bluuebunny/crossref_metadata_2025_split huggingface dataset:
A historical perspective on peripheral reflex cardiovascular control from animals to man
Authors: Sleight Peter 
Published: July 2014

New Findings
What is the topic of this review?
This review concerns the history of baroreflex control of blood pressure in animals and man. It deals mainly with mechanisms at a subcortical level and so complements the earlier review by Coote (2007).
What advances does it highlight?
New studies now confirm that the arterial baroreflex does control long‐term level of blood pressure through mechanisms which involve electrolyte and water excretion via nervous control of the kidney. The review also describes recent data on human blood pressure control using implanted devices to unilaterally stimulate the carotid baroreceptors, effective over several years with minimal complications. Music therapy is also discussed.
Although drug treatment of human hypertension has greatly improved, there is renewed interest in non‐drug methods of blood pressure reduction. Animal experiments have now shown that arterial baroreflexes do control long‐term blood pressure levels, particularly by nervously mediated renal excretion of sodium and water. This Paton Lecture provides a review of the historical development of knowledge of peripheral circulatory control in order to supplement prior Paton Lectures concerned with cerebral cortical and other areas of influence. I also discuss how improved understanding of nervous control of the circulation has led to current methods of non‐drug blood pressure control in man by implanted carotid baroreceptor pacemakers or by renal denervation. Finally, the role of other therapy, particularly listening to music, is reviewed.
Safety of Attenuated Smallpox Vaccine LC16m8 in Immunodeficient Mice
Authors: Yokote Hiroyuki , Shinmura Yasuhiko , Kanehara Tomomi , Maruno Shinichi , Kuranaga Masahiko , Matsui Hajime , Hashizume So 
Published: July 2014

ABSTRACT
Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients.
Evaluation of Protective Efficacy of Live Attenuated Salmonella enterica Serovar Gallinarum Vaccine Strains against Fowl Typhoid in Chickens
Authors: Łaniewski Paweł , Mitra Arindam , Karaca Kemal , Khan Ayub , Prasad Rajeev , Curtiss Roy , Roland Kenneth L. 
Published: July 2014

ABSTRACTSalmonella entericaserovar Gallinarum is the etiological agent of fowl typhoid, which constitutes a considerable economic problem for poultry growers in developing countries. The vaccination of chickens seems to be the most effective strategy to control the disease in those areas. We constructedS. Gallinarum strains with a deletion of the global regulatory genefurand evaluated their virulence and protective efficacy in Rhode Island Red chicks and Brown Leghorn layers. Thefurdeletion mutant was avirulent and, when delivered orally to chicks, elicited excellent protection against lethalS. Gallinarum challenge. It was not as effective when given orally to older birds, although it was highly immunogenic when delivered by intramuscular injection. We also examined the effect of apmimutant and a combination offurdeletions with mutations in thepmiandrfaHgenes, which affect O-antigen synthesis, andansB, whose product inhibits host T-cell responses. TheS. Gallinarum Δpmimutant was only partially attenuated, and the ΔansBmutant was fully virulent. The ΔfurΔpmiand ΔfurΔansBdouble mutants were attenuated but not protective when delivered orally to the chicks. However, a ΔpmiΔfurstrain was highly immunogenic when administered intramuscularly. All together, our results show that thefurgene is essential for the virulence ofS. Gallinarum, and thefurmutant is effective as a live recombinant vaccine against fowl typhoid.
HIV Integrase Inhibitors Block Replication of Alpha-, Beta-, and Gammaherpesviruses
Authors: Yan Zhipeng , Bryant Kevin F. , Gregory Sean M. , Angelova Magdalena , Dreyfus David H. , Zhao Xue Zhi , Coen Donald M. , Burke Terrence R. , Knipe David M. 
Published: July 2014

