Investigation of photodarkening in tandem-pumped Yb-doped fibers.

Investigation of photodarkening (PD) in Yb-doped fibers tandem-pumped at 1018 nm is reported. For a homemade Yb-doped aluminosilicate double-clad fiber (YADF), the transmitted power of a 633 nm probe beam is reduced by 2.4% over 2 hours for the tandem pumping configuration at 1018 nm, which is significantly smaller than 33.3% for a laser diode (LD) pumping at 976 nm. A tandem-pumped Yb fiber amplifier also shows a much smaller decrease in the amplified output power over time than a LD-pumped Yb fiber amplifier. Based on fluorescence spectra of the YADF, we can not only associate PD of the YADF to intrinsic oxygen deficiency centers or Tm3+ impurities but also confirm the impact of the excited Yb3+ ion density on PD. The benefits of the tandem pumping in a high-power Yb fiber laser system will be discussed.

Navigation programs, are they helpful for perioperative care with thyroid cancer patients?

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.

Risk factors for peri-anaesthetic dental injury.

In this retrospective case-control study, we evaluated peri-operative dental injury risk factors following tracheal intubation. Ninety-four of 290,415 patients experienced dental injury following tracheal intubation over a 10-y period. A control group was matched for surgery type and intubating anaesthetist. The incidence of dental injury was 0.03%. Univariate analysis revealed that previous and current difficult intubation, male gender, hepatitis, neurological disease, anticonvulsant use, pre-existing poor dentition and the use of airway devices (other than a laryngoscope) were associated with dental injury. Multivariate analysis revealed that predictors of dental injury were: history of hepatitis, odds ratio (95% CI) 10.1 (1.02-100.3); poor dentition, 8.8 (3.9-20.0); alternative airway device use, 3.1 (1.2-8.0); and intubation difficulty, 3.7 (1.0-13.3). As well as confirming previously reported risk factors for dental injury during tracheal intubation, this study also suggests hepatitis and the use of alternative airway devices as additional risk factors.

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration.

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.

Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death.

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase and its dysregulation is implicated in neurodegenerative diseases. Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5-mediated phosphorylation disrupts the interaction between CHIP and truncated apoptosis-inducing factor (tAIF) without affecting CHIP's E3 ligase activity, resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral transduction assay shows that knockdown of Cdk5 or overexpression of CHIP(S20A), but not CHIP(WT), attenuates tAIF-mediated neuronal cell death induced by hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP negatively regulates its neuroprotective function, thereby contributing to neuronal cell death progression following neurotoxic stimuli.

Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters.

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.

FV-162 is a novel, orally bioavailable, irreversible proteasome inhibitor with improved pharmacokinetics displaying preclinical efficacy with continuous daily dosing.

Approved proteasome inhibitors have advanced the treatment of multiple myeloma but are associated with serious toxicities, poor pharmacokinetics, and most with the inconvenience of intravenous administration. We therefore sought to identify novel orally bioavailable proteasome inhibitors with a continuous daily dosing schedule and improved therapeutic window using a unique drug discovery platform. We employed a fluorine-based medicinal chemistry technology to synthesize 14 novel analogs of epoxyketone-based proteasome inhibitors and screened them for their stability, ability to inhibit the chymotrypsin-like proteasome, and antimyeloma activity in vitro. The tolerability, pharmacokinetics, pharmacodynamic activity, and antimyeloma efficacy of our lead candidate were examined in NOD/SCID mice. We identified a tripeptide epoxyketone, FV-162, as a metabolically stable, potent proteasome inhibitor cytotoxic to human myeloma cell lines and primary myeloma cells. FV-162 had limited toxicity and was well tolerated on a continuous daily dosing schedule. Compared with the benchmark oral irreversible proteasome inhibitor, ONX-0192, FV-162 had a lower peak plasma concentration and longer half-life, resulting in a larger area under the curve (AUC). Oral FV-162 treatment induced rapid, irreversible inhibition of chymotrypsin-like proteasome activity in murine red blood cells and inhibited tumor growth in a myeloma xenograft model. Our data suggest that oral FV-162 with continuous daily dosing schedule displays a favorable safety, efficacy, and pharmacokinetic profile in vivo, identifying it as a promising lead for clinical evaluation in myeloma therapy.

