Differential Impact of Surface Conduction and Electroosmotic Flow on Ion Transport Enhancement by Microscale Auxiliary Structures.

Our research investigates the impact of auxiliary structures on ion transport in electrochemical systems such as batteries and microscale desalination units, whose importance for sustainable development has increased dramatically in recent decades. The electrochemical systems typically feature ion-selective surfaces, such as electrodes and ion exchange membranes, where ion depletion can cause performance issues including metal dendrite formation and flow instability. Recent research has shown that auxiliary structures in these electrochemical systems can enhance ion transfer near ion-selective surfaces, thereby resolving the instability problem and improving the energy conversion efficiency of the system. Our study leverages recent advancements in nanoscale electrokinetics to model these auxiliary structures as pillar arrays near an ion exchange membrane in a microchannel. We examine how these structures enhance ion transports relative to the characteristic length scale of microchannel depth and pillars' proximity to the ion-selective surface. Results show that the effect of the pillars varies significantly with their placement. Specifically, in deeper microchannels, where electrokinetic convection is stronger, the closer the auxiliary structure is to the ion-selective membrane, the better the ion transfer. However, in the thinner microchannel, the proximity of the auxiliary structure to the ion selective membrane has a less significant correlation with the ion transfer. Therefore, this finding highlights the importance of spatial arrangement of the auxiliary structures in improving the performance of electrochemical devices. Conclusively, this study can help to better understand energy conversion systems such as fuel cells, salinity gradient power generation systems, and electrochemical desalination systems, where auxiliary structures can be used in the vicinity of ion-selective surfaces. Especially, our fundamental electrokinetic study provides an effective means for designing the efficient electrochemical platforms utilizing micro/nanofluidics.

Optimizing targeting strategies for lithotripsy through in-vitro and in vivo studies with consideration of respiratory regularity.

BACKGROUND: This work aimed to identify a method to achieve improved stone targeting and safety in shockwave lithotripsy by accounting for respiration. METHODS: We set up an electromotive device simulating renal movement during respiration to place artificial stones within the phantom gel, measuring stone weight changes before and after shockwave exposure and the cavitation damage. We conducted clinical trials using respiratory masks and sensors to monitor and analyze patient respiration during shockwave lithotripsy. RESULTS: The in vitro efficiency of lithotripsy was higher when adjusted for respiration than when respiration was not adjusted for. Slow respiration showed the best efficiency with higher hit rates when not adjusted for respiration. Cavitation damage was also lowest during slow respiration. The clinical study included 52 patients. Respiratory regularity was maintained above 90% in regular respiration. When respiration was regular, the lithotripsy rate was about 65.6%, which stayed at about 40% when respiration was irregular. During the lithotripsy, the participants experienced various events, such as sleep, taking off their masks, talking, movement, coughing, pain, nervousness, and hyperventilation. The generation of shockwaves based on respiratory regularity could reduce pain in patients. CONCLUSION: These results suggest a more accurate lithotripsy should be performed according to respiratory regularity.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Comparison of functional and oncological outcomes between uterus-sparing radical cystectomy and standard radical cystectomy in females: A retrospective study.

PURPOSE: This study aimed to compare the functional and oncological outcomes of females who underwent uterus-sparing radical cystectomy (USRC) and standard radical cystectomy (SRC). MATERIALS AND METHODS: Between February 2009 and December 2020, 90 female patients who underwent radical cystectomy with urinary diversion were included in this study, comprising the USRC and SRC groups. Functional outcomes were assessed in 63 patients who only underwent radical cystectomy with neobladder formation. Questionnaire scores, clean intermittent catheterization (CIC) rate, and urinary continence rate were analyzed. Oncological outcomes were assessed in 86 patients, regardless of the urinary diversion type. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared. RESULTS: CIC rate was significantly lower in the USRC group than in the SRC group (14.7% vs. 48.0%; p=0.005). The continence rate was significantly higher in the USRC group than in the SRC group (85.3% vs. 40.0%; p=0.001). There were no significant differences in OS (p=0.890), CSS (p=0.700), or RFS (p=0.270) between the two groups. In multivariate analysis, uterine preservation did not significantly increase the hazard ratio (HR) of OS (HR, 0.62; 95% CI, 0.18-2.11; p=0.450), CSS (HR, 0.99; 95% CI, 0.22-4.40; p=0.990), or RFS (HR, 0.46; 95% CI, 0.19-1.11; p=0.840). CONCLUSIONS: USRC resulted in higher continence rates and lower CIC rates than SRC without negatively affecting oncological outcomes. Hence, with thorough deliberation, USRC should be considered for females undergoing radical cystectomy.

