cssi/SciSciGPT-SciSciNet huggingface dataset:
Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: cross-tolerance to carbamazepine but not valproate or diazepam.

Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on seizure stage, afterdischarge (AD), and seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on amygdala-kindled seizures. The implications of these results for clinical therapeutics remain to be evaluated.
Wireless Telemedicine Systems for Diagnosing Sleep Disorders with Zigbee Star Network Topology

Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition, the proposed system provides real time monitoring of physiological signals at remote locations using Wi-Fi.
SU-GG-BRC-04: Electronic Versus HDR Ir-192 Brachytherapy: Organ Dose Comparisons for Breast Cancer Using a Monte Carlo Patient Phantom

Purpose: To quantify and compare the dose delivered to multiple organs‐at‐risk (OARs) in a female patient undergoing Xoft Axxent electronic (KVB) and high‐dose rate Ir‐192 (IBB) intracavitary balloon brachytherapy for breast cancer.Materials and Methods: A previous study has indicated that the dose to OARs such as the lungs and heart play a critical role in treatment planning. The anatomy of a female patient was represented by an adult female computational phantom which consists of over 140 organs. A balloon was inserted into a lumpectomy cavity in the left breast of the virtual patient. The Monte Carlo N‐Particle eXtended (MCNPX) code was used to simulate photon transport through the patient for hypothetical KVB and IBB scenarios. MCNPX's F6 tally was used to calculate the absorbed dose in organs distant from the treatment site. Results: In general, the KVB organdoses were more than a factor of 2 smaller than those of IBB because the low‐energy x‐rays are less penetrating. The distribution of organdoses shows a profound pattern depending on the distance, location, and organ shape. The largest doses were observed for organs such as the left lung and heart which are closest to the radiation source. For KVB, the doses received by the left lung and heart wall were 9.0% and 5.5% of that received by the planning target volume. These values were 11.0% and 11.3% for the IBB scenario. Conclusions: This paper reports, for the first time, a systematic comparison of multiple organdoses received from KVB and IBB. KVB may have safety advantages because its dose rate falls off faster than for IBB. As a previous clinical study found the target dose to be similar for these two methods, information on how healthy organs are irradiated will help decide when each modality is appropriate.
Comparison of two splitting algorithms for 2-D modelling of advection-dominated solute transport in groundwater

Abstract This paper reports on two alternating directions splitting algorithms, one cast in the Local One Dimensional (LOD) and the other in the standard Fractional Time Stepping (FTS) format. Both algorithms employ an adaptation of the pseudo-viscosity technique and use the principal directions of transport as coordinates. In the LOD approach, only one dimension appears in each splitting step. In the FTS method, computation is implicit in only one dimension but other dimensions are present in each splitting step. Stability and accuracy constraints on the grid parameters are diagrammed for both schemes. Test problems in one and two dimensions are solved. The analysis shows that the slight accuracy advantage of the FTS format over the LOD format must be traded off against tighter grid design prescriptions and, frequently, also against higher computing cost.
Ionic basis for electrical properties of tonic fibres in rat extraocular muscles

1. The ionic conductances underlying some of the electrophysiological properties of multiply innervated or tonic fibres of rat extraocular muscles were examined in vitro with double-barrelled micro-electrodes.2. Exposure of the muscle to a Cl-free saline did not change the effective resistance (R(eff)) of tonic fibres which was 5.14 +/- 0.45 MOmega (n = 7) in control saline and 4.78 +/- 0.45 MOmega (n = 12) in Cl-free saline (P > 0.1). In contrast, in singly innervated or twitch fibres Cl removal increased R(eff) from 1.77 +/- 0.21 MOmega (n = 19) to 2.69 +/- 0.12 MOmega (n = 22) (P < 0.001).3. Tonic fibres with membrane potentials restored to - 80 mV by injecting current responded to intracellular depolarizing pulses with a brief, slow response (slow peak potential) which added to the rising phase of the electrotonic potential. The slow peak potential began at a membrane potential of - 40 to - 35 mV and was graded. Increasing depolarizations evoked faster and larger responses which did not over-shoot the zero level of membrane potential.4. The slow peak potential was not blocked by 10 muM-D-600 hydrochloride but was markedly reduced by the absence of Na and by 10 muM-tetrodotoxin. The response was broadened about five times by 25 mM-tetraethylammonium.5. Raising bath temperature from 21-25 degrees C to 37 degrees C reversibly depressed and shortened the slow peak potential but did not transform it into an action potential.6. It is concluded that the characteristic high R(eff) of tonic fibres results from a lack of a membrane conductance to Cl and that the slow peak potential involves the transient activation of Na and K channels which are pharmacologically similar to the respective channels of twitch fibres.
A physiologic biomarker for cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA), a common small-vessel disease of older adults characterized by accumulation of amyloid-β in leptomeningeal and cortical blood vessels, is a well-established cause of intracerebral hemorrhage.1 Recent years have seen the emergence of clinical research reports establishing associations between CAA, ischemic brain injury, and vascular cognitive impairment (VCI). CAA patients had a higher load of chronic microvascular white matter hyperintensities (WMH), small infarcts, as well as a high degree of WMH progression.2,3 A more recent report showed that vascular amyloid load strongly correlated with ischemic WMH in CAA.4
Plasma proteins take their toll on the joint in osteoarthritis