ABSTRACT

The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity
in vitro
, and the viral terminase, which is essential for viral DNA cleavage and packaging. Therefore, we hypothesized that HIV integrase inhibitors might also inhibit HSV replication by targeting ICP8 and/or the terminase. To test this, we evaluated the effect of 118-D-24, a potent HIV integrase inhibitor, on HSV replication. We found that 118-D-24 inhibited HSV-1 replication in cell culture at submillimolar concentrations. To identify more potent inhibitors of HSV replication, we screened a panel of integrase inhibitors, and one compound with greater anti-HSV-1 activity, XZ45, was chosen for further analysis. XZ45 significantly inhibited HSV-1 and HSV-2 replication in different cell types, with 50% inhibitory concentrations that were approximately 1 µM, but exhibited low cytotoxicity, with a 50% cytotoxic concentration greater than 500 µM. XZ45 blocked HSV viral DNA replication and late gene expression. XZ45 also inhibited viral recombination in infected cells and ICP8 recombinase activity
in vitro
. Furthermore, XZ45 inhibited human cytomegalovirus replication and induction of Kaposi’s sarcoma herpesvirus from latent infection. Our results argue that inhibitors of enzymes with RNase H-like folds may represent a general antiviral strategy, which is useful not only against HIV but also against herpesviruses.

IMPORTANCE
The herpesviruses cause considerable morbidity and mortality. Nucleoside analogs have served as effective antiviral agents against the herpesviruses, but resistance can arise through viral mutation. Second-line anti-herpes drugs have limitations in terms of pharmacokinetic properties and/or toxicity, so there is a great need for additional drugs for treatment of herpesviral infections. This study showed that the HIV integrase inhibitors also block herpesviral infection, raising the important potential of a new class of anti-herpes drugs and the prospect of drugs that combat both HIV and the herpesviruses.
IQGAP1 Is Important for Activation of Caspase-1 in Macrophages and Is Targeted by Yersinia pestis Type III Effector YopM
Authors: Chung Lawton K. , Philip Naomi H. , Schmidt Valentina A. , Koller Antonius , Strowig Till , Flavell Richard A. , Brodsky Igor E. , Bliska James B. 
Published: July 2014

ABSTRACT

YopM is a leucine-rich repeat (LRR)-containing effector in several
Yersinia
species, including
Yersinia pestis
and
Y. pseudotuberculosis
. Different
Yersinia
strains encode distinct YopM isoforms with variable numbers of LRRs but conserved C-terminal tails. A 15-LRR isoform in
Y. pseudotuberculosis
YPIII was recently shown to bind and inhibit caspase-1 via a YLTD motif in LRR 10, and attenuation of YopM
−
YPIII was reversed in mice lacking caspase-1, indicating that caspase-1 inhibition is a major virulence function of YopM
YPIII
. To determine if other YopM proteins inhibit caspase-1, we utilized
Y. pseudotuberculosis
strains natively expressing a 21-LRR isoform lacking the YLTD motif (YopM
32777
) or ectopically expressing a
Y. pestis
15-LRR version with a functional (YopM
KIM
) or inactivated (YopM
KIM
D
271
A) YLTD motif. Results of mouse and macrophage infections with these strains showed that YopM
32777
, YopM
KIM
, and YopM
KIM
D
271
A inhibit caspase-1 activation, indicating that the YLTD motif is dispensable for this activity. Analysis of YopM
KIM
deletion variants revealed that LRRs 6 to 15 and the C-terminal tail are required to inhibit caspase-1 activation. YopM
32777
, YopM
KIM
, and YopM
KIM
deletion variants were purified, and binding partners in macrophage lysates were identified. Caspase-1 bound to YopM
KIM
but not YopM
32777
. Additionally, YopM
KIM
bound IQGAP1 and the use of
Iqgap1

−/−

macrophages revealed that this scaffolding protein is important for caspase-1 activation upon infection with YopM
−
Y. pseudotuberculosis
. Thus, while multiple YopM isoforms inhibit caspase-1 activation, their variable LRR domains bind different host proteins to perform this function and the LRRs of YopM
KIM
target IQGAP1, a novel regulator of caspase-1, in macrophages.