Risk Factors for Transurethral Coagulation for Hemostasis During Holmium Laser Enucleation of the Prostate.

PURPOSE: We aimed to identify risk factors for transurethral coagulation (TUC) using bipolar electrocautery for hemostasis during holmium laser enucleation of the prostate (HoLEP) surgery for benign prostatic hyperplasia (BPH). METHODS: We analyzed the clinical outcomes of HoLEP surgery performed by a single surgeon between January 2010 and April 2020 at the Seoul National University Hospital. Patient characteristics and perioperative parameters were used to identify the risk factors for TUC. The TUC group was defined as a case of conversion to hemostasis using electrocautery during the hemostasis step after enucleation. RESULTS: Of 1,563 patients, 357 underwent TUC (TUC group; 22.8%) as an adjuvant (n=299, 19.1%) or salvage (n=58, 3.7%) therapy. Patients in the TUC group were older (mean±standard deviation, 70.6±7.3 years vs. 69.3±7.0 years; P=0.002), had more 5-alpha reductase inhibitor (5-ARI) use (35.6% vs. 25.9%, P<0.001), higher serum prostate-specific antigen (PSA) (5.4 ±4.8 ng/mL vs. 3.8 ±4.5 ng/mL, P <0.001), larger total prostate volume (TPV) (89.5 ±44.7 mL vs. 66.0 ±32.6 mL, P<0.001), and larger transitional zone volume (TZV) (57.3±34.9 mL vs. 37.7±24.2 mL, P<0.001) than those who did not undergo TUC (non-TUC group). In univariate logistic regression analysis, age, 5-ARI use, PSA, TPV, and TZV correlated with TUC, whereas in multivariate logistic regression analysis, only TZV was associated with TUC. The odds ratios (ORs) of TUC were analyzed per TZV quartile. Compared to TZV<22.3 mL, the OR was 2.42 in 34.1 mL≤TZV<53.5 mL (95% confidence interval [CI], 1.58-3.72; P<0.001), 5.17 in ≥53.5 mL (95% CI, 3.44-7.77; P<0.001). CONCLUSION: The risk of TUC during HoLEP surgery increases in patients with TZV >35 mL. Therefore, TUC may be potentially necessary in patients with a large transition zone volume in patients with BPH.

Surgical Parameters Related to Excessive Intrarenal Pressure during Minimally Invasive Percutaneous Nephrolithotomy in the Supine Position: A Prospective Observational Clinical Study.

Objective: Excessive intrarenal pressure (IRP) during surgery for renal stones is related to postoperative complications due to systemic absorption of bacteria and endotoxins. This study is aimed at evaluating factors that induce excessive IRP in minimally invasive percutaneous lithotripsy (mini-PCNL) in the supine position. Methods: 27 patients underwent mini-PCNL for intrarenal stones under supine position and were analyzed in this study. The IRP changes were measured at the phases of "baseline," "table tilting," "upper-pole navigation," "stone fragmentation," and "vacuum cleaning effect." The relationship between the mean IRP and cumulative time of IRP ≥ 30 cmH2O was analyzed by according to the surgical parameters. Multiple regression analysis showed the effect of the surgical parameters on postoperative fever-related IRP elevation. Results: Mean age was 59.3 ± 14.6 years. The mean stone burden was 24.6 ± 8.1 mm3. IRP was higher than baseline (31.6 ± 12.1) during upper-pole navigation (60.0 ± 22.9, p = 0.003) and stone fragmentation (46.2 ± 9.9, p < 0.001). The subgroup's IRP baseline < 20 cmH2O significantly increased during the upper-pole navigation. Changes in IRP at each stage were affected by baseline IRP (p < 0.001), operation methods (p = 0.021), number of calyces with stones (p = 0.034), and laser energy of Joules (p = 0.041) and frequency (p = 0.038). Conclusion: In supine mini-PCNL, the IRP was higher during laser fragmentation and upper-pole navigation. The table tilting procedure can be helpful in selected patients. The vacuum cleaner effect did not affect IRP.