[(18)F] FP-CIT PET study in parkinsonian patients with leukoaraiosis.

BACKGROUNDS: Leukoaraiosis may present with slowly progressive parkinsonism indistinguishable from primary degenerative parkinsonism. Both leukoaraiosis and degenerative parkinsonism are an age-related disorder. Thus, comorbidity is expected to be common in elderly patients with parkinsonism. However, no systematic study has been reported on the clinical features indicating concomitant nigrostriatal dopaminergic denervation (NDD) in parkinsonian patients with leukoaraiosis. METHODS: We performed [(18)F] FP-CIT positron emission tomography studies in 42 consecutive parkinsonian patients with diffuse leukoaraiosis, but no basal ganglia vascular lesions. RESULTS: Twenty (48%) of the 42 patients had coexisting NDD. Compared to parkinsonian patients with isolated leukoaraiosis, those with coexisting NDD more frequently had asymmetric onset. They had similar degree of parkinsonian motor deficits in the legs, but greater rigidity and resting tremor in the arms. Consequently, they had less prominent lower body parkinsonism. They more frequently showed favorable response to levodopa treatment. They had similar burden of regional and total leukoaraiosis. Among a variety of clinical variables and MRI findings, only asymmetric onset and more than 30% improvement in UPDRS motor score by levodopa treatment were valuable indicators of coexisting NDD. CONCLUSIONS: We would like to recommend dopaminergic functional imaging studies for all parkinsonian patients with leukoaraiosis. Further studies are needed to confirm sensitivity and specificity of asymmetric onset and good levodopa response for the prediction of coexisting NDD in a different group of parkinsonian patients with leukoaraiosis.

Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial.

BACKGROUND: Nefopam has been used as an adjuvant to opioid analgesia after operation. We investigated the efficacy of nefopam as an adjunct to fentanyl-based intravenous patient-controlled analgesia (IV PCA) on post-operative pain relief in patients undergoing renal transplantation. METHODS: Ninety-eight patients undergoing elective renal transplantation were randomised into two groups: nefopam or control groups. The former received nefopam (160 mg in 200 ml at a rate of 4 ml/h) whereas the latter received normal saline during the first 48 h after reperfusion of grafted kidney. Pain intensity scores, cumulative dose of fentanyl, and the incidence of adverse events were assessed at 1, 6, 12, 24, and 48 h post-operatively. Serum creatinine and estimated glomerular filtration rate were evaluated on post-operative days 1, 2, 4, and 7. RESULTS: The cumulative fentanyl consumption during the first 48 h after operation was 19% less in the nefopam group than that in the control group (1005 ± 344 µg vs. 1246 ± 486 µg, mean ± SD; P = 0.006). Pain intensity scores at rest and on coughing were significantly lower in the nefopam group throughout the first 12 and 48 h after operation, respectively. Adverse events and early graft function were comparable between the groups, except a significantly lower incidence of drowsiness observed in the nefopam group (4% vs. 21%, P = 0.027). CONCLUSION: In combination with fentanyl PCA, nefopam reduced post-operative fentanyl consumption with superior analgesia after renal transplantation.

Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia.

The purpose of this study was to investigate the effects of dexmedetomidine on biventricular systolic and diastolic function using transoesophageal echocardiography. Cardiac function was assessed in 30 healthy patients who received total intravenous anaesthesia with propofol and remifentanil. The echocardiographic examinations were performed just before and 20, 40 and 60 min after dexmedetomidine or saline administration. Patients who received dexmedetomidine, compared with saline after 20 min, had a lower mean (SD) heart rate (56.7 (5.2) vs. 67.1 (7.1) beats.min(-1) ), higher systolic blood pressure (125.7 (18.9) vs. 109 (7.9) mmHg), and lower cardiac output (2.9 (0.5) vs. 3.7 (1.0) l.min(-1) ), respectively (all p < 0.05). In contrast, no changes were observed in biventricular systolic and diastolic indices in either group, and there were no inter-group differences at any time point. Dexmedetomidine, as an adjuvant to total intravenous anaesthesia, does not impair biventricular systolic and diastolic function in healthy patients, but decreases cardiac output by reducing heart rate.

