bluuebunny/crossref_metadata_2025 huggingface dataset:
A Shape-Morphing Mechanism With Sliding Panels
Authors: Yu Aaron , Xi Fengfeng (Jeff) , Moosavian Amin
Published: March 2017

Unlike a traditional yeaechanism, where typically only the pose of the moving platform is of significance, a shape-morphing mechanism requires additional provisions. Mainly, any covers or skin panels that enclose the mechanism have to conform to additional constraints to avoid interference and clashing of said covers and achieve certain shapes during morphing. This paper presents a new method for kinematic modeling and analysis of such six degree-of-freedom (DOF) shape-morphing mechanisms enclosed by a number of rigid sliding panels. This type of mechanism has applications in aircraft morphing, where the shape of the enclosing skin is of significant importance in the design. Based on traditional parallel robot kinematics, the proposed method is developed to model the motions of multisegmented telescopic rigid panels that are attached via additional links to the base and platform of a driving mechanism. When the robot actuators are locked, each panel will have 3DOFs. The DOFs are utilized to satisfy constraints among adjacent panels, such as maintaining parallelism and minimal gap. Through this modeling and analysis, nonlinear formulations are adopted to optimize orientations of adjacent sliding panels during motion over the workspace of the mechanism. This method will help design a set of permissible panels used to enclose the mechanism while remaining free of collision. A number of cases are simulated to show the effectiveness of the proposed method. The effect of increased mobility is analyzed and validated as a potential solution to reduce panel collisions.
A Line Geometric Approach to Kinematic Acquisition of Geometric Constraints of Planar Motion
Authors: Wu Jun , Li Xiangyun , Ge Q. J. , Gao Feng , Liu Xueyin
Published: March 2017

This paper examines the problem of geometric constraints acquisition of planar motion through a line-geometric approach. In previous work, we have investigated the problem of identifying point-geometric constraints associated with a motion task which is given in a parametric or discrete form. In this paper, we seek to extend the point-centric approach to the line-centric approach. The extracted geometric constraints can be used directly for determining the type and dimensions of a physical device such as mechanical linkage that generates this constrained motion task.
Two Types of Truth in the Physics Classroom
Authors: Keeports David
Published: March 2017

On the first day of class I ask my students, “What makes a true statement true?” Then I tell them that they might be surprised to learn that there are only two types of true statements in physics, and I encourage them to try to discover the two categories.
Arduino-Based Data Acquisition into Excel, LabVIEW, and MATLAB
Authors: Nichols Daniel
Published: March 2017

Data acquisition equipment for physics can be quite expensive. As an alternative, data can be acquired using a low-cost Arduino microcontroller. The Arduino has been used in physics labs where the data are acquired using the Arduino software. The Arduino software, however, does not contain a suite of tools for data fitting and analysis. The data are typically gathered first and then imported manually into an analysis program. There is a way, however, that allows data gathered by the Arduino to be imported in real time into a data analysis package. Illustrated in this article are add-ins for Excel, MATLAB, and LabVIEW that import data directly from the Arduino and allow for real-time plotting and analysis.
Can Newton’s Third Law Be “Derived” from the Second?
Authors: Gangopadhyaya Asim , Harrington James
Published: March 2017

Newton’s laws have engendered much discussion over several centuries. Today, the internet is awash with a plethora of information on this topic. We find many references to Newton’s laws, often discussions of various types of misunderstandings and ways to explain them. Here we present an intriguing example that shows an assumption hidden in Newton’s third law that is often overlooked. As is well known, the first law defines an inertial frame of reference and the second law determines the acceleration of a particle in such a frame due to an external force. The third law describes forces exerted on each other in a two-particle system, and allows us to extend the second law to a system of particles. Students are often taught that the three laws are independent. Here we present an example that challenges this assumption. At first glance, it seems to show that, at least for a special case, the third law follows from the second law. However, a careful examination of the assumptions demonstrates that is not quite the case. Ultimately, the example does illustrate the significance of the concept of mass in linking Newton’s dynamical principles.
The Four-Ball Gyro and Motorcycle Countersteering
Authors: Galli J. Ronald , Carroll Bradley W.
Published: March 2017