Rapid and accurate nanoelectrokinetic diagnosis of drug-resistant bacteria.

Increased antimicrobial resistance presents a major threat to public health, and it is a global health problem due to the rapid globalization and transmission of infectious diseases. However, fast and precise diagnosis tool is lacking, and inappropriate antibiotic prescription leads to the unforeseen production of drug-resistant bacteria. Here, we report a Rapid and Accurate Nanoelectrokinetic Diagnostic System (RANDx) for detecting drug-resistant bacteria, which cause a common infectious disease called Urinary Tract Infection (UTI), within 7 min. We develop nanoelectrokinetic paper-based analytic device (NEK-PAD) as a sample prep module of RANDx and obtain >100-fold post-wetting preconcentration by balancing between ion concentration polarization (ICP) and radial imbibition for a constant flow rate. Simultaneously with preconcentration, our cathodic nanochannel design enables NEK-PAD to extract drug-resistant enzymes without denaturation and accelerate enzyme-linked reactions under electrical spontaneous heating at approximately 37 °C. Finally, using a cell phone camera, we detect label-free drug-resistant bacteria as low as 104 cfu/mL, which is higher than clinically required threshold (>105 cfu/mL) by enhancing 1000 times of the limit of detection (LOD) of colorimetric nitrocefin assay. We believe that the RANDx will be an innovative precision medicine tool for UTI and other infectious diseases in limited remote settings.

Containment Liner Plate Void Defect Detection Technique Using Phased Array Ultrasonic Testing and Acoustic Resonance Method.

The CLP (containment liner plate) of a nuclear power plant protects the internal system from the external environment and sudden changes in internal pressure or temperature, and it is a structure that blocks and protects radioactive materials leaking inside and outside in the event of a nuclear accident and is composed of a liner plate, reinforcing bars, tendons, and concrete. Recently, corrosion on the rear side of the liner plate and concrete voids has emerged as a severe defect in nuclear power plants across South Korea. Therefore, in this study, we proposed a new inspection method that a line-type inspection method applied phased array ultrasonic testing and the area inspection method applied acoustic resonance method using developed moveable tapper. The acoustic signals were signal-processed and reproduced to a mapping image following the inspection area, and with the image, it was possible to determine the type of defect. Furthermore, an automated inspection system for within the CLP was proposed.

Clinical characteristics and treatment outcomes of patients with pneumonia caused by Raoultella planticola.

BACKGROUND: Raoultella planticola, considered to be an environmental organism, is a rare cause of human infections. Although in recent years the frequency of R. planticola infections reported in the literature has increased, few cases of pneumonia caused by R. planticola have been described. Here, we investigate the clinical characteristics, management, and clinical outcomes of pneumonia caused by R. planticola. METHODS: Consecutive patients with pneumonia caused by R. planticola were included. The medical records of patients with R. planticola pneumonia treated at Dankook University Hospital from January 2011 to December 2017 were collected. RESULTS: A total of 11 adult patients with R. planticola pneumonia were diagnosed and treated [10 males and 1 female; median age, 70 years (range: 51-79 years)]; 5 patients had underlying malignant conditions (45.5%). Antibacterial susceptibility testing showed that all isolates of R. planticola were susceptible to cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and beta-lactams/beta-lactamase inhibitors. Chest imaging revealed consolidation (8/11, 72.7%), ground-glass opacity (5/11, 45.5%), pleural effusion (5/11, 45.5%), and micronodules (3/11, 27.3%). Four patients (36.4%) required mechanical ventilation; three survived but one died of multiple organ dysfunction syndrome (principally pneumonia and septic shock). CONCLUSIONS: R. planticola pneumonia occurred mainly in patients with underlying risk factors such as malignant disease, cerebral infarction or hemorrhage, and chronic obstructive pulmonary disease. The organism was sensitive to most antibiotics, and the clinical outcomes were favorable after empirical antibiotic therapy.

