Higher GU Research Articles

Influence of different finishing, aging with coffee, and repolishing protocols on the properties of nanoparticle composite resins.

Considering the variability of finishing protocols for composite resins, the literature does not offer a consensus about the influence of these approaches to obtain a final polishing and whether the physical properties of these composite resins change at different analysis times. Therefore, the study analyzed the microhardness, roughness, color stability, and gloss of a nanocomposite resin with different finishing, aging with coffee, and repolishing protocols. Nanocomposite resin samples were divided into three finishing protocol groups: Diamond burs (F and FF), multi-fluted tungsten carbide burs (18 and 30 flutes), and coarse and medium abrasive discs (Soflex-3M). All protocols used spiral rubber tips (F and FF) for polishing. Knoop microhardness (KHN), roughness (Ra), color changes (ΔE00 and YI), and gloss (GU) were analyzed. Scanning electron microscopy provided images of resins and finishing and polishing instruments. Resin KHN (p<0.001) decreased, and Ra (p<0.001), ΔE00 (p<0.001), and YI (p<0.001) increased after aging with coffee, regardless of finishing protocol. Abrasive discs showed lower color changes, YI, and Ra and higher GU. Repolishing restored KHN and Ra but not ΔE00 (p>0.05) and YI (p>0.05). Abrasive disc finishing reduced roughness and yellowness and increased nanocomposite resin gloss after aging with coffee. Key words:Color, Composite resins, Dental materials, Staining, Surface properties.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group

IntroductionRadiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. Material and methodA retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. Results709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35–50) and 14 Gy (10–20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). ConclusionThis bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

Organic Enrichment at Aqueous Interfaces: Cooperative Adsorption of Glucuronic Acid to DPPC Monolayers Studied with Vibrational Sum Frequency Generation.

Surface tension, surface-specific vibrational spectroscopy and differential scanning calorimetry measurements were all used to test cooperative adsorption of glucuronic acid (GU) to DPPC monolayers adsorbed to the aqueous/vapor interface. Experiments were performed using GU solutions prepared in Millipore water and in carbonate/bicarbonate solutions buffered to a pH of 9.0. The effects of GU on DPPC monolayer structure and organization were carried out with tightly packed monolayers (40 Å2/DPPC) and monolayers in their liquid condensed phase (55 Å2/molecule). Surface tension data show that GU concentrations of 50 mM lead to expanded DPPC monolayers with diminished surface tensions (or higher surface pressures) at a given DPPC coverage relative to monolayers on pure water. With unbuffered solutions, GU induces significant ordering within liquid condensed monolayers although the effects of GU on tightly packed DPPC monolayers are less pronounced. GU also induces a second, higher melting temperature in DPPC vesicles implying that GU (at sufficiently high concentrations) strengthens lipid-lipid cohesion, possibly by replacing water solvating the DPPC headgroups. Together, these observations all support a cooperative adsorption mechanism. In buffer solutions, the effects of dissolved GU on DPPC structure and organization are muted. Only at sufficiently high GU concentrations (when the solution's buffering capacity has been exceeded) do the data again show evidence of cooperative adsorption. These findings place limits on cooperative adsorption's ability to enrich interfacial organic content in alkaline environmental systems such as oceans.

Four-year outcomes of hypofractionated proton therapy for localized prostate cancer.

80 Background: Hypofractionated radiation therapy (HFRT) is an effective treatment for localized prostate cancer (LPC). This study was performed to determine the toxicity profile and biochemical-clinical failure (BCF) rates for patients with LPC treated with hypofractionated proton therapy (HFPT). Methods: Between 2010 and 2017, 184 men were enrolled on a trial of 70Gy in 28 fractions of HFPT for low to intermediate-risk LPC. Androgen suppression (AS) was allowed. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Urinary and erectile quality of life changes were captured using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) Questionnaire, respectively. Results: Median follow-up was 49.2 months. Enrolled patients had low-risk [LR] (n = 18), favorable intermediate-risk [FIR] (n = 78), and unfavorable intermediate-risk [UIR] (n = 88) disease. Twenty-six percent of patients received neoadjuvant and concurrent AS, with a median duration of 6 months. Four-year rates of BCF free survival were 95.7%, 94.4%, 98.7%, and 93.2% in the overall group and the LR, FIR, and UIR cohorts, respectively (p = .21). Overall survival at 4 years was 97.3%. No deaths were attributable to prostate cancer. Median IPSS before and 1 year post-HFPT were 6 and 7 for LR patients, 6 and 6 for FIR patients, and 8 and 7 for UIR patients. Median IIEF-5 before and 1 year post-HFPT were 21 and 18 for LR patients, 18 and 16.5 for FIR patients, and 15 and 10.5 for UIR patients. The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic (GU) toxicities were 3.8% and 12.5%, respectively. One acute grade 3 GI toxicity was reported. The 4-year incidence of late grade 2 or higher GU and GI toxicity was 7.6% and 13.6%, respectively. One late grade 3 GI toxicity was reported. The predominant late grade 2 GI and GU toxicities were rectal bleeding and urinary frequency, respectively, accounting for 79% and 57% events. All late toxicities were transient. Conclusions: HFPT is associated with low rates of toxicity in the treatment of prostate cancer. Further analyses are warranted to assess long term toxicity and understand differences between proton and photon HFRT. Clinical trial information: NCT01352429.

