Search

Background A rosette-forming glioneuronal tumor (RGNT), a rare brain tumor, presents as a benign feature with a favorable outcome. To date, a few cases with aggressive behaviors, such as recurrence or dissemination, but none with malignant transformation, have been reported. We describe 1 case that recurred as glioblastoma after complete resection of the benign RGNT. Case Description A man aged 58 years presented with headache and dizziness without neurologic symptoms. Magnetic resonance imaging showed a 4 × 2.5 cm, well-demarcated mass in the left cerebellar hemisphere. The patient underwent gross total resection of the tumor and a diagnosis of RGNT was made. There was no evidence of recurrence on serial follow-up. However, a recurrent heterogeneous enhancing mass in the previous surgical cavity was observed on a 7-year postoperative magnetic resonance imaging scan. Reoperation was performed and a histopathological study revealed a glioblastoma. Conclusions To the best of our knowledge, this is the first case of spontaneous malignant transformation of an RGNT. Our case may be helpful in better understanding the biological behavior and clinical outcome of RGNT. We emphasize the malignant potential of this rare tumor and the necessity of future large-scaled research for most appropriate therapeutic strategies.

Since the mid-1980s, the volatility of major macro variables has decreased remarkably, known as the Great Moderation. Even though a great deal of literature addresses the sources of the Great Moderation, its association with potential changes in the dynamics of consumption or output has not been investigated rigorously. This paper reports two empirical findings: i) a faster adjustment of output to changes in its long-run random walk component and ii) a faster adjustment of consumption to changes in permanent income (as approximated by the random walk component of real output) since the mid-1980s. Our interpretation is that a faster diffusion of technology shocks induced by improved information technology may be responsible for the former. In the presence of precautionary savings, a change in the consumer behavior induced by lower uncertainty about future income may be responsible for the latter. The change in output dynamics itself may also be responsible for the change in consumer behavior, as implied by Deaton (1991).

Gross total resection for glioblastoma (GBM) has been associated with better prognosis. However, it is not always feasible, and the threshold for the extent of resection required for better prognosis has been controversial. Therefore, we compared the survival and clinical outcomes of patients with GBM who had undergone partial resection (PR) or biopsy.Of the 110 patients, 32 and 78, who had undergone PR and biopsy, respectively, were enrolled to identify any differences in clinical outcomes. No differences were found in patient demographics between the 2 groups, except for tumor location and mean tumor volume (P = 0.02 and P0.01, respectively). Propensity score matching between the PR and biopsy groups was performed, in which 20 patients each in the PR and biopsy groups were matched.The overall survival (OS) and progression-free survival (PFS) did not differ significantly between the PR and biopsy groups (P = 0.84 and P = 0.48, respectively). After propensity score matching, the differences in OS and PFS between the 2 groups were still not statistically significant (P = 0.51 and P = 0.75, respectively). The hazard ratios for OS and PFS for the PR group compared with biopsy were 0.98 and 0.73, respectively; however, the difference was not statistically significant (P = 0.96 and P = 0.39, respectively). The surgical complication rate was greater in the PR group (14 of 32; 43.7%) than in the biopsy group (9 of 78; 11.5%; P0.01).PR failed to improve survival compared with biopsy for patients with GBM. Moreover, the surgical complication rate in the PR group was greater than that in the biopsy group.

This paper provides a comprehensive analysis of the causes of a recent structural change in the aggregate earnings-returns relation (from negative to positive). We do this by rigorously estimating the date of the structural change and then, by examining intertemporal variation in the news components, as well as those in the expected components, of both aggregate earnings and returns. We also discuss how sources of the change in the relation are related to the Great Moderation, i.e., a reduction in the economy-wide macroeconomic uncertainty that started in the mid-1980s and affected the stock market since the early 1990s. The sources that we identify include i) an increase in the relative importance of cash flow news contained in stock returns; ii) a decrease in the importance of discount rate news contained in aggregate earnings; and iii) a decrease in the persistence or the predictability of aggregate earnings and returns. Our findings suggest that reduced macroeconomic uncertainty provides a comprehensive explanation for the change in the aggregate earnings-returns relation.

Background Pleomorphic xanthoastrocytoma (PXA) is a very rare glial neoplasm. The clinical behavior of PXA is not uniform, and the purpose of this study was to investigate the clinical characteristics of adult PXA and identify prognostic factors. Methods Twenty-five patients aged 18 years or older who were diagnosed with PXA between 2002 and 2016 were analyzed. Results Twenty-one patients (84%) had PXA World Health Organization (WHO) grade II and 4 patients (16%) had anaplastic PXA (WHO grade III). The median overall survival of PXA WHO grade II and III was 97 and 56 months, respectively. The 3-year progression-free survival of PXA WHO grade II and III was 65.1% and 50%, respectively (P = 0.37 and 0.21). Diffusion-weighted imaging, perfusion-weighted imaging, and positron emission tomography findings failed to predict the histologic grade of PXA and recurrence of PXA WHO grade II. Tumor size >40 mm and presence of evident peritumoral edema (ePTE) were prognostic factors for poor progression-free survival (hazard ratios, 4.4 and 15.2, respectively; P = 0.03 and 0.01) according to a univariate analysis. In the recurrent and silent PXA grade II groups, ePTE was present in 87.5% and 23.1% of cases, respectively (P Conclusions The clinical and radiologic features of PXA are not uniform. Tumor size and ePTE are possible prognostic factors for adult PXA. Also, peritumoral edema may be associated with recurrence in PXA WHO grade II. PXA showed a high recurrence rate, and thus close follow-up is needed.

