Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Transmembrane Domain 4/Extracellular Loop 2 Junction of the Human Gonadotropin-releasing Hormone Receptor in Ligand Binding and Receptor Conformational Selection*

Recent crystal structures of G protein-coupled receptors (GPCRs) show the remarkable structural diversity of extracellular loop 2 (ECL2), implying its potential role in ligand binding and ligand-induced receptor conformational selectivity. Here we have applied molecular modeling and mutagenesis studies to the TM4/ECL2 junction (residues Pro174(4.59)–Met180(4.66)) of the human gonadotropin-releasing hormone (GnRH) receptor, which uniquely has one functional type of receptor but two endogenous ligands in humans. We suggest that the above residues assume an α-helical extension of TM4 in which the side chains of Gln174(4.60) and Phe178(4.64) face toward the central ligand binding pocket to make H-bond and aromatic contacts with pGlu1 and Trp3 of both GnRH I and GnRH II, respectively. The interaction between the side chains of Phe178(4.64) of the receptor and Trp3 of the GnRHs was supported by reciprocal mutations of the interacting residues. Interestingly, alanine mutations of Leu175(4.61), Ile177(4.63), and Met180(4.66) decreased mutant receptor affinity for GnRH I but, in contrast, increased affinity for GnRH II. This suggests that these residues make intramolecular or intermolecular contacts with residues of transmembrane (TM) domain 3, TM5, or the phospholipid bilayer, which couple the ligand structure to specific receptor conformational switches. The marked decrease in signaling efficacy of I177A and F178A also indicates that IIe177(4.63) and Phe178(4.64) are important in stabilizing receptor-active conformations. These findings suggest that the TM4/ECL2 junction is crucial for peptide ligand binding and, consequently, for ligand-induced receptor conformational selection.
The effect of cultural background on the usage of complementary and alternative medicine for chronic pain management.

BACKGROUND Chronic pain is a debilitating problem with significant impact on healthcare utilization in the US. Many chronic pain patients use complementary or alternative medicine (CAM) in addition to standard pharmacologic therapy. OBJECTIVE The aim of our study was to identify differences in the characteristics of usage of CAM for chronic pain control among several ethnic groups. DESIGN We recruited 92 consecutive patients seeking treatment at the pain clinic and interviewed them using a questionnaire. RESULTS The most common pain complaint was back pain (55.4%) and the mean pain duration for all chronic pain problems was 9.8 years. Approximately 81% of respondents were using or have used CAM before. The commonest CAM used by patients in our study included massage therapy, spiritual healing as well as the consumption of mineral and vitamin supplements. Sixty-three percent of them were satisfied with CAM treatment compared to 56% of patients who were satisfied with prescription therapy. However, there was no difference in the use of CAM among the different ethnic groups (P > 0.05). CONCLUSION Our study demonstrates that CAM is used very frequently in patients with chronic pain. However, it did not show any ethnic or racial differences in CAM utilization.
Low-cost through silicon vias (TSVs) with wire-bonded metal cores and low capacitive substrate-coupling

The three-dimensional (3D) integration of electronics and/or MEMS-based transducers is an emerging technology that vertically interconnects stacked dies using through silicon vias (TSVs). They enable the realization of devices with shorter signal lengths, smaller packages and lower parasitic capacitances, which can result in higher performance and lower costs. This paper presents a novel low-cost fabrication technique for metal-filled TSVs using bonded gold-wires as conductive path. In this concept the wires are surrounded by polymer, which acts both as an electrical insulator causing low capacitive coupling towards the substrate and as a buffer for thermo-mechanical stress.
Enhancing the Reliability and Throughput of Neurosphere Culture on Hydrogel Microwell Arrays