Incompatibility mechanism of Crotonis Semen Pulveratum and Glycyrrhizae Radix et Rhizoma based on diuretic effect and intestinal flora structure

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.

Hypofractionated stereotactic body radiotherapy for localized prostate cancer – first Nordic clinical experience

Background: The use of hypofractionated stereotactic body radiotherapy (SBRT) as primary treatment modality in clinically localized prostate cancer (PCa) is emerging, because the low α/β-ratio favors the use of high dose per fraction in PCa. There is a need for more data about SBRT, especially in high-risk PCa patients. The purpose of this retrospective study was to evaluate the safety and the short-term efficacy of robotic SBRT in a clinical patient cohort with localized PCa including also high-risk patients (D’Amico risk stratification).Materials and methods: A total of 240 consecutive patients with clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnife®). All risk groups (D’Amico risk stratification) were represented as follows: 48 (22%), 59 (27%) and 111 (51%) of the patients representing low-, intermediate- and high-risk group, respectively. Data on acute and intermediate-term toxicities and early PSA responses were analyzed.Results: Neither acute grade 3 or higher GU nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients experienced intermediate-term toxicity requiring diagnostic interventions, the rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low, 1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten (4.6%) patients. With the median follow-up time of 23 months the biochemical relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate- and high-risk group, respectively.Conclusions: The toxicity of robotic SBRT in a large clinical cohort of PCa patients was tolerable and the early PSA response was good in all risk groups. The hypofractionated SBRT offers a possibility to high dose per fraction and to provide the whole radiotherapy treatment within two to three weeks.

Toxicity, quality of life outcomes, and dosimetric impact in phase III trial of hypofractionated or standard fractionated proton therapy for low-risk prostate cancer patients: PCG GU 002.

48 Background: The purpose of this study is to identify differences in toxicity, quality of life (QOL), and dosimetric endpoints among patients with low-risk prostate adenocarcinoma treated with either standard fractionation or hypofractionation proton-beam therapy. Methods: We analyzed the results of the first 75 patients treated in our phase III trial comparing 38Gy relative biological effectiveness (RBE) in 5 fractions (fx) (n = 46) vs. 79.2Gy (RBE) in 44 fx. (n = 29). All patients had low-risk prostate cancer and were treated with proton radiation using fiducial markers and daily image guidance. We evaluated American Urological Association (AUA) Symptom Index, adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains at pretreatment and 3, 6, 12, 18, 24, 36 and 48 months. Doses to the prostate were selected based on similar long term effects to normal tissue based on an α/β = 3.5 for an EQD2 of 76Gy. Results: The median follow-up was 36 months for both groups; 23 (30%) patients reached a follow-up of 48 months. We observed a small difference in AUA score (3.2 vs. 8.6, p = 0.002) at 1-year favoring the 79.2Gy arm. AUA scores were not statistically different at 18 months and after. Similarly, EPIC Urinary symptoms favored the 79.2Gy arm at 1 year (92.3 vs. 84.5, p = 0.009) and 18 months (92.3 vs. 85.3, p = 0.03); bother scores were not significantly different at any other time points. G2 or higher GU toxicity was similar between arms (p = 0.8). No differences in EPIC Bowel symptoms, EPIC Sexual symptoms, or bowel G2 or higher toxicities were seen. One death was observed in the 38Gy arm due to an unrelated case of multiple myeloma. The bladder V80 (79.2Gy arm, p = 0.04) and V39 (38Gy arm, p = 0.05) were predictive for G2 or higher GU AE. There was no association observed between rectal dose and G2 or higher rectal toxicity. Conclusions: Patients treated in the hypofractionated and standard arms tolerated treatment well. A small and temporary difference in the GU domain was seen favoring the standard arm. As predicted long term effects on the GU domain and bowel were similar for both arms, suggesting that the α/β is similar to 3.5 for long term effects. Clinical trial information: 01230866.