Objective Pituitary apoplexy can cause severe neuro-ophthalmologic or endocrinologic sequelae, requiring timely treatment. The present study was performed to evaluate postoperative neurologic outcomes and to identify their risk factors in patients who underwent transsphenoidal surgery for pituitary apoplexy. Methods Forty-one consecutive patients with pituitary apoplexy who underwent transsphenoidal surgery were reviewed retrospectively. The initial rates of visual acuity (VA) decrease, visual field (VF) defect, and ocular palsy were 34.1%, 46.3%, and 68.3%, respectively. The median maximal diameter and tumoral volume was 2.6 cm (range, 2.0–4.6 cm) and 5.3 cm3 (range, 2.4–38.8 cm3), respectively. Seventeen patients (41.5%) underwent surgery within 7 days. The median follow-up duration was 45 months (range, 12–196 months). Results At the last follow-up, 62.9% (22/35) of patients had made a full recovery from preoperative neurologic deficits, with partial recovery observed in the remaining patients. The rates of improvement and full recovery from VA decrease were 92.9% and 57.1%, respectively; those from VF defect were 94.7% and 36.8%, respectively; and those from ocular palsy were 100.0% and 96.4%, respectively. On multivariate analysis, initial visual impairment score (≥20) was the only significant risk factor for postoperative neurologic sequelae (P Conclusions Ocular palsy was fully recovered in 96.4% patients with pituitary apoplexy after transsphenoidal surgery. Initial visual impairment status was found to be more strongly associated with postoperative neurologic recovery than surgical timing.

The untranscribed DNA sequences of the intergenic spacer regions (ISR) in the groESL were analyzed to resolve the ambiguity within phylogenetically close GRAS and non-GRAS species. The sequencing results of amplified polymerase chain reaction (PCR) products using groESL-ISR-specific primers accurately distinguished L. plantarum and L. pentosus, which were not distinguished by 16 S rRNA sequences. Furthermore, the 20 selected major probiotics species were divided into several groups according to the length (22–91 bp) and homology (65–99%) of their ISR sequences, and this discrimination was consistent with core-genome-based differentiation. Therefore, ISR sequence-based species identification showed more accurate results than 16 S rRNA sequence-based identification and represented genome-based speciation.

The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins. These ionic complexes were shown to have efficient cellular uptake properties. The optimum conditions including the molar ratio between cargo protein and carrier, and the treatment time have been defined. Several protein cargoes were successfully examined with differing sizes and molecular weights: green fluorescent protein (MW 27kDa), albumin (66kDa), concanavalin A (102kDa), and immunoglobulin G (150kDa). These non-covalent complexes were also found to have excellent transdermal penetration ability into the mouse skin. The skin penetration depth was studied histologically by light microscopy as well as two-photon microscopy thus generating a depth profile. These complexes were largely found in the epidermis and dermis layers, i.e. down to ca. 100μm depth of the mouse skin. Our synthetic Sor-G8 carrier was found to be substantially more efficient that Arg8 in both the intracellular transduction and the transdermal delivery of proteins. The mechanism of the cellular uptake of the complex was briefly studied, and the results suggested macropinocytosis.

Background Hypophysitis is a rare disease entity mimicking a pituitary adenoma. Despite crucial disease involving a pituitary gland which is a main component of the hormonal axis, there have been minimal researches regarding the hypophysitis. In this study, we described the constellation of the preoperative findings including clinical, radiologic, and endocrinologic features, as well as postoperative outcomes of the hypophysitis. Methods The authors reviewed the data retrospectively of a total of 2814 patients who underwent microsurgery at our institution to treat a pituitary mass lesion. Among them, the patients proven as hypophysitis in histologic examination were enrolled, followed by stratification into tumor-associated hypophysitis and isolated hypophysitis depending on the existence of associated tumor lesion. As a result, a total 21 cases were enrolled consisting of the 13 cases of tumor-associated and the 8 cases of isolated hypophysitis. In this study, the isolated hypophysitis was focused on the analysis. All patients with isolated hypophysitis were evaluated the clinical, radiologic, and endocrinologic tests preoperatively. After microsurgery, all patients had a minimum follow up of 6 months (6∼72 months). The clinical symptoms, endocrinologic tests, and brain MRI were checked at every 6 months during first 2 year, since then, at every 12 months. Results Among 2814 cases of pituitary mass lesion underwent microsurgery, the hypophysitis were found 21 cases (0.74 %). The 13 cases were the tumor-associated hypophysitis, consisting of rathke's cleft cyst (7 cases), craniopharyngioma (3 cases), pituitary adenoma (2 cases), and germinoma (1 case). The 8 cases were the isolated hypophysitis including lymphocytic (4 cases), granulomatous (3 cases), and IgG4-related (1 case) hypophysitis. The patients presented a wide range of clinical symptoms from general weakness to panhypopituitarism. In addition, the most remarkable radiologic features of the isolated hypophysitis were infundibular thickening and the low signal intensity in T1WI and T2WI. All 8 patients with isolated hypophysitis presented endocrinologic deficiency with various extent in a preoperative biochemistry. After surgery, the hormonal status were not changed in 4 patients (50%), however, aggravated in 4 patients (50%). The 3 patients (37.5%) complained visual field defects in preoperative ophthalmologic test, but improved all after surgery. Conclusion In this study, the preoperative clinical manifestations, radiologic and endocrinologic features of hypophysitis were described comprehensively. In addition, we also revealed the long-term outcomes of hypophysitis in the aspect of visual function and endocrinologic outcomes. Preexisting visual field defects were improved in all patients (3 cases). However, all patients presented endocrinologic deficiency in preoperative biochemistry, among them, the 4 patients (50 %) were unchanged and the 4 patients (50 %) were exacerbated after surgery. In conclusion, the visual outcomes were satisfactory, however, the endocrinologic outcomes were vice versa, because the preoperative endocrinologic deterioration was unchanged or even aggravated after surgery in some cases.

NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model. Promoter analysis revealed that NOX5-L expression is regulated by STAT5A in breast cancer cells. Based on our novel findings, we suggest that inhibition of NOX5-L may be a promising therapeutic strategy that exerts anti-cancer effects via the modulation of ROS-mediated cell signaling.