IMPORTANCE
Activation of caspase-1, mediated by macromolecular complexes termed inflammasomes, is important for innate immune defense against pathogens. Pathogens can, in turn, subvert caspase-1-dependent responses through the action of effector proteins. For example, the
Yersinia
effector YopM inhibits caspase-1 activation by arresting inflammasome formation. This caspase-1 inhibitory activity has been studied in a specific YopM isoform, and in this case, the protein was shown to act as a pseudosubstrate to bind and inhibit caspase-1. Different
Yersinia
strains encode distinct YopM isoforms, many of which lack the pseudosubstrate motif. We studied additional isoforms and found that these YopM proteins inhibit caspase-1 activation independently of a pseudosubstrate motif. We also identified IQGAP1 as a novel binding partner of the
Yersinia pestis
YopM
KIM
isoform and demonstrated that IQGAP1 is important for caspase-1 activation in macrophages infected with
Yersinia
. Thus, this study reveals new insights into inflammasome regulation during
Yersinia
infection.
On palindromic width of certain extensions and quotients of free nilpotent groups
Authors: Bardakov Valeriy G. , Gongopadhyay Krishnendu 
Published: July 2014

In [Bardakov and Gongopadhyay, Palindromic width of free nilpotent groups, J. Algebra 402 (2014) 379–391] the authors provided a bound for the palindromic widths of free abelian-by-nilpotent group ANn of rank n and free nilpotent group N n,r of rank n and step r. In the present paper, we study palindromic widths of groups [Formula: see text] and [Formula: see text]. We denote by [Formula: see text] the quotient of the group Gn = 〈x1, …, xn〉, which is free in some variety by the normal subgroup generated by [Formula: see text]. We prove that the palindromic width of the quotient [Formula: see text] is finite and bounded by 3n. We also prove that the palindromic width of the quotient [Formula: see text] is precisely 2(n - 1). As a corollary to this result, we improve the lower bound of the palindromic width of N n,r. We also improve the bound of the palindromic width of a free metabelian group. We prove that the palindromic width of a free metabelian group of rank n is at most 4n - 1.
Acinetobacter baumanniiInfection in Prior ICU Bed Occupants Is an Independent Risk Factor for Subsequent Cases of Ventilator-Associated Pneumonia
Authors: Tsakiridou Eirini , Makris Demosthenes , Daniil Zoe , Manoulakas Efstratios , Chatzipantazi Vasiliki , Vlachos Odysseas , Xidopoulos Grigorios , Charalampidou Olympia , Zakynthinos Epaminondas 
Published: July 2014

Objective. We aimed to evaluate risk factors for ventilator-associated pneumonia (VAP) due toAcinetobacter baumannii(AbVAP) in critically ill patients.Methods. This was a prospective observational study conducted in an intensive care unit (ICU) of a district hospital (6 beds). Consecutive patients were eligible for enrolment if they required mechanical ventilation for>48 hours and hospitalization for>72 hours. Clinical, microbiological, and laboratory parameters were assessed as risk factors for AbVAP by univariate and multivariate analysis.Results. 193 patients were included in the study. Overall, VAP incidence was 23.8% and AbVAP, 11.4%. Previous hospitalization of another patient withAcinetobacter baumanniiinfection was the only independent risk factor for AbVAP (OR (95% CI) 12.016 (2.282–19.521)P<0.001). ICU stay(25±17versus12±9   P<0.001), the incidence of other infections (OR (95% CI) 9.485 (1.640–10.466)P=0.002)(urinary tract infection, catheter related infection, and bacteremia), or sepsis (OR (95% CI) 10.400 (3.749–10.466)P<0.001)were significantly increased in patients with AbVAP compared to patients without VAP; no difference was found with respect to ICU mortality.Conclusion. ICU admission or the hospitalization of patients infected byAcinetobacter baumanniiincreases the risk of AbVAP by subsequent patients.
The Value of Modern Mammography Screening in the Control of Breast Cancer: Understanding the Underpinnings of the Current Debates
Authors: Smith Robert A. 
Published: July 2014

