High Level Of Suppression Research Articles

What Conditions Affect Initial HIV Treatment Success?

Highly active antiretroviral therapy has substantially improved the outlook for persons with HIV, and the combination of clinical trial data and experience has provided guidance for the best use of highly active antiretroviral therapy to balance efficacy, safety, tolerability, and adherence. The nonnucleoside reverse transcriptase inhibitors (NNRTIs) and several of the boosted protease inhibitors (PIs, eg, lopinavir/ritonavir) have shown high levels of viral suppression and CD4 count increases as initial therapy. Preliminary evidence suggests that NNRTI regimens may be more forgiving of certain levels of nonadherence than PIs. The evidence also shows that not all agents or combinations of agents are appropriate for all HIV patients. Patient factors such as lipids and triglycerides, hyperglycemia/diabetes, renal function, weight, gender, probability of and desire for pregnancy, initial CD4 count, race, and mental health status will all need to be considered to select the best therapy for the individual.

Band-Notched Design for UWB Antennas

A method to form a notch band is presented. We etch complementary split-ring resonators in the T-stub region of a CPW-feed ultrawideband (UWB) antenna. Due to limited space in this region, we connect two resonators together so that they have a common slot edge. Compared with two separated CSSRs, this new design not only occupies less space but also yields high mismatch losses. It is found that high mismatch losses and deep suppression level can be obtained at the desired notch band.

Serum Level of Hepcidin and Erythropoietic Activity after Hematopoietic Stem Cell Transplantation.

Hepcidin, first identified in human urine as a bactericidal peptide, is now considered a central molecule that regulates iron metabolism. Synthesis of hepcidin is known to be up-regulated by at least two signals: iron signal and interleukin-6 (IL-6) signal. The existence of a third signal, an erythropoiesis-associated pathway, has recently been suggested by several researchers experimenting with a mouse model treated with either chemotherapy or irradiation. However, the finding has not yet been clarified in human clinical settings partly because of difficulty in quantitatively measuring the serum level of hepcidin. Therefore, we monitored and assessed the association between the serum level of hepcidin and erythropoietic activity before and after stem cell transplantation for hematological malignancies, because the conditioning regimen followed by SCT dramatically changes the status of erythropoiesis in patients. The serum level of hepcidin-25 was quantitatively measured using a liquid chromatography tandem mass spectrometry-based assay system with synthetic isotopic hepcidin as an internal control, which made our quantification much more reliable and reproducible with very small intra- and inter-assay CVs. (Intra-assay and inter-assay CVs were <6.7% and <8.8%, respectively.) We also measured serum levels of various iron-related parameters and IL-6 as well as bone morphogenetic protein (BMP)-2 and BMP-4. The level of serum hepcidin-25 at week -1 was high (mean ± SD; 74.9 ± 93.9 ng/ml), compared to that in control sera from 28 healthy volunteers (mean ± SD; 21.9 ± 12.3 ng/ml), and the level further increased and peaked at week+1 after SCT (mean ± SD; 255.9 ± 99.3 ng/ml), possibly due to the high level of IL-6 and suppression of erythropoiesis. The hepcidin level of patients at week+4 with delayed erythropoiesis (reticulocyte count less than 40,000 /μl) was significantly higher (p<0.02) than that in those with rapid erythropoiesis (reticulocyte count more than 80,000 /μl). The result did not change even if cases were limited to those without elevated IL-6 levels to exclude the influence of IL-6 on hepcidin expression. Transferrin saturation increased to almost 100% after conditioning therapy and slowly decreased concurrent with erythroid recovery. In contrast, the serum ferritin level tended to increase even after erythroid engraftment irrespective of serum IL-6 or hepcidin levels and the volume of blood cell transfusions after SCT. The level of serum BMP-2 was significantly elevated at all of these time points after SCT compared to that in control sera from 6 healthy volunteers. Among these findings, the level of serum hepcidin-25 was inversely and precisely correlated with reticulocyte counts during and after SCT, suggesting that serum hepcidin-25 may be a good indicator of erythropoietic activity as well as iron utilization by erythropoiesis. These findings indicated that hepcidin is regulated by erythropoiesis through a putative erythropoiesis-associated factor. High serum hepcidin levels observed in SCT patients might have contributed to the disturbance of iron homeostasis and increased serum ferritin levels. Further investigation is needed to clarify the clinical significance of hepcidin in SCT settings.

