Transverse instability in nonparaxial systems with four-wave mixing.

We present a two-dimensional coupled nonlinear Schrödinger-like system with spatial diffractions, degree of birefringence, and four-wave mixing. This system describes two physical contexts: optical pulse propagation beyond the paraxial approximation in a weakly birefringence waveguide and light propagation near exciton-polariton resonance in semiconductor superlattice materials. We find that such systems naturally support different types of diffraction profiles, including spherical, ellipsoidal, and hyperbolic structures. We then study the transverse instability of the two-dimensional system caused by an infinitesimal perturbation-induced continuous-wave solution. Also, we find out how various physical parameters, such as nonparaxiality, degree of birefringence, power, and four-wave mixing, affect the modulational instability (MI) process, in particular. We explore the existence of bright solitary wave solutions for the proposed system as the influence of MI is closely related to the latter in a nutshell.

Tunable nonlinear spectra of anti-directional couplers.

We produce transmission and reflection spectra of the anti-directional coupler (ADC) composed of linearly coupled positive- and negative-refractive-index arms, with intrinsic Kerr nonlinearity. Both reflection and transmission feature two highly amplified peaks at two distinct wavelengths in a certain range of values of the gain, making it possible to design a wavelength-selective mode-amplification system. We also predict that a blend of gain and loss in suitable proportions can robustly enhance reflection spectra that are detrimentally affected by the attenuation, in addition to causing red and blue shifts owing to the Kerr effect. In particular, ADC with equal gain and loss coefficients is considered in necessary detail.

Nonlinear anti-directional couplers with gain and loss.

Following the concept of PT-symmetric couplers, we propose a linearly coupled system of nonlinear waveguides, made of positive- and negative-index materials, which carry, respectively, gain and loss. We report novel bi- and multistability states pertaining to transmitted and reflective intensities, which are controlled by the ratio of the gain and loss coefficients, and phase mismatch between the waveguides. These states offer transmission regimes with extremely low threshold intensities for transitions between coexisting states, and very large amplification ratios between the input and output intensities leading to an efficient way of controlling light with light.

Tailoring PT-symmetric soliton switch.

We theoretically demonstrate soliton steering in parity-time (PT)-symmetric coupled nonlinear dimers. We show that if the length of the PT-symmetric system is set to 2π, contrary to the conventional one that operates satisfactorily well only at the half-beat coupling length, the PT dimer remarkably yields an ideal soliton switch exhibiting almost 99.99% energy efficiency with an ultralow critical power.

Cubic-quintic nonlinear Helmholtz equation: Modulational instability, chirped elliptic and solitary waves.

We study the formation and propagation of chirped elliptic and solitary waves in the cubic-quintic nonlinear Helmholtz equation. This system describes nonparaxial pulse propagation in a planar waveguide with Kerr-like and quintic nonlinearities along with spatial dispersion originating from the nonparaxial effect that becomes dominant when the conventional slowly varying envelope approximation fails. We first carry out the modulational instability (MI) analysis of a plane wave in this system by employing the linear stability analysis and investigate the influence of different physical parameters on the MI gain spectra. In particular, we show that the nonparaxial parameter suppresses the conventional MI gain spectrum and also leads to a nontrivial monotonic increase in the gain spectrum near the tails of the conventional MI band, a qualitatively distinct behavior from the standard nonlinear Schrödinger system. We then study the MI dynamics by direct numerical simulations, which demonstrate the production of ultrashort nonparaxial pulse trains with internal oscillations and slight distortions at the wings. Following the MI dynamics, we obtain exact elliptic and solitary wave solutions using the integration method by considering physically interesting chirped traveling wave ansatz. In particular, we show that the system features intriguing chirped antidark, bright, gray, and dark solitary waves depending upon the nature of nonlinearities. We also show that the chirping is inversely proportional to the intensity of the optical wave. In particular, the bright and dark solitary waves exhibit unusual chirping behavior, which will have applications in the nonlinear pulse compression process.

Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms.

To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm.

Review of Radiofrequency Ablation in Tonsillectomy.