Influence of zonal dosimetry on prostate brachytherapy outcomes.

PurposeTo examine the influence of zone-specific dosimetry on outcomes during permanent prostate implantation (PI), where the peripheral zone (PZ) and transitional zone (TZ) may receive varying radiation doses.Material and methodsFour hundred and sixteen patients treated with I-125 PI (target dose: 144 Gy) between 1996 and 2003 were included in this Institutional Review Board (IRB) approved, retrospective analysis. Whole prostate (WP), TZ, and PZ were contoured, and zone-specific D90 and V100 were computed. Their influence on biochemical failure (BF) was evaluated using Cox proportional hazards analysis.ResultsThe median age and initial prostate-specific antigen (PSA) was 68 years and 6.1 ng/ml, respectively, and the median follow-up time was 8.8 years. There were 329 subjects with Gleason score (GS) 6 disease (79.1%), and 82 subjects had GS 7 disease (19.7%). Androgen deprivation therapy (ADT) was used in 20.4% of patients. Median D90 and V100% in the WP, PZ, and TZ were 141.2 Gy, 156.1 Gy, and 134.5 Gy; and 88.8%, 93.3%, and 84.2%, respectively. Ten-year rates for biochemical recurrence-free survival, distant metastasis-free survival, and prostate cancer-specific mortality were 82.4%, 92.4%, and 0.97% respectively. Only initial PSA, GS7+ disease, ADT, and PSA frequency were significant on multivariate analysis. Ten-year rates of grade 3 or higher GU and GI toxicity was 10.9% and 1.8%, respectively. TZ V200 and TZ V300 were significantly associated with late genitourinary toxicity.ConclusionsThe TZ received significantly lower doses of radiation compared to the PZ. On multivariate analysis, no dosimetric parameter was associated with efficacy. Higher TZ doses may be associated with higher late GU toxicity without improving efficacy.

Strong epistatic selection on the RNA secondary structure of HIV.

A key question in evolutionary genomics is how populations navigate the adaptive landscape in the presence of epistasis, or interactions among loci. This problem can be directly addressed by studying the evolution of RNA secondary structures, for which there is constraint to maintain pairing between Watson-Crick (WC) sites. Replacement of a nucleotide at one site of a WC pair reduces fitness by disrupting binding, which can be restored via a compensatory replacement at the interacting site. Here, I present the first genome-scale analysis of epistasis on the RNA secondary structure of human immunodeficiency virus type 1 (HIV-1). Comparison of polymorphism frequencies at ancestrally conserved sites reveals that selection against replacements is ∼2.7 times stronger at WC than at non-WC sites, such that nearly 50% of constraint can be attributed to epistasis. However, almost all epistatic constraint is due to selection against conversions of WC pairs to unpaired (UP) nucleotides, whereas conversions to GU wobbles are only slightly deleterious. This disparity is also evident in pairs with second-site compensatory replacements; conversions from UP nucleotides to WC pairs increase median fitness by ∼4.2%, whereas conversions from GU wobbles to WC pairs only increase median fitness by ∼0.3%. Moreover, second-site replacements that convert UP nucleotides to GU wobbles also increase median fitness by ∼4%, indicating that such replacements are nearly as compensatory as those that restore WC pairing. Thus, WC peaks of the HIV-1 epistatic adaptive landscape are connected by high GU ridges, enabling the viral population to rapidly explore distant peaks without traversing deep UP valleys.

Impact of Change From CTCAE Version 3 to CTCAE Version 4 on Urologic Toxicity Scores in Prostate Cancer

3.4%) and incontinence (nZ 1; 0.5%; 7-years actuarial risk of 1.8%). Late grade 2 or higher GU toxicity was associated with a higher bladder volume receiving 70 Gy or higher dose (p Z .02), there was no association with any of other parameters examined. Conclusions: The volume of bladder neck exposed to higher doses may possibly be related to the radiation cystitis, most common late GU toxicity in our cohort with localized prostate cancer treated to 78 grays IMRT. Author Disclosure: H. Inokuchi: None. T. Mizowaki: None. I. Ikeda: None. K. Takayama: None. Y. Norihisa: None. M. Hiraoka: None.

