New prenyl flavanone and diarylbutanol from Uvaria siamensis stem bark and their α-glucosidase inhibitory activity.

One new prenyl flavanone (1), (2S)-8-prenyl-5,6-dihydroxy-7-methoxyflavanone, and one new diarylbutanol (2), (7'S)-3'-hydroxy-linderagatin-A, were isolated from the stem bark of Uvaria siamensis (Annonaceae), along with five known compounds, eriodictyol (3), quercetin (4), paprazine (5), N-trans-caffeoyltyramine (6), and N-trans-feruloyltyramine (7). Their structures were determined through extensive spectroscopic analyses and comparison with the literature. The α-glucosidase inhibitory potential of 1-7 was evaluated. Compound 6 showed the highest inhibitory activity against α-glucosidase and exhibited superior potency compared to the positive control, with an IC50 value of 0.12 µM.

Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. DESIGN: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. CONCLUSIONS: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

A novel modification of frozen elephant trunk technique: unique protocol from one institution.

OBJECTIVE: We aim to present a novel surgical technique of Frozen Elephant Trunk (FET) to treat complex thoracic aortic diseases in one stage and report its short-term outcomes. PATIENTS AND METHODS: Between December 2019 and 30 April 2021, twenty-five patients underwent FET operation at Viet Duc University Hospital. The mean age of the patients was 55.9 (±9.9, range 33-72) years. Eighteen (72%) of the patients were men. Thoracic aortic aneurysm was presented in three (12%) patients. Among seventeen (68%) of the patients undergoing the aortic dissection, eleven (44%) were treated acute type A aortic dissection. Type A intramural hematoma was presented in three (12%) patients. Four (16%) of the patients had undergone previous aortic operations, four (16%) of them had Marphan syndrome and two (11.1%) of them had stage 3 chronic kidney disease. All patients underwent FET procedure by unique protocol. Brain protection was achieved by antegrade bilateral selective cerebral perfusion and moderate hypothermia (28°C) in all cases; besides cerebral tissue oximetry monitoring was used to control brain oxygenation. RESULTS: There were no perioperative deaths, and all patients are still alive during mild-term follow-up period. Sixteen (88.9%) patients received isolated FET, while a Bentall procedure during FET was performed in two (8%) patients and right coronary artery bypass was in one (4%) case. The duration of cardiopulmonary bypass, cross-clamping, circulatory arrest, and total operation were 176.7 (±48.1, range 102-330), 106 (±39.8, range 63-205), 32.7 (±9.6, range 20-58), and 365.6 (±53.6, range 270-480) min, respectively. There was no bleeding following surgery. Prolonged ventilation required tracheotomy was documented in two (8%) patients, hemodialysis caused acute renal failure was in five (20%) patients, cerebral shock was in one (4%) patient, and type 1A endoleak in 2 (8%) patients. CONCLUSIONS: Our modification of FET technique was feasible, effective, and safe, with good postoperative outcomes.

Using the health beliefs model to explore children's attitudes and beliefs on air pollution.

OBJECTIVES: Traffic-related air pollution (TRAP) negatively impacts children's health. Self-protective measures are available, but population uptake is variable. It is essential to understand human beliefs and behaviours related to air pollution in order to understand the lack of self-protection in communities. As a prelude to undertaking a comprehensive assessment of children's attitudes and beliefs on the health effects of TRAP exposure, we sought to develop and validate an appropriate instrument. STUDY DESIGN: This study used exploratory sequential mixed methods. METHODS: This instrument, based on the constructs of the health belief model (HBM), aimed to determine factors predicting wearing a mask to protect against TRAP exposure. An initial literature-based questionnaire was modified using in-depth interviews, focus group discussions, and a quantitative survey pilot. This study included 121 school students and nine professional experts in Vietnam. The questionnaire was tested for content validity, agreement, test-retest reliability, and internal consistency. RESULTS: The concordance of questionnaire items between two repeated assessments ranged from 47.2% to 78.3%, intraclass correlation coefficients ranged from 0.16 to 0.87 and Cronbach's internal reliability coefficient for the instrument was 0.60. CONCLUSION: The self-administered instrument, based on the HBM, is suitable to understand health attitudes and beliefs related to self-protective behaviours to reduce TRAP exposure.

Power stabilization of a diode laser with an acousto-optic modulator.

Laser power fluctuations can significantly reduce the device performances in various applications. High frequency fluctuations impact the signal-to-noise ratio, while slow variations can reduce the device repeatability or accuracy. Here we report experimental investigations on the power stabilization of a diode laser with an acousto-optic modulator. In the frequency domain, the relative power noise is reduced at the level of 2.2 × 10-8 Hz-1/2 in the range 1-100 kHz. The slow variations are studied in the time domain. The relative Allan standard deviation is measured at the level of 6 × 10-7 at 100 s averaging time. Above 100 s, the instability increases and reaches 2 × 10-6 at 10 000 s.

