W. , Greenwood R. C. , Charlier B. L. A. , Hammond S. J. , Ross D. K. , Anand M. , Franchi I. A. , Abernethy F. A. J. , Grady M. M.
Published: February 2017

The Emmaville eucrite is a relatively poorly studied basaltic achondrite with an anomalous oxygen isotope signature. In this study, we report comprehensive mineralogical, petrographic, and geochemical data from Emmaville in order to understand its petrogenesis and relationship with the basaltic eucrites. Emmaville is an unusually fine‐grained, hornfelsic‐textured metabasalt with pervasive impact melt veins and mineral compositions similar to those of typical basaltic eucrites. The major and trace element bulk composition of Emmaville is also typical of a basaltic eucrite. Three separated individual lithologies were also analyzed for O isotopes; a dark gray fraction (E1), a shocked lithology (E2), and a lighter gray portion (E3). Fractions E1 and E2 shared similar O isotope compositions to the bulk sample (E‐B), whereas the lighter gray portion (E3) is slightly elevated in Δ17O and significantly elevated in δ18O compared to bulk. No evidence for any exogenous material is observed in the thin sections, coupled with the striking compositional similarity to typical basaltic eucrites, appears to preclude a simple impact‐mixing hypothesis. The O‐isotopes of Emmaville are similar to those of Bunburra Rockhole, A‐881394, and EET 92023, and thus distinct from the majority of the HEDs, despite having similarities in petrology, mineral, and bulk compositions. It would, therefore, seem plausible that all four of these samples are derived from a single HED‐like parent body that is isotopically distinct from that of the HEDs (Vesta) but similar in composition.
Transporters as information processors in bacterial signalling pathways
Authors: Piepenbreier Hannah , Fritz Georg , Gebhard Susanne
Published: February 2017

Transporters are essential players in bacterial growth and survival, since they are key for uptake of nutrients on the one hand, and for defence against endogenous and environmental stresses on the other hand. Remarkably, in addition to their primary role in substrate translocation, it has become clear that some transporters have acquired a secondary function as sensors and information processors in signalling pathways. In this review, we describe recent advances in our understanding of the role of transporters in such signalling cascades, and discuss some of the emergent dynamic behaviour found in hallmark examples. A particular focus is placed on new insights into mechanistic details of information transfer between transporters and regulatory proteins. Quantitative considerations reveal that these signalling complexes can implement a remarkable diversity of regulatory logic functions, where the transporter can act as activity switch, as positive or negative reporter of transport flux, or as a signalling hub for the integration of multiple inputs. Such a dual use of transport proteins not only enables efficient substrate translocation but is also an elegant strategy to integrate important information about the cell's external conditions with its current physiological state.
Clinical application of a gadolinium‐based capsule as an MRI contrast agent in slow transit constipation diagnostics
Authors: Zhi M. , Zhou Z. , Chen H. , Xiong F. , Huang J. , He H. , Zhang M. , Su M. , Gao X. , Hu P.
Published: February 2017

Background

As a traditional method for the assessment of colon dynamics, radio‐opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium‐based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients.

Methods

Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium‐based capsules simultaneously. All subjects underwent X‐ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared.

Key Results

The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (rs) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively.

Conclusions and Inferences

As a MRI contrast label, gadolinium‐based capsules exhibit results comparable to ROMs in colon motility measurements.
Clinal population divergence in an adaptive parental environmental effect that adjusts seed banking
Authors: Lampei Christian , Metz Johannes , Tielbörger Katja
Published: February 2017

Bet‐hedging via between‐year seed dormancy is a costly strategy for plants in unpredictable environments. Theoretically, fitness costs can be reduced through a parental environmental effect when the environment is partly predictable. We tested whether populations from environments that differ in predictability diverged in parental effects on seed dormancy.

Common garden‐produced seeds of the two annual plant speciesBiscutella didymaandBromus fasciculatuscollected along an aridity gradient were grown under 12 irrigation treatments. Offspring germination was evaluated and related to environmental correlations between generations and their fitness consequences at the four study sites.

One species exhibited strong seed dormancy that increased with unpredictability in seasonal precipitation. The parental effect on seed dormancy also increased proportionally with the environmental correlation between precipitation in the parental season and seedling density in the following season; this correlation increased from mesic to arid environments. Because fitness was negatively related to density, this parental effect may be adaptive. However, the lack of dormancy in the second species indicates that bet‐hedging is not the only strategy for annual plants in arid environments.