Pelvic Lymph Nodes Displacement in High-Risk Prostate Cancer Patients Treated With Image-Guided IMRT With 2 Independent Target Volumes

Purpose/Objective(s): To report initial experience of biochemical outcomes and the acute and late toxicity in 200 patients with clinically localized prostate cancer treated with volumetric modulated arc therapy (VMAT). Materials/Methods: Between November 2007 and September 2011, 200 patients with clinically localized prostate cancer were treated with VMAT using daily cone-beam computed tomography acqusition. Treatment planning systems used were avoidance conformal-based in 77 patients and multileaf collimator-based in 123 patients. All plans were generated on an inverse-planning approach. A total of 182 patients (91%) were treated to 76 Gy, and 18 patients (9%) were treated to Z < 72 Gy. Acute and late toxicities were scored according to CTCAE grading scales. PSA relapse was defined according to Phoenix definition. The mean follow-up time was 50 months (range: 7-85 months). Results: Two patients (1%) developed acute Grade 2 or worse GI toxicity. Thirty-nine patients (19%) developed acute Grade 2 GU symptoms, and no one experienced Grade 3 GU toxicity. Six patients (3%) developed late Grade 2 rectal bleeding. Two patients (1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 5year actuarial likelihood of late Grade 2 or higher rectal bleeding was 3.4%. Twenty patients (10%) experienced late Grade 2 GU toxicity, and no one developed Grade 3 GU toxicity. The 5-year actuarial likelihood of late Grade 2 or higher GU toxicity was 11.6%. The 5-year actuarial PSA relapse-free survival rates for low-, intermediate-, and high-risk group patients stratified according to NCCN criteria, were 100%, 91,8%, and 85.3%, respectively. Conclusions: Our initial data demonstrate the feasibility of VMAT in patients with localized prostate cancer. Acute and late rectal toxicities seem to be dramatically reduced compared with what has been observed with conventional radiation therapy techniques. Short-term PSA control rates were excellent. Based on our promising initial experiences, VMAT is an established novel conformal radiation delivery method for localized prostate cancer at our institution. Further studies in a larger population are required to determine long-term results in VMAT. Author Disclosure: K. Shiraishi: None. K. Yamamoto: None. A. Haga: None. A. Sakumi: None. K. Nakagawa: None.

176 NUMBER NEEDED TO TREAT AND RISK BENEFIT ANALYSIS OF DENOSUMAB VERSUS ZOLEDRONIC ACID IN THE TREATMENT OF CASTRATE-RESISTANT PROSTATE CANCER PATIENTS WITH BONE METASTASES

cancer between 1988 and 2005, 2,156 of them had chart-recorded smoking histories. These patients were classified by their smoking histories as never smokers, current smokers, former smokers, and smokers whose current smoking status was unknown. Variables considered regarding tobacco habit included quantity of tobacco use represented by pack-years, duration of the smoking, and, for former smokers, how long before the initiation of radiation therapy the patient quit smoking, when available. Radiation toxicity was graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events. RESULTS: Univariate analysis demonstrated that smoking was associated with increased late GU grade 2 and higher toxicities experienced during EBRT (p .003). Multivariate analyses demonstrated the following variables as significantly associated with an increased risk of grade 2 and higher GU toxicities: smoker vs. non-smoker (p 0.004), older age (p 0.002), higher radiation (p 0.0001), and 3D-conformal radiation therapy (3D-CRT) vs. intensity-modulated radiation therapy (IMRT) (p 0.02). No significant association was found between the quantity of tobacco use, represented by pack-years, and toxicity. For GI toxicity, the following variables were associated with increased risks of late rectal grade 2 and higher toxicity: smoker vs. non-smoker (p 0.02), 3D-CRT vs. IMRT (p 0.0001), higher radiation dose (p 0.0001) and age (p 0.0003). CONCLUSIONS: A significant correlation between smoking and increased urinary and rectal toxicities after EBRT for prostate cancer patients was observed. Specifically, smokers are at higher risk for both late GU and late GI grade 2 and higher toxicities.

The Pore of the Voltage-Gated Proton Channel

In classical tetrameric voltage-gated ion channels four voltage-sensing domains (VSDs), one from each subunit, control one ion permeation pathway formed by four pore domains. The human Hv1 proton channel has a different architecture, containinga VSD, but lacking a pore domain. Since its location is not known, we searched for the Hv permeation pathway. We find that mutation of the S4 segment's third arginine R211 (R3) compromises proton selectivity, enabling conduction of a metal cation and even of the large organic cation guanidinium, reminiscent of Shaker's omega pore. In the open state, R3 appears to interact with an aspartate (D112) that is situated in the middle of S1 and is unique to Hv channels. The double mutation of both residues further compromises cation selectivity. We propose that membrane depolarization reversibly positions R3 next to D112 inthe transmembrane VSD to form the ion selectivity filter in the channel's open conformation.