Most two-wheel motorcycle riders know that, at highway speeds, if you want to turn left you push on the left handlebar and pull on the right handlebar. This is called countersteering. Countersteering is counterintuitive since pushing left and pulling right when the front wheel is not spinning would turn the wheel to the right. All good motorcycle instructors teach countersteering but few understand the physics of why it works, even though there is considerable discussion about it among motorcycle riders. This paper gives a simplified explanation of gyroscopic precession and then applies this to the front wheel of a motorcycle using two steps: 1) explaining how the wheel’s lean is initiated, and 2) explaining how the lean will cause the wheel to turn. To assist with this discussion and to demonstrate the conclusions, a “wheel” was constructed using copper pipe, a bicycle wheel hub, and one pound of lead in each of four “balls” at the end of the spokes (see Fig. 1).
Studying the Solar System Can Be More Than Just “Stamp Collecting”
Authors: LoPresto Michael C.
Published: March 2017

While teaching his first-ever introductory college astronomy course, I heard a graduate student make the comment that compared to other areas of astronomy, studying the solar system is just “stamp collecting.” Coverage of the solar system in an introductory college astronomy course certainly could consist mostly of showing images and reporting facts, but by using observations that can be made from images and also data and other known facts about the objects, instruction on solar system topics can be more conceptual, involving just as much inquiry and discovery as any area of astronomy or physics.
Demystifying electric flux and Gauss’s law
Authors: McManus Jeff
Published: March 2017

Many physics students have experienced the difficulty of internalizing concepts in electrostatics. After studying concrete, measurable details in mechanics, they are challenged by abstract ideas such as electric fields, flux, Gauss’s law, and electric potential. There are a few well-known hands-on activities that help students get experience with these ideas. Perhaps the most popular are field-mapping activities in many forms ranging from metal electrodes in a shallow dish of water to metal pens and conductive paper. My experience of teaching with these activities in my AP Physics course left me disappointed and my students still mystified. Over the last several years, I have developed some hands-on activities that have helped my students better understand and apply these concepts. In this column, I will describe one such activity, a flux calculation that presents an opportunity to apply Gauss’s law.
Cycling Versus Uphill Walking: Impact on Locomotor Muscle Fatigue and Running Exercise
Authors: Pageaux Benjamin , Theurel Jean , Lepers Romuald
Published: March 2017

Purpose:To describe the effects of uphill walking versus cycling exercises on knee-extensor (KE) neuromuscular properties and subsequent running exercise.Methods:Nine athletes performed 4 different sessions (1 familiarization and 3 experimental sessions, visit 2–4). Visit 2 (cycling +10-km condition) consisted of the completion of 1-h cycling followed by a 10-km running time trial. Visit 3 consisted of the completion of 1-h uphill walking followed by a 10-km running exercise (RE). During the fourth visit, athletes only ran 10 km. Visits 3 and 4 were randomized. The uphill walking and cycling exercises were performed at the same intensity, and pacing of the RE was similar between conditions. Neuromuscular function of the KE was assessed before warm-up, after first exercise, and after RE. Heart rate and rating of perceived exertion (RPE) were recorded during all exercises.Results:RPE during RE was greater following the 1-h cycling and uphill walking exercises than during RE alone. KE force (−21%), twitch torque (−20%), doublet torque (−16%), and twitch rate of force development (−13%) significantly decreased following cycling exercise and not after uphill walking exercise. Postactivation potentiation was observed after uphill walking and RE. KE force-production capacity partially recovered after running in the cycling +10-km condition.Conclusion:Uphill walking and running induced postactivation potentiation, limiting the decrease in KE force postexercise. Despite different alterations in force-production capacity induced by cycling and uphill walking, both exercises increased perception of effort during the subsequent RE.
Staying Out of Range: Increasing Attacking Distance in Fencing
Authors: Turner Anthony N. , Marshall Geoff , Noto Angelo , Chavda Shyam , Atlay Nathan , Kirby David
Published: March 2017