Abstract
Since the introduction of mammography screening, debates about the value of screening have endured and been contentious. Recent reviews of the randomized controlled trials reach different conclusions about the absolute benefit of screening, as do evaluations of population trends in breast cancer mortality and the evaluations of service screening. Conclusions about the value of screening commonly are expressed in terms of the balance of benefits and harms, which can differ greatly even when derived seemingly from the same data. It can be shown when different estimates are adjusted to a common screening and follow-up scenario, differences in balance sheet estimates diminish substantially. The strong evidence of benefit associated with exposure to modern mammography screening suggests that it is time to move beyond the randomized controlled trial estimates of benefit and consider policy decisions on the basis of benefits and harms estimated from the evaluation of current screening programs. Cancer Epidemiol Biomarkers Prev; 23(7); 1139–46. ©2014 AACR.
FcγRIIaandFcγRIIIaPolymorphisms and Cetuximab Benefit in the Microscopic Disease
Authors: Sclafani Francesco , Gonzalez de Castro David , Cunningham David , Hulkki Wilson Sanna , Peckitt Clare , Capdevila Jaume , Glimelius Bengt , Roselló Keränen Susana , Wotherspoon Andrew , Brown Gina , Tait Diana , Begum Ruwaida , Thomas Janet , Oates Jacqueline , Chau Ian 
Published: July 2014

AbstractPurpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer.Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation from the Hardy–Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P = 0.058) and FcγRIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003).Conclusion: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles. Clin Cancer Res; 20(17); 4511–9. ©2014 AACR.
A new species of Chileotrecha Maury, 1987 (Solifugae: Ammotrechidae) from Argentina with notes on the genus
Authors: IURI HERNÁN A. , IGLESIAS MÓNICA S. , AFFILASTRO ANDRÉS A. OJANGUREN 
Published: July 2014

The monotypic genus Chileotrecha Maury, 1987, includes Chileotrecha atacamensis Maury, 1987 from Atacama and Coquimbo regions in Chile. We describe Chileotrecha argentinensis n. sp., which is the first record of the genus from Argentina. Phylogenetic relationships of Chileotrecha with other genera of Ammotrechidae are discussed based on external morphology. We report for the first time the presence of blunt and clubbed setae in Ammotrechidae. We also report for the first time the presence of two pairs of microsetae in the posterior margin of genital plate and in the posterior margin of spiracular sternites I and II, and the presence of a single microseta on each side of postspiracular sternite I.
Satellite Observations of an Unusual Cloud Formation near the Tropopause
Authors: Ferlay Nicolas , Garrett Timothy J. , Minvielle Fanny 
Published: July 2014

Abstract
This paper describes observations of a field of deep and regular cloud formations that spans several hundreds of kilometers at the top of a midlatitude frontal system in the North Pacific storm track. Space-based imagery of the event from active and passive measurements reveals smooth, clearly defined cloud lobes approximately 10 km across and 2–4 km deep that resemble upside-down mammatus. These observations, together with theoretical arguments and prior modeling work, suggest that the lobes were part of a deepening turbulent mixed layer that formed as a consequence of strong cloud-top radiative cooling. Over the course of a day, the cloud-top formation evolved to leave behind a sheet of cumuliform cirrus that stretched hundreds of kilometers across. The potential is for such clouds to facilitate mixing across the tropopause, much as cloud-top cooling drives the entrainment of free-tropospheric air into stratocumulus-topped boundary layers.
On the Sensitivity of Zonal-Index Persistence to Friction
Authors: Zurita-Gotor Pablo 
Published: July 2014