Background Despite advances in skull base surgery, achieving effective surgical management of jugular foramen schwannomas (JFSs) that avoids postoperative cranial nerve (CN) deficits remains a challenge. Subtotal resection followed by radiosurgery (rather than radical resection) is increasingly being viewed as a better treatment strategy. Here, an institutional database was retrospectively analyzed for outcomes after surgical treatment of JFSs to evaluate the optimal strategy for managing JFSs. Methods Twenty-two patients with JFSs were operated on by either radical resection ( n = 13) or conservative resection plus radiosurgery ( n = 9). These 2 different groups were compared in terms of early (≤4 weeks after surgery) and late postoperative functional outcome and oncologic control. Results No deaths occurred in either group, but there were 3 surgery-related complications in the radical resection group. Postoperative CN deficits and additional procedures related to CN morbidity were generally higher in the radical resection group, but the differences were not statistically significant. The conservative surgery group showed a statistically significant improvement in the level of dysphagia and dysphagia-related functional state in the late postoperative period. There was 1 case of recurrence after radical resection over a mean follow-up period of 73 months. All tumors in the conservative surgery group were controlled over a mean period of 34 months. Conclusions Our results suggest that conservative resection of JFSs via a familiar intracranial approach plus radiosurgery may be an effective surgical alternative for improving functional outcome with adequate oncologic control.

Thermal conductance switches enable active and reconfigurable thermal control and management for a wide variety of applications. We demonstrate a thermal conductance switch based on the actuation of liquid droplets in a co-planar electro-wetting-on-dielectric (EWOD) configuration. By eliminating the need for relative motions of two heat transfer surfaces, the device provides a significant advantage in the mechanical design of adaptive thermal control systems. Proof-of-concept devices are constructed and characterized to confirm the mechanism of droplet detachment and attachment for thermal switching. Numerical simulation is performed to elucidate the experimentally measured thermal performance and identify thermocapillary flows as an important contributor to heat transfer for certain dielectric liquids. The present work provides a proof-of-concept demonstration of novel thermal conductance switches and offers physical insights to help systematically design the switches for practical applications.

In their out-of-sample predictions of stock returns in the presence of structural breaks, Lettau and Van Nieuwerburgh (2008) implicitly assume that economic agents’ perception of the regime-specific mean for the dividend-price ratio is time-invariant within a regime. In this paper, we challenge this assumption and employ least squares learning with constant gain (or constant-gain learning) in estimating economic agents’ time-varying perception for the mean of dividend-price ratio. We obtain better out-of-sample predictions of stock returns than in Lettau and Van Nieuwerburgh (2008) for both the U.S. and Japanese stock markets. Our empirical results suggest that economic agents’ learning plays an important role in the dynamics of stock returns.

microRNAs (miRNAs) are frequently dysregulated in many human cancers including colorectal cancer (CRC) and are useful candidate biomarkers in liquid biopsy of cancer for their stability in the blood.We compared the expression of microRNA-9 (miR-9) in tissues (n = 357) and sera (n = 109) of CRC patients to determine whether miR-9 in serum reflects that in the cancer tissue in parallel. Also, we examined the miR-9 role in CRC by in vitro functional studies in four CRC cell lines.On multivariate analysis of colorectal cancer tissues and sera, miR-9 low expressions were significantly associated pN stage (tissues; p 0.01, serum; p = 0.013), and clinical stage (tissues; p 0.01, serum; p = 0.031). Moreover, patients with low miR-9 expression had shorter survival than those with high miR-9 expression (log-rank test, tissue; p = 0.021, serum; p = 0.011). miR-9 level in serum reflects that in the tumor. The CRC cells with low miR-9 expression was significantly increased cell proliferation, migration, invasion and colony formation than cells with high miR-9 expression.Serum miR-9 is an useful early detection marker in liquid biopsy of CRC and overexpression of miR-9 in CRC may be a novel prognostic marker as well.

This paper revisits the non-Markovian regime switching model considered by Chib and Dueker (2004), who employ an autoregressive continuous latent variable in order to specify the dynamics of the latent regime-indicator variable. We show that, in spite of the non-Markovian nature of the regime indicator variable, the Markovian property of this continuous latent variable allows us to easily estimate the model within the Bayesian framework without any approximations. In particular, we show that the conventional Gibbs sampling is enough in generating the regime indicator variable as well as the continuous latent variable conditional on all the parameters of the model and data. For an application to business cycle modeling of postwar US real GDP, a modified version of Hamilton’s (1989) Markovian switching model is slightly preferred to a non-Markovian switching model by the Bayesian model selection criterion. For an application to volatility modeling of the weekly stock return, a non-Markovian switching model with endogenous switching or the leverage effect is strongly preferred to Markovian switching models.

We evaluated the relationship between interferon-induced transmembrane protein 1 (IFITM1) expression, epithelial-mesenchymal transition (EMT) signature and angiogenesis in lung adenocarcinoma. Additionally, we examined prognostic significance of IFITM1 according to pTNM stage to confirm that IFITM1 can serve as a complement to the pTNM stage. A total of 141 lung adenocarcinoma specimens were evaluated retrospectively by immunohistochemical staining for IFITM1, EMT markers (e-cadherin, β-catenin, and vimentin), and CD31 to measure microvessel density. IFITM1was expressed in 46.8% of the specimens. IFITM1 expression was significantly correlated with increased microvessel density (P = 0.048). However, IFITM1 expression was not associated with three EMT markers. In a multivariate analysis, IFITM1 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.59, P = 0.01). Online database with data from 720 lung adenocarcinoma patients also revealed a negative prognostic significance of IFITM1 (P 0.001). Furthermore, high IFITM1 expression was significantly correlated with decreased OS rates in each pTNM stage. IFITM1 is significantly correlated with angiogenesis and it may be used as a useful additional prognostic marker to aid pTNM classification.

While Perron and Wada (2009) show that postwar U.S. real GDP follows a trend stationary process (TSP) based on the maximum likelihood approach, our analysis based on the Bayesian approach shows that it is a difference stationary process (DSP) with the stochastic trend component explaining most of the variations in real GDP. One goal of this paper is to provide a comprehensive analysis on the sources of such different results and to suggest that more credibility should be conferred to the Bayesian inference. Another goal naturally is to re-investigate the trend-cycle decompositions within the Bayesian framework. This is done by employing a model that incorporates time variation in both the mean and variance. The Bayesian approach to model selection prefers a DSP model to a TSP model, even though the evidence is less than decisive. Empirical results also show that there exists convincing evidence that the cycle from the DSP model, which is small in magnitude and noisy, has out-of-sample predictive power for future output growth at short horizons. The highly persistent TSP cycle without any predictive power may be related to spurious periodicity discussed in Nelson and Kang (1981).