The most common disease involving the tonsils among children and adults is chronic tonsillitis. There are different surgical techniques described in literature for the treatment of diseases involving the tonsils. Of these, the most routinely performed and the traditional method is conventional dissection tonsillectomy. The main disadvantage of this method is bleeding and postoperative pain. Radiofrequency ablation is found to overcome this limitation due to its mechanism of action. Both monopolar and bipolar radiofrequency ablation can be used in the surgical management. The effectiveness of monopolar radiofrequency has been proved in different fields of medicine. Hence new studies can be directed in comparing monopolar radiofrequency ablation with other techniques of tonsillectomy.

Germline variants and phenotypic spectrum in a Canadian cohort of individuals with diffuse gastric cancer.

Background: CDH1 pathogenic variants (pvs) cause most cases of inherited diffuse gastric cancer (dgc), but have low detection rates and vary geographically. In the present study, we examined hereditary causes of dgc in patients in Ontario. Methods: CDH1 testing through single-site or multi-gene panels was conducted for patients with dgc meeting the 2015 International Gastric Cancer Linkage Consortium (igclc) criteria, or with isolated dgc at less than 50 years of age, or with a strong family history of cancer identified at the Zane Cohen Centre (zcc). All CDH1-positive patients at zcc, regardless of cancer history, were summarized. Results: In 15 of 85 patients with dgc (17.6%), a pv or likely pv was identified through CDH1 single-site (n = 43) or multi-gene panel (n = 42) testing. The detection rate was 9.4% overall (8 of 85) and 11% using igclc criteria (7 of 65). No CDH1 pvs were identified in patients with isolated dgc at less than 40 years of age, but 1 pv was identified in a patient with isolated dgc at less than 50 years of age. Multi-gene panels identified 9 pvs (21.4%), including CDH1, STK11, ATM, BRCA2, MLH1, and MSH2. Review of 81 CDH1 carriers identified 10% with dgc (median age: 48 years; range: 38-59 years); 41% were unaffected (median age: 53 years; range: 26-89 years). Observed malignancies other than dgc or lobular breast cancer (lbc) included colorectal, gynecologic, kidney or bladder, prostate, testicular, and ductal breast cancers. Lobular-breast cancer was seen only in 3 families. Conclusions: In Ontario, the detection rate of CDH1 pvs in patients with dgc was low: no pvs were identified in patients with isolated dgc at less than 40 years of age, and 1 was identified in a patient with isolated dgc at less than 50 years of age. Isolated lbc with no dgc was observed in CDH1-positive families, as were pathology-confirmed nondgc or non-lbc malignancies, which had not previously been reported. Given a phenotype that overlaps with other hereditary conditions, multi-gene panels are recommended for all patients with dgc at less than 50 years of age and for those meeting igclc criteria.

Canadian guidelines on the management of colorectal peritoneal metastases.

Modern management of colorectal cancer (crc) with peritoneal metastasis (pm) is based on a combination of cytoreductive surgery (crs), systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy (hipec). Although the role of hipec has recently been questioned with respect to results from the prodige 7 trial, the role and benefit of a complete crs were confirmed, as observed with a 41-month gain in median survival in that study, and 15% of patients remaining disease-free at 5 years. Still, crc with pm is associated with a poor prognosis, and good patient selection is essential. Many questions about the optimal management approach for such patients remain, but all patients with pm from crc should be referred to, or discussed with, a pm surgical oncologist, because cure is possible. The objective of the present guideline is to offer a practical approach to the management of pm from crc and to reflect on the new practice standards set by recent publications on the topic.

Glove and instrument changing to prevent tumour seeding in cancer surgery: a survey of surgeons' beliefs and practices.

Background: Some surgeons change gloves and instruments after the extirpative phase of cancer surgery with the intent of reducing the risk of local and wound recurrence. Although this practice is conceptually appealing, the evidence that gloves or instruments act as vectors of cancer-cell seeding in the clinical setting is weak. To determine the potential effect of further investigation of this question, we surveyed the practices and beliefs of a broad spectrum of surgeons who operate on cancer patients. Methods: Using a modified Dillman approach, a survey was mailed to all 945 general surgeons listed in the College of Physicians and Surgeons of Ontario public registry. The survey consisted of multiple-choice and free-text response questions. Responses were tabulated and grouped into themes, including specific intraoperative events and surgeon training. Predictive variables were analyzed by chi-square test. Results: Of 459 surveys returned (adjusted response rate: 46%), 351 met the inclusion criteria for retention. Of those respondents, 52% reported that they change gloves during cancer resections with the intent of decreasing the risk of tumour seeding, and 40%, that they change instruments for that purpose. The proportion of respondents indicating that they take measures to protect the wound was 73% for laparoscopic cancer resections and 31% for open resections. Training and years in practice predicted some of the foregoing behaviours. The most commonly cited basis for adopting specific strategies to prevent tumour seeding was "gut feeling," followed by clinical training. Most respondents believe that it is possible or probable that surgical gloves or instruments harbour malignant cells, but that a cancer recurrence proceeding from that situation is unlikely. Conclusions: There is no consensus on how gloves and instruments should be handled in cancer operations. Further investigation is warranted.