Our results provide the first evidence for clinal variation in the relative strength of parental effects along environmental gradients.
Comparison of treatment outcome between symptomatic and asymptomatic impacted mandibular third molars: a pilot study
Authors: Anyanechi C.E. , Saheeb B.D.
Published: February 2017

Aim

To determine and compare the treatment outcome between symptomatic and asymptomatic impacted mandibular third molars in the same patients who presented with bilateral impacted mandibular third molars.

Methods

This preliminary study was done at the Dental and Maxillofacial Surgery Clinic of our institution over a period of 18 months. The variables analysed were age, gender, socio‐economic class, duration of symptoms before treatment, types of impaction and complaints during the follow‐up. Descriptive and bivariate statistics were computed and the P value was set at 0.05.

Results

The sample was composed of 27 patients, and their ages ranged from 18 to 41 years with a mean age of 31 ± 2.3 years. There were more males than females, with male: female ratio of 1.1:1. The complication rate was 8 (29.6%) in 5/27 (18.5%) patients under symptomatic wisdom teeth impaction while in asymptomatic impacted teeth, the rate was 2 (7.4%) in 2/27 (7.4%) patients and this difference was significant (P = 0.02). The complications occurred only in patients in the lower socio‐economic class (P = 0.01) and in symptomatic cases, the longer the duration of symptoms before treatment, the more the complications (P = 0.001). The complications following treatment were alveolar osteitis, numbness of the ipsilateral lower lip and hypersensitivity of the adjacent second molar.

Conclusion

This study shows that the surgical extractions of symptomatic and asymptomatic impacted mandibular third molars were associated with post‐operative complications that were more in the symptomatic cases. The findings in this study may have to be investigated further in a future study.
Individual versus Village Lending: Evidence from Montenegro
Authors: Beck Thorsten , Behr Patrick
Published: February 2017

This paper analyzes differences in loan performance across two Montenegrin microfinance institutions with different lending techniques using a sample of individuals borrowing from both institutions. We make use of administrative data from both institutions over the period 2004–2013. While one institution relies on village associations for screening and monitoring of borrowers, the other institution uses the individual liability approach. We find that the likelihood to go into arrears is higher for the institution with a strictly individual lending technique, while the likelihood of going into arrears over 30 days is higher for the institution working with village associations. These results are robust to a variety of additional tests, including different definitions of arrears and subsamples. Our findings suggest that the institution using an individual lending technique provides certain flexibility to its clients, while the village‐based microfinance institution might face more strategic default behavior. We provide evidence that once a borrower is in arrears, (s)he is more likely to stay in arrears for more than 30 days in branches with a higher share of borrowers in arrears and in the village‐based lender. Our findings provide evidence that a village‐ or group‐based lending technique is not necessarily superior to the individual lending technique in terms of loan performance.
Hopelessness Predicts Suicide Ideation But Not Attempts: A 10‐Year Longitudinal Study
Authors: Qiu Tianyou , Klonsky E. David , Klein Daniel N.
Published: February 2017

Hopelessness is one of the most commonly cited risk factors for suicidal behaviors. However, several retrospective studies suggest that hopelessness, while strongly correlated with suicide ideation, does not distinguish attempters from ideators without attempts. This study is the first to utilize a prospective design to disambiguate the relationship of hopelessness to ideation versus attempts. Participants were 142 depressed patients followed up over 10 years. Hopelessness and suicidality (ideation and attempts) were assessed using validated questionnaires and structured interviews. Both retrospective and prospective analyses revealed that hopelessness was higher among those reporting any suicidality (ideation or attempts) compared with nonsuicidal individuals. However, hopelessness failed to meaningfully distinguish attempters from ideators in both retrospective and prospective analyses. Taken together with results from previous studies, our findings suggest hopelessness is best conceptualized as a risk factor for suicide ideation but not progression from ideation to attempts.
Plasma treated with amotosalen and ultraviolet A light retains activity for hemostasis after 5 days post‐thaw storage at 1 to 6oC
Authors: Erickson Anna , Waldhaus Katie , David Tovo , Huang Norman , Rico Salvador , Corash Laurence , Mufti Nina , Benjamin Richard J.
Published: February 2017

BACKGROUND

Plasma thawed and stored at 1 to 6°C for up to 5 days (thawed plasma [TP]) provides rapid availability in emergencies and reduces plasma waste, but it carries risks of coagulation factor loss or activation, bacterial outgrowth, and viral contamination. We characterized changes in amotosalen/ultraviolet A (UVA) light pathogen‐reduced, fresh‐frozen plasma (FFP) and plasma frozen within 24 hours (PF24) with post‐thaw storage.