In their recent study, Sohn and colleagues identify multiple plasma proteins in the synovial fluid of patients with osteoarthritis (OA) and demonstrate the capacity of several of the proteins to activate macrophages via the innate immune receptor Toll-like receptor-4 (TLR-4). The authors speculate that the plasma proteins transit into the synovial compartment at sites of tissue damage where the endothelial barrier may be compromised, thus bringing them into contact with the articular surface and cells within the synovium. These results demonstrate a novel mechanism by which synovial inflammation can be initiated in patients with OA and how this process may contribute to the pathogenesis of OA joint pathology.
DICER1 Expression and Outcomes in Endometrioid Endometrial Adenocarcinoma

BACKGROUND: The objective of this study was to determine whether lower expression levels of DICER1 are associated with disease recurrence in patients with endometrioid endometrial cancer. The authors also explored DNA methylation and haploinsufficiency as potential mechanisms related to altered DICER1 expression in these tumors. METHODS: DICER1 expression was assessed by quantitative polymerase chain reaction in a selected cohort of endometrioid endometrial tumors (N = 169). Loss of heterozygosity analyses were conducted using 2 single nucleotide polymorphisms, and combined bisulfate restriction analysis was used to assess methylation in the 5′-untranslated region of DICER1 in representative tumors. The correlations between DICER1 expression and clinicopathologic variables, including overall survival (OS) and disease-free survival (DFS), were assessed using nonparametric rank-sum tests and Cox proportional hazard models as appropriate. Survival distributions were described using the Kaplan-Meier method. A nested case-control analysis was conducted to confirm the association between transcript levels and disease recurrence. RESULTS: Lower DICER1 expression (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.05-1.75; P = .02) and advanced disease stage (HR, 2.79; 95%CI, 1.59-4.90; P < .001) were associated with worse DFS. Three variables were associated significantly with reduced OS: age (HR, 1.04; 95%CI, 1.02-1.06; P < .0001), advanced disease stage (HR, 6.41; 95%CI, 3.57-11.52; P < .0001), and high tumor grade (HR, 2.96; 95%CI, 1.46-5.99; P = .003). Nested case-control analyses confirmed that there were lower DICER1 transcript levels in patients who had recurrent disease (P = .01). Deletion of DICER1 sequences was an infrequent event (5% of analyzed patients), and no methylation was observed in the 5′ DICER1 regulatory region. CONCLUSIONS: Lower DICER1 transcript levels were correlated with disease recurrence and worse DFS survival in patients with endometrioid endometrial cancer. The factors that influence DICER1 transcript levels in primary endometrial cancers remain unknown. Cancer 2011. © 2010 American Cancer Society.
Gas chromatographic-mass spectral analysis of the five-carbon β-, γ-, and δ-amino alkanoic acids

Abstract A gas chromatographic separation method and electron impact mass spectra obtained by gas chromatography-mass spectrometry are presented for N-trifluoroacetyl-2-butyl esters of the nine possible five-carbon β-, γ-, and δ-amino alkanoic acids. Mass spectral fragmentation patterns are rationalized in terms of amino acid struture, and general criteria are described for distinguishing between amino position and chain isomers of aliphatic amino acids based on mass spectra of their N-trifluoroacetyl-2-butyl esters.
Leveraging Proteomics to Understand Plant–Microbe Interactions

Understanding the interactions of plants with beneficial and pathogenic microbes is a promising avenue to improve crop productivity and agriculture sustainability. Proteomic techniques provide a unique angle to describe these intricate interactions and test hypotheses. The various approaches for proteome analysis generally include protein/peptide separation and identification, but can also provide quantification and the characterization of post-translational modifications. In this review, we discuss how these techniques have been applied to the study to plant-microbe interactions. We also present some areas where this field of study would benefit from the utilization of newly developed methods that overcome previous limitations. Finally, we reinforce the need for expanding, integrating, and curating protein databases, as well as the benefits of combining protein-level datasets with genetics and other high-throughput large-scale approaches for a systems-level understanding of plant-microbe interactions.
Local Labor Market Fluctuations and Physical Activity among Adults in the United States, 1990–2009