Genetic characterization of Vietnamese Yellow cattle using mitochondrial DNA and Y-chromosomal haplotypes and genes associated with economical traits.

Vietnamese Yellow cattle are native cattle well adapted to local tropical environment. The aim of this study was to investigate genetic characteristics of the Yellow cattle using molecular markers. We investigated the nucleotide sequences of mitochondrial DNA and SRY gene on Y chromosome, and genotyped SREBP-1, SCD1, EDG1, NCAPG, DGAT1, MC1R, and HSP70 genes in the Yellow cattle population. The sequence analysis of the mitochondrial DNA showed that most of the cattle possesses zebu (Bos indicus) type I1 haplotype, suggesting relatively low genetic diversity in maternal lineage. The sequence analysis of the SRY gene indicates that while most of the males possess zebu type haplotype, taurine (Bos taurus) type haplotype was also observed, suggesting gene-flow from taurine cattle. The results of the genotyping of the functional genes showed that the NCAPG, SCD, MC1R, and HsSP70 genes are polymorphic in the population, whereas the SREBP-1, EDG1, and DGAT1 genes are monomorphic. Particularly, the presence of the desirable and undesirable alleles of the NCAPG and HSP70 genes, respectively, will be important for the selection of animals by potential performances in meat productivity and fertility. The present findings will be informative for future conservation and breeding of the Vietnamese Yellow cattle.

Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer.

Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.

A comparison of the pharmacokinetics and safety of enzalutamide in subjects with hepatic impairment and matched healthy subjects.

WHAT IS KNOWN AND OBJECTIVE: Enzalutamide is an androgen receptor inhibitor approved for treatment of metastatic castration-resistant prostate cancer. Enzalutamide is highly protein bound and eliminated primarily by hepatic metabolism; therefore, it is important to understand whether enzalutamide pharmacokinetics is altered by hepatic impairment. METHODS: Pharmacokinetic data were obtained from two non-randomized, open-label, single-dose, phase 1 studies conducted in patients with mild (Child-Pugh class A, n = 6) or moderate (Child-Pugh class B, n = 8) hepatic impairment (NCT01901133) or severe (Child-Pugh class C, n = 8) hepatic impairment (NCT02138162) and their corresponding matched healthy controls; data from both studies are presented here. Subjects with hepatic impairment had liver cirrhosis (n = 19) or chronic hepatitis (n = 3). All subjects received a single oral dose of 160 mg enzalutamide under fasting conditions, with blood samples collected predose and up to 49 days post-dose. RESULTS AND DISCUSSION: Exposure to enzalutamide active moieties, based on the area under the curve of the sum of enzalutamide and N-desmethyl enzalutamide (an active metabolite with similar potency to enzalutamide), increased by 13%, 18% and 4% in subjects with mild, moderate and severe hepatic impairment, respectively, relative to matched controls. Compared with healthy controls, the mean maximum plasma concentration for enzalutamide active moieties was 24% higher in subjects with mild hepatic impairment and 11% and 41% lower in subjects with moderate and severe hepatic impairment, respectively. Enzalutamide was generally well tolerated, with no clinically significant trends in abnormal laboratory findings, vital signs or electrocardiograms. WHAT IS NEW AND CONCLUSIONS: No major differences in single-dose pharmacokinetics were observed in subjects with hepatic impairment vs. matched healthy controls. Therefore, these studies indicate that no initial dose adjustment is necessary when administering enzalutamide to patients with hepatic impairment.

Note: Efficient diode laser line narrowing using dual, feed-forward + feed-back laser frequency control.

We have achieved distributed feedback laser diode line narrowing by simultaneously acting on the diode current via a feed-back loop and on an external electrooptic phase modulator in feed-forward actuator. This configuration turns out to be very efficient in reaching large bandwidth in the phase correction: up to 15 MHz with commercial laser control units. About 98% of the laser power undergoes narrowing. The full width at half maximum of the narrowed optical spectrum is of less than 4 kHz. This configuration appears to be very convenient as the delay in the feed-forward control electronics is easily compensated for by a 20 m optical fiber roll.

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

BACKGROUND: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. METHODS: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. RESULTS: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. CONCLUSIONS: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials.

BACKGROUND: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. METHODS: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments. RESULTS: First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score -16.95 (-26.47, -7.44) and -9.69 (-16.10, -3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change -0.24 (-0.39, -0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone. CONCLUSIONS: SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.