STUDY DESIGN AND METHODS

Amotosalen/UVA light‐treated FFP and PF24 were thawed after approximately 3 to more than 12 months of frozen storage and held at 1 to 6°C for 5 days. Global assessments of coagulation and hemostatic, antithrombotic, and activation markers indicative of function were assessed.

RESULTS

Day 5, thawed amotosalen/UVA light‐treated FFP and PF24 contained levels of Factors II, V, VIII, IX, X, von Willebrand factor ristocetin cofactor (vWF:RCo), fibrinogen, antithrombin III (ATIII), protein C, and protein S similar to the levels measured in Day 5 TP, as described in the Circular of Information. Thrombin generation was robust on Day 5 (amotosalen/UVA: FFP = 1866 ± 402 nM/minute; PF24 = 1800 ± 277 nM/minute). Most factor activities on Day 5, including von Willebrand factor‐cleaving protease (ADAMTS‐13), were more than 90% of Day 0 values, except for known labile Factors V and VIII and protein S. All units contained greater than 0.4 IU/mL protein S and α2 plasmin inhibitor on Day 5. Global functional indices, including thrombin‐antithrombin complexes, nonactivated thromboplastin time, and thrombin‐generation peak height, did not indicate activation of the coagulation cascade, although isolated units showed raised levels of Factor VIIa and Complement 3a.

CONCLUSION

Amotosalen/UVA light‐treated FFP and PF24 demonstrated retention of procoagulant and antithrombotic activity after 5 days post‐thaw storage at 1 to 6°C.
A High Performance Voice Coil Actuator for Optomechatronic Applications
Authors: Hicks Dion , Rahman Taufiq , Krouglicof Nicholas
Published: February 2017

Voice coil actuators (VCAs) are simple electro-mechanical devices, which are capable of generating linear motion in response to an electrical input. The generic cylindrical design of commercially available actuators imposes a large variety of limitations on the end user. The most prominent is the requirement to design and fit extra components to the actuator in order to increase functionality. To solve this issue, a novel voice coil actuator was created, which reconfigures the standard cylindrical design with one of a rectangular structure. The novel actuator incorporates planar magnets in a modified Halbach array configuration to ensure compactness and an exceptionally intense, uniform magnetic field. The moving coil is substituted with a printed circuit board (PCB) encompassing numerous current conducting traces. The board contains a miniature linear rail and bearing system, unified drive electronics, and highly adaptive position feedback circuitry resulting in a compact, highly dynamic and accurate device. In pursuit of optomechatronic applications, two distinct parallel kinematic mechanisms (PKMs) were developed to utilize the high dynamics and accuracy of the novel actuator. These devices were configured to function in only rotational degrees-of-freedom (DOF) and because of their underlying kinematic structures can be referred to as parallel orientation manipulators (POMs). In particular, two structures were defined, 2-PSS/U and 3-PSS/S, in order to constrain their payloads to two and three degrees of rotational freedom, respectively. The resultant manipulators are highly dynamic, precise and fulfill size, weight, and power requirements for many applications such as sense and avoidance and visual tracking.
Residual Stress State of X65 Pipeline Girth Welds Before and After Local and Furnace Post Weld Heat Treatment
Authors: Ren Yao , Paradowska Anna , Wang Bin , Eren Elvin , Jin Janin Yin
Published: February 2017

This research investigated the effects of global (in other words, furnace-based) and local post weld heat treatment (PWHT) on residual stress (RS) relaxation in API 5L X65 pipe girth welds. All pipe spools were fabricated using identical pipeline production procedures for manufacturing multipass narrow gap welds. Nondestructive neutron diffraction (ND) strain scanning was carried out on girth welded pipe spools and strain-free comb samples for the determination of the lattice spacing. All residual stress measurements were carried out at the KOWARI strain scanning instrument at the Australian Nuclear Science and Technology Organization (ANSTO). Residual stresses were measured on two pipe spools in as-welded condition and two pipe spools after local and furnace PWHT. Measurements were conducted through the thickness in the weld material and adjacent parent metal starting from the weld toes. Besides, three line-scans along pipe length were made 3 mm below outer surface, at pipe wall midthickness, and 3 mm above the inner surface. PWHT was carried out for stress relief; one pipe was conventionally heat treated entirely in an enclosed furnace, and the other was locally heated by a flexible ceramic heating pad. Residual stresses measured after PWHT were at exactly the same locations as those in as-welded condition. Residual stress states of the pipe spools in as-welded condition and after PWHT were compared, and the results were presented in full stress maps. Additionally, through-thickness residual stress profiles and the results of one line scan (3 mm below outer surface) were compared with the respective residual stress profiles advised in British Standard BS 7910 “Guide to methods for assessing the acceptability of flaws in metallic structures” and the UK nuclear industry's R6 procedure. The residual stress profiles in as-welded condition were similar. With the given parameters, local PWHT has effectively reduced residual stresses in the pipe spool to such a level that it prompted the thought that local PWHT can be considered a substitute for global PWHT.
Acoustic differentiation of Shiho- and Naisa-type short-finned pilot whales in the Pacific Ocean
Authors: Van Cise Amy M. , Roch Marie A. , Baird Robin W. , Aran Mooney T. , Barlow Jay
Published: February 2017