Being physically active is a key health promotion strategy. The late-2000s economic downturn, labeled the “Great Recession,” could have profound impact on individuals' health behaviors including engagement in physical activity. We investigated the relationship between local labor market fluctuations and physical activity among adults 18 years and older in the United States by linking individual-level data in the Behavioral Risk Factor Surveillance System 1990–2009 waves to unemployment rate data by residential county and survey month/year. The association between labor market fluctuations and physical activity was examined in multivariate regressions with county and month/year fixed effects. Deteriorating labor market conditions were found to predict decreases in physical activity—a one percentage point increase in monthly county unemployment rate was on average associated with a reduction in monthly moderate-intensity physical activity of 0.18 hours. There was some preliminary evidence on the heterogeneous responses of physical activity to local labor market fluctuations across age and income groups and races/ethnicities. Findings of this study suggest special attentions to be paid to the potential detrimental impact of major recessions on physical activity. This correlational study has design and measurement limitations. Future research with longitudinal or experimental study design is warranted.
HUMAN PAPILLOMAVIRUS INFECTION OF THE CERVIX IN ADOLESCENTS

Infection with human papillomavirus (HPV) is of current interest in adolescents because of its link with malignant and premalignant lesions of the uterine cervix. This study was undertaken to determine the prevalence of cervical HPV infection in adolescents and to characterize factors associated with HPV positivity. Subjects were recruited from an adolescent clinic in an urban teaching hospital. All sexually active females aged 13-21 who were to have a Pap smear were asked to participate. Specimens for HPV analysis were obtained by cervicovaginal (CV) saline lavage. DNA was extracted from cells and hybridized with radiolabeled HPV 6, 11, 16 and 18 probes in a Southern blot experiment. For the first 69 participants in the study the mean age was 18.0 years; 48% were Black, 38% Hispanic and 14% White. The mean gynecologic age was 5.9 years and the mean number of years of sexual experience was 2.4. 26/69 (37.7%) had HPV present in the CV cells. There were no significant differences in any of the above characteristics when HPV(+) and HPV(-) patients were compared. Having two or more lifetime sexual partners resulted in more HPV infections than having only one partner (43% vs 28%, NS). 3/23 (13%) of those who were HPV positive and 2/42 (4.8%) of HPV negative patients had Pap smears that were suspicious or atypical. This study reveals a very high prevalence of HPV infection in adolescents which may in part reflect the more sensitive technique of CV lavage and suggests a need for surveillance of this at risk population.
Prediction of posttranslational modifications using intact-protein mass spectrometric data.

We present a Web-based application that uses whole-protein masses determined by mass spectrometry to identify putative co- and posttranslational proteolytic cleavages and chemical modifications. The protein cleavage and modification engine (PROCLAME) requires as input an intact mass measurement and a precursor identification based on peptide mass fingerprinting or tandem mass spectrometry. This approach predicts mass-modifying events using a depth-first tree search, bounded by a set of rules controlled by a custom-built fuzzy logic engine, to explore a large number of possible combinations of modifications accounting for the experimental mass. Candidates are saved during a search if they are within a user-specified instrument mass accuracy; the total number of possible candidates searched is based on a specified fuzzy cutoff score. Candidates are scored and ranked using a simple probabilistic model. There is generally not enough information in an intact mass measurement to determine a single unique protei...
NMR chemical shift reagents in structural determination of lipid derivatives: IV. Methylcis- andtrans-9,10-epoxystearate and methylerythro- andthreo-9,10-dihydroxystearate

Chemical shift reagents were used to expand the amount of structural information obtainable from NMR studies of derivatives of methyl oleate and elaidate:methylcis-9,10-epoxystearate, methyltrans-9,10-epoxystearate, methyl erythro-9,10-dihydroxystearate, and methyl threo-9,10-dihydroxystearate. Chemical shift reagent studies of methyltrans-9,10-epoxystearate and methyl threo-9,10-dihydroxystearate afforded the most information. Chemical shift reagent studies of methylcis-9,10-epoxystearate and methyl erythro-9,10-dihydroxystearate were decidedly inferior. The series of complementary interpretive techniques previously developed during chemical shift reagent studies of monofunctional fatty esters and model polyfunctional fatty esters were found to be applicable in the current study. However, to avoid ambiguity in several proton assignments, supplementary spin decoupling experiments were necessary.
Effect of broiler age, feed withdrawal, and transportation on levels of coliforms, Campylobacter, Escherichia coli and Salmonella on carcasses before and after immersion chilling