Shigella flexneri serotype 1c derived from serotype 1a by acquisition of gtrIC gene cluster via a bacteriophage.

BACKGROUND: Shigella spp. are the primary causative agents of bacillary dysentery. Since its emergence in the late 1980s, the S. flexneri serotype 1c remains poorly understood, particularly with regard to its origin and genetic evolution. This article provides a molecular insight into this novel serotype and the gtrIC gene cluster that determines its unique immune recognition. RESULTS: A PCR of the gtrIC cluster showed that serotype 1c isolates from different geographical origins were genetically conserved. An analysis of sequences flanking the gtrIC cluster revealed remnants of a prophage genome, in particular integrase and tRNA(Pro) genes. Meanwhile, Southern blot analyses on serotype 1c, 1a and 1b strains indicated that all the tested serotype 1c strains may have had a common origin that has since remained distinct from the closely related 1a and 1b serotypes. The identification of prophage genes upstream of the gtrIC cluster is consistent with the notion of bacteriophage-mediated integration of the gtrIC cluster into a pre-existing serotype. CONCLUSIONS: This is the first study to show that serotype 1c isolates from different geographical origins share an identical pattern of genetic arrangement, suggesting that serotype 1c strains may have originated from a single parental strain. Analysis of the sequence around the gtrIC cluster revealed a new site for the integration of the serotype converting phages of S. flexneri. Understanding the origin of new pathogenic serotypes and the molecular basis of serotype conversion in S. flexneri would provide information for developing cross-reactive Shigella vaccines.

Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL.

BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PATIENTS AND METHODS: PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs). RESULTS: Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls. CLINICAL TRIAL IDENTIFIER: NCT01212991, ClinicalTrials.gov.

Temporal and spatial patterns of diarrhoea in the Mekong Delta area, Vietnam.

This study examined the temporal and spatial patterns of diarrhoea in relation to hydro-meteorological factors in the Mekong Delta area in Vietnam. A time-series design was applied to examine the temporal pattern of the climate-diarrhoea relationship using Poisson regression models. Spatial analysis was applied to examine the spatial clusters of diarrhoea using Global Moran's I and local indicators of spatial autocorrelation (LISA). The temporal pattern showed that the highest peak of diarrhoea was from weeks 30-42 corresponding to August-October annually. A 1 cm increase in river water level at a lag of 1 week was associated with a small [0·07%, 95% confidence interval (CI) 0·01-0·1] increase in the diarrhoeal rate. A 1 °C increase in temperature at lag of 2 and 4 weeks was associated with a 1·5% (95% CI 0·3-2·7) and 1·1% (95% CI 0·1-2·3) increase in diarrhoeal risk, respectively. Relative humidity and diarrhoeal risk were in nonlinear relationship. The spatial analysis showed significant clustering of diarrhoea, and the LISA map shows three multi-centred diarrhoeal clusters and three single-centred clusters in the research location. The findings suggest that climatic conditions projected to be associated with climate change have important implication for human health impact in the Mekong Delta region.

Body mass index and risk of pneumonia: a systematic review and meta-analysis.

The aims of our meta-analysis were to examine the pattern and gender's influence on body mass index (BMI) - pneumonia relationship. Published studies were searched from PubMed, Web of Science, Cochrane Library databases using keywords of pneumonia, BMI and epidemiologic studies. Random-effects analysis was applied to estimate pooled effect sizes from individual studies. The Cochrane Q-test and index of heterogeneity (I(2) ) were used to evaluate heterogeneity, and Egger's test was used to evaluate publication bias. Random-effects meta-regression was applied to examine the pattern and gender's influence on BMI-pneumonia relationship. A total of 1,531 studies were initially identified, and 25 studies finally were included. The pooled relative risk (RR) and meta-regression model revealed a J-shaped relationship between BMI and risk of community-acquired pneumonia (underweight, RR 1.8, 95% confidence interval [CI], 1.4-2.2, P < 0.01; overweight, 0.89, 95%CI, 0.8-1.03, P, 0.1; obesity, 1.03, 95% CI, 0.8-1.3, p. 8) and U-shaped relationship between BMI and risk of influenza-related pneumonia (underweight, RR 1.9, 95% CI, 1.2-3, P < 0.01; overweight, 0.89, 95% CI, 0.79-0.99, P, 0.03; obesity, 1.3, 95% CI, 1.05-1.63, p. 2; morbidity obesity, 4.6, 95% CI, 2.2-9.8, P < 0.01); whereas, no difference in risk of nosocomial pneumonia was found across the BMI groups. Gender difference did not make significant contribution in modifying BMI-pneumonia risk relationship.

Risk of pneumonia in relation to body mass index in Australian Aboriginal people.