Divergence in acoustic signals used by different populations of marine mammals can be caused by a variety of environmental, hereditary, or social factors, and can indicate isolation between those populations. Two types of genetically and morphologically distinct short-finned pilot whales, called the Naisa- and Shiho-types when first described off Japan, have been identified in the Pacific Ocean. Acoustic differentiation between these types would support their designation as sub-species or species, and improve the understanding of their distribution in areas where genetic samples are difficult to obtain. Calls from two regions representing the two types were analyzed using 24 recordings from Hawai‘i (Naisa-type) and 12 recordings from the eastern Pacific Ocean (Shiho-type). Calls from the two types were significantly differentiated in median start frequency, frequency range, and duration, and were significantly differentiated in the cumulative distribution of start frequency, frequency range, and duration. Gaussian mixture models were used to classify calls from the two different regions with 74% accuracy, which was significantly greater than chance. The results of these analyses indicate that the two types are acoustically distinct, which supports the hypothesis that the two types may be separate sub-species.
Blueprint for a microwave trapped ion quantum computer
Authors: Lekitsch Bjoern , Weidt Sebastian , Fowler Austin G. , Mølmer Klaus , Devitt Simon J. , Wunderlich Christof , Hensinger Winfried K.
Published: February 2017

Design to build a trapped ion quantum computer with modules connected by ion transport and voltage-driven quantum gate technology.
Interactions between demography and environmental effects are important determinants of population dynamics
Authors: Gamelon Marlène , Grøtan Vidar , Nilsson Anna L. K. , Engen Steinar , Hurrell James W. , Jerstad Kurt , Phillips Adam S. , Røstad Ole W. , Slagsvold Tore , Walseng Bjørn , Stenseth Nils C. , Sæther Bernt-Erik
Published: February 2017

Warmer winters alter the dynamics of a local bird population and reduce immigration rate due to density-dependent feedback.
Quasi–solid state rechargeable Na-CO
2
batteries with reduced graphene oxide Na anodes
Authors: Hu Xiaofei , Li Zifan , Zhao Yaran , Sun Jianchao , Zhao Qing , Wang Jianbin , Tao Zhanliang , Chen Jun
Published: February 2017

High-performance quasi–solid state Na-CO
2
batteries are constructed with polymer electrolyte and a reduced graphene oxide Na anode.
Imaging rotational dynamics of nanoparticles in liquid by 4D electron microscopy
Authors: Fu Xuewen , Chen Bin , Tang Jau , Hassan Mohammed Th. , Zewail Ahmed H.
Published: February 2017

Ultrafast studies using liquid cells

Advances in microscopy techniques aim to make it possible to study materials under more realistic conditions, such as in liquid cells, or to use fast probes to capture dynamics. Fu
et al.
combined liquid cell transmission electron microscopy with ultrafast pump-probe spectroscopy to perform time-resolved studies of nanoscale objects (see the Perspective by Baum). They successfully captured the change in rotational dynamics of coupled gold nanoparticles and also observed the dynamics as two particles fused together in a liquid environment.

Science
, this issue p.
494
; see also p.
458
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair
Authors: Sibanda Bancinyane L. , Chirgadze Dimitri Y. , Ascher David B. , Blundell Tom L.
Published: February 2017

Activating DNA repair

DNA double-strand breaks must be repaired efficiently to avoid cell death or cancer. The break ends can either be directly ligated by nonhomologous end joining (NHEJ) or more accurately repaired by homologous recombination that uses information from the sister chromatid. Sibanda
et al.
present a high-resolution x-ray structure of a key component of the DNA repair machinery, the DNA-dependent kinase catalytic subunit (DNA-PKcs), bound to a C-terminal peptide of Ku80. The structure suggests that Ku80 presents the DNA ends for repair to a DNA-PKcs dimer and that activity is modulated by interactions between the monomers. Binding of either Ku80 or BRCA1, which may compete for the same binding site on DNA-PKcs, could provide a switch between NHEJ and homologous recombination.