To avoid being hit, fencers typically adopt an out-of-range position, which was hypothesized to be governed by body- and action-scaled affordances. This theory was measured in elite and national-level junior (under 20 y of age) fencers. Associations between “reachability” of lunging and step-lunging attacks were assessed against height, arm span, leg span, body mass, and lower-body power and then compared across level. Reachability was determined as the distance covered by fencers during these attacks and was reported as actual and estimated distances. Elite fencers are better at estimating their lunging and step-lunge distance compared to nationally ranked junior fencers (−0.9% vs 7.3% and 5.4% vs 10.9%, respectively). Surprisingly, elite fencers’ actual and estimated distances for these was less than the junior fencers’ (222.6 vs 251.5 cm and 299.3 vs 360.2 cm, respectively), and significantly so in the former. Finally, only arm span (r = .81) and leg span (r = .71) were significantly correlated to estimated lunging distance, and this was only in elite fencers. Findings suggest that better fencers can accurately predict their attack range and that reachability appears to be positively influenced by arm and leg span; these may feed in to talent identification. Given that distances were less in elite fencers, findings suggest that timing and distance estimation are key skills to master and that the mastery of these in offensive actions can mitigate, to a large extent, the physical benefits of an opponent’s greater height.
Associations of Physical Activity, Sedentary Time, and Screen Time With Cardiovascular Fitness in United States Adolescents: Results From the NHANES National Youth Fitness Survey
Authors: Porter Anna K. , Matthews Krystin J. , Salvo Deborah , Kohl Harold W.
Published: March 2017

Background:

Most US adolescents do not meet guidelines of at least 60 daily minutes of moderate- to vigorous-intensity physical activity. In addition, sedentary behaviors among this age group are of increasing concern. This study examined the association of movement behaviors with cardiovascular fitness among US adolescents.

Methods:

Data from the 2012 NHANES National Youth Fitness Survey were used to assess the association of movement behaviors (physical activity, sedentary time, screen time) with cardiovascular fitness among adolescent males and females. Multiple logistic regressions were used to test the independent and interactive effects of movement behaviors on cardiovascular fitness.

Results:

Among females, physical activity was directly associated with cardiovascular fitness; no significant association was observed between sedentary behaviors and CVF. Among males, sedentary time moderated the relationship between physical activity and cardiovascular fitness, such that a significant, direct association was only observed among those with high sedentary time (OR: 5.01; 95% CI: 1.60, 15.70).

Conclusions:

Results from this cross-sectional analysis suggest that among female US adolescents, physical activity, but not sedentary behavior, is associated with cardiovascular fitness. Among males, the interaction between physical activity and sedentary time seems to be important for cardiovascular fitness. Longitudinal studies are warranted to confirm these findings.
Psychosocial Predictors of Physical Activity Change Among College Students in an Obesity Prevention Trial
Authors: Arigo Danielle , Rohde Paul , Shaw Heather , Stice Eric
Published: March 2017

Background:

Moderate-to-vigorous physical activity (MVPA) is critical for maintaining a healthy weight, although little is known about psychological barriers to maintaining MVPA in at-risk groups. Identifying characteristics associated with poor MVPA maintenance in obesity prevention programs could improve participant outcomes.

Methods:

Toward this end, we examined predictors of MVPA in an obesity prevention trial for college students at risk for weight gain (n = 333; 72% female, mean BMI = 23.4 kg/m2). Participants engaged in 1 of 3 weight control interventions and in 4 assessments over 12-month follow-up (ie, measured height/weight, self-reports of psychosocial characteristics, 4 days of accelerometer wear).

Results:

Multilevel modeling analyses showed that across conditions, participants decreased total MVPA minutes per week over 12 months (B = –5.48, P < .01). Baseline self-report scores for both impulsiveness and cognitive dissonance regarding engaging in unhealthy behaviors negatively predicted MVPA over time. Participants higher (vs. lower) in baseline impulsiveness (B = –6.89, P = .03) and dissonance (B = –4.10, P = .04) began the study with more MVPA minutes, but showed sharper declines over time.

Conclusions:

Targeted MVPA-focused intervention for students who show elevated impulsiveness and cognitive dissonance may improve both MVPA and weight control outcomes for these individuals.
Acute Effects of Walking Exercise on Stair Negotiation in Sedentary and Physically Active Older Adults
Authors: Kunzler Marcos R. , da Rocha Emmanuel S. , Bobbert Maarten F. , Duysens Jacques , Carpes Felipe P.
Published: March 2017

Background:

In negotiating stairs, low foot clearance increases the risk of tripping and a fall. Foot clearance may be related to physical fitness, which differs between active and sedentary participants, and be acutely affected by exercise. Impaired stair negotiation could be an acute response to exercise. Here we determined acute changes in foot clearances during stair walking in sedentary (n = 15) and physically active older adults (n = 15) after prolonged exercise.

Methods:

Kinematic data were acquired during negotiation with a 3-steps staircase while participants walked at preferred speed, before and after 30 min walking at preferred speed and using a treadmill. Foot clearances were compared before and after exercise and between the groups.