The neurosphere assay is the standard retrospective assay to test the self‐renewal capability and multipotency of neural stem cells (NSCs) in vitro. However, it has recently become clear that not all neurospheres are derived from a NSC and that on conventional cell culture substrates, neurosphere motility may cause frequent neurosphere “merging” [Nat Methods 2006;3:801–806; Stem Cells 2007;25:871–874]. Combining biomimetic hydrogel matrix technology with microengineering, we developed a microwell array platform on which NSC fate and neurosphere formation can be unequivocally attributed to a single founding cell. Using time‐lapse microscopy and retrospective immunostaining, the fate of several hundred single NSCs was quantified. Compared with conventional neurosphere culture methods on plastic dishes, we detected a more than 100% increase in single NSC viability on soft hydrogels. Effective confinement of single proliferating cells to microwells led to neurosphere formation of vastly different sizes, a high percentage of which showed stem cell phenotypes after one week in culture. The reliability and increased throughput of this platform should help to better elucidate the function of sphere‐forming stem/progenitor cells independent of their proliferation dynamics.
UWB signal detection using eigen-based receiver

Wireless ultra-wideband (UWB) receivers usually employ a deterministic clean pulse or a pulse derived from a Gaussian waveform as a template for correlation. A deterministic template is not expected to have the capability of correlating highly with random UWB signals all the time. The resulting mismatch, however, can significantly degrade the system error performance. We therefore optimize a deterministic template to achieve the maximum energy capture capability in the sense of ensemble average. The UWB correlator using the optimal deterministic template can be employed along with combining to enhance signal detection. The resulting receivers outperform their counterparts using a clean pulse, as evidenced by theoretical analysis and numerical results based on real UWB data.
Detection of Epstein‐Barr Viral RNA in Sinonasal Undifferentiated Carcinoma from Western and Asian Patients

Undifferentiated carcinoma of the nasopharynx has a well-known association with Epstein-Barr virus (EBV), but only an inconsistent relationship has been identified in undifferentiated carcinomas occurring at other sites. We investigated 22 formalin-fixed, paraffin-embedded cases of sinonasal undifferentiated carcinomas (SNUCs) occurring in Western and Asian patients. A highly sensitive in situ hybridization method was performed using an antisense oligonucleotide probe to the EBER1 gene of EBV. We identified EBV RNA in seven of 11 SNUCs from Asian patients, but in none of the Western SNUC patients (0/11). The EBER1 signal was present in all or virtually all of the tumor cell nuclei in the seven EBV-RNA-positive Asian SNUCs. The latent membrane pro-tein-1 (LMP1) of EBV was not identified in any of the five positive cases tested. Our results suggest that genetic predisposition or environmental/geographical cofactors play an important role in determining the strength of the association of SNUC with EBV.
Intraperitoneal Administration of Autologous Tolerogenic Dendritic Cells for Refractory Crohn's Disease: A Phase I Study.

BACKGROUND AND AIMS Ex vivo-generated autologous tolerogenic dendritic cells [tolDCs] can restore immune tolerance in experimental colitis. The aim of this study was to determine the safety and tolerability of administration of autologous tolDCs in refractory Crohn's disease [CD] patients. METHODS A phase-I, single-centre, sequential-cohorts, dose-range study was designed. Stable tolDCs were generated ex vivo from monocytes following a previously developed protocol, and administered by sonography-guided intraperitoneal injection. Six sequential refractory-CD cohorts were established: the first three cohorts received a single intraperitoneal injection of tolDCs at escalating doses [2 x 10(6)/5 x 10(6)/10 x 10(6)]; and the last three cohorts received three biweekly intraperitoneal injections at same escalating doses. Safety was sequentially evaluated. Patients were assessed from week 0 to 12 and followed up for 1-year period for safety. RESULTS Nine patients were included. No adverse effects were detected during tolDC injection or follow-up. Three patients withdrew from the study due to CD worsening. Crohn's Disease Activity Index [CDAI] decreased from 274 [60] {mean (standard deviation [SD])} to 222 [113] [p = 0.3]; one [11%] patient reached clinical remission [CDAI < 150] and two [22%] clinical response [CDAI decrease ≥ 100]. Crohn's Disease Endoscopic Index of Severity [CDEIS] decreased from 18 [5] to 13 [8] [p = 0.4]; lesions improved markedly in three patients [33%]. Quality of life (inflammatory bowel disease questionnaire [IBDQ]) changed from 125 [27] to 131 [38] [p = 0.7]; remission [IBDQ at Week 12 ≥ 170] was reached in one [11%] case and response [IBDQ score increase ≥ 16] in two [22%]. CONCLUSIONS Intraperitoneal administration of autologous tolDCs appears safe and feasible in refractory CD patients. Further studies should be developed to test clinical benefit, determine the optimal administration route and dose, and monitor the immune responses; See [www.eudract. ema.europa. eu, EudraCT number 2007-003469-42; www.aemps. gob.es number PEI 08-049].
Accountants on the UK boards of directors and the market for accountancy and audit services