Localization of ice nucleation activity and the iceC gene product in Pseudomonas syringae and Escherichia coli.

Ice nucleation activity and the iceC gene product were quantified in different subcellular fractions of the Pseudomonas syringae source strain and in Escherichia coli containing the cloned iceC gene to determine the activity of this protein in different subcellular locations. Ice nuclei were nearly completely retained during isolation of cell envelopes but exhibited a decrease in the temperature at which they were expressed. Ice nucleation activity was found in Triton X-100 insoluble membrane fragments as well as in slowly sedimenting and high-density membrane fragments. Nearly all ice nucleation activity was associated with the outer membrane because the partitioning of 3-ketodeoxyoctonate (a lipopolysaccharide component) and ice nuclei in cell fractions were similar to and opposite that of NADH oxidase (a cytoplasmic membrane component). The iceC gene product had an apparent mass of 150,000 Da based on migration in SDS-polyacrylamide gels. This protein was not found in soluble cell components. Nearly all of the iceC gene product, which occurred in low abundance, was associated with the outer membrane of both P. syringae and E. coli. Therefore, the iceC gene product is located at and is maximally active in or on the outer membrane of cells of the source strain and heterologous strains.

A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami.

The lab-on-a-chip concept has led to several point-of-care (POC) diagnostic microfluidic platforms. However, few of these can process raw samples for molecular diagnosis and fewer yet are suited for use in a resource-limited setting without permanent electrical infrastructure. We present here a very low cost paper microfluidic device for POC extraction of bacterial DNA from raw viscous samples--a challenge for conventional microfluidic platforms. This is an example of "microfluidic origami" in that the system is activated by folding; demonstrated here is room temperature cell lysis and DNA extraction from pig mucin (simulating sputum) spiked with E. coli without the use of external power. The microfluidic origami device features dry reagent storage and rehydration of the lysis buffer. We demonstrate DNA extraction from samples with a bacterial load as low as 33 CFU ml(-1). Extraction times, starting from the raw sample, have been optimized to about 1.5 h without the use of external power, or to within 1 h using an oven or a heater block. The fabrication of this paper microfluidic device can be translated into high volume production in the developing world without the need for a semiconductor clean room or a microfabrication facility. The sample preparation can be performed with the addition of just the sample, water, ethanol and elute buffer to the device, thus reducing chemical hazards during transport and handling.

Phospholipid requirement for expression of ice nuclei in Pseudomonas syringae and in vitro.

Delipidation of partially purified outer membranes of Pseudomonas syringae by various delipidating agents resulted in a significant loss of ice nucleation activity associated with the cell envelopes of this and other ice nucleation active bacteria. Lipopolysaccharide depletion of such membranes caused no reduction in ice nucleation activity. Both phospholipid content and ice nucleation activity of membranes were decreased by a similar fractional amount with time after treatment with phospholipase A2. A proportional quantitative relationship between loss of ice nucleation activity and lipid removal with increasing concentrations of sodium cholate and sodium dodecyl sulfate (SDS) was also observed. Significant linear relationships between the amount of lipid removed by phospholipase A2, sodium cholate, and SDS and the loss of ice nucleation activity in P. syringae outer membranes were observed. However, the slopes of these linear relationships for membranes treated with phospholipase A2 (m = 0.80), SDS (m = 0.94), and sodium cholate (m = 0.53) differed. The lower slope value for cholate-treated membranes indicated a partial substitution of sodium cholate for the phospholipids removed. The ice nucleation activity of delipidated outer membranes was restored by reconstitution with various phospholipids in a cholate dialysis procedure. Lipid classes differed in their ability to restore ice nucleation activity to sodium cholate-treated outer membranes. These results suggest that a hydrophobic environment provided either by lipids or certain detergent micelles is required for proper assembly and structural organization of an oligomeric ice protein complex enabling its expression as an ice nucleus.