Late Toxicity in High-risk Prostate Cancer Treated with Androgen Suppression and Hypofractionated Intensity Modulated Radiotherapy

Late Toxicity in High-risk Prostate Cancer Treated with Androgen Suppression and Hypofractionated Intensity Modulated Radiotherapy

Synthetic MicroRNA Designed to Target Glioma-Associated Antigen 1 Transcription Factor Inhibits Division and Induces Late Apoptosis in Pancreatic Tumor Cells

To determine whether the synthetic microRNAs (miRNA) could effectively target tumor cells we designed several miRNA complementary to glioma-associated antigen-1 (Gli-1) mRNA and investigated their ability to inhibit tumor cell proliferation. The sonic hedgehog pathway is an early and late mediator of tumorigenesis in epithelial cancers. Activation of sonic hedgehog signaling seems to precede transformation of tissue stem cells to cancerous stem cells, with the Gli-1 transcription factor functioning as a mediator of environmental signals. Inhibiting cancer cell proliferation by targeting the Gli-1 effector pathway is difficult to achieve by chemotherapeutic agents or short interfering RNA. We hypothesized that targeting the 3'-untranslated region of Gli-1 mRNA would effectively inhibit tumor cell proliferation. To test this hypothesis, we used synthetic miRNAs of our own design and corresponding duplex/small temporal RNAs by introducing three-nucleotide loops in the 3'-untranslated region Gli-1 sequence of high GU content. We found that miRNA (Gli-1-miRNA-3548) and its corresponding duplex (Duplex-3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells. The miRNAs mediated delayed cell division and activation of late apoptosis in MiaPaCa-2 cells. This is the first demonstration of inhibition of pancreatic tumor cell division by designed miRNA. Gli-1 miRNAs should significantly add to the general understanding of the mechanisms of metastasis and contribute toward the design of better treatments for epithelial cancers.

MRNA sequence features that contribute to translational regulation in Arabidopsis

DNA microarrays were used to evaluate the regulation of the proportion of individual mRNA species in polysomal complexes in leaves of Arabidopsis thaliana under control growth conditions and following a mild dehydration stress (DS). The analysis determined that the percentage of an individual gene transcript in polysomes (ribosome loading) ranged from over 95 to <5%. DS caused a decrease in ribosome loading from 82 to 72%, with maintained polysome association for over 60% of the mRNAs with an increased abundance. To identify sequence features responsible for translational regulation, ribosome loading values and features of full-length mRNA sequences were compared. mRNAs with extreme length or high GU content in the 5′-untranslated regions (5′-UTRs) were generally poorly translated. Under DS, mRNAs with both a high GC content in the 5′-UTR and long open reading frame showed a significant impairment in ribosome loading. Evaluation of initiation A+1UG codon context revealed distinctions in the frequency of adenine in nucleotides −10 to −1 (especially at −4 and −3) in mRNAs with different ribosome loading values. Notably, the mRNA features that contribute to translational regulation could not fully explain the variation in ribosome loading, indicating that additional factors contribute to translational regulation in Arabidopsis.

De novo design, synthesis, and characterization of a pore-forming small globular protein and its insertion into lipid bilayers.

The question of how to design a water-soluble globular protein remains. We report here the synthesis of a native-like and pore-forming small globular protein (SGP, 69 amino acid residues). The protein was designed to have four helices: a Trp-containing short hydrophobic helix in the middle surrounded by three Tyr-containing long basic amphiphilic helices. Size-exclusion chromatography and CD measurements indicated that in buffer solution SGP is monomeric with a 50% helical structure. SGP did not completely denature even at high temperature (90 degrees C) and at relatively high Gu x HCl concentration so that the denaturant concentration at the midpoint of the transition is 5 M. Dye binding studies and fluorescence energy transfer experiments showed that SGP possesses a hydrophobic binding site and its Trp of the central helix is present at a relatively hydrophobic region and accepts the energy from Tyr(s) in other amphiphilic helices, indicating that SGP takes a stable globular-like structure in aqueous solution. From the depth-dependent fluorescent studies using egg PC liposomes containing n-doxyl fatty acids and brominated phospholipid as quenchers, it was found that the hydrophobic central alpha-helix is able to enter spontaneously into the lipid bilayers and the Trp in the central alpha-helix is located at about the middle of the alkyl chain in the outer layer of the phospholipid bilayer. The peptide is also able to increase the membrane permeability with two modes of current (basal current and single ion channel) in planar phospholipid bilayers, indicating the spontaneous insertion of the protein into the lipid bilayer (basal current) and then the formation of a uniform size of channel pore (14 pS). SGP is useful as a basic and starting model to find good amino acid sequences that fold to a desired protein structure and to search translocation mechanisms from aqueous solution into lipid bilayers.