Purpose The role of elective nodal irradiation (ENI) in radiotherapy for esthesioneuroblastoma (ENB) has not been clearly defined. We analyzed treatment outcomes of patients with ENB and the frequency of cervical nodal failure in the absence of ENI. Methods and Materials Between August 1996 and December 2007, we consulted with 19 patients with ENB regarding radiotherapy. Initial treatment consisted of surgery alone in 2 patients; surgery and postoperative radiotherapy in 4; surgery and adjuvant chemotherapy in 1; surgery, postoperative radiotherapy, and chemotherapy in 3; and chemotherapy followed by radiotherapy or concurrent chemoradiotherapy in 5. Five patients did not receive planned radiotherapy because of disease progression. Including 2 patients who received salvage radiotherapy, 14 patients were treated with radiotherapy. Elective nodal irradiation was performed in 4 patients with high-risk factors, including 3 with cervical lymph node metastasis at presentation. Results Fourteen patients were analyzable, with a median follow-up of 27 months (range, 7–64 months). The overall 3-year survival rate was 73.4%. Local failure occurred in 3 patients (21.4%), regional cervical failure in 3 (21.4%), and distant failure in 2 (14.3%). No cervical nodal failure occurred in patients treated with combined systemic chemotherapy regardless of ENI. Three cervical failures occurred in the 4 patients treated with ENI or neck dissection (75%), none of whom received systemic chemotherapy. Conclusions ENI during radiotherapy for ENB seems to play a limited role in preventing cervical nodal failure. Omitting ENI may be an option if patients are treated with a combination of radiotherapy and chemotherapy.

Studies of development and change in partisan fortunes in the US emphasize epochs of partisan stability, separated by critical events or turning points. In this paper we study partisan electoral changes in the US Congress using the method of Markov switching. Our estimates are based on election changes from 1854, roughly the date of the establishment of the modern incarnation of the two-party system, to the present. For the Senate, we estimate partisan balance both from 1856 and from 1914, the period of direct elections. Our discrete-state method performs better than one based on smooth cycles, and is more consistent with the existing theory. We use the Markov switching method to estimate an underlying unobserved state parameter, ‘partisan regime’. The method allows the direct estimation of critical transition points between Republican and Democratic partisan coalitions. Republican regimes characterized House elections during three periods: 1860 through 1872, 1894 through 1906, and 1918 through 1928. Senate results were roughly similar. Every recession caused a realignment prior to 1932, but since then none has. For the Senate, the two-state model does not fit adequately. We estimate a three-state model in which a Republican regime dominated from 1914 through 1928; a Democratic regime characterized the period 1930–1934, and a Democratic-leaning regime characterized the period 1938 to the present (1936 is a transition year). The driver for historical realignments up to 1930 seems to have been economic distress, at least for the House. Each recession before 1930 is associated with a realignment, but after 1930, no recession produced a realignment. Since then, however, economic downturns have not led to realignments. We speculate that better economic management since World War II, resulting in shallower recessions, is the cause. For the Senate, however, we detect only one fundamental regime shift: that during the Great Depression.

As an alternative or supplement to small batteries, the much-anticipated micro-direct methanol fuel cell (μDMFC) faces several key technical issues such as methanol crossover, reactant delivery, and byproduct release. This paper addresses two of the issues, removal of CO 2 bubbles and delivery of methanol fuel, in a non-prohibitive way for system miniaturization. A recently reported bubble-driven pumping mechanism is applied to develop active μDMFCs free of an ancillary pump or a gas separator. The intrinsically generated CO 2 bubbles in the anodic microchannels are used to pump and circulate the liquid fuel before being promptly removed as a part of the pumping mechanism. Without a discrete liquid pump or gas separator, the widely known packaging penalty incurred within many micro-fuel-cell systems can be alleviated so that the system's power/energy density does not decrease dramatically as a result of miniaturization. Since the power required for pumping is provided by the byproduct of the fuel cell reaction, the parasitic power loss due to an external pump is also eliminated. The fuel circulation is visually confirmed, and the effectiveness for fuel cell applications is verified during continuous operation of a μDMFC for over 70 min with 1.2 mL of 2 M methanol. The same device was shown to operate for only 5 min if the pumping mechanism is disabled by blocking the gas venting membrane. Methanol consumption while utilizing the reported self-circulation mechanism is estimated to be 46%. Different from common pump-free fuel delivery approaches, the reported mechanism delivers the fuel actively and is independent of gravity.

Teicoplanin, a glycopeptide antibiotic, is composed of five main components, denoted T-A2-1 to T-A2-5. We investigated the use of glycerol as a carbon source affecting the teicoplanin components and its acyl moieties. As a result, we show the change of teicoplanin components, as well as an increase of total teicoplanin yields, caused by the addition of glycerol to the production medium. Analysis of the total cell lipids upon the addition of glycerol also showed a corresponding change in the proportion of teicoplanin, suggesting that glycerol strongly affects a change of teicoplanin branched acyl moieties.

A Streptomyces gulbargensis newly isolated, thermotolerant feather-degrading bacterial strain was investigated for its ability to produce keratinase enzyme. Maximum keratinolytic activity was observed at 45 degrees C and pH 9.0 at 120 h of incubation. Activity was completely stable (100%) between 30 and 45 degrees C and pH 7.0-9.0, respectively. Addition of starch to the growth medium affects the activity by means of increase in keratinase secretion. After seven days of cultivation, 10-fold increase (14.3 U ml(-1)) in keratinase activity was observed in the presence of 3g starch (per liter) of the medium. The enzyme was monomeric and had a molecular mass of 46 kDa. The enzyme activity was significantly inhibited by CaCl(2) and partly inhibited by EDTA, whereas, Na(2)SO(3) enhance the enzyme activity by 2.9 times more. In addition, native chicken feather was completely degraded at 96 h of incubation. The results obtained showed that newly isolated strain S. gulbargensis could be a useful in biotechnology in terms of valorization of keratin-containing wastes or in the leather industry.