Effects of Diffuse Colonization of Grape Berries byUncinula necatoron Bunch Rots, Berry Microflora, and Juice and Wine Quality

ABSTRACT Production of grape (principally cultivars of Vitis vinifera) for high-quality wines requires a high level of suppression of powdery mildew (Uncinula necator syn. Erysiphe necator). Severe infection of either fruit or foliage has well-documented and deleterious effects upon crop and wine quality. We found that berries nearly immune to infection by U. necator due to the development of ontogenic resistance may still support diffuse and inconspicuous mildew colonies when inoculated approximately 3 weeks post-bloom. Fruit with diffuse mildew colonies appear to be healthy and free of powdery mildew in late-season vineyard assessments with the naked eye. Nonetheless, presence of these colonies on berries was associated with (i) elevated populations of spoilage microorganisms; (ii) increased evolution of volatile ethyl acetate, acetic acid, and ethanol; (iii) increased infestation by insects known to be attracted to the aforementioned volatiles; (iv) increased rotting by Botrytis cinerea; and (v) increased frequency of perceived defects in wines prepared from fruit supporting diffuse powdery mildew colonies. Prevention of diffuse infection requires extending fungicidal protection until fruit are fully resistant to infection. Despite a perceived lack of improvement in disease control due to the insidious nature of diffuse powdery mildew, potential deleterious effects upon crop and wine quality thereby would be avoided.

Selection for and evaluation of an avocado orchard soil microbially suppressive to Phytophthora cinnamomi

A survey was undertaken in southern California in 1999–2000 to search for an avocado soil that exhibits natural suppression to avocado root rot caused by Phytophthora cinnamomi. The Somis-1 soil, which had consistent massive degradation of P. cinnamomi hyphal mats, low P. cinnamomi populations and good tree health, was shown to be a soil with a high level of microbial suppression to P. cinnamomi in greenhouse studies. Other soils chosen for study, which seemed to demonstrate some type of suppression in the field as evidenced by high P. cinnamomi soil populations yet with good tree health, did not demonstrate microbial suppression in greenhouse studies. These soils may represent a type of suppression which is ephemeral or highly dependent on specific environmental factors. The suppression of the Somis-1 soil was transferable to a conducive soil with as little as 1% natural soil mixed with 99% fumigated soil. The suppression was gradually eliminated in soil pre-treated at various temperatures from 25° to 90°C. The suppression in the Somis-1 soil did not correspond with cellulase or laminarinase activity or soil microbial activity. The suppression appeared to correspond with moderately well-drained soils as found in the Somis-1 soil, which drained at a rate that might be conducive to the growth and activity of microorganisms antagonistic to P. cinnamomi.

Selective accumulation of Trichoderma species in soils suppressive to radish damping-off disease after repeated inoculations with Rhizoctonia solani, binucleate Rhizoctonia and Sclerotium rolfsii

Artificial suppression of radish damping-off disease was induced by repeated soil inoculations with Rhizoctonia solani, binucleate Rhizoctonia (BNR) and Sclerotium rolfsii in pot systems. Soils repeatedly inoculated with R. solani and BNR showed suppressive to disease caused by R. solani and S. rolfsii, while soils repeatedly inoculated with S. rolfsii were suppressive to disease caused by S. rolfsii but not by R. solani. Species of Trichoderma were consistently isolated from soils repeatedly inoculated with R. solani, BNR and S. rolfsii. These Trichoderma spp. accumulated selectively in relation to the fungal species that was repeatedly added to the soils. The ratios of the frequencies of T. viride, T. harzianum and T. hamatum were 5:2:2 and 8:5:2 in soils repeatedly inoculated with R. solani and BNR, respectively. In S. rolfsii- inoculated soils, T. koningii was predominantly isolated. T. viride, T. harzianum and T. hamatum isolates obtained from either R.solani or BNR after repeated additions to the soils suppressed radish damping-off disease caused after challenge inoculations with R. solani or S. rolfsii. Among the Trichoderma species, T. viride consistently yielded high levels of suppression. However, isolates of T. koningii obtained from S. rolfsii-infested soils suppressed disease caused by S. rolfsii but failed to suppress disease caused by R. solani. Generally, the species of Trichoderma accumulated in a selective pattern that was closely related to the species of fungal pathogen used to induce the suppressive soil.

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.