Controllable pH Manipulations in Micro/Nanofluidic Device Using Nanoscale Electrokinetics.

Recently introduced nanoscale electrokinetic phenomenon called ion concentration polarization (ICP) has been suffered from serious pH changes to the sample fluid. A number of studies have focused on the origin of pH changes and strategies for regulating it. Instead of avoiding pH changes, in this work, we tried to demonstrate new ways to utilize this inevitable pH change. First, one can obtain a well-defined pH gradient in proton-received microchannel by applying a fixed electric current through a proton exchange membrane. Furthermore, one can tune the pH gradient on demand by adjusting the proton mass transportation (i.e., adjusting electric current). Secondly, we demonstrated that the occurrence of ICP can be examined by sensing a surrounding pH of electrolyte solution. When pH > threshold pH, patterned pH-responsive hydrogel inside a straight microchannel acted as a nanojunction to block the microchannel, while it did as a microjunction when pH < threshold pH. In case of forming a nanojunction, electrical current significantly dropped compared to the case of a microjunction. The strategies that presented in this work would be a basis for useful engineering applications such as a localized pH stimulation to biomolecules using tunable pH gradient generation and portable pH sensor with pH-sensitive hydrogel.

Surface conduction and electroosmotic flow around charged dielectric pillar arrays in microchannels.

Dielectric microstructures have been reported to have a negative influence on permselective ion transportation because ions do not migrate in areas where the structures are located. However, the structure can promote the transportation if the membrane is confined to a microscopic scale. In such a scale where the area to volume ratio is significantly large, the primary driving mechanisms of the ion transportation transition from electro-convective instability (EOI) to surface conduction (SC) and electroosmotic flow (EOF). Here, we provide rigorous evidence on how the SC and EOF around the dielectric microstructures can accelerate the ion transportation by multi-physics simulations and experimental visualizations. The microstructures further polarize the ion distribution by SC and EOF so that ion carriers can travel to the membrane more efficiently. Furthermore, we verified, for the first time, that the arrangements of microstructures have a critical impact on the ion transportation. While convective flows are isolated in the crystal pillar configuration, the flows show an elongated pattern and create an additional path for ion current in the aligned pillar configuration. Therefore, the fundamental findings of the electrokinetic effects on the dielectric microstructures suggest an innovative application in micro/nanofluidic devices with high mass transport efficiency.

Ultrathin conformal devices for precise and continuous thermal characterization of human skin.

Precision thermometry of the skin can, together with other measurements, provide clinically relevant information about cardiovascular health, cognitive state, malignancy and many other important aspects of human physiology. Here, we introduce an ultrathin, compliant skin-like sensor/actuator technology that can pliably laminate onto the epidermis to provide continuous, accurate thermal characterizations that are unavailable with other methods. Examples include non-invasive spatial mapping of skin temperature with millikelvin precision, and simultaneous quantitative assessment of tissue thermal conductivity. Such devices can also be implemented in ways that reveal the time-dynamic influence of blood flow and perfusion on these properties. Experimental and theoretical studies establish the underlying principles of operation, and define engineering guidelines for device design. Evaluation of subtle variations in skin temperature associated with mental activity, physical stimulation and vasoconstriction/dilation along with accurate determination of skin hydration through measurements of thermal conductivity represent some important operational examples.

Radiological anatomical consideration of conjoined nerve root with a case review.

Nerve root anomalies are frequently underrecognized regardless of the advances in imaging studies; they are also underappreciated and underreported when encountered surgically. The classification of conjoined nerve roots is based on whether the nerve root emerges at an abnormal level or from an anastomotic branch. In the present report, we describe case with a conjoined nerve root that emerged at a more caudal level than that normally observed that was an undiagnosed on preoperative imaging studies. We also discuss the atypical imaging features obtained through preoperative imaging studies. As observed in the present case, preoperative recognition and diagnosis of such anomalies offer the best opportunity of performing a successful procedure and preventing inadvertent damage to nerve roots intraoperatively.