This paper proposes a two-step maximum likelihood estimation (MLE) procedure to deal with the problem of endogeneity in Markov-switching regression models. A joint estimation procedure provides us with an asymptotically most efficient estimator, but it is not always feasible, due to the ‘curse of dimensionality’ in the matrix of transition probabilities. A two-step estimation procedure, which ignores potential correlation between the latent state variables, suffers less from the ‘curse of dimensionality’, and it provides a reasonable alternative to the joint estimation procedure. In addition, our Monte Carlo experiments show that the two-step estimation procedure can be more efficient than the joint estimation procedure in finite samples, when there is zero or low correlation between the latent state variables.

We show that, for a class of univariate and multivariate Markov-switching models, exact calculation of the Beveridge–Nelson (BN) trend/cycle components is possible. The key to exact BN trend/cycle decomposition is to recognize that the latent first-order Markov-switching process in the model has an AR(1) representation, and that the model can be cast into a state-space form. Given the state-space representation, we show that impulse-response function analysis can be processed with respect to either an asymmetric discrete shock or to a symmetric continuous shock. The method presented is applied to Kim, Morley, Piger’s [Kim, C.-J., Morley, J., Piger, J., 2005. Nonlinearity and the permanent effects of recessions. Journal of Applied Econometrics 20, 291–309] univariate Markov-switching model of real GDP with a post-recession ‘bounce-back’ effect and Cochrane’s [Cochrane, J.H., 1994. Permanent and transitory components of GNP and stock prices. Quarterly Journal of Economics 109, 241–263] vector error correction model of real GDP and real consumption extended to incorporate Markov-switching. The parameter estimates, the BN trend/cycle components, and the impulse-response function analysis for each of these empirical models suggest that the persistence of US real GDP has increased since the mid-1980’s.

Following Hamilton [1989. A new approach to the economic analysis of nonstationary time series and the business cycle. Econometrica 57, 357–384], estimation of Markov regime-switching regressions typically relies on the assumption that the latent state variable controlling regime change is exogenous. We relax this assumption and develop a parsimonious model of endogenous Markov regime-switching. Inference via maximum likelihood estimation is possible with relatively minor modifications to existing recursive filters. The model nests the exogenous switching model, yielding straightforward tests for endogeneity. In Monte Carlo experiments, maximum likelihood estimates of the endogenous switching model parameters were quite accurate, even in the presence of certain model misspecifications. As an application, we extend the volatility feedback model of equity returns given in Turner et al. [1989. A Markov model of heteroskedasticity, risk, and learning in the stock market. Journal of Financial Economics 25, 3–22] to allow for endogenous switching.

A tilt sensor has been realized based on electrolytic solution, which is filled in a micromachined 400 μm-deep cavity and responded relative to tilt angle due to the gravity. The device consists of anisotropically etched deep cavity to contain electrolytic solution and Au/NiCr metal electrodes to detect the electrical signal formed on non-planar surfaces from the substrate surface to the bottom of the cavity. The tilting motion of the device changes the immersed area of the electrodes in the electrolytic solution and the unbalanced ratio of the elecrical siganal is monitored by the change in its resistance. Injected electrolyte solution should be carefully determined because it must have not only small resistance but also small viscosity. Potassium hydroxide (KOH) solution is chosen as the electrolyte due to the relatively high ionic conductance and it is diluted with methanol for an optimized concentration considering the viscosity. The fabricated electrolytic tilt sensor is excited by an alternating current to prevent electrolysis in the electrolyte-filled cavity and measured by Wheatstone bridge circuit to read the variation of resistance with respect to an incoming inclination. Experiments reveal that the resistance of KOH electrolyte is smallest at 5 wt% in its concentration and 800 Hz in the driving frequency. The tested Micro Electro Mechanical Systems (MEMS)-based electrolytic tilt sensor with KOH solution shows a resolution of approximately 50 mV per 1° of inclination angle change and operating angle range of ±60°. The measured output characteristic of the fabricated MEMS-based electrolytic tilt sensor sustains comparison with other conventional electrolytic tilt sensors. Moreover, MEMS-based sensor prevails in its small size, low cost and possible mass production.

In a previous study, we found that the phylogenetic analysis of partial rpoB sequences can be used effectively to phylogenetically differentiate Streptomyces spp. [B.J. Kim, C.J. Kim, J. Chun, Y.H. Koh, S.H. Lee, J.W. Hyun, C.Y. Cha, Y.H. Kook, Phylogenetic analysis of the genera Streptomyces and Kitasatospora based on partial RNA polymerase beta-subunit gene (rpoB) sequences, Int. J. Syst. Evol. Microbiol. 54 (2004) 593-598]. In the present study, we analyzed the partial rpoB gene sequences of 19 reference Streptomyces strains associated with potato scab. Furthermore, to empirically confirm the usefulness of rpoB gene analysis for the phylogenetic differentiation of Streptomyces spp., we applied the proposed system to 27 potato scab isolates obtained from the Korean provinces of Jeju-do and Kangwon-do. Phylogenetic relationships among these isolates using the devised rpoB gene-based methods were generally similar to those reported for 16S rRNA gene-based analysis. Isolates from potato scab lesion in Korea were also clearly differentiated into their phylogenetic groups by this method. In addition, the deduced RpoB amino acid sequences were also found to be useful for differentiating these strains. Our data demonstrate that the rpoB gene-based method can be used as a means of complementing other genetic methods such as 16S rRNA gene analysis or DNA-DNA hybridization to phylogenetically differentiate potato scab related Streptomyces spp.