Results:

Sedentary older adults presented larger (0.5 cm for lead and 2 cm for trail leg) toe clearances in ascent, smaller (0.7 cm) heel clearance in the leading foot in descent, and larger (1 cm) heel clearance in the trailing foot in descent than physically active.

Conclusion:

Sedentary older adults negotiate stairs in a slightly different way than active older adults, and 30 min walking at preferred speed does not affect clearance in stair negotiation.
PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer
Authors: Caromile Leslie Ann , Dortche Kristina , Rahman M. Mamunur , Grant Christina L. , Stoddard Christopher , Ferrer Fernando A. , Shapiro Linda H.
Published: March 2017

Prostate-specific membrane antigen is both a diagnostic marker and an indicator for personalized therapeutic intervention for cancer patients.
Efficacy of the Investigational Antifungal VT-1161 in Treating Naturally Occurring Coccidioidomycosis in Dogs
Authors: Shubitz Lisa F. , Roy Michael E. , Trinh Hien T. , Hoekstra William J. , Schotzinger Robert J. , Garvey Edward P.
Published: March 2017

Coccidioidomycosis can be a chronic, systemic fungal infection requiring long-term to lifetime medication. Thus, there is a need for improved antifungal agents with greater efficacy and reduced toxicity. VT-1161 has a low affinity for mammalian cytochromes and potently inhibits fungal CYP51 with proven efficacy in murine models of central nervous system (CNS) and respiratory coccidioidomycosis. Dogs experience coccidioidomycosis similar to humans and are a useful preclinical model for naturally occurring disease. Twenty-four client-owned dogs diagnosed with respiratory coccidioidomycosis based on radiography, serology, clinical signs, and clinicopathologic abnormalities were treated with a loading dose of VT-1161 for 14 days, followed by 46 days of a lower maintenance dose. Twelve dogs received a high dose (29 mg/kg loading, 6 mg/kg maintenance) and 12 received a low dose (10 mg/kg loading, 1.6 mg/kg maintenance). Response to treatment was assessed by calculating the reduction in disease scores at exit compared to disease scores at enrollment. Overall, 20 of 24 (83%) dogs had ≥50% reduction in enrollment disease scores at exit (
P
< 0.001), with no difference between the high- and low-dose groups (
P
= 0.66). Time-weighted average plasma concentrations for the high- and low-dose groups were 39 ± 5 μg/ml and 19 ± 2 μg/ml, respectively. In this open-label study, VT-1161 was efficacious for the treatment of respiratory coccidioidomycosis in naturally infected dogs. Combined with previously reported murine data, this finding supports the further development of VT-1161 for the treatment of coccidioidomycosis in humans.
Antibiotic Prophylaxis Is Associated with Subsequent Resistant Infections in Children with an Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection
Authors: Das Sibani , Adler Amanda L. , Miles-Jay Arianna , Kronman Matthew P. , Qin Xuan , Weissman Scott J. , Burnham Carey-Ann D. , Elward Alexis , Newland Jason G. , Selvarangan Rangaraj , Sullivan Kaede V. , Zaoutis Theoklis , Zerr Danielle M.
Published: March 2017

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant
Enterobacteriaceae
. We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant
Escherichia coli
and
Klebsiella
spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and
fumC-fimH
(
E. coli
) or
tonB
(
Klebsiella pneumoniae
) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with
E. coli
sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.
The Pseudomonas aeruginosa PrrF Small RNAs Regulate Iron Homeostasis during Acute Murine Lung Infection
Authors: Reinhart Alexandria A. , Nguyen Angela T. , Brewer Luke K. , Bevere Justin , Jones Jace W. , Kane Maureen A. , Damron F. Heath , Barbier Mariette , Oglesby-Sherrouse Amanda G.
Published: March 2017