Feasibility of C2 translaminar screw as an alternative or salvage of C2 pedicle screws in atlantoaxial instability.

STUDY DESIGN: A retrospective outcome study. OBJECTIVE: The purpose of this study was to analyze the clinical outcomes of our experience with the C2 translaminar screw technique and evaluate its feasibility as an alternative or salvage of the pedicle screw. SUMMARY OF BACKGROUND DATA: Pedicle screws are the most biomechanically stable screws for use in atlantoaxial fixation. However, in cases with elevated risk of neurovascular complications or failure of screw insertion attempts, a reliable alternative technique is required. METHODS: Fourteen patients with atlantoaxial instability underwent posterior fixation with C2 translaminar screws. Indications included traumatic instability, atlantoaxial subluxation, os odontoideum, and fusion failure after anterior fixation of a type II odontoid process fracture. A total of 26 screws were inserted and all patients were assessed both clinically and radiographically. RESULTS: No procedure-related complications or hardware failures were observed during the follow-up. Postoperative computed tomographic scans revealed laminar breach in 3 patients and none of these resulted in neurological symptoms. Radiographically demonstrated bony fusion was established in 11 patients (91.7%) at follow-up over 6 months, and 5 patients with initial neurological deficit demonstrated at least 1 grade improvement by Frankel grade. CONCLUSIONS: C2 translaminar screws provide surgeons with an expanded option for posterior fusion in high cervical lesions. This technique is safe and easy to adopt with a favorable rate of successful fusion. We believe that preoperative planning using computed tomographic scan is mandatory and use of an additional connector may reduce the stress and strain of the screws.

Relationship between strain rate imaging and coronary flow reserve in assessing myocardial viability after acute myocardial infarction.

OBJECTIVES: To evaluate the relationship between strain rate (SR) imaging and coronary flow reserve (CFR) in assessing viability of akinetic myocardium after acute myocardial infarction (MI). METHODS: Forty patients with acute first ST-elevation MI were analyzed. SR imaging and CFR by intracoronary flow measurement were obtained on the same day, 3~5 days after primary percutaneous coronary intervention. Viability of the akinetic myocardium was determined on 6-week echocardiography. RESULTS: Systolic SR (SRs, -0.42 ± 0.10 vs. -0.35 ± 0.11 per second, P = 0.03), early diastolic SR (SRe, 0.68 ± 0.31 vs. 0.41 ± 0.22 per second, P = 0.003), and systolic strain (Ss, -5.9 ± 3.4 vs. -2.5 ± 4.0%, P = 0.04) were greater in akinetic, but viable myocardium of 21 patients than in akinetic and nonviable myocardium of 19 patients. CFR was also higher in patients with akinetic, but viable myocardium (2.0 ± 0.5 vs. 1.5 ± 0.5, P < 0.001). SRs, SRe, and Ss were significantly related to CFR (r =-0.50, r = 0.58, r =-0.56, respectively, all P ≤ 0.001) and SRe was most related to CFR (P < 0.001). The sensitivity and specificity to predict myocardial viability were 85.7% and 68.4% for CFR (cutoff = 1.75), and 90.5% and 57.9% for SRe (cutoff = 0.37 per second), respectively. CONCLUSIONS: The degree of myocardial deformation determined by SR imaging was related to the degree of microvascular integrity determined by CFR, and can be used as a noninvasive method to predict myocardial viability after acute MI.

Remote cerebellar hemorrhage complicated after supratentorial surgery: retrospective study with review of articles.