Science
, this issue p.
520
The structure of the yeast mitochondrial ribosome
Authors: Desai Nirupa , Brown Alan , Amunts Alexey , Ramakrishnan V.
Published: February 2017

The yeast mitoribosome

Mitochondria are eukaryotic organelles that produce ATP, the energy source of the cell. They have dedicated ribosomes (mitoribosomes) that encode some of the membrane proteins that are essential to ATP production. Desai
et al.
present a high-resolution structure of the 75-component yeast mitoribosome, determined by electron cryomicroscopy. Mitoribosomes share an ancestor with modern bacterial ribosomes. Comparing the structure of the yeast mitoribosome with mammalian mitoribosomes suggests how they have evolved differently to perform species-specific functions.

Science
, this issue p.
528
Bringing probability judgments into policy debates via forecasting tournaments
Authors: Tetlock Philip E. , Mellers Barbara A. , Scoblic J. Peter
Published: February 2017

Political debates often suffer from vague-verbiage predictions that make it difficult to assess accuracy and improve policy. A tournament sponsored by the U.S. intelligence community revealed ways in which forecasters can better use probability estimates to make predictions—even for seemingly “unique” events—and showed that tournaments are a useful tool for generating knowledge. Drawing on the literature about the effects of accountability, the authors suggest that tournaments may hold even greater potential as tools for depolarizing political debates and resolving policy disputes.
Biomimetic temperature-sensing layer for artificial skins
Authors: Di Giacomo Raffaele , Bonanomi Luca , Costanza Vincenzo , Maresca Bruno , Daraio Chiara
Published: February 2017

Pectin films mimic the sensing mechanism of viper pit membranes to finely detect temperature changes.
The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination
Authors: Hu Yong , Li Wei , Gao Ting , Cui Yan , Jin Yanwen , Li Ping , Ma Qingjun , Liu Xuan , Cao Cheng
Published: February 2017

Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.

IMPORTANCE
The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.
Immunization with Low Doses of Recombinant Postfusion or Prefusion Respiratory Syncytial Virus F Primes for Vaccine-Enhanced Disease in the Cotton Rat Model Independently of the Presence of a Th1-Biasing (GLA-SE) or Th2-Biasing (Alum) Adjuvant
Authors: Schneider-Ohrum Kirsten , Cayatte Corinne , Bennett Angie Snell , Rajani Gaurav Manohar , McTamney Patrick , Nacel Krystal , Hostetler Leigh , Cheng Lily , Ren Kuishu , O'Day Terrence , Prince Gregory A. , McCarthy Michael P.
Published: February 2017

Respiratory syncytial virus (RSV) infection of children previously immunized with a nonlive, formalin-inactivated (FI)-RSV vaccine has been associated with serious enhanced respiratory disease (ERD). Consequently, detailed studies of potential ERD are a critical step in the development of nonlive RSV vaccines targeting RSV-naive children and infants. The fusion glycoprotein (F) of RSV in either its postfusion (post-F) or prefusion (pre-F) conformation is a target for neutralizing antibodies and therefore an attractive antigen candidate for a pediatric RSV subunit vaccine. Here, we report the evaluation of RSV post-F and pre-F in combination with glucopyranosyl lipid A (GLA) integrated into stable emulsion (SE) (GLA-SE) and alum adjuvants in the cotton rat model. Immunization with optimal doses of RSV F antigens in the presence of GLA-SE induced high titers of virus-neutralizing antibodies and conferred complete lung protection from virus challenge, with no ERD signs in the form of alveolitis. To mimic a waning immune response, and to assess priming for ERD under suboptimal conditions, an antigen dose de-escalation study was performed in the presence of either GLA-SE or alum. At low RSV F doses, alveolitis-associated histopathology was unexpectedly observed with either adjuvant at levels comparable to FI-RSV-immunized controls. This occurred despite neutralizing-antibody titers above the minimum levels required for protection and with no/low virus replication in the lungs. These results emphasize the need to investigate a pediatric RSV vaccine candidate carefully for priming of ERD over a wide dose range, even in the presence of strong neutralizing activity, Th1 bias-inducing adjuvant, and protection from virus replication in the lower respiratory tract.

IMPORTANCE
RSV disease is of great importance worldwide, with the highest burden of serious disease occurring upon primary infection in infants and children. FI-RSV-induced enhanced disease, observed in the 1960s, presented a major and ongoing obstacle for the development of nonlive RSV vaccine candidates. The findings presented here underscore the need to evaluate a nonlive RSV vaccine candidate during preclinical development over a wide dose range in the cotton rat RSV enhanced-disease model, as suboptimal dosing of several RSV F subunit vaccine candidates led to the priming for ERD. These observations are relevant to the validity of the cotton rat model itself and to safe development of nonlive RSV vaccines for seronegative infants and children.
Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis
Authors: Haley Shannon L. , Tzvetkov Evgeni P. , Meuwissen Samantha , Plummer Joseph R. , McGettigan James P.
Published: February 2017

Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP.