Heart rate variability dynamics during controlled hypotension with nicardipine, remifentanil and dexmedetomidine.

BACKGROUND: This study was done to investigate how nicardipine, remifentanil and dexmedetomidine affect the balance of the autonomic nervous system in patients receiving controlled hypotension under general anaesthesia by evaluating heart rate variability indices. METHODS: Sixty-two patients were randomly allocated to either the nicardipine-sevoflurane (Group N, n = 21), remifentanil-sevoflurane (Group R, n = 21) or dexmedetomidine-sevoflurane (Group D, n = 20) group for controlled hypotension during orthognathic surgery. Electrocardiogram data acquisition was done after vital sign stabilization following anaesthesia induction (T1) and 30 min after controlled hypotension was induced (T2). RESULTS: Total power and low frequency (LF) power was significantly decreased at T2 compared with T1 in all groups, while a decrease in high frequency (HF) power was only observed in Group N (P < 0.001). LF/HF ratios of Group R and D were significantly suppressed at T2 compared with T1 (P = 0.001 and P < 0.001, respectively), but was increased Group N (P = 0.009). The LF/HF ratio of Group N was significantly higher than Group R and D at T2 (P < 0.001 in both), with Group D showing a significantly lower LF/HF ratio compared with Group R (P < 0.001). CONCLUSIONS: Remifentanil and dexmedetomidine did not have sympathetic nervous system-stimulating effects during controlled hypotension, while remifentanil seemed to be superior in preserving the overall balance in autonomic nervous system activity. Nicardipine was found to stimulate the sympathetic nervous system, which may be problematic in patients vulnerable to disturbances in the autonomic nervous system.

Identification of the effects of aging-related gene-matrix metalloproteinase on allograft outcomes in kidney transplantation.

BACKGROUND: Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients. METHODS: Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3). RESULTS: The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022). CONCLUSIONS: Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation.

Randomized controlled comparison of combined general and epidural anesthesia versus general anesthesia on diaphragmatic function after laparoscopic prostatectomy.

BACKGROUND: Little is known about the effect of anesthetic technique on postoperative diaphragmatic function, which is associated with postoperative morbidity and recovery in patients undergoing laparoscopic pelvic surgery. The aim of this trial was to study the effect of combined general and epidural anesthesia versus general anesthesia on postoperative diaphragmatic function measured by ultrasonography in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP). METHODS: Fifty-four patients undergoing RALRP were enrolled prospectively. Study population was randomized to receive general (group G, N.=27) or combined general and epidural (group GE, N.=27) anesthesia. Diaphragmatic inspiratory amplitude (DIA), and inspiration and expiration time (Ti and Te, respectively) were measured by M-mode ultrasonography during quiet/deep breathing and sniffing before the surgery and on postoperative days (POD) 1 and 2. Diaphragmatic inspiratory and expiratory velocities (DIV and DEV) were also calculated (DIA/Ti and DIA/Te, respectively). Spirometry was performed in addition to ultrasonography. RESULTS: DIA during deep breathing and sniffing was significantly decreased on POD 1 in group G, while it was preserved in group GE. These reductions in diaphragmatic function were restored to preoperative values on POD 2 in both groups. Vital capacity and peak expiratory flow were diminished in group G on POD 1 and 2. However, spirometry revealed no impairment in group GE except for vital capacity on POD 1. The correlation coefficients (R2) between diaphragmatic function and spirometry variables ranged from 0.231 to 0.286. Postoperaitve pain was comparable. CONCLUSION: Combined general and epidural anesthesia may attenuate the severity of postoperative diaphragmatic dysfunction after RALRP compared to conventional general anesthesia.

Effects of single-dose dexmedetomidine on the quality of recovery after modified radical mastectomy: a randomised controlled trial.