A study was conducted to determine effects of bird age at slaughter, feed withdrawal, and transportation on levels of coliforms, Campylobacter, Escherichia coli, and Salmonella on carcasses before and after immersion chilling. Broilers were processed at 42, 49, and 56 d of age after a 12-h feed withdrawal period or a 0-h feed withdrawal period (full fed). At each age, broilers were processed from two commercial farms previously identified as Campylobacter positive. One week before slaughter, broilers were gavaged with nalidixic acid-resistant Salmonella. During bleeding, cotton plugs were inserted into the cloaca of each carcass. Whole-carcass rinses (WCR) were performed before and after immersion chilling with 20 ppm sodium hypochlorite, and rinses were analyzed for coliforms, Campylobacter, E. coli and Salmonella. Log10 counts for coliforms, Campylobacter, and E. coli were (P < 0.05) affected by bird age at slaughter. Feed withdrawal (FW) affected only Campylobacter on carcasses of older broilers (56 d of age). Chilling with sodium hypochlorite resulted in log10 reductions of 1.2, 1.3, 1.4, and 0.5 for coliforms, Campylobacter, E. coli, and Salmonella, respectively. Under the conditions of this experiment, it appears that contamination on the exterior of birds entering the processing facility is critical to carcass bacterial counts. Moreover, carcass bacterial counts did not vary when microbial counts of broilers were comparable. FW may increase prechill carcass counts for E. coli and Campylobacter, but it appears to have no effect on postchill carcass counts when sodium hypochlorite is used in the chilling operation.
Response to Comment on: Chakkera et al. Can New-Onset Diabetes After Kidney Transplant Be Prevented? Diabetes Care 2013;36:1406-1412.

Hecking et al. raise several important questions in their letter (1). First, compared with classic type 2 diabetes, how important is insulin sensitivity in the development of new-onset diabetes after transplantation (NODAT)? Second, compared with type 1 or type 2 diabetes, is NODAT more rapid in onset? Finally, what are the relative contributions of lifestyle intervention and exogenous insulin in prevention or early therapy of NODAT? Abnormalities in both insulin sensitivity and insulin secretion are central to the development of type 2 diabetes and NODAT. We hypothesized in our article that both increase in insulin resistance and impairment in insulin …
Seismic investigation of near-surface geological structure in the Paducah, Kentucky, area: application to earthquake hazard evaluation

Abstract Seismics method were used to evaluate shallow geological conditions at 33 sites in the vicinity of Paducah, Kentucky. A combined set of P- and S-wave seismic refraction and reflection soundings were used, in addition to local borehole information, to produce structure maps of (1) a shallow ( 160 m deep). Shear-wave velocity contrasts across the shallow unconformity were generally 2-to-1 while the contrast at the top of the Paleozoic bedrock exceeds 5-to-1. These seismic boundaries have been determined to be very important in modelling and interpreting earthquake ground motion amplification in the Paducah area. The quality and accuracy of the data, and the cost effective nature of the methods, suggest that other communities in areas at risk to damage from seismic activity, with foundation conditions comparable to Paducah, might benefit from similar characterization in order (1) to identify seismically hazardous, near-surface, geological conditions, and (2) to develop geological models that could be used in computer simulations of site response.
A transactional view of entrepreneurship: a Deweyan approach

Neoclassical and Marxian theorists have generally failed to explain entrepreneurship, and for an obvious reason. To apply the calculus of optimization, neoclassical theorists have to treat the set of resources as an object that exists 'initself,' i.e., independent of the acting subject. On the other hand, Marxian theorists, in advocating the labor theory of value, have to treat labor activity as an expression of an abstract ability which can be easily measured across the diverse concrete activities. John Dewey, throughout his writing stretching over half a century, has undermined the objectivist view of means and of labor activity. Dewey, in fact, objected to the means-end dichotomy. This opens a window for a theory of entrepreneurship.
Constrained nurse staffing analysis

Abstract Nurse work force management has been described as a multi-phase sequential planning and control process. Previous research has addressed this process by focusing on the development of phase-specific problem solving methodologies. For practicing managers, it may be more beneficial to evaluate various policy options that management may pursue in addressing the nurse work force issue in light of the nationwide shortage of qualified nurses. This research evaluates management policy at the staffing phase since these decisions have the broadest impact on nurse work force utilization. The impact of nurse staffing policy options on annual nursing labor costs are evaluated for a large public hospital in the State of Florida. A linear programming staffing model served as the research vehicle for the study and response surface methodology was used to investigate the relationship between labor costs and the policy options. Service level, nurse labor availability, nurse staffing mix and flex-staff assignment had the most significant effects on annual nursing labor costs. The implications of these findings for work force management and suggestions for future research are presented.
A case study: productivity and quality gains using an object-oriented framework

The Neuro-Oncology Information System (NOIS) supports researchers and other personnel throughout the United States engaged in brain tumor research. Graphical user interfaces that allow data input into the NOIS have been evolving over several years. This paper describes the design and implementation of the NOIS Input Forms as they migrated from a procedural approach to a static object-oriented approach, and finally to a framework approach in which not only static components were reused, but also the patterns of interaction among the components. The paper documents a significant gain in productivity and quality that was realized when using the framework design paradigm. Copyright © 1999 John Wiley & Sons, Ltd.
Interspecific Hybrid Inviability in Crosses of Arachis hypogaea × A. stenosperma can be Overcome by in vitro Embryo Maturation or Somatic Embryogenesis