The efficient inhibition of angiogenesis is considered as a promising strategy for the treatment of angiogenesis-related diseases including cancer. Herein, we report that embellistatin, a bicyclic ketone compound known as a microtubule polymerization inhibitor, exhibits anti-angiogenic activity. Embellistatin inhibited in vitro angiogenesis of bovine aortic endothelial cells (BAECs) such as bFGF-induced invasion and tube formation as well as bFGF-induced mouse corneal angiogenesis in vivo. Notably, embellistatin exhibited stronger inhibition activity for the growth of BAECs than that of normal and cancer cell lines. Cell cycle analysis revealed that the compound arrests cell cycle at G2/M phase, which is associated with the increased expression of p21(WAF1) and p53 partly. These results demonstrate that embellistatin may serve the basis for the development of new anti-angiogenic agents.

The literature documents that low stock returns are associated with increased volatility, but two competing explanations have proved difficult to disentangle. A negative return increases leverage, making equity value more volatile. However, an increase in volatility that persists causes stock prices to drop. We follow Bekaert and Wu [Bekaert, G., Wu, G., 2000. Asymmetric volatility and risk in equity markets. Review of Financial Studies 13, 1–42.] in controlling for leverage, but distinguish between volatility regimes that persist from less persistent changes using GARCH. For post-World War II returns on the value-weighted portfolio of all NYSE stocks, we find that changes in the volatility regime are reflected in stock returns but not in GARCH.

In this paper, we consider estimation of a time-varying parameter model for a forward-looking monetary policy rule, by employing ex post data. A Heckman-type (1976. The common structure of statistical models of truncation, sample selection, and limited dependent variables and a simple estimator for such models. Annals of Economic and Social Measurement 5, 475–492) two-step procedure is employed in order to deal with endogeneity in the regressors. This allows us to econometrically take into account changing degrees of uncertainty associated with the Fed's forecasts of future inflation and GDP gap when estimating the model. Even though such uncertainty does not enter the model directly, we achieve efficiency in estimation by employing the standardized prediction errors for inflation and GDP gap as bias correction terms in the second-step regression. We note that no other empirical literature on monetary policy deals with this important issue. Our empirical results also reveal new aspects not found in the literature previously. That is, the history of the Fed's conduct of monetary policy since the early 1970s can in general be divided into three subperiods: the 1970s, the 1980s, and the 1990s. The conventional division of the sample into pre-Volcker and Volcker–Greenspan periods could mislead the empirical assessment of monetary policy.

This paper provides a framework for dealing with endogeneity problems in the time-varying parameter models. A Heckman-type two-step MLE procedure is derived for consistent estimation of the hyper-parameters as well as correct inferences on the time-varying coefficients [Heckman, J.J., 1976, The common structure of statistical models of truncation, sample selection, and limited dependent variables and a simple estimator for such models, Annals of Economic and Social Measurement, 5, 475–492.].

The maximum likelihood estimation of a Markov-switching regression model based on the Hamilton filter is not valid in the presence of endogenous explanatory variables. However, we show that there exists an appropriate transformation of the model that allows us to directly employ the Hamilton filter. The transformed model explicitly allows for a vector of bias correction terms as additional regressors, and the new disturbance term is uncorrelated with all the regressors in the transformed model. Within this framework, a quasi maximum likelihood estimation procedure is presented. A procedure to test for endogeneity based on the Wald statistic or the likelihood ratio statistic is also presented.

Optical actuation of liquid droplets has been experimentally demonstrated for the first time using a novel optoelectrowetting (OEW) principle. The optoelectrowetting surface is realized by integrating a photoconductive material underneath a two-dimensional array of electrowetting electrodes. Contact angle change as large as 308 has been achieved when illuminated by a light beam with an intensity of 65 mW/cm 2 . A micro-liter droplet of deionized water has been successfully transported by a 4 mW laser beam across a 1 cm � 1 cm OEW surface. The droplet speed is measured to be 7 mm/s. Light actuation enables complex microfluidic functions to be performed on a single chip without encountering the wiring bottleneck of two-dimensional array of electrowetting electrodes. Published by Elsevier Science B.V.

Background The authors present a retrospective clinical analysis of meningeal hemangiopericytomas. The long-term outcome and biologic behavior, including local recurrence and extraneural distant metastasis, are elucidated. Method Clinical records and radiologic findings of 31 cases with meningeal hemangiopericytoma treated at Seoul National University Hospital and Asian Medical Center between 1982 and 1999 were carefully reviewed. The final outcome was determined by direct or phone contact and questionnaire by mail. The duration of follow-up was from 1 to 216 months (mean 77). All patients underwent craniotomy and Simpson Grade I or II resection was possible in 24 patients. Conventional radiotherapy was given in 11 patients (in 5 after total excision and in 6 for residual mass) and stereotactic radiosurgery was conducted in 6 cases. Results Intracranial recurrence was seen in 12 cases (38.7%) and the mean period before the first recurrence was 104 months. The recurrence was at the primary site in 11 cases and diffuse leptomeningeal seeding occurred in the remaining case. The 5-year recurrence free rate was 59.2% and the extent of excision was the significant factor (72.7% in total excision group and 20.8% in the incomplete excision group, p = 0.006). In four patients (12.9%), extraneural metastases developed at an average of 107 months. Six patients died during the follow-up period; however, 2 of these died of unrelated causes. Conclusions Complete excision is the most important factor in reducing recurrence. However, recurrence may occur even after complete excision. Careful long-term follow-up is mandatory because of the long disease-free interval.

Stereotactic spinal radiotherapy is a promising technology for use in the multidisciplinary management of benign and malignant spinal tumors. We present two patients with residual metastatic spinal tumors and their treatment with CyberKnife (Accuray, Sunnyvale, CA, USA) after decompression and instrumentation, one of which was successful and the other not. A 73-year-old male patient was admitted with bilateral extremity weakness (Grade IV) and voiding difficulty that had developed 2 days previously. CyberKnife treatment for the residual tumor after surgery with decompression and instrumentation was attempted, but could not be performed due to imaging interference caused by the instrumentation. A second patient, a 49-year-old male, was admitted with right extremity weakness and voiding difficulty that had developed 5 months previously. In this patient, we were able to perform CyberKnife treatment on the residual tumor after decompression and instrumentation. Based on these two patients, we believe that fiducial-free CyberKnife treatment is not suitable for treatment of residual metastatic spinal tumors at the upper thoracic levels, after decompression with instrumentation. This is due to the difficulties in matching digitally reconstructed radiographs with live radiographic images, as a result of the larger inclination and smaller vertebral body surface at the upper thoracic level.