Does a stable isotopically labeled internal standard always correct analyte response?: A matrix effect study on a LC/MS/MS method for the determination of carvedilol enantiomers in human plasma

A stable isotopically labeled (SIL) analogue is believed to be the most appropriate internal standard in a quantitative bioanalytical liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay. It is assumed that a SIL internal standard always compensates for variability in chemical derivatization, sample extraction and LC/MS/MS analysis due to its nearly identical chemical and physical properties to the unlabeled analyte. Hence, the analyte to internal standard peak area ratio should be constant despite any variations in sample processing or analysis. However, in our laboratories, a deuterium labeled internal standard of carvedilol demonstrated an unexpected behavior—the analyte to internal standard peak area ratio changed with two specific lots of commercially supplied human plasma. Several experiments, including dilution of the extract with LC mobile phase and post-column infusion of the carvedilol solution followed by the injection of extracted blank plasma, have indicated that a high level of matrix suppression affected the ionization of the carvedilol- S enantiomer and its deuterated internal standard differently in these two lots of plasma. For the first time, it was clearly demonstrated that a slight difference in retention time between the analyte and the SIL internal standard, caused by deuterium isotope effect, has resulted in a different degree of ion suppression between these two analogues. This difference was significant enough to change the analyte to internal standard peak area ratio and affect the accuracy of the method.

Acceptability and suppression of negative emotion in anxiety and mood disorders.

The present study investigated perceived acceptability and suppression of negative emotion in participants with anxiety and mood disorders. Sixty participants with these disorders and 30 control participants watched an emotion-provoking film and completed self-report measures of their experience and regulation of emotions. The film elicited similar increases in negative emotion for clinical and nonclinical participants; however, clinical participants judged their resulting emotions as less acceptable and suppressed their emotions to a greater extent. The higher level of suppression in the clinical group was attributable to females in the clinical group suppressing their emotions more than females in the nonclinical group. For all participants, high levels of suppression were associated with increased negative emotion during the film and during a postfilm recovery period. Further analyses showed that appraising emotions as unacceptable mediated the relationship between negative emotion intensity and use of suppression in the clinical group. This study extends the literature on emotion regulation to a clinical sample and suggests that judging emotions as unacceptable and suppressing emotions may be important aspects of the phenomenology of emotional disorders.

Rolling Out Antiretrovirals in Africa: There Are Still Challenges Ahead

In their article “Lessons Learned from Highly Active Antiretroviral Therapy in Africa” Akileswaran et al. review the effectiveness of HAART programs in Africa. They report positive health outcomes including high levels of treatment adherence and virological suppression that are comparable to those of industrialized countries. Most of these studies however were performed in settings with significant external financial support and the duration of patient follow-up was relatively short. Also many of the studies are only currently available as abstracts and as a result a critical analysis of the strengths and weaknesses of the various programs is not possible. There is no doubt that the availability of antiretroviral drugs in Africa from the President’s Emergency Plan for AIDS Relief; the Global Fund for AIDS Tuberculosis and Malaria; and other donor programs is an extremely important life-saving initiative especially when it is strategically linked to well-organized community-based HIV-prevention programs. However the challenge to roll out antiretrovirals in Africa to all those who need them and to obtain achievable long-term results is daunting. In this commentary we detail some of these challenges. (excerpt)

Serum Nestorone® and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen–ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen

Objectives This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings (“rings”) releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days. Methods Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 μg/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE. Results One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19–22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94–95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study. Conclusion Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Selection of Clonostachys rosea isolates from Brazilian ecosystems effective in controlling Botrytis cinerea

Clonostachys spp. were isolated from soil samples, and living and dead leaves of different plant species. Twelve isolates which sporulated well when cultured on agar media were compared regarding the capacity of establishing and suppressing Botrytis cinerea in leaves of Rosa hybrida ‘Sandra,’ Fragaria × ananassa ‘Dover,’ Lycopersicon esculentum ‘Kada,’ and Eucalyptus globulus. The isolates established in leaves of each plant species, but leaf area with conidiophores (SFCA) varied with the stage of leaf development. In rose, SFCA varied from 3.0 to 13.9% on senescing leaves and 3.4 to 10.0% on green leaves. SFCA was higher in young leaves of E. globulus and tomato (1.4–15.6% and 1.4–8.0%, respectively) than on senescing leaves (0.8–3.5% and 1.0–5.2%, respectively). In strawberry, SFCA varied from 0.7 to 6.2% on completely expanded leaves. Clonostachys rosea isolates reduced B. cinerea sporulation on leaves of rose (81.0–97.4% reduction), strawberry (87.6–96.8%), E. globulus (63.7–89.7%), and tomato (100% reduction). Four isolates of C. rosea were selected based on high levels of SFCA and suppression of B. cinerea. When leaf discs of the four hosts inoculated with these C. rosea isolates were challenged with isolates of B. cinerea of variable levels of aggressiveness, SFCA and pathogen suppression varied with the combination. Efficiency of C. rosea isolates in suppressing sporulation of B. cinerea varied among hosts but was always above 80%. The four selected Brazilian isolates of C. rosea are potential biocontrol agents for Botrytis blight management in Brazilian agricultural systems.