Summary Certain crosses of Arachis hypogaea × A. stenosperma did not produce viable F 1 hybrid seed when pods were left on the plant to mature. The cause of embryo abortion is unknown but probably was related to incompatibility between hybrid embryo and maternal tissues that may have resulted in nutritional deficiency. Viable hybrid embryos were rescued using three protocols: 1) in vitro embryo maturation and germination; 2) culture of shoot-root embryo axis attached to a single cotyledon in a cytokinin-rich medium; and 3) production of somatic embryos from the excised cotyledon. The rescue of viable hybrid embryos was accomplished with nearly 100 % efficiency using protocol 1. Both protocols 2 and 3 were found to be less efficient methods but may have advantages over protocol 1 under certain circumstances. Frequency of somatic embryogenesis appeared to be genotype dependent. Several interspecific hybrid plants were recovered with all three methods.
Establishing “Normal” Values for Liver Function Tests after Reconstruction of Biliary Injuries

Background Abnormalities of liver function tests (LFT) are sometimes taken as evidence of a less than optimal result after repair of a biliary injury. Rather than indicating liver or anastomotic dysfunction, moderate LFT elevations can be "normal" for these patients. This study's aim was to determine LFT reference values after biliary-enteric anastomosis for biliary injury repair in persons who have had an excellent postoperative course for > 6 months. Study Design Of 113 patients repaired, 73 were identified with the following characteristics: LFT available at ≥ 6 months after repair, no biliary tract symptoms, no underlying liver disease, and biliary injury sustained during cholecystectomy. Outside LFT results were standardized to Barnes-Jewish Hospital reference values. One set of LFT per patient was collected at the following times points after repair: 6 months to 2 years, 2 to 5 years, and > 5 years. Results For each distribution, the 97.5 th p97.5ercentile values for alkaline phosphatase (≥ 166 IU/L) and total bilirubin (≥ 1.3 mg/dL) were elevated relative to Barnes-Jewish Hospital standard values. Values for alanine aminotransferase and aspartate aminotransferase were more variable. Conclusions Moderate LFT elevations exceeding standard reference values are common after repair of a biliary injury in patients who have had excellent results. Alkaline phosphatase values fall with time after repair so that comparisons should take into account time from repair. Values ≤ 97.5 th percentile limits described here should not be taken as evidence of liver or anastomotic dysfunction.
State-Dependent cAMP Binding to Functioning HCN Channels Studied by Patch-Clamp Fluorometry

One major goal of ion channel research is to delineate the molecular events from the detection of the stimuli to the movement of channel gates. For ligand-gated channels, it is challenging to separate ligand binding from channel gating. Here we studied the cyclic adenosine monophosphate (cAMP)-dependent gating in hyperpolarization-activated cAMP-regulated (HCN) channel by simultaneously recording channel opening and ligand binding, using the patch-clamp fluorometry technique with a unique fluorescent cAMP analog that fluoresces strongly in the hydrophobic binding pocket and exerts regulatory effects on HCN channels similar to those imposed by cAMP. Corresponding to voltage-dependent channel activation, we observed a robust, close-to-threefold increase in ligand binding, which was more pronounced at subsaturating ligand concentrations than higher concentrations. This observation supported the cyclic allosteric models and indicated that protein allostery can be implemented through differentiating ligand binding affinities between resting and active states. The kinetics of ligand binding largely matched channel activation. However, during channel deactivation, ligand unbinding was slower than channel closing, suggesting a delayed response to membrane potential by the ligand binding machinery. Our results provide what we believe to be new insights into the cAMP-dependent gating in HCN channel and the interpretation of protein allostery for general ligand-gated channels and receptors.
A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response.

Background The objective of this phase I trial was to determine dose-limiting toxicities (DLT) and the maximally tolerated dose of the radiosensitizer Nelfinavir in combination with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC). Methods Nelfinavir (dose level 1: 625 mg orally [PO] twice a day; dose level 2: 1250 mg PO twice a day) was administered for 7 to 14 days before and concurrently with concurrent chemoradiotherapy to patients with biopsy confirmed IIIA or IIIB unresectable NSCLC. Five patients were treated at dose level 1; eight patients were treated at dose level 2. Patients were treated with concurrent chemoradiotherapy to a dose of 66.6 Gy. DLTs were defined as any treatment-related grade 4 hematologic toxicity requiring a break in therapy or nonhematologic grade 3 or higher toxicity except esophagitis and pneumonitis. Results Sixteen patients were enrolled and 13 patients received at least one dose of nelfinavir. Twelve patients were treated with nelfinavir and concurrent chemoradiotherapy. No DLTs have been observed at either dose level. The maximum tolerated dose of nelfinavir was therefore 1250 mg PO twice a day. Six patients experienced grade 4 leukopenia. One patient experienced grade 4 thromobcytopenia. Median follow-up for all 12 response-evaluable patients was 31.6 months and for survivors is 23.5 months. Nine of the 12 patients had evaluable posttreatment positron emission tomography/computed tomography with metabolic response as follows: overall response: 9/9 (100%); complete response: 5/9 (56%); and partial response: 4/9 (44%). Conclusion Nelfinavir administered with concurrent chemoradiotherapy is associated with acceptable toxicity in stage IIIA/IIIB NSCLC. The metabolic response and tumor response data suggest that nelfinavir has promising activity in this disease.
Why Targets Matter: Toward a More Inclusive Model of Collective Violence