IMPORTANCE
Effective RABV PEP is currently resource- and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the requirements for rabies immunoglobulin (RIG) and multiple vaccinations for effective prevention of clinical rabies, a more rapidly protective vaccine is needed. This work presents a successful approach to rapidly generate antibody-secreting PCs in response to vaccination by targeting the extrafollicular B cell pathway. We demonstrate that the improved early antibody responses induced by rRABV-mBAFF confer improved protection against RABV in a PEP model. Significantly, activation of the early extrafollicular B cell pathway, such as that demonstrated here, could improve the efficacy of vaccines targeting other pathogens against which rapid protection would decrease morbidity and mortality.
HIV-1 Vpu Downmodulates ICAM-1 Expression, Resulting in Decreased Killing of Infected CD4
+
T Cells by NK Cells
Authors: Sugden Scott M. , Pham Tram N. Q. , Cohen Éric A.
Published: February 2017

HIV-1 Vpu is known to alter the expression of numerous cell surface molecules. Given the ever-increasing list of Vpu targets identified to date, we undertook a proteomic screen to discover novel cell membrane proteins modulated by this viral protein. Plasma membrane proteome isolates from Vpu-inducible T cells were subjected to
s
table isotope labeling of amino acids in cell culture (SILAC)-based mass spectrometry analysis, and putative targets were validated by infection of primary CD4
+
T cells. We report here that while intercellular adhesion molecule 1 (ICAM-1) and ICAM-3 are upregulated by HIV-1 infection, expression of Vpu offsets this increase by downregulating these molecules from the cell surface. Specifically, we show that Vpu is sufficient to downregulate and deplete ICAM-1 in a manner requiring the Vpu transmembrane domain and a dual-serine (S52/S56) motif necessary for recruitment of the beta-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP) component of the Skp, Cullin, F-box (SCF
β-TrCP
) E3 ubiquitin ligase. Vpu interacts with ICAM-1 to induce its proteasomal degradation. Interestingly, the E3 ubiquitin ligase component β-TrCP-1 is dispensable for ICAM-1 surface downregulation yet is necessary for ICAM-1 degradation. Functionally, Vpu-mediated ICAM-1 downregulation lowers packaging of this adhesion molecule into virions, resulting in decreased infectivity. Importantly, while Vpu-mediated downregulation of ICAM-3 has a limited effect on the conjugation of NK cells to HIV-1-infected CD4
+
T cells, downregulation of ICAM-1 by Vpu results in a reduced ability of NK cells to bind and kill infected T cells. Vpu-mediated ICAM-1 downregulation may therefore represent an evolutionary compromise in viral fitness by impeding the formation of cell-to-cell contacts between immune cells and infected T cells at the cost of decreased virion infectivity.

IMPORTANCE
The major barrier to eradicating HIV-1 infection is the establishment of treatment-resistant reservoirs early in infection. Vpu-mediated ICAM-1 downregulation may contribute to the evasion of cell-mediated immunity during acute infection to promote viral dissemination and the development of viral reservoirs. By aiding the immune system to clear infection prior to the development of reservoirs, novel treatments designed to disrupt Vpu-mediated ICAM-1 downregulation may be beneficial during acute infection or as a prophylactic treatment.
TgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite Toxoplasma gondii
Authors: Jeffers Victoria , Kamau Edwin T. , Srinivasan Ananth R. , Harper Jonathan , Sankaran Preethi , Post Sarah E. , Varberg Joseph M. , Sullivan William J. , Boyle Jon P.
Published: February 2017

We report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite
Toxoplasma gondii
. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the development of new therapies for toxoplasmosis and other related parasitic diseases.
Renal cell carcinoma metastasis involving vertebral hemangioma: dual percutaneous treatment by navigational bipolar radiofrequency ablation and high viscosity cement vertebroplasty
Authors: Zerlauth Jean-Baptiste , Meuli Reto , Dunet Vincent
Published: February 2017