This paper deals with electrowetting (EW) and electrowetting-on-dielectric (EWOD) principles applied to microfluidic devices. EW and EWOD are principles that can control wettability of liquids on solid surfaces using electric potential. While EW is controlling wettability of a certain electrolyte on a metal electrode by varying electric energy across the electrical double layer (EDL), EWOD applies to virtually any aqueous liquid by varying electric energy across the thin dielectric film between the liquid and conducting substrate. These driving mechanisms have many advantages. By electrically changing the wettability of each of the electrode patterns on a surface, a liquid on these electrodes can be shaped and driven along the active electrodes, making microfluidics extremely simple both for device fabrication and operation. It is also worth noting that, driven by surface tension, the mechanism becomes more effective as the size of the device becomes smaller. This paper describes fundamental concepts and the proof-of-concept experiments, modeling and design, microfabrication processes, and initial testing results for the microfluidic devices based on the EW and EWOD principles.

Hypoglossal-facial crossover is the most popular method of reconstructing the facial nerve in facial palsy resulting from proximal facial-nerve injury near the brainstem. Conventional hypoglossal-facial crossover involves performing a partial hypoglossal-nerve section or incision and an interpositional nerve graft to bridge the gap between the two nerves, which sometimes results in hemiglossal atrophy and its sequelae. Furthermore, the nerve graft may delay recovery and make facial reanimation weak. To solve these problems, we attempted to perform 'pure end-to-side anastomosis' (without section of the hypoglossal nerve) between the hypoglossal and facial nerves in four patients with facial palsy. In two patients (group I) a sural-nerve graft was used to bridge the gap between the two nerves. In the other two patients (group II) the intratemporal facial nerve was mobilised to the neck and one tension-free end-to-side anastomosis was performed. Facial symmetry and tone at rest were restored in all cases. Facial reanimation was achieved in group II after 8 months. Despite the small number of cases, we believe that the technique of hypoglossal-facial crossover with 'pure end-to-side anastomosis' and mobilisation of the intratemporal facial nerve can decrease donor-nerve morbidity in facial-nerve rehabilitation.

When volatility feedback is taken into account, there is strong evidence of a positive tradeoff between stock market volatility and expected returns on a market portfolio. In this paper, we ask whether this intertemporal tradeoff between risk and return is responsible for the reported evidence of mean reversion in stock prices. There are two relevant findings. First, price movements not related to the effects of Markov-switching market volatility are largely unpredictable over long horizons. Second, time-varying parameter estimates of the long-horizon predictability of stock returns reject any systematic mean reversion in favour of behaviour implicit in the historical timing of the tradeoff between risk and return.

The mechanical properties of single-crystalline silicon are measured by uniaxial tension tests from microscale beam specimens patterned by four different common silicon etchants — KOH, EDP, TMAH and XeF2. SOI wafers are used to prepare test samples, which are 3–5 μm thick, 20–100 μm wide, and 6 mm long beam specimens; these are monolithically mounted on a temporary frame. A uniaxial tension test has been designed to accommodate microscale test requirements such as sample handling, sample alignment, and friction elimination. Stress and strain are measured using a commercial load cell and a laser interferometry system, respectively. Young's modulus of silicon in the 〈110〉 direction is measured to be 169.2±3.5 GPa, very close to the widely accepted value of 168.9 GPa obtained from a macroscale sample by an ultrasonic method. The fracture strength in the 〈110〉 direction is measured to vary from 0.6 to 1.2 GPa, and is apparently affected by the etching process employed to make the microscale specimen. As surface defects are expected to be the main factor determining the strength of the specimen, surface morphology is examined not only as a function of etchants but also as a function of mask-to-crystal direction misalignment after KOH etching. In the case of samples prepared by KOH etching, measured fracture strengths are 0.94 and 0.72 GPa from samples with 0° and 2° misalignments, respectively.

The successful design, modeling, fabrication, and testing of high-aspect-ratio large deflection in-plane microactuators are presented. The large displacement, in-plane actuators have a unique application in the area of fluid flow control. Unlike previously used electromagnetically actuated microflap in which motion was normal to the substrate, we introduce a novel design that alters the local fluid flow by moving the actuators parallel to the substrate. This new approach of `in-plane motion' allows for a condition free of `form drag'. Furthermore, electrostatic drive allows for lower power consumption (μW). The actuator includes microplates that are 60×200 μm 2 . These microplates, when moved parallel to the substrate surface, induces a `spanwise velocity' into the flow field above them. This induced velocity field, when applied to the near-wall streaks (regions of high shear drag), would increase the transport of high-speed fluid away from the wall, therefore causing reduction in viscous drag. The actuators are made from silicon-on-insulator (SOI) wafers using a one mask deep reactive-ion-etching (DRIE) process. The microplates are suspended by a high-aspect-ratio cantilever structure (2 μm wide, 6–18 μm thick silicon) to ensure robustness against any disturbances in the out-of-plane direction. We present experimental verification of both the induced Stoke's flow and a local fluid flow created by our in-plane microactuators.

A decade ago Fama and French [Fama, E.G., French, K.R., 1988. Permanent and temporary components of stock prices. J. Political Econ. 96 (2) 246–273] estimated that 40% of variation in stock returns was predictable over horizons of 3–5 yr, which they attributed to a mean reverting stationary component in prices. While it has been clear that the Depression and war years exert a strong influence on these estimates, it has not been clear whether the large returns of that period contribute to the information in the data or rather are a source of noise to be discounted in estimation. This paper uses the Gibbs-sampling-augmented randomization methodology to address the problem of heteroskedasticity in estimation of multi-period return autoregressions. Extending the sample period to 1995, we find little evidence of mean reversion. Examining subsamples, only 1926–1946 provides any evidence of mean reversion, while the post war period is characterized by mean aversion. A test of structural change suggests that this difference between pre and post war periods is significant.