Efforts to develop a unified model of collective violence have been limited by the diverse array of events analyzed, from terrorist attacks to riots. This article seeks to develop a more inclusive theoretical and analytic framework by exploring the targets of violence, something that has received little disaggregated attention. We argue that consideration of who or what is targeted during the course of an event, together with collectivity size and the conditional role it may play, offers new theoretical insight into collective violence dynamics. Our analysis draws from newspaper records on a diverse range of collectivities, from parties to rallies to riots. We find that in many contexts, collectivity size increases the likelihood of violence against some targets, notably state actors, while reducing attacks on others. These findings provide the basis for a broader discussion of why unpacking targets is so critical to understanding the dynamics of collective violence.
Renal transplantation in diabetic patients is confirmed therapy while pancreas transplantation should be performed only in an investigational setting.

Abstract Kidney transplantation is now firmly established as the standard treatment for all diabetic patients with end-stage renal fallure. In an analysis of all renal transplants at the University of Minnesota between June 1, 1980 and May 31, 1987, there were no differences in renal allograft functional survival rates for diabetic and nondiabetic recipients. At one year the survival rates were 84% (n=151) and 86% (n=260) for those treated with azathioprine, prednisone and ALG; 86% (n=101) and 87% (n=104) for those treated with cyclosporine-prednisone, and 92% (n=165) and 89% (n=191) for those treated with triple therapy (cyclosporine, azathioprine, and prednisone). Pancreas transplantation remains an investigational procedure for nonuremic diabetic patients but may be considered therapeutic in diabetic renal allograft recipients because such patients are obligated to immunosuppression and only the surgical risks of pancreas transplantation need to be considered, which are now aceptably low. Recipients of pancreas transplants performed simultaneous with the kidney have patient and pancreas graft survival rates of >90% and ±60% at several institutions, including our own. The potential for benefit of pancreas transplantation, however, is greater in the nonuremic nonkidney transplant patient, and pancreas transplantations are being performed in such patients at a few institutions. An early beneficial effect of pancreas transplantation preexisting proliferative retinopathy has not been discerned, although long-term retinopathy has been stable in patients with functioning grafts. Preliminary studies have shown a beneficial effect on neuropathy and on microscopic lesions of diabetic nephropathy, but at the expense of cyclosporine toxicity. Pancreas transplantation as a solitary procedure will not realize its full potential until nontoxic, immunosuppressive regimens are available. At this time, pancreas transplatation is appropriate in selected patients with complications of diabetes that would otherwise progress to a stage more serious than the potential side effects of chronic immunosuppression, but it should be performed only in an investigational setting at institutions committed to long-term, formal protocol follow-up studies.
Global stability of a two-species piecewise linear volterra ecosystem

Abstract This paper extends the results of Goh [1], and Takeuchi and Adachi [2,3] concerning the generalized linear Volterra model. We introduce a piecewise linear Volterra model for a two- species system. The solution of the steady-state problem is then shown to be equivalent to finding the solution to the Generalized Linear Complementarity Problem. We show when this nonnegative equilibrium is unique and globally asymptotically stable in the sense of Goh [1].
Integration of thin-film ZnO strain sensors into hard disk drives

This work developed a novel application of piezo-electric thin-film sensing technology by incorporating ZnO strain sensors into a hard disk drive (HDD) to support the high-bandwidth, nanometer-level positioning required to achieve terabit-per-square-inch data densities. First, ZnO sensors were fabricated directly onto a HDD suspension component, which was a unique and challenging process since the substrate was made of steel. The instrumented suspension was then incorporated into an experimental HDD, along with a miniaturized instrumentation circuit and PZT actuation elements. The sensors demonstrated excellent sensitivity to structural vibration modes that contribute to displacement in the off-track direction. A simple active mode damping controller was implemented on these instrumented PZT-actuated prototypes to demonstrate suppression of high-frequency vibration modes.
Asymmetric syntheses of α,α,γ-trisubstituted-γ-butyrolactones and 2,2,3-trisubstituted glutaric acid derivatives from chiral benzamides

Abstract The enantioselective conversion of aromatic carboxylic acids to acyclic structural units containing three stereogenic centers is described.
Severe sodium channel blockade and cardiovascular collapse due to a massive Lamotrigine overdose