BACKGROUND: Dexmedetomidine is a highly selective α2 agonist with analgesic, anxiolytic, and anti-inflammatory properties. We investigated the effect of a single dose of dexmedetomidine on patient-perceived quality of recovery and clinical recovery variables after modified radical mastectomy under general anesthesia in this randomized, double-blind, placebo-controlled study. METHODS: After Institutional Review Board approval, ninety two female patients were randomly allocated to receive intravenously either saline (Group C, N.=46) or 0.5 µg/kg of dexmedetomidine (Group D, N.=46) five min before the end of surgery. The quality of recovery was assessed using a 40-item quality-of-recovery scoring system (QoR-40) preoperatively and 24 h after surgery. Pain intensity, rescue analgesics, and postoperative nausea and vomiting (PONV) were assessed at postanesthesia care unit (PACU), 1-6 h, and 6-24 h after surgery. RESULTS: Postoperative global QoR-40 scores were higher in Group D compared with Group C (181 [175-187] vs. 174 [154.5-181.5], P=0.004); postoperative QoR-40 scores were improved in the dimensions of emotional state, physical comfort, and psychological support. Total amount of tramadol during 24 h after surgery was significantly lower in Group D than in Group C (54 vs. 76 mg, P=0.006). The incidence of PONV was lower in Group D than in Group C in PACU (21% vs. 43%, P=0.026) and 6-24 h period after surgery (10% vs. 41%, P=0.012). Heart rate and mean blood pressure were significantly lower in Group D as compared with Group C at 5 min after administration of dexmedetomidine, 1 min after extubation, and 20 min after arrival in PACU. CONCLUSION: The use of a single dose dexmedetomidine improved the quality of recovery and reduced analgesic requirements and the incidence of PONV in the early postoperative period after modified radical mastectomy.

Extraskeletal myxoid chondrosarcoma of the neck.

Extraskeletal myxoid chondrosarcoma is a rare malignant soft-tissue tumour that is typically in the deep soft tissues of the lower extremity. The tumour is usually a well-defined, multinodular soft-tissue mass without calcifications. A 62-year-old woman with a history of nasopharyngeal cancer presented with a palpable mass in the anterior neck. Radiologically, the lesion was a well-defined soft-tissue mass with the extensive calcifications on various imaging examinations. Although this lesion was histopathologically diagnosed as extraskeletal myxoid chondrosarcoma, the unusual imaging findings were challenging and very intriguing.

Effects of a 1:1 inspiratory to expiratory ratio on respiratory mechanics and oxygenation during one-lung ventilation in the lateral decubitus position.

Prolonged inspiratory to expiratory (I:E) ratio ventilation may have both positive and negative effects on respiratory mechanics and oxygenation during one-lung ventilation (OLV), but definitive information is currently lacking. We therefore compared the effects of volume-controlled ventilation with I:E ratios of 1:1 and 1:2 on respiratory mechanics and oxygenation during OLV. Fifty-six patients undergoing thoracoscopic lobectomy were randomly assigned volume-controlled ventilation with an I:E ratio of 1:1 (group 1:1, n=28) or 1:2 (group 1:2, n=28) during OLV. Arterial and central venous blood gas analyses and respiratory variables were recorded 15 minutes into two-lung ventilation, at 30 and 60 minutes during OLV, and 15 minutes after two-lung ventilation was re-initiated. Peak and plateau airway pressures in cmH2O [standard deviation] during OLV were significantly lower in group 1:1 than in group 1:2 (P <0.01) (19 [3] and 23 [4]; 16 [3] and 19 [5], respectively). The arterial to end-tidal carbon dioxide tension difference was significantly lower in group 1:1 than in group 1:2 (P <0.01), (0.5 [0.3] and 1.1 [0.5]). There were no significant differences in PaO2 during OLV between the two groups (OLV30, P=0.856; OLV60, P=0.473). In summary, volume-controlled ventilation with an I:E ratio of 1:1 reduced peak and plateau airway pressures improved dynamic compliance and efficiency of alveolar ventilation, but it did not improve arterial oxygenation in a substantial manner. Furthermore, the associated increase in mean airway pressure might have reduced cardiac output, resulting in a lower central venous oxygen saturation.

Prurigo pigmentosa: a clinicopathologic study of 16 cases.