The case of a 70-year-old woman with progressive renal cell carcinoma (RCC) metastatic invasion of a L3 vertebral hemangioma treated by dual percutaneous radiofrequency ablation (RFA) and vertebroplasty is reported. The patient was surgically treated for RCC in 2001. Chemotherapy and immunotherapy were introduced in 2013 for ovarian, bladder and cerebral metastatic disease. An asymptomatic L3 benign hemangioma was noticed at this time. One-year CT and MRI follow-up studies demonstrated a nodular isolated soft tissue lesion involving the anterior edge of the hemangioma. Percutaneous treatment consisted of a L3 vertebral body unipedicular approach to perform a biopsy, RFA with a navigational bipolar RFA device and vertebroplasty using high viscosity cement. Histopathological examination confirmed metastasis of RCC. The 5-month spinal MRI and CT examinations demonstrated complete disappearance of the tumor.
Pregnancy in a patient with congenital analbuminaemia
Authors: Hu Hillary , Nayyar Roshini , Berglund Lucinda Jean , Anderson Elizabeth Anne
Published: February 2017

Congenital analbuminaemia is a rare autosomal recessive disorder that is characterised by a severe reduction or total absence of serum albumin. This condition has implications for therapeutics as a large proportion of commonly used drugs are plasma protein bound where albumin is the primary component of plasma protein. This is the first case report of pregnancy in a patient with congenital analbuminaemia in the medical literature. In the absence of drug dosage guidelines for patients with congenital analbuminaemia, a list of drugs which may be required for this patient during pregnancy, delivery and/or emergency situations were compiled by a multidisciplinary team. Our patient suffered from polyhydramnios during her pregnancy which was successfully managed with albumin transfusions and had a normal vaginal delivery with no complications in the intrapartum or postpartum period. The management and unique challenges of pregnancy in a patient with congenital analbuminaemia are discussed.
Role of Non-Government Organizations in Engaging Medical Students in Research
Authors: Manoranjan Branavan , Dey Ayan K , Wang Xin , Kuzyk Alexandra , Petticrew Karen , Carruthers Chris , Arnold Ian
Published: February 2017

The continued decline in medical trainees entering the workforce as clinician-scientists has elevated the need to engage medical students in research. While past studies have shown early exposure to generate interest among medical students for research and academic careers, financial constraints have limited the number of such formal research training programs. In light of recent government budget cuts to support research training for medical students, non-government organizations (NGOs) may play a progressively larger role in supporting the development of clinician-scientists. Since 2005, the Mach-Gaensslen Foundation has sponsored 621 Canadian medical student research projects, which represents the largest longitudinal data set of Canadian medical students engaged in research. We present the results of the pre- and post-research studentship questionnaires, program evaluation survey and the 5-year and 10-year follow-up questionnaires of past recipients. This paper provides insight into the role of NGOs as stakeholders in the training of clinician-scientists and evaluates the impact of such programs on the attitudes and career trajectory of medical students. While the problem of too few physicians entering academic and research-oriented careers continues to grow, alternative-funding strategies from NGOs may prove to be an effective approach in developing and maintaining medical student interest in research.
Counting of oscillatory modes of valence quarks forming qqq baryons for three quark flavors u, d, s
Authors: Kabana Sonia , Minkowski Peter
Published: February 2017

We present the unique properties of oscillatory modes of [Formula: see text] light quarks — [Formula: see text], [Formula: see text], [Formula: see text] — using the [Formula: see text] broken symmetry classification. [Formula: see text] stands for the space rotation group generated by the sum of the three individual angular momenta of quarks in their c.m. system. The baryonic multiplets are shown to emerge from the picture of oscillating quarks in three space dimensions in the center-of-mass system of the baryons. All oscillatory modes are fully relativistic with a finite number of oscillators and this is forming the unique harmonic oscillator with these properties. The density of states as a function of mass-square is calculated. This estimate is of relevance for the accounting of the missing states of unobserved hadrons, as the here estimated baryonic multiplets include both the observed and the unobserved (or “missing”) hadrons. The estimate is conceptually different from Hagedorn’s model and is based on field theory of QCD.
The cardiovascular system after exercise
Authors: Romero Steven A. , Minson Christopher T. , Halliwill John R.
Published: February 2017

Recovery from exercise refers to the time period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It also refers to specific physiological processes or states occurring after exercise that are distinct from the physiology of either the exercising or the resting states. In this context, recovery of the cardiovascular system after exercise occurs across a period of minutes to hours, during which many characteristics of the system, even how it is controlled, change over time. Some of these changes may be necessary for long-term adaptation to exercise training, yet some can lead to cardiovascular instability during recovery. Furthermore, some of these changes may provide insight into when the cardiovascular system has recovered from prior training and is physiologically ready for additional training stress. This review focuses on the most consistently observed hemodynamic adjustments and the underlying causes that drive cardiovascular recovery and will highlight how they differ following resistance and aerobic exercise. Primary emphasis will be placed on the hypotensive effect of aerobic and resistance exercise and associated mechanisms that have clinical relevance, but if left unchecked, can progress to symptomatic hypotension and syncope. Finally, we focus on the practical application of this information to strategies to maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities of this state. We will explore appropriate field measures, and discuss to what extent these can guide an athlete’s training.
The role of the hippocampus in navigation is memory
Authors: Eichenbaum Howard
Published: February 2017