Pseudomonas aeruginosa
is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs (sRNAs), which block the expression of iron-containing proteins under iron-depleted conditions. The PrrF sRNAs also promote the production of the
Pseudomonas
quinolone signal (PQS), a quorum sensing molecule that activates the expression of several virulence genes. The tandem arrangement of the
prrF
genes allows for expression of a third sRNA, PrrH, which is predicted to regulate gene expression through its unique sequence derived from the
prrF1-prrF2
intergenic (IG) sequence (the PrrH
IG
sequence). Previous studies showed that the
prrF
locus is required for acute lung infection. However, the individual functions of the PrrF and PrrH sRNAs were not determined. Here, we describe a system for differentiating PrrF and PrrH functions by deleting the PrrH
IG
sequence [
prrF
(ΔH
IG
)]. Our analyses of this construct indicate that the PrrF sRNAs, but not PrrH, are required for acute lung infection by
P. aeruginosa
. Moreover, we show that the virulence defect of the Δ
prrF1-prrF2
mutant is due to decreased bacterial burden during acute lung infection.
In vivo
analysis of gene expression in lung homogenates shows that PrrF-mediated regulation of genes for iron-containing proteins is disrupted in the Δ
prrF1-prrF2
mutant during infection, while the expression of genes that mediate PrrF-regulated PQS production are not affected by
prrF
deletion
in vivo
. Combined, these studies demonstrate that regulation of iron utilization plays a critical role in
P. aeruginosa
's ability to survive during infection.
Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii
Authors: Müller Gabriela L. , Tuttobene Marisel , Altilio Matías , Martínez Amezaga Maitena , Nguyen Meaghan , Cribb Pamela , Cybulski Larisa E. , Ramírez María Soledad , Altabe Silvia , Mussi María Alejandra
Published: March 2017

Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogenAcinetobacter baumannii, light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of theA. baumanniilifestyle.

IMPORTANCEThe discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogenAcinetobacter baumannii. In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In addition, tolerance to antibiotics and catalase levels are also influenced by light, likely contributing to bacterial persistence in adverse environments, as is the expression of the type VI secretion system and efflux pumps. Overall, a profound influence of light on the lifestyle ofA. baumanniiis suggested to occur.
Control of Recombination Directionality by the Listeria Phage A118 Protein Gp44 and the Coiled-Coil Motif of Its Serine Integrase
Authors: Mandali Sridhar , Gupta Kushol , Dawson Anthony R. , Van Duyne Gregory D. , Johnson Reid C.
Published: March 2017

The serine integrase of phage A118 catalyzes integrative recombination between
attP
on the phage and a specific
attB
locus on the chromosome of
Listeria monocytogenes
, but it is unable to promote excisive recombination between the hybrid
attL
and
attR
sites found on the integrated prophage without assistance by a recombination directionality factor (RDF). We have identified and characterized the phage-encoded RDF Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination. This interaction is sufficient to inhibit integration, but a second interaction involving the N-terminal end of Gp44 is also required to activate excision. We provide evidence that these two contacts modulate the trajectory of the CC motifs as they extend out from the integrase core in a manner dependent upon the identities of the four
att
sites. Our results support a model whereby Gp44 shapes the Int-bound complexes to control which
att
sites can synapse and recombine.

IMPORTANCE
Serine integrases mediate directional recombination between bacteriophage and bacterial chromosomes. These highly regulated site-specific recombination reactions are integral to the life cycle of temperate phage and, in the case of
Listeria monocytogenes
lysogenized by A118 family phage, are an essential virulence determinant. Serine integrases are also utilized as tools for genetic engineering and synthetic biology because of their exquisite unidirectional control of the DNA exchange reaction. Here, we identify and characterize the recombination directionality factor (RDF) that activates excision and inhibits integration reactions by the phage A118 integrase. We provide evidence that the A118 RDF binds to and modulates the trajectory of the long coiled-coil motif that extends from the large carboxyl-terminal DNA binding domain and is postulated to control the early steps of recombination site synapsis.
Use of a Phosphorylation Site Mutant To Identify Distinct Modes of Gene Repression by the Control of Virulence Regulator (CovR) in Streptococcus pyogenes
Authors: Horstmann Nicola , Sahasrabhojane Pranoti , Yao Hui , Su Xiaoping , Shelburne Samuel A.
Published: March 2017

Control of the virulence regulator/sensor kinase (CovRS) two-component system (TCS) serves as a model for investigating the impact of signaling pathways on the pathogenesis of Gram-positive bacteria. However, the molecular mechanisms by which CovR, an OmpR/PhoB family response regulator, controls virulence gene expression are poorly defined, partly due to the labile nature of its aspartate phosphorylation site. To better understand the regulatory effect of phosphorylated CovR, we generated the phosphorylation site mutant strain 10870-CovR-D53E, which we predicted to have a constitutive CovR phosphorylation phenotype. Interestingly, this strain showed CovR activity only for a subset of the CovR regulon, which allowed for classification of CovR-influenced genes into D53E-regulated and D53E-nonregulated groups. Inspection of the promoter sequences of genes belonging to each group revealed distinct promoter architectures with respect to the location and number of putative CovR-binding sites. Electrophoretic mobility shift analysis demonstrated that recombinant CovR-D53E protein retains its ability to bind promoter DNA from both CovR-D53E-regulated and -nonregulated groups, implying that factors other than mere DNA binding are crucial for gene regulation. In fact, we found that CovR-D53E is incapable of dimerization, a process thought to be critical to OmpR/PhoB family regulator function. Thus, our global analysis of CovR-D53E indicates dimerization-dependent and dimerization-independent modes of CovR-mediated repression, thereby establishing distinct mechanisms by which this critical regulator coordinates virulence gene expression.