This study examined the relationship between body mass index (BMI) and the risk of pneumonia in Aboriginal Australians. A total of 677 adults aged 20-60 years were followed up from the baseline examination during 1992-1995 to June 2012. The pneumonia events were identified through hospital records. Pneumonia incident rates were calculated according to BMI groups. Hazard ratios were computed using Cox regression adjusting for age, smoking and alcohol consumption status. The incident rate of pneumonia was 13.3/1000 person-years, and this rate was significantly higher in females than males (hazard ratio = 1.5). Compared to males with normal BMI (18.5-24.9 kg/m²), the adjusted hazard ratio was 3.5 for males with lowest BMI (P < 0.01). Low BMI was significantly associated with a higher risk of hospitalized pneumonia for Aboriginal males. However, the U-shaped trend of this association indicates that the risk of pneumonia is likely to be associated with both low and high BMI.

HIV-1 mother-to-child transmission, post-test counselling, and antiretroviral prophylaxis in Northern Viet Nam: a prospective observational study.

BACKGROUND: Pregnant women fear being identified as HIV-1-infected and this has hampered prevention programmes and the calculation of transmission rates in Viet Nam. We introduced post-test counselling, antiretroviral prophylaxis, and formula feeding, and determined the vertical transmission rate in parts of Northern Viet Nam. METHODS: HIV infection was identified in 234 pregnant women; 182 (77.8%) accepted follow-up of their children. Counselling was given on 3-7 occasions for altogether approximately 6 h on antiretroviral prophylaxis and formula feeding to avoid transmission, and on the importance of surveillance of the child. All children were formula-fed. A polymerase chain reaction (PCR) was used for the diagnosis of HIV-1 in the children. One hundred and thirty-five of the 182 mothers allowed ≥ 3 blood samples to be taken from birth to ≥ 1 y of age, 32/182 provided a birth sample only, and 15/182 provided a sample later only. Nevirapine was given at delivery to 93/135 (69%) women, and to 128/135 (95%) children. Additionally, combination therapy was given to 15/135 (11%) who entered the study before delivery, and azidothymidine to their children for 1 week. RESULTS: Nine of 135 (6.7%) children became infected and 2/15 of the others, giving altogether 11/150 infected (7.3%). Intrauterine transmission was identified in 7/167 (4.2%) children by a positive PCR test at birth. PCR was negative at birth but positive at 1 month in 2/135 (1.5%), pointing to delivery-associated transmission. Thus, intrauterine transmission accounted for 78% (7/9). None of the uninfected children died, but 3/11 (p =0.004) of the HIV-1-infected died (in AIDS). CONCLUSION: Post-test confidential counselling, formula feeding, and antiretroviral prophylaxis resulted in low rates of delivery-associated and late HIV-1 transmissions.

A novel glucosyltransferase involved in O-antigen modification of Shigella flexneri serotype 1c.

The O antigen of serotype 1c differs from the unmodified O antigen of serotype Y by the addition of a disaccharide (two glucosyl groups) to the tetrasaccharide repeating unit. It was shown here that addition of the first glucosyl group is mediated by the previously characterized gtrI cluster, which is found within a cryptic prophage at the proA locus in the bacterial chromosome. Transposon mutagenesis was performed to disrupt the gene responsible for addition of the second glucosyl group, causing reversion to serotype 1a. Colony immunoblotting was used to identify the desired revertants, and subsequent sequencing, cloning, and functional expression successfully identified the gene encoding serotype 1c-specific O-antigen modification. This gene (designated gtrIC) was present as part of a three-gene cluster, similar to other S. flexneri glucosyltransferase genes. Relative to the other S. flexneri gtr clusters, the gtrIC cluster is more distantly related and appears to have arrived in S. flexneri from outside the species. Analysis of surrounding sequence suggests that the gtrIC cluster arrived via a novel bacteriophage that was subsequently rendered nonfunctional by a series of insertion events.

Strong influence of nonlinearity and surface plasmon excitations on the lateral shift.

When surface plasmons are excited at a metal-dielectric interface, the electromagnetic field takes a very large value near the interface. If the dielectric is a nonlinear Kerr medium, then the effect of nonlinearity can be greatly amplified due to the field enhancement. In this paper, we calculate the lateral shift of p wave beams incident on metal-dielectric multilayer systems in the Otto configuration in a numerically exact manner, using the invariant imbedding method of wave propagation in nonlinear stratified media. In the linear case, we find that the lateral shift becomes very large at the incident angles where the surface plasmons are excited. As the nonlinearity is turned on, the value of the lateral shift changes rapidly. We find that even a small change of the intensity of the incident wave can cause a huge change of the lateral shift. We propose that this phenomenon can be applied to designing precise optical switches operating at small powers.