Low-loss, multimode 5-IDT SAW filter

Longitudinally coupled resonator filters provide unbalanced-balanced operation with wide bandwidth, low loss, and high suppression levels. However, reducing the insertion loss in the 1.8-2.2 GHz range remains a challenging problem because at high frequencies the resistive losses arising from the relatively wide aperture of the filter may degrade the performance. A 5-interdigital transducer (IDT) filter has six gaps at which the periodicity of the grating is broken, resulting in additional loss due to scattering into the bulk. In this paper, we show that replacing the gaps between the transducers with short transducer sections having their pitch different from that of the main transducers reduces the insertion loss of the device. We present devices with balun operation at 1842 MHz with wide bandwidth of 4.5% and -40 dB suppression, with a minimum insertion loss less than 1 dB in the best devices, and a maximum insertion loss of -1.2 dB in the passband. The passband is quite flat, with <1 dB ripple. We also discuss the layout of the contact pads and the connections, and its effect on the device performance and balance characteristics.

Dynamic nonlinear cochlear model predictions of click-evoked otoacoustic emission suppression

A comprehensive set of results from 2-click suppression experiments on otoacoustic emissions (OAEs) have been presented by Kapadia and Lutman [Kapadia, S., Lutman, M.E., 2000a. Nonlinear temporal interactions in click-evoked otoacoustic emissions. I. Assumed model and polarity-symmetry. Hear. Res. 146, 89–100]. They found that the degree of suppression of an OAE evoked by a test click varied systematically with the timing and the level of a suppressor click, being greatest for suppressor clicks occurring some time before the test click, particularly at lower levels of suppression. Kapadia and Lutman also showed that although the general shape of the graph of suppression against suppressor click timing could be predicted by a static power law model, this did not predict the asymmetry with respect to the timing of the suppressor click. A generalised automatic gain control (AGC) is presented as a simple example of a dynamic nonlinear system. Its steady state nonlinear behaviour, as quantified by its level curve, and its dynamic behaviour, as quantified by its transient response, can be independently set by the feedback gain law and detector time constant, respectively. The previously reported suppression results, with the asymmetry in the timing, are found to be predicted better by such an AGC having a level curve with a slope of about 0.5 dB/dB, and a detector time constant of about twice the period at the characteristic frequency. Although this gives adequate predictions for high suppression levels, it under predicts the suppression and the asymmetry for lower levels. Further research is required to establish whether simple peripheral feedback models can explain OAE suppression of this type.

Weed suppression in Vigna unguiculata with a spring-seeded brassicaceae green manure

A spring-seeded commercial blend of Brassica juncea L. and Sinapis alba L. was evaluated for biomass production, glucosinolate content, and weed suppression in Vigna unguiculata in Kibler, AR; Bixby, OK; and Pendleton, SC in 2003. Brassica biomass at termination prior to planting Vigna unguiculata was 272–752 g/m 2. Total glucosinolate production at mechanical termination of the green manure ranged from 8600–26,700 μmol/m 2. Glucosinolate production and type varied among locations, with the major glucosinolates in Brassica shoots being 2-propenyl and p-hydroxybenzyl. 2-Phenylethyl comprised 35–48% of the total glucosinolates in roots at each location. Weed suppression also varied across locations, with a high level of suppression at Pendleton only. At 8 weeks after planting Vigna unguiculata at Pendleton, weed biomass was 118 g/m 2 in green manure plots compared with 413 g/m 2 in non-amended plots. The weed suppression from the green manure at Pendleton improved Vigna unguiculata yields by an average of 415 kg/ha over non-amended plots. These results illustrate the potential for using Brassicaceae green manures as weed suppressants in Vigna unguiculata. However, reasons for variability in weed suppression and glucosinolate production among environments need further investigation before wide-spread adoption of this integrated weed management strategy.