Several previous studies have provided empirical evidence concerning the pricing of audit services among different accountancy firms. These studies have examined the form of the auditor fee function by generally performing cross-sectional regressions of audit fees on a set of explanatory variables. This study is the first to investigate whether an "alumni effect" prevails the UK audit market and whether any "alumni effect" influences the pricing of audit services. The "alumni effect" has been defined in this study as the association between the auditor of the company where the director/chartered accountant is currently employed and the accounting firm that the director/chartered accountant originally qualified with, as a chartered accountant. The study has constructed an alumni network by matching the current director of the UK public company with the accountancy firm s/he qualified with as chartered accountant. By doing this, the "alumni effect" variable has been created which is a non-price factor conjectured to translate into price effects. The study provides a theoretical analysis and explanation of the "alumni effect" by combining several theories in microeconomics, organisational behaviour and socialisation of accountants. Using chi-square tests it provides evidence that an "alumni effect" does prevail the UK audit market for publicly traded companies. A classical regression model was constructed for the functional relationship between external audit fee and independent variables measuring the "alumni effect" and audit firm size. Other factors such as client size and complexity, client risk to fail, etc. are controlled for in the cross-sectional models. The findings show that the "alumni effect" leads to higher audit fees when a finance director, chairman or/and chief executive is/are alumni of the incumbent auditor in the large companies segment of the audit market. The findings also indicate that when the audit firm size is partitioned into three classes then a price premium is revealed.
The relationship between strategic entrepreneurship and performance of small and medium enterprises in Malaysia

The objective of this research is to determine the relationship between entrepreneurial orientation (EO), entrepreneurial values (EV), knowledge creation process (KCP), and the performance of Small and Medium Enterprises (SMEs) in Malaysia. This research analyzes these contributing variables to strategic entrepreneurship and their relationships with the performance of SMEs. There are a number of views on strategic entrepreneurship, which most have propensity for opportunity-seeking and advantage seeking behavior that require combined theories in entrepreneurship and strategic management. However, a few scholars argue that it is actually a balance of exploration and exploitation activities which correspond to the firm's capability to explore opportunities internally plus externally, and allow the sustaining of wealth creation. The research employs a quantitative and survey method, and data were collected from owner/managers of SMEs throughout peninsular Malaysia. Out of the 370 responses collected, only 335 were usable in this research. The data were analysed using multiple regressions. The findings reveal that exploration and exploitation depicted in entrepreneurial orientation, entrepreneurial values and knowledge creation process respectively were significant predictors in strategic entrepreneurship and exhibited positive influence to the performance of SMEs in Malaysia. This research contributes theoretically to the enhancement of the understanding as well as the analysis of the strategic entrepreneurship model in SMEs. It provides another empirical supports to the three variables of EO, EV and KCP where EO having the biggest strength and contribution to the firm performance. In managerial contribution aspect, the findings provide opportunities for the SMEs to engage strategic entrepreneurship activities and develop sustaining competitive advantages thereby shoring up their performance.
Gesture Formalization for Multitouch