IMPORTANCE
Streptococcus pyogenes
causes a wide variety of diseases, ranging from superficial skin and throat infections to life-threatening invasive infections. To establish these various disease manifestations,
Streptococcus pyogenes
requires tightly coordinated production of its virulence factor repertoire. Here, the response regulator CovR plays a crucial role. As an OmpR/PhoB family member, CovR is activated by phosphorylation on a conserved aspartate residue, leading to protein dimerization and subsequent binding to operator sites. Our transcriptome analysis using the monomeric phosphorylation mimic mutant CovR-D53E broadens this general notion by revealing dimerization-independent repression of a subset of CovR-regulated genes. Combined with promoter analyses, these data suggest distinct mechanisms of CovR transcriptional control, which allow for differential expression of virulence genes in response to environmental cues.
Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus
Authors: Yeow Toh Peng , Pacini Giovanni , Tura Andrea , Hor Chee Peng , Lim Shueh Lin , Tan Florence Hui Sieng , Tong Chin Voon , Hong Janet Yeow Hua , Md Zain Fuziah , Holst Jens Juul , Wan Mohamud Wan Nazaimoon
Published: March 2017

Objective

Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM.

Research design and methods

This case–control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG−BCIV)/BCOG).

Results

The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001).

Conclusions

Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM.

Trial registration number

NMRR-12-1042-13254.
Kids in Communities Study (KiCS) study protocol: a cross-sectional mixed-methods approach to measuring community-level factors influencing early child development in Australia
Authors: Goldfeld Sharon , Villanueva Karen , Tanton Robert , Katz Ilan , Brinkman Sally , Woolcock Geoffrey , Giles-Corti Billie
Published: March 2017

Introduction

Healthy childhood development in the early years is critical for later adult health and well-being. Early childhood development (ECD) research has focused primarily on individual, family and school factors, but largely ignored community factors. The Kids in Communities Study (KiCS) will test and investigate community-level influences on child development across Australia.

Methods and analysis

Cross-sectional mixed-methods study exploring community-level effects in 25 Australian local communities; selection based on community socioeconomic status (SES) and ECD using the Australian Early Development Census (AEDC), a population measure of child development, to create a local community ‘diagonality type’, that is, those performing better or worse (off-diagonal), or as expected (on-diagonal) on the AEDC relative to their SES. Data collection includes stakeholder interviews, parent and service provider focus groups, and surveys with general community residents and service providers, mapping of neighbourhood design and local amenities and services, analysis of policy documents, and the use of existing sociodemographic and early childhood education and care data. Quantitative data will be used to test associations between local community diagonality type, and ECD based on AEDC scores. Qualitative data will provide complementary and deeper exploration of these same associations.

Ethics and dissemination

The Royal Children's Hospital Human Research Ethics Committee approved the study protocol (#30016). Further ethics approvals were obtained from State Education and Health departments and Catholic archdioceses where required. ECD community-level indicators will eventually be derived and made publically available. Findings will be published in peer-reviewed journals, community reports, websites and policy briefs to disseminate results to researchers, and key stakeholders including policymakers, practitioners and (most importantly) the communities involved.
Use of standard risk screening and assessment forms to prevent harm to older people in Australian hospitals: a mixed methods study
Authors: Redley Bernice , Raggatt Michelle
Published: March 2017

Background

Standard risk screening and assessment forms are frequently used in strategies to prevent harm to older people in hospitals. Little is known about good practices for their use.

Objective

Scope the preventable harms addressed by standard forms used to screen and assess older people and how standard forms are operationalised in hospitals across Victoria, Australia.

Methods

Mixed methods study: (1) cross-sectional audit of the standard risk screening and assessment forms used to assess older people at 11 health services in 2015; (2) nine focus groups with a purposive sample of 69 participants at 9 health services. Descriptive analysis examined the number of items on forms, preventable harms assessed and sources of duplication. Qualitative thematic analysis of focus group data identified themes explaining issues commonly affecting how health services used the forms.