Simultaneous measurement of atmospheric temperature, humidity, and aerosol extinction and backscatter coefficients by a combined vibrational?pure-rotational Raman lidar

Implementation of the pure-rotational Raman (PRR) lidar method for simultaneous measurement of atmospheric temperature, humidity, and aerosol extinction and backscatter coefficients is reported. The isolation of two wavelength domains of the PRR spectrum and the suppression of the elastically scattered light is carried out by a double-grating polychromator. Experiments involving elastic backscatter from dense clouds and a solid target confirm the high level of suppression of the elastic light in the corresponding acquisition channels of the two selected PRR domains. Calibration of the temperature channel was done both by comparison with an experimentally verified atmospheric temperature model profile and by inter-comparison with radiosondes. Night-time temperature profiles with high vertical resolution were obtained up to the lower stratosphere. The PRR temperature profile combined with the water vapor mixing ratio obtained from the ro-vibrational Raman channel is used to estimate the relative humidity.

Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients.

Boosted protease inhibitor regimens combine ritonavir with a second, 'boosted' protease inhibitor to enhance patient exposure to the latter agent, thereby preventing or overcoming resistance and allowing less frequent dosing, potentially improving adherence. The advantages offered by ritonavir boosting are primarily attributable to the drug's pharmacokinetic properties. Ritonavir's inhibition of the cytochrome P-450 CYP3A4 enzyme reduces the metabolism of concomitantly administered protease inhibitors and changes their pharmacokinetic parameters, including area under the curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin) and half-life (t1/2). As a result, the bioavailability of the boosted protease inhibitor is increased and improved penetration into HIV reservoirs may be achieved. Boosted protease inhibitor regimens that utilize a low dose of ritonavir (100-200 mg) appear to offer the best balance of efficacy and tolerability. At this dose, ritonavir boosts the bioavailability of the second protease inhibitor without contributing significantly to the side effect profile of the regimen. In clinical trials, regimens boosted with low dose ritonavir have demonstrated high levels of viral suppression in both antiretroviral naïve patients and patients who previously failed antiretroviral therapy, including protease inhibitor therapy. Side effects observed have generally been similar to those associated with the boosted protease inhibitor. Based upon their enhanced drug exposure and demonstrated efficacy, the boosted ritonavir regimens should be among the first options considered for use in clinical practice.

Evaluation of Postemergence Herbicide Combinations for Long-Term Trumpetcreeper (Campsis radicans) Control in Corn (Zea mays)1

Field trials were conducted in Virginia during 2000 and 2001 to evaluate long-term trumpetcreeper control in corn with dicamba, BAS 654 plus dicamba, 2,4-D, CGA 152005 plus primisulfuron, halosulfuron, primisulfuron, and mesotrione. Each of these herbicides was applied alone as a single postemergence (POST) treatment or as a component of a POST herbicide combination. Trumpetcreeper suppression ratings 3 mo after treatment (MAT) revealed a general trend toward higher levels of suppression with combinations of dicamba, BAS 654 plus dicamba, or 2,4-D with any of the sulfonylurea herbicides and lower levels of suppression with applications of any of the sulfonylurea herbicides alone. Combinations of dicamba, BAS 654 plus dicamba, or 2,4-D with mesotrione also provided some of the highest levels of trumpetcreeper suppression 3 MAT in both years. At 1 yr after treatment (YAT), 2,4-D alone, BAS 654 plus dicamba, CGA 152005 plus primisulfuron plus 280 g ai/ha dicamba, primisulfuron plus 280 g/ha dicamba, primisul...

Discussion 2

Discussion 2

Supressão da atividade saprofítica de Rhizoctonia spp. em solos de jardim clonal de Eucalyptus

Avaliou-se a eficiência de Trichoderma longibranchiatum (UFV-1), de T. inhamatum (UFV-2 e UFV-3), compostos de casca e folhas de eucalipto contra Rhizoctonia spp., aplicados em solo de jardim clonal de eucalipto (Eucalyptus sp.). Em solos artificialmente infestados com Rhizoctonia spp., sob condições controladas, os antagonistas UFV-2 e UFV-3 apresentaram níveis elevados de supressividade, quando se aumentou a fonte alimentar na formulação, de 5 a 50 g de farelo de trigo por litro. No campo, o antagonista UFV-3 não teve efeito significativo na redução do inóculo de Rhizoctonia spp. Compostos de casca de eucalipto apresentaram diferentes graus de supressão a Rhizoctonia spp., dependendo da origem e do lote do composto. A incorporação de folhas de eucalipto ao solo favoreceu o aumento do inóculo de Rhizoctonia spp.