Size of bacterial ice-nucleation sites measured in situ by radiation inactivation analysis.

Four bacterial species are known to catalyze ice formation at temperatures just below 0 degrees C. To better understand the relationship between the molecular structure of bacterial ice-nucleation site(s) and the quantitative and qualitative features of the ice-nucleation-active phenotype, we determined by gamma-radiation analysis the in situ size of ice-nucleation sites in strains of Pseudomonas syringae and Erwinia herbicola and in Escherichia coli HB101 carrying the plasmid pICE1.1 (containing a 4-kilobase DNA insert from P. syringae that confers ice-nucleation activity). Lyophilized cells of each bacterial strain were irradiated with a flux of gamma radiation from 0 to 10.2 Mrad (1 Mrad = 10(6) J/kg). Differential concentrations of active ice nuclei decreased as a first-order function of radiation dose in all strains as temperature was decreased from -2 degrees C to -14 degrees C in 1 degrees C intervals. Sizes of ice nuclei were calculated from the gamma-radiation flux at which 37% of initial ice nuclei active within each 1 degrees C temperature interval remained. The minimum mass of a functional ice nucleus, active only between -12 degrees C and -13 degrees C, was about 150 kDa for all strains. The size of ice nuclei increased logarithmically with increasing temperature from -12 degrees C to -2 degrees C, where the estimated nucleant mass was 19,000 kDa. The ice nucleant in these three bacterial species may represent an oligomeric structure, composed at least in part of an ice gene product that can self-associate to assume many possible sizes.

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung.

OBJECTIVE: To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. DESIGN: Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. SETTING: A research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats. INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME) or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS: Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. MAIN RESULTS: Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.

An ice nucleation reporter gene system: identification of inducible pathogenicity genes in Pseudomonas syringae pv. phaseolicola.

We have constructed derivatives of the transposon Tn3 that allow an ice nucleation gene (inaZ) to be used as 'reporter' of the transcriptional activity of genes into which it is inserted. In these derivatives (Tn3-Ice and Tn3-Spice), the lacZYA sequences of transposon Tn3-HoHo1 were replaced with inaZ lacking its native promoter. The ice nucleation activity of virB::inaZ fusions in the correct transcriptional orientation was inducible by acetosyringone, a plant metabolite which activates the vir operon of Agrobacterium tumefaciens Ti plasmids, while fusions in the opposite orientation were unresponsive to the inducer. Tn3-Spice was also used to investigate the expression of a cluster of genes (hrp) which control pathogenicity and hypersensitivity elicited by Pseudomonas syringae pv. phaseolicola. An inducible region was identified which is expressed at low levels in vitro but becomes activated when the bacteria come into contact with the susceptible host, bean. Activation of this region occurred within 2 h post-inoculation and was nearly complete by the time the bacteria began to multiply in the leaf tissue. The inaZ reporter appears to be at least 10(5)-fold more sensitive than lacZ in P.s.phaseolicola. Thus, the inaZ fusion system provides a sensitive, convenient and inexpensive tool for the study of bacterial gene expression, particularly during plant pathogenesis, and should be generally useful as a reporter gene system in Gram-negative bacteria.

Deficiency of Src homology 2-containing phosphatase 1 results in abnormalities in murine neutrophil function: studies in motheaten mice.