Since multitouch interfaces are steadily moving out of the experimental niche, the demand for comprehensive programming support increases. Between the formation of de facto standards for multitouch gestures by the industry, and continued research and experimentation by developers or academia, the abstraction of gesture properties becomes essential. This paper contributes a revision of the Gesture Formalization for Multitouch (GeForMT) gesture description language. This language aims at a short and concise syntax, which is still able to capture the complexity of multitouch gestures. We report on a previously missing reference architecture and practical implementation. Based on a study comparing the revised GeForMT language with other formalization approaches for multitouch gestures, we introduce an editor for GeForMT.Copyright © 2013 John Wiley & Sons, Ltd.
Packet scheduling based on Geo/sup Y//G//spl infin/ input process modeling for streaming video

We introduce a new stochastic process called Geo/sup Y//G//spl infin/ input process with beta-distributed batch size and Weibull-like autocorrelation function in order to model video traffic. Investigating the overflow probability of a queueing system by large deviation theory, we develop a streaming scheduling algorithm by applying the overflow analysis result to estimating the packet deadline-missing probability. Through experiments with 30-minute long movie traces, we show that our proposed scheduling scheme outperforms existing schemes based on fractional Brownian motion and Markovian models.
Alkaline secretion by frog gastric glands measured with pH microelectrodes in the gland lumen

1 In the present work we have measured the pH of the secreted fluid within the gland lumen of isolated but intact gastric mucosa of Ranaesculenta. Tissues were mounted in a double chamber allowing continuous perfusion of the mucosal and serosal compartment, and the measurements were made with double‐barrelled pH glass microelectrodes inserted into the glands from the serosal surface under microscopic inspection. 2 During inhibition of H+ secretion by cimetidine (100 μm) the luminal gland pH (pHgl) averaged 7.60 ± 0.05 pH units (mean ±s.e.m.; n= 35), a value significantly higher than bath solution pH (7.45 ± 0.02; P < 0.001) and also higher than intracellular pH of oxyntopeptic cells (pHi), which averaged 7.53 ± 0.06 (n= 18). 3 Stimulation of acid secretion with histamine (500 μm) reversibly decreased pHgl to values which could be as low as 2.5. Together with electrophysiological criteria this response was routinely used to verify the proper location of the microelectrode tip within the gland lumen. 4 Stimulation with carbachol (100 μm) or pentagastrin (50 μm) in the presence of cimetidine rapidly and reversibly increased pHgl by 0.10 ± 0.01 pH units (n= 24; P < 0.001) and 0.09 ± 0.02 pH units (n= 6; P < 0.05), respectively. 5 The observation that gastric gland fluid is more alkaline than the bath solutions and that carbachol or pentagastrin further alkalinize it strongly suggests that oxyntopeptic cells participate in gastric alkaline secretion at least under cholinergic stimulation.
A decision support system for the bimodal dial-a-ride problem

A bimodal dial-a-ride problem (BDARP) considered in this paper is a dial-a-ride problem that involves two transportation modes: paratransit vehicles and fixed route buses. Riders in such a system might be transferred between different transportation modes during the service process. The motivation of this research is that by efficiently coordinating paratransit vehicles with fixed route buses we can improve the accessibility and efficiency of a dial-a-ride system. In this paper, we design a decision support system (DSS) which automatically constructs efficient paratransit vehicle routes and schedules for the BDARP. This DSS has been tested using actual data from the Ann Arbor Transportation Authority (AATA) in Ann Arbor, MI. The results show that this DSS produces an average increase of 10% in the number of requests that can be accommodated and an average decrease of 10% in the number of paratransit vehicles required, as compared to the manual results where no fixed route buses are involved.
Determinants Of Enforcement Action By The Financial Supervisory Service Of Korea From The Perspective Of Audit Firms