Previous work reported that heteroskedasticity did not affect the sampling distribution of the variance ratio, or had assumed that the investigator knew a priori the pattern of heteroskedasticity. This paper uses the Gibbs sampling approach in the context of a three state Markov-switching model to show how heteroskedasticity affects inference and suggest two strategies for valid inference. We find that test procedures which ignore the pattern of heteroskedasticity are biased, rejecting the null hypothesis of no mean reversion too often. We present a resampling strategy that standardizes historical returns, using the Gibbs sampling approach to allow for uncertainty in parameters and states while conditioning on the information in the data. A second strategy is to estimate the VR from standardized data. Again, Gibbs sampling makes appropriate use of the information in the data. For CRSP stock returns 1926–86 we find that evidence of mean reversion is substantially weakened. Gibbs sampling estimates of VRs are closer to unity, and the pattern shifts to shorter lags. There is weak evidence of mean reversion in returns on equal-weighted portfolios and essentially none for the value-weighted. Thus, when returns from high variance periods are appropriately standardized, the sample evidence for mean reversion changes in pattern and significance.

Five different procedures commonly used to rinse and dry released microstructures are compared: evaporation drying with deionized (DI) water or methanol, sublimation drying with t-butyl alcohol orp-dichlorobenzene, and supercritical drying with COz. For objectivecomparison, identical test structures, made by the MCNC Multi-User EMS Processes (MUMPS), are used in evaluating the drying techniques. The test chips contain arrays of surface-micromachined polysilicon cantilevers (2 km thick, 2 pm gap from the substrate) with varying widths and lengths. Some beams feature dimples or tips to quantify their anti-stiction effect. This study reveals, for the first time, that the maximum beam length obtainable increases as the beam width increases for the cases of sublimation and supercritical dryin,, 0 opposite to the previously known case of evaporation drying. Both sublimation drying methods as well as supercritical drying rendered good results, releasing cantilevers up to 700 km in length without stiction. We also introduce a new setup that considerably improves the way sublimation is used to dry microstructures. 0 1998 Elsevier Science S.A.

A new and simple surface-modification technique is proposed to reduce sticking of microstructures fabricated by surface micromachining. This technique realizes a very rugged surface at the polysilicon substrate, resulting in reduced sticking through a decrease of real contact area. The surface, which consists of honeycomb-shaped grain holes at the polysilicon substrate layer, is defined by a two-step dry etch without an additional masking step for photolithography or deposition of thin films. By varying the time for etching the grain holes of the polysilicon substrate, controlled surface roughness can be obtained. Test structures, including polysilicon cantilever beams of various lengths, fabricated by surface micromachining with the proposed surface modification show a doubled detachment length without sticking to the substrate.

Optically active epoxy alcohol, (R)-2-butyryloxymethylglycidol3 which is the precursor of a tert-alcohol chiral building block was obtained in high enantiomeric purity, 98.7% e.e., by lipase-catalyzed asymmetric hydrolysis using a phosphate buffer and organic co-solvent system in 95% of chemical yield.

In this paper, Hamilton's (1988, 1989) Markov-switching model is extended to a general state-space model. This paper also complements Shumway and Stoffer's (1991) dynamic linear models with switching, by introducing dependence in the switching process, and by allowing switching in both measurement and transition equations. Building upon ideas in Hamilton (1989), Cosslett and Lee (1985), and Harrison and Stevens (1976), a basic filtering and smoothing algorithm is presented. The algorithm and the maximum likelihood estimation procedure is applied in estimating Lam's (1990) generalized Hamilton model with a general autoregressive component. The estimation results show that the approximation employed in this paper performs an excellent job, with a considerable advantage in computation time. A state–space representation is a very flexible form, and the approach taken in this paper therefore allows a broad class of models to be estimated that could not be handled before. In addition, the algorithm for calculating smoothed inferences on the unobserved states is a vastly more efficient one than that in the literature.

The literature documents that low stock returns are associated with increased volatility, but two competing explanations have proved difficult to disentangle. A negative return increases leverage making equity value more volatile. However, volatility feedback increases the risk premium when a surprise rise in volatility is expected to persist. We follow Bekaert and Wu (2000) in controlling for leverage, but distinguish between volatility regimes that persist from less persistent changes using GARCH. Supporting volatility feedback, we find changes in volatility regime are reflected in stock returns, but not GARCH. Further, variation in leverage is not important in explaining volatility dynamics.

In this paper, we provide a unified framework for LIML (limited information maximum likelihood) IV (instrumental variables) estimation to deal with endogeneity problems in the time-varying parameter models. For this purpose, we derive a Heckman-type (1976) two-step maximum likelihood estimation (MLE) procedure. The proposed two-step procedure, based on the conventional Kalman filter, provides consistent estimates of the hyper-parameters, as well as correct inferences on the time-varying coefficients. However, the use of the conventional Kalman filter in the second step would result in an invalid conditional covariance matrix for the time-varying coefficients. The correction for the conditional covariance matrix can be made by employing an augmented Kalman filter proposed in this paper. The basic model and the two-step procedure is also extended to handle the issue of heteroscedasticity in the disturbance terms. This is done by considering a time-varying parameter model for Campbell and Mankiw's (1989) consumption function.

This paper provides a unified framework for a two-step MLE procedure to deal with the problem of endogeneity in Markov-switching regression models. Two important issues are considered. First, a consistent estimation of the Markov-switching regression equation of interest is considered. Second, obtaining correct standard errors of the coefficients estimates in the second step is considered, in light of Pagan's (1984) 'generated regressors.' Our Monte Carlo experiments provide the validity of the proposed methods in small samples. The model and the proposed methods are applied to Campbell and Mankiw's (1989) consumption function, by allowing for possibilities of structural breaks in the sensitivity of consumption growth to the predictable component of income growth. Empirical results suggest that during the 1970's and 1980's, when uncertainty in future income growth was highest, the measure of sensitivity was high and statistically significant, while it was not significant in the rest of the sample.