Background. Cardiac arrest due to lamotrigine (LTG) has been reported after co-ingestion with bupropion, but severe sodium channel blockade in the absence of other toxins has not been described. We report a case of cardiac arrest and status epilepticus following a massive LTG overdose. Case Report. A 48 year-old female was brought to the ED with seizure-like activity subsequent to ingesting 7.5 g of LTG. Vital signs were HR 131, BP 107/68, T 99.4°F, RR 16. She was intubated in the ED for a low GCS. Initial ECG demonstrated a narrow-complex normal sinus rhythm, and her labs were unremarkable. Three hours after intubation she developed status epilepticus, and a pulseless wide-complex tachycardia. She was aggressively resuscitated during which time pulses were periodically reestablished, but lost each time seizures recurred. She was not stabilized until the convulsions were terminated with vecuronium. Her post-resuscitation ECG demonstrated a junctional tachycardia with a 3 mm R-wave in aVR. The LTG level wa...
Kinetics of V̇O2 and V̇CO2 in the horse and comparison of five methods for determination of maximum oxygen uptake

To determine whether maximum oxygen uptake (VO2max) in the horse in influenced by type of exercise test, five different protocols were evaluated in eight untrained Thoroughbreds exercised on a treadmill. With all protocols, horses were given a 5 min warm-up on a 10 per cent treadmill slope. Three protocols were at a 10 per cent slope and included: 1) increasing the running speed by 1 to 2 m/sec every 60 secs from 4 m/sec to a maximum of 12 m/sec; 2) running at 12 m/sec until fatigue; and 3) running for 3 to 4 mins at speeds ranging from 6 to 12 m/sec with rest pauses between exercise bouts. The fourth protocol employed a 24 per cent slope where animals exercised for 5 mins at 2 m/sec followed by 3 mins at 5 m/sec, and 2 mins at 6 m/sec. The fifth test involved running at 11 m/sec while the slope of the surface was increased every 2 mins until the horses could not maintain the pace. A plateau in VO2 occurred in all protocols except when exercise was performed on a 24 per cent slope. Slow speed exercise at a steep grade (24 per cent) produced the highest VO2 (P < 0.05) even though there was no plateau in the VO2. A steady state for VO2 and VCO2 existed 90 secs after the onset of exercise with all protocols which involved 2 mins or more at each speed. The VO2 and VCO2 values at all speeds of the rapid incremental exercise test were not different to those found at steady state in the third exercise protocol.
Identification of a Lymantria dispar Nucleopolyhedrovirus Isolate That Does Not Accumulate Few-Polyhedra Mutants during Extended Serial Passage in Cell Culture

During Lymantria dispar multinucleocapsid nucleopolyhedrovirus (LdMNPV) replication in cell culture, few-polyhedra (FP) mutants arise at a high frequency and become predominant after only a few serial passages. The formation of LdMNPV FP mutants was an impediment to successful production of polyhedra in cell culture bioreactors. We have isolated and characterized a strain of LdMNPV, termed 122b, that did not accumulate FP mutants after extended serial passage in cell culture. Wild-type virus strains exhibited decreased polyhedra production and increased budded virus (BV) release, and FP mutants were the predominant virus type present after only a few serial passages in L. dispar 652Y cells. In contrast, isolate 122b exhibited stable polyhedra and BV production through 14 serial passages. Isolate 122b produced more BV than wild-type virus and essentially the same amount of BV as FP mutants. FP mutants derived from isolate 122b were isolated and partially characterized. These mutants produced approximately 10-fold fewer polyhedra than 122b and essentially the same amount of BV as 122b. These results suggest that FP mutants will not become predominant during serial propagation of 122b because 122b FP mutants do not release more BV than 122b. Isolate 122b was also found to be capable of generating productive infections at higher
Analytical Modeling and Numerical Simulation of Capacitive Silicon Bulk Acoustic Resonators

This paper introduces two newly developed models of capacitive silicon bulk acoustic resonators (SiBARs). The first model is analytical and is obtained from an approximate solution of the linear elastodynamics equations for the SiBAR geometry. The second is numerical and is based on finite-element, multi-physics simulation of both acoustic wave propagation in the resonator and electromechanical transduction in the capacitive gaps of the device. This latter model makes it possible to compute SiBAR performance parameters that cannot be obtained from the analytical model, e.g. the relationship between transduction area and insertion loss. Comparisons with measurements taken on a set of silicon resonators fabricated using electron-beam lithography show that both models can predict the resonant frequencies of SiBARs with a relative error smaller than 1%.
From “Easy Phonetics” to the Syllabary: An Orthographic Division of Labor in Cherokee Language Education