BACKGROUND: Prurigo pigmentosa is a rare inflammatory disease of unknown origin. It is characterized by the sudden onset of pruritic erythematous papules, usually involving the trunk and neck, which coalesce to form reticulated, mottled patches. METHODS: We studied 16 patients with prurigo pigmentosa. The patients were selected from those attending the outpatient Department of Dermatology at the Kyung Hee University Hospital from January 2002 to January 2010. All clinical information was retrospectively collected from medical records. The serum concentrations of ketones (acetoacetic acid, 3-hydroxybutyrate acid [3-OHBA]) were examined in four patients, and a test for ketone in the urine was performed in 10 patients. RESULTS: The age at the time of diagnosis ranged from 18 to 36 years (mean age: 23.5 years), and the female : male ratio was 14 : 2. Skin lesions were almost always characterized by recurrent pruritic erythematous papules that had resolved, leaving a peculiar, reticulate hyperpigmentation. Eight of 16 patients showed a chronological relationship between a prurigo pigmentosa appearance of skin lesions and dieting or fasting. Histopathological findings were either of fully developed lesions (4/16) or late lesions (12/16). Most patients responded well to minocycline treatment. Ketosis was observed in six patients. CONCLUSIONS: In conclusion, we propose that ketosis was caused by fasting, and that diet may contribute to the pathogenesis of prurigo pigmentosa. Thus, physicians need to warn that excessive fasting can cause prurigo pigmentosa.

AFM study of the differential inhibitory effects of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) against Gram-positive and Gram-negative bacteria.

(-)-Epigallocatechin-3-gallate (EGCG), a main constituent of tea catechins, affects Gram-positive and Gram-negative bacteria differently; however, the underlying mechanisms are not clearly understood. Atomic force microscopy (AFM) was used to compare morphological alterations in Gram-positive and Gram-negative bacteria induced by EGCG and by H(2)O(2) at sub-minimum inhibitory concentrations (MICs). EGCG initially induced aggregates in the cell envelopes of Staphylococcus aureus and eventually caused cell lysis, which was not observed in cells treated with H(2)O(2). It initially induced nanoscale perforations or microscale grooves in the cell envelopes of Escherichia coli O157:H7 which eventually disappeared, similar to E. coli cells treated with H(2)O(2). An E. coli O157:H7 tpx mutant, with a defect in thioredoxin-dependent thiol peroxidase (Tpx), was more severely damaged by EGCG when compared with its wild type. Similar differing effects were observed in other Gram-positive and Gram-negative bacteria when exposed to EGCG; it caused aggregated in Streptococcus mutans, while it caused grooves in Pseudomonas aeruginosa. AFM results suggest that the major morphological changes of Gram-negative bacterial cell walls induced by EGCG depend on H(2)O(2) release. This is not the case for Gram-positive bacteria. Oxidative stress in Gram-negative bacteria induced by EGCG was confirmed by flow cytometry.

Calibrated nanoscale capacitance measurements using a scanning microwave microscope.

A scanning microwave microscope (SMM) for spatially resolved capacitance measurements in the attofarad-to-femtofarad regime is presented. The system is based on the combination of an atomic force microscope (AFM) and a performance network analyzer (PNA). For the determination of absolute capacitance values from PNA reflection amplitudes, a calibration sample of conductive gold pads of various sizes on a SiO(2) staircase structure was used. The thickness of the dielectric SiO(2) staircase ranged from 10 to 200 nm. The quantitative capacitance values determined from the PNA reflection amplitude were compared to control measurements using an external capacitance bridge. Depending on the area of the gold top electrode and the SiO(2) step height, the corresponding capacitance values, as measured with the SMM, ranged from 0.1 to 22 fF at a noise level of ~2 aF and a relative accuracy of 20%. The sample capacitance could be modeled to a good degree as idealized parallel plates with the SiO(2) dielectric sandwiched in between. The cantilever/sample stray capacitance was measured by lifting the tip away from the surface. By bringing the AFM tip into direct contact with the SiO(2) staircase structure, the electrical footprint of the tip was determined, resulting in an effective tip radius of ~60 nm and a tip-sample capacitance of ~20 aF at the smallest dielectric thickness.