Results

152 standard assessment forms from 11 Victorian health services included over 3700 items with 17% duplicated across multiple forms. Assessments of skin integrity and mobility loss (including falls) were consistently included in forms; however, nutrition, cognitive state, pain and medication risks were inconsistent; and continence, venous thromboembolism risk and hospital acquired infection from invasive devices were infrequent. Qualitative analyses revealed five themes explaining issues associated with current use of assessment forms: (1) comprehensive assessment of preventable harms; (2) burden on staff and the older person, (3) interprofessional collaboration, (4) flexibility to individualise care and (5) information management. Examples of good practice were identified.

Conclusions

Current use of standard risk screening and assessment forms is associated with a high burden and gaps in assessment of several common preventable harms that can increase risk to older people in hospital. Improvement should focus on streamlining forms, increased guidance on interventions to prevent harm and facilitating front-line staff to manage complex decisions.
The barriers associated with emergency medical service use for acute coronary syndrome: the awareness and influence of an Australian public mass media campaign
Authors: Cartledge Susie , Finn Judith , Straney Lahn , Ngu Phillip , Stub Dion , Patsamanis Harry , Shaw James , Bray Janet
Published: March 2017

Background

Emergency medical services (EMS) transport to hospital is recommended in acute coronary syndrome (ACS) guidelines, but only half of patients with ACS currently use EMS. The recent Australian Warning Signs campaign conducted by the Heart Foundation addressed some of the known barriers against using EMS. Our aim was to examine the influence of awareness of the campaign on these barriers in patients with ACS.

Methods

Interviews were conducted with patients admitted to an Australian tertiary hospital between July 2013 and April 2014 with a diagnosis of ACS. Patient selection criteria included: aged 35–75 years, competent to provide consent, English speaking, not in residential care and medically stable. Multivariable logistic regression was used to examine factors associated with EMS use.

Results

Only 54% of the 199 patients with ACS interviewed used EMS for transport to hospital. Overall 64% of patients recalled seeing the campaign advertising, but this was not associated with increased EMS use (52.0%vs56.9%, p=0.49) or in the barriers against using EMS. A large proportion of patients (43%) using other transport thought it would be faster. Factors associated with EMS use for ACS were: age >65 years, ST-elevation myocardial infarction, a sudden onset of pain and experiencing vomiting.

Conclusion

In medically stable patients with ACS, awareness of the Australian Warning Signs campaign was not associated with increased use of EMS or a change in the barriers for EMS use. Future education strategies could emphasise the clinical role that EMS provide in ACS.
Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes
Authors: Bruel Ange-Line , Franco Brunella , Duffourd Yannis , Thevenon Julien , Jego Laurence , Lopez Estelle , Deleuze Jean-François , Doummar Diane , Giles Rachel H , Johnson Colin A , Huynen Martijn A , Chevrier Véronique , Burglen Lydie , Morleo Manuela , Desguerres Isabelle , Pierquin Geneviève , Doray Bérénice , Gilbert-Dussardier Brigitte , Reversade Bruno , Steichen-Gersdorf Elisabeth , Baumann Clarisse , Panigrahi Inusha , Fargeot-Espaliat Anne , Dieux Anne , David Albert , Goldenberg Alice , Bongers Ernie , Gaillard Dominique , Argente Jesús , Aral Bernard , Gigot Nadège , St-Onge Judith , Birnbaum Daniel , Phadke Shubha R , Cormier-Daire Valérie , Eguether Thibaut , Pazour Gregory J , Herranz-Pérez Vicente , Goldstein Jaclyn S , Pasquier Laurent , Loget Philippe , Saunier Sophie , Mégarbané André , Rosnet Olivier , Leroux Michel R , Wallingford John B , Blacque Oliver E , Nachury Maxence V , Attie-Bitach Tania , Rivière Jean-Baptiste , Faivre Laurence , Thauvin-Robinet Christel
Published: March 2017

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in theOFD1gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3,TMEM107,INTU,KIAA0753andIFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42,TMEM138,TMEM231andWDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype.
Lifestyle medicine course for family medicine residents: preliminary assessment of the impact on knowledge, attitudes, self-efficacy and personal health
Authors: Malatskey Lilach , Bar Zeev Yael , Tzuk-Onn Adva , Polak Rani
Published: March 2017

Purpose

The WHO estimates that by 2020 two-thirds of the diseases worldwide will be the result of unhealthy lifestyle habits. Less than half of primary care physician graduates feel prepared to give lifestyle behaviour counselling. Our objective was to evaluate the impact of lifestyle medicine (LM) course on self-reported knowledge, attitudes, self-efficacy and health behaviour of family medicine residents.