In this study, we examine the determinants of enforcement action by the Financial Supervisory Service of Korea from the perspective of audit firms. Enforcement action is an indication of audit failure. Both client- and audit firm-specific factors are involved in its occurrence. Most published studies of enforcement after audit failure focus on client characteristics because details about audit firms from financial statements and information about organizational structure are not publicly available. However, examining the issues surrounding enforcement from the perspective of audit firms may also be valuable in elucidating the potential determinants of audit failure resulting in enforcement action. Utilizing publicly available data from audit firms in South Korea, we identify several audit firm characteristics as determinants of enforcement action. The results of our empirical analysis reveal that the likelihood of audit failure is positively associated with the ratio of accounts receivable to total assets, the ratio of audit fees to total revenue, the ratio of partners to the total number of CPAs, CEO ownership, and age of audit firms. In addition, the likelihood of audit failure is negatively associated with ownership concentration and profitability. These associations are more pronounced in non-affiliated audit firms than affiliated audit firms. Several useful implications for regulators are described for improving audit quality by means of enforcement action.
Aerobic, thermophilic, semi‐continuous treatment of cattle slurry with whey and jam

Aerobic thermophilic treatment (ATT) of cattle slurry and industrial food waste (whey and jam) was conducted semi‐continuously, with the aim of developing the ATT process. We could improve the final products in terms of hygiene, environmental effects and heat production. In addition we tried to solve the foaming problem mechanically. The trial was done by using a farm‐scale bioreactor with a total volume of 12 m3 and a theoretical retention time of some 15 days. Temperature increased to 55 °C at the end of the trial. The process could be an efficient method for the control of foam. Using the waste food (whey and jam) improved the process.
A new uni-planar compact CPW fed surface wave launcher for leaky wave antenna applications at 24 GHz

A new uni-planar, compact and broadband surface wave launcher fed by a coplanar CPW is introduced. The launcher outperforms its previously reported Yagi-Uda based counterparts in terms of bandwidth, size and robustness. Being so compact in the lateral size allows two launchers to be arranged in a side-by-side configuration that have applications in scanning at a single frequency by means of substrate beam steering technique. All design aspects were considered such as surface wave excitation efficiency, CPW leakage, matching, bandwidth, directivity and modal purity.
Did Firms Substitute Dividends for Share Repurchases after the 2003 Reductions in Shareholder Tax Rates?

This paper tests whether firms altered their dividend and share repurchase policies in response to the 2003 reductions in shareholder tax rates. We predict that firms substituted dividends for repurchases, because the reduction in dividend tax rates exceeded the reduction in the capital gains tax rates. As expected, we find substitution and find that it is increasing in the percentage of the company owned by individual investors, the only shareholders affected by the legislation. These findings are consistent with boards of directors considering the tax preferences of individual stockholders (particularly officers and managers) when setting dividend and share repurchase policies.
Interaction between complement subcomponent C1q and the Klebsiella pneumoniae porin OmpK36

The interaction between C1q, a subcomponent of the complement classical pathway component C1, and OmpK36, a porin protein from Klebsiella pneumoniae, was studied in a solid-phase direct-binding assay, inhibition assays with the purified globular and collagen-like regions of C1q, and cross-linking experiments. We have shown that the binding of C1q to the OmpK36 porin of the serum-sensitive strain K. pneumoniae KT707 occurs in an in vivo situation and that this binding leads to activation of the complement classical pathway and the subsequent deposition of complement components C3b and C5b-9 on the OmpK36 porin. Scatchard analysis of the binding of [125I]C1q to the OmpK36 porin showed two binding sites with dissociation constants of 1.5 and 75 nM. The decrease of [125I]C1q binding to the OmpK36 porin in buffer with increasing salt concentrations and the pIs of the C1q subcomponent (10.3) and OmpK36 porin (4.5) suggest that charged amino acids are involved in the binding phenomenon. In inhibition assays, only the globular regions of C1q inhibited the interaction between C1q and OmpK36 porin, demonstrating that C1q binds to porin through its globular region and not through the collagen-like stalks.