There is considerable research on the neurobiological mechanisms within the hippocampal system that support spatial navigation. In this article I review the literature on navigational strategies in humans and animals, observations on hippocampal function in navigation, and studies of hippocampal neural activity in animals and humans performing different navigational tasks and tests of memory. Whereas the hippocampus is essential to spatial navigation via a cognitive map, its role derives from the relational organization and flexibility of cognitive maps and not from a selective role in the spatial domain. Correspondingly, hippocampal networks map multiple navigational strategies, as well as other spatial and nonspatial memories and knowledge domains that share an emphasis on relational organization. These observations suggest that the hippocampal system is not dedicated to spatial cognition and navigation, but organizes experiences in memory, for which spatial mapping and navigation are both a metaphor for and a prominent application of relational memory organization.
Sharp Bounds of the Hyper-Zagreb Index on Acyclic, Unicylic, and Bicyclic Graphs
Authors: Gao Wei , Jamil Muhammad Kamran , Javed Aisha , Farahani Mohammad Reza , Wang Shaohui , Liu Jia-Bao
Published: February 2017

The hyper-Zagreb index is an important branch in the Zagreb indices family, which is defined as∑uv∈E(G)‍(d(u)+d(v))2, whered(v)is the degree of the vertexvin a graphG=(V(G),E(G)). In this paper, the monotonicity of the hyper-Zagreb index under some graph transformations was studied. Using these nice mathematical properties, the extremal graphs amongn-vertex trees (acyclic), unicyclic, and bicyclic graphs are determined for hyper-Zagreb index. Furthermore, the sharp upper and lower bounds on the hyper-Zagreb index of these graphs are provided.
Analysis of Severe Injury Accident Rates on Interstate Highways Using a Random Parameter Tobit Model
Authors: Park Minho , Lee Dongmin
Published: February 2017

In this study, a random parameter Tobit regression model approach was used to account for the distinct censoring problem and unobserved heterogeneity in accident data. We used accident rate data (continuous data) instead of accident frequency data (discrete count data) to address the zero cell problems from data where roadway segments do not have any recorded accidents over the observed time period. The unobserved heterogeneity problem is also considered by using random parameters, which are parameter estimates that vary across observations instead of fixed parameters, which are parameter estimates that are fixed/constant over observations. Nine years (1999–2007) of panel data related to severe injury accidents in Washington State, USA, were used to develop the random parameter Tobit model. The results showed that the Tobit regression model with random parameters is a better approach to explore factors influencing severe injury accident rates on roadway segments under consideration of unobserved heterogeneity problems.
Risk assessment models for venous thromboembolism in acutely ill medical patients
Authors: Stuck Anna , Spirk David , Schaudt Jil , Kucher Nils
Published: February 2017

Although the use of thromboprophylaxis is recommended for acutely ill medical patients at increased risk of venous thromboembolism (VTE), it remains unclear which risk assessment model (RAM) should be routinely used to identify at-risk patients requiring thromboprophylaxis. We therefore aimed to describe existing RAMs, and to compare these tools in terms of validity and applicability for clinical decisionmaking. We performed a comprehensive systematic search in MEDLINE from the date of initiation until May 2016 for studies in acutely ill medical patients investigating validity of RAMs for VTE. Two reviewers independently screened the title, abstract, and full text, and evaluated the characteristics of studies, and the composition, evidence of validation, and results on validity of the RAMs. We included 11 studies assessing eight RAMs: 4-Element RAM, Caprini RAM, a full logistic model, Geneva risk score, IMPROVE-RAM, Kucher Model, a “Multivariable Model”, and Padua Prediction Score. The 4-Element RAM, IMPROVE-RAM, Multivariable Model, and full logistic model had derivation by identifying factors with predictive power. The other four RAMs were empirically generated based on consensus guidelines, published data, and clinical expertise. The Kucher Model, the Padua Prediction Score, the Geneva Risk Score and the IMPROVE-RAM underwent multicenter external validation. The Kucher Model, the Padua Prediction Score, and the Geneva Risk Score improved rates of thromboprophylaxis or clinical outcomes. In conclusion, existing RAMs to evaluate the need of thromboprophylaxis in acutely ill medical patients are difficult to compare and none fulfills the criteria of an ideal RAM. Nevertheless, the adequacy of thromboprophylaxis may be improved by implementing one of the validated RAMs.