Abstract
Friction is an important parameter in atmospheric modeling that may affect internal variability in a number of ways. It directly damps the annular-mode variability, but it also helps to maintain it through baroclinic feedbacks. Also, by determining the mean strength and position of the midlatitude jet, friction affects the internal dynamics that drive this variability. This work investigates the relevance of all of these factors for the sensitivity of the persistence of annular variability to changes in the zonal-mean friction using an idealized quasigeostrophic two-layer model. This model produces realistic variability, yet it is so simple that one can cleanly separate the different effects. It is found that the sensitivity of persistence to friction is dominated by the direct damping effect, while changes in the eddy momentum forcing and in the mean jet are not as important.
As in more complex models, the persistence of the jet anomalies in this model decreases at all lags with increasing friction, but the long-time decorrelation decay rate of these anomalies is remarkably insensitive to friction. Although this implies that the eddy feedback must increase with friction to maintain the anomalies against the enhanced damping, it is shown that this is not due to baroclinic effects. A model that assumes that the eddy forcing does not change with friction can reproduce reasonably well the numerical results. The crucial factor that determines the model’s sensitivity to friction is the spectral structure of the eddy momentum forcing.
Deepening of the Atlantic Water Core in the Canada Basin in 2003–11
Authors: Zhong Wenli , Zhao Jinping 
Published: July 2014

AbstractIn 2004, a cold mode of Atlantic Water (AW) entered the western Canada basin, replacing the anomalously warm AW that resided in the basin since the 1990s. This slightly colder AW was denser than the 1990s warm mode; it gradually filled most of the western basin by 2009. The enhanced surface stress curl led to the spinup of the Beaufort Gyre and convergence of freshwater. The spinup also resulted in a deepening of the AW core at the center of the gyre and in shoaling of the AW core at the margins of the gyre. The density versus depth relationship revealed in this study shows that the depth of the maximum AW temperature was mainly controlled by the density structure before 2007; thus, it is the case when the denser water was deeper and the case when the lighter water was shallower around the basin. However, this relationship was reversed to become the case when the denser water was shallower and the case when the lighter water was deeper since 2008 inside the Beaufort Gyre. The combined effect of density and sea ice retreat that enhanced surface stress curl determined the depth of the AW inside the Beaufort Gyre since 2008. The deepening of the AW core and expanding of the area where the AW deepening occurred had a profound effect on the large-scale circulation in the Arctic Ocean.
Clinical thromboembolic detterrent stockings application: Are thromboembolic detterrent stockings in practice matching manufacturers application guidelines
Authors: Bowling K , Ratcliffe C , Townsend J , Kirkpatrick U 
Published: July 2014

Background Thromboembolic detterrent (TED) stockings have been shown to be effective in the reduction of thromboembolic events in post operative patients. These manufactured stockings create graduated compression from ankle to calf. Aim To assess whether the manufacturers' recommendations for application were being met in a District general hospital setting and whether this achieved the desired gradient of compression. Methods We carried out pressure measurements on 100 legs in post-operative patients and recorded reasons for poorly fitting stockings. Pressure measurements were taken at standard positions around calf and ankle using a pre-calibrated subbandage pressure measuring device. Results About 20% of stockings were worn incorrectly by patients. Median pressure applied at the ankle was 13 mmHg (range, 6.5–18.5) compared to the manufacturers' intended compression of 18 mmHg. Only 14% of the stockings showed an acceptable gradation of reduced pressure between ankle and calf. About 23% of the stockings exerted a positive pressure at calf level compared to the ankle. Conclusion Most TED stockings do not produce a standardised Siegel profile pressure gradient decrease from ankle to calf. This may be due in part to fluid changes after surgery in combination with the large variation in size of lower limbs. Our District general hospital utilises three of the six sizes of TED stocking, and remeasurement was not taking place every 24 h as per guidance. This as the result show not only negates the benefit of TED stockings but may also exert harm in terms of venous thromboembolism risk. This finding adds further weight to the argument of whether TED stockings may not be having the desired prophylactic effect and may even be resulting in harm in select cases.