Neutrophils, an essential component of the innate immune system, are regulated in part by signaling pathways involving protein tyrosine phosphorylation. While protein tyrosine kinase functions in regulating neutrophil behavior have been extensively investigated, little is known about the role for specific protein tyrosine phosphatases (PTP) in modulating neutrophil signaling cascades. A key role for Src homology 2 domain-containing phosphatase 1 (SHP-1), a PTP, in neutrophil physiology is, however, implied by the overexpansion and inappropriate activation of granulocyte populations in SHP-1-deficient motheaten (me/me) and motheaten viable (me(v)/me(v)) mice. To directly investigate the importance of SHP-1 to phagocytic cell function, bone marrow neutrophils were isolated from both me/me and me(v)/me(v) mice and examined with respect to their responses to various stimuli. The results of these studies revealed that both quiescent and activated neutrophils from motheaten mice manifested enhanced tyrosine phosphorylation of cellular proteins in the 60- to 80-kDa range relative to that detected in wild-type congenic control neutrophils. MOTHEATEN: neutrophils also demonstrated increased oxidant production, surface expression of CD18, and adhesion to protein-coated plastic. Chemotaxis, however, was severely diminished in the SHP-deficient neutrophils relative to control neutrophils, which was possibly attributable to a combination of defective deadhesion and altered actin assembly. Taken together, these results indicate a significant role for SHP-1 in modulating the tyrosine phosphorylation-dependent signaling pathways that regulate neutrophil microbicidal functions.

Conformational difference between PDE4 apoenzyme and holoenzyme.

The type 4 cAMP-specific phosphodiesterases (PDE4s) are Mg(2+)-dependent hydrolases that catalyze the hydrolysis of 3', 5'-cAMP to AMP. Previous studies indicate that PDE4 exists in two conformations that bind the inhibitor rolipram with affinities differing by more than 100-fold. Here we report that these two conformations are the consequence of PDE4 binding to its metal cofactor such as Mg(2+). Using a fluorescence resonance energy transfer (FRET)-based equilibrium binding assay, we identified that L-791,760, a fluorescent inhibitor, binds to the apoenzyme (free enzyme) and the holoenzyme (enzyme bound to Mg(2+)) with comparable affinities (K(d) approximately 30 nM). By measuring the displacement of the bound L-791,760, we have also identified that other inhibitors bind differentially with the apoenzyme and the holoenzyme depending upon their structure. CDP-840, SB-207499, and RP-73401 bind preferentially to the holoenzyme. The conformational-sensitive inhibitor (R)-rolipram binds to the holoenzyme and apoenzyme with affinities (K(d)) of 5 and 300 nM, respectively. In contrast to its high affinity (K(d) approximately 2 microM) and active holoenzyme complex, cAMP binds to the apoenzyme nonproductively with a reduced affinity (K(d) approximately 170 microM). These results demonstrate that cofactor binding to PDE4 is responsible for eliciting its high-affinity interaction with cAMP and the activation of catalysis.

Effect of adrenoreceptors on endotoxin-induced cytokines and lipid peroxidation in lung explants.

Lung tissue may be an important source of systemic inflammation associated with sepsis and the acute respiratory distress syndrome (ARDS). An ex vivo model of freshly explanted lung tissue in culture was developed to evaluate the ability of lipopolysaccharide (LPS) to directly stimulate lung tissues under conditions where indirect mechanisms such as recruitment of blood-derived inflammatory cells could not be implicated. Under control conditions, lung explants produced a high level of macrophage inflammatory protein-2 (MIP-2). Eight hours after LPS challenge, there were marked increases in the production of tumor necrosis factor-alpha (TNF-alpha) from 0.18 +/- 0.04 to 4.13 +/- 0.23 ng/ml/g tissue (p < 0.05), MIP-2 from 60.0 +/- 7.4 to 165.6 +/- 10.3 ng/ml/g tissue (p < 0.05), and tissue lipid peroxidation (malonaldehyde from 27.6 +/- 2.5 to 48.4 +/- 17.5 microM/g tissue; and 4-hydroxyalkenal from 34.0 +/- 3.0 to 59.7 +/- 18.8 microM/g tissue, both p < 0.05) from lung explants. Treatment with the beta-adrenoreceptor agonist isoproterenol (1 ng/ml) attenuated LPS-induced release of TNF-alpha and lipid peroxidation in association with an increase in intracellular cAMP levels. The adenylate cyclase activator, forskolin, also inhibited LPS-induced changes in TNF-alpha and lipid peroxidation. In conclusion, increasing intracellular levels of cAMP through beta-adrenoreceptor activation can attenuate the acute inflammatory response induced in the lung by LPS. LPS did not significantly impair the beta-adrenoreceptor reactivity in lung explants. Lung explants allow for the quantitative assessment of pulmonary inflammatory responses independent of influences from the circulation, and thus may be a useful ex vivo model to investigate cellular and molecular mechanisms of lung injury.