OBJECTIVE: Remote cerebellar hemorrhage (RCH) is one of the rare complications occurring after supratentorial surgery, and its pathomechanism is poorly understood. We report 10 cases of RCH from our institution and review 154 cases from a database in order to delineate incidence, common presentation, risk factors, and outcomes of this complication. In addition, the means of prevention are discussed. METHODS: We reviewed the medical records of 10 patients who experienced RCH after undergoing supratentorial surgery at our institution between 2001 and 2008. A database search in Medline revealed 154 cases of RCH in the English literature. Characteristic features were analyzed and compared. RESULTS: There were 10 cases of RCH among 3307 supratentorial surgery cases, indicating a 0.3% incidence. All patients had characteristic imaging features of RCH, namely a streaky bleeding pattern in the superior folia of the cerebellum. Seven patients had a history of preoperative hypertension. Four cases were related to cerebral aneurysms, and other four developed after the removal of brain tumors. Cerebrospinal fluid (CSF) drainage apparatuses were installed postoperatively in all cases. Outcomes according to modified Rankin scale (mRS) were good in 7 patients, with 1 fatal case. CONCLUSION: RCH is a rare complication after supratentorial surgery, and the exact etiology still remains uncertain. Hypertension and perioperative loss of CSF seem positively correlated with RCH, but no single risk factor is totally responsible. Patients with RCH should be closely observed to improve their prognosis.

Comparison of low vs moderate dose of atorvastatin in clopidogrel resistance after coronary stenting in Korean patients with acute coronary syndrome.

BACKGROUND: The effect of atorvastatin 10 mg vs 40 mg in clopidogrel resistance and clinical events after coronary stenting was compared in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Platelet aggregation was measured before clopidogrel administration and 4 h, 24 h, 5 days, and 8 months later in 130 ACS patients. Stented patients were randomly assigned to atorvastatin either 10 mg (n=65) or 40 mg (n=65), and received an oral loading dose of 300 mg of clopidogrel followed by 75 mg/day for 8 months. Measurement of platelet aggregation was done by the turbimetric method. The mean % changes in inhibition of platelet aggregation were 35.5 +/-8.3, 50.9 +/-10.1, 38.3 +/-8.3, 40.0 +/-6.8 in the Atorvastatin 10 mg Group and 31.0 +/-7.6, 43.7 +/-9.8, 45.0 +/-10.3, 43.5 +/-7.8 (4 h, 24 h, 5 days, and 8 months, respectively, after 300 mg of clopidogrel pretreatment) in the Atorvastatin 40 mg Group with no significant differences between the 2 groups. Cardiovascular events showed no significant differences during the follow-up. CONCLUSIONS: Atorvastatin 10 mg or 40 mg co-administered with clopidogrel for 8 months did not affect the antiplatelet potency of clopidogrel and showed no significant differences in the clinical events in ACS patients.

Repression of TNF-alpha-induced IL-8 expression by the glucocorticoid receptor-beta involves inhibition of histone H4 acetylation.

Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)beta, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRalpha. However, recent data suggest that GRbeta is not a dominant negative inhibitor of GRalpha in the transrepressive process and has its own functional role. We investigated the functional role of GRbeta expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-alpha-induced IL-8 release in an airway epithelial cell line. GRbeta expression was induced by treatment of epithelial cells with either dexamethasone or TNF-alpha. GRbeta was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-alpha-induced IL-8 transcription was not affected by GRbeta overexpression, rather GRbeta had its own weak suppressive activity on TNF-alpha-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRbeta overexpression, but TNF-alpha-induced histone H4 acetylation at the IL-8 promoter was decreased with GRbeta overexpression. This study suggests that GRbeta overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRbeta induces its own histone deacetylase activity around IL-8 promoter site.

Profiling the thermodynamic softness of adenoviral promoters.

We showed previously that anharmonic DNA dynamical features correlate with transcriptional activity in selected viral promoters, and hypothesized that areas of DNA softness may represent loci of functional significance. The nine known promoters from human adenovirus type 5 were analyzed for inherent DNA softness using the Peyrard-Bishop-Dauxois model and a statistical mechanics approach, using a transfer integral operator. We found a loosely defined pattern of softness peaks distributed both upstream and downstream of the transcriptional start sites, and that early transcriptional regions tended to be softer than late promoter regions. When reported transcription factor binding sites were superimposed on our calculated softness profiles, we observed a close correspondence in many cases, which suggests that DNA duplex breathing dynamics may play a role in protein recognition of specific nucleotide sequences and protein-DNA binding. These results suggest that genetic information is stored not only in explicit codon sequences, but also may be encoded into local dynamic and structural features, and that it may be possible to access this obscured information using DNA dynamics calculations.