Methods

Based on the Israeli syllabus for the study of LM, we delivered five face to face 20 H courses. Pre/post data were collected by knowledge, attitudes, self-efficacy and personal health survey:

Results

A total of 112 family medicine residents participated in one of the five courses, of which 91 (81.3%) filled both pre and post surveys. Participates showed an improvement in self-reported knowledge and capacity to manage patients in regard to smoking, weight management and physical activity. An improvement was noted in personal health behaviour of overweight participant’s in regard to self-reported physical activity.

Conclusions

A comprehensive LM syllabus based course has a positive impact on family medicine residents LM counselling abilities. We suggest that LM course should be considered as a potential permanent addition to the family medicine residency programme.
Membrane filter properties and application of the filter to undrained cyclic triaxial test of unsaturated materials
Authors: Wang Hailong , Koseki Junichi , Nishimura Tomoyoshi , Miyashita Yukika
Published: March 2017

Properties of the membrane filter recently introduced as an alternative to the ceramic disk are revealed through diffusion and hydraulic conductivity tests. It is shown that diffusion of air through the membrane filter is significantly affected by suction magnitude and that hydraulic conductivity of the membrane filter can easily be affected by the quality of water used in the test. The application of the membrane filter to the soil-water characteristic curve tests (SWCC tests) shows that similar SWCCs can be obtained by employing pressure plate apparatuses with either the ceramic disks or the membrane filter installed, and that repeatability of the SWCC by using the membrane filter pressure plate apparatus is reasonably good. The application of the membrane filter to the undrained cyclic loading test of unsaturated sandy materials shows that the response (the duration to measure the equilibrated pore-water pressure of unsaturated materials) of the membrane filter pedestal in a modified triaxial system may be as short as ∼2 s in certain test conditions, and fairly good pore-water pressure and air pressure measurements can be obtained during undrained cyclic loading with a loading frequency of 0.1 Hz.
Can THF hydrogen bond to glycine as strong as water?
Authors: Kaur Damanjit , Chopra Geetanjali , Kaur Rajinder
Published: March 2017

Hydrogen bond complexation between glycine and THF and between glycine and water involving four lowest-energy glycine conformers have been studied. The complexes have been investigated in the gas phase at the ab initio molecular orbital theory (MP2) with aug-cc-pVDZ basis set and density functional theory (B3LYP) with aug-cc-pVTZ basis set. Bader’s theory of atoms in molecules (AIM), natural bond orbital (NBO), and symmetry adapted perturbation theory (SAPT) analyses are employed to elucidate the interaction characteristics in the complexes. The premise that the hydrogen bond donor ability of the O–H group of the carboxyl group dominates the interaction between glycine and THF and between glycine and water is confirmed. It is found that in comparison with water, THF binds more strongly to glycine. The quantum studies indicate that contribution of N–H···O and C–H···O hydrogen bonds in the complexes, although lower in magnitude to O–H···O interactions, play an important role in the stability of complexes. The blue and red shifts in the stretching frequencies of the hydrogen bond donors X–H (X = O, C, N) have also been related to stabilization energies. Decomposition of the stabilization energy based on the SAPT method clearly indicates the dominant role of the electrostatic interactions in all the complexes under study; however, induction and dispersion interaction terms are relatively higher in glycine–THF complexes.
Molecular description of carbon graphite and crystal cubic carbon structures
Authors: Baig Abdul Qudair , Imran Muhammad , Khalid Waqas , Naeem Muhammad
Published: March 2017

Graph theory plays a vital role in modeling and designing any chemical structure or chemical network. Chemical graph theory helps in understanding the molecular structural properties of a molecular graph. The molecular graph consists of atoms called vertices and chemical bonds between atoms called edges. In this article, we study the chemical graphs of carbon graphite and crystal structure of cubic carbon. Moreover, we compute and give closed formulas of degree-based additive topological indices, mainly the first and second Zagreb indexes, general Randić index, atom bond connectivity index, geometric arithmetic index, fourth atom bond connectivity index, and fifth geometric arithmetic index of carbon graphite denoted by CG(m, n) for t levels, and crystal structure cubic carbon denoted for n levels.