Drawing on classroom participant-observation and interviews conducted among the Eastern Band of Cherokee Indians, this article describes the ways in which literacy practices in Cherokee language education perpetuate and teach local categories of knowledge, behavior, and persons. I describe the semiotic functioning of the native-developed Cherokee syllabary, as well as its place among four Cherokee orthographies. This work contributes to our understanding of the multiple functions and meanings of writing systems in use in language education and other cultural contexts, and demonstrates the importance of analyzing the full range of semiotic implications of any particular writing system.
Hyperfine Structure in the Electronic Spectrum of ReO

Hyperfine structure in the spectrum of the molecule rhenium monoxide (ReO) has been observed for the first time by recording the [14.0] 7/2–X 5/2 (0, 0) band near 712 nm at sub-Doppler resolution using intermodulated fluorescence spectroscopy. Hyperfine splittings due to both the 185Re and 187Re isotopes (I = 5/2) have been resolved and assigned. A least-squares fit to the observed transitions has produced accurate values for the rotational, magnetic hyperfine and electric quadrupole constants for both electronic states. The hyperfine constants are discussed in relation to the electronic configurations of the two states. In particular, the ground state magnetic hyperfine constant is found to be consistent with a 1σ22σ21π 41δ33σ2 (X 2Δ i ) electronic configuration, where the 1δ orbital containing the unpaired electron is a Re 5dδ non-bonding orbital.
High-resolution detection and mapping of genomic DNA alterations in neuroblastoma.

We used array-based comparative genomic hybridization (aCGH) to measure genomic copy number alterations (CNAs) in 42 neuroblastoma cell lines with known 1p36.3, 2p24 (MYCN), 11q23, and 17q23 allelic status. All cell lines showed CNAs, with an average of 22.0% of the genome of each sample showing evidence of gain (11.6%) or loss (10.4%). MYCN amplification was detected in 81% of cell lines, but other regions with high-level genomic amplification were observed only rarely. Gain of 17q material was present in 75% of the samples, and four discrete genomic regions at 17q23.2–17q25.3 were defined. Novel regions of gain were identified, including a 2.6-Mb subtelomeric region at 5p that includes the telomerase reverse transcriptase gene (TERT), which was found in 45% of the cell lines. Hemizygous deletions were noted at 1p36.23– 1p36.32 and 11q23.3–11q25 in 60% and 36%, respectively, of the samples, with other frequent (>25%) regions of deletion localized to 1p32.1, 3p21.31–3p22.1, 5q35.2–5q35.3, 7q31.2, 7q34, 9q22.3–9q24.1, 10q26.11–10q26.12, 16q23.1–16q24.3, 18q21.32–18q23, and 20p11.21–20p11.23. A smallest region of overlap (SRO) for CNAs was mapped across all experiments and in each case was consistent with or refined the published data. A single cell line showed a homozygous deletion at 3p22.3, which was verified, and this location was refined by FISH and PCR. There was outstanding concordance of aCGH with PCR-based CNA detection methods. Several potential cooperating loci were identified, including deletion of 11q23– 25, which was highly associated with both regional gain and loss at multiple chromosomal loci but was inversely correlated with the deletion of 1p36. Taking all of this together indicates that aCGH can accurately measure CNAs in the neuroblastoma genome and facilitate gene discovery efforts by high-throughput refinement of candidate loci. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/10452257/suppmat/index.html. V V C 2005 Wiley-Liss, Inc.
Online distributed calibration of a large network of wireless cameras using dynamic clustering

We present a cluster-based distributed algorithm for calibrating large networks of wireless cameras. Due to the complex nature of sensing modality of a camera sensor, the work presented here differs significantly from the previous localization methods. Our system does not require any beacon nodes; it only utilizes object features of moving objects in the scene extracted from image sequences. The algorithm is fully distributed, and the localization estimates can be improved as more object features are acquired in the network. We show simulations of our system using a graphical simulator we developed specifically for wireless camera sensor networks. Early results indicate that our system is capable of localizing a large network of cameras in an energy-efficient way.
Age-related emotional bias in processing two emotionally valenced tasks

Previous studies suggest that older adults process positive emotions more efficiently than negative emotions, whereas younger adults show the reverse effect. We examined whether this age-related difference in emotional bias still occurs when attention is engaged in two emotional tasks. We used a psychological refractory period paradigm and varied the emotional valence of Task 1 and Task 2. In both experiments, Task 1 was emotional face discrimination (happy vs. angry faces) and Task 2 was sound discrimination (laugh, punch, vs. cork pop in Experiment 1 and laugh vs. scream in Experiment 2). The backward emotional correspondence effect for positively and negatively valenced Task 2 on Task 1 was measured. In both experiments, younger adults showed a backward correspondence effect from a negatively valenced Task 2, suggesting parallel processing of negatively valenced stimuli. Older adults showed similar negativity bias in Experiment 2 with a more salient negative sound ("scream" relative to "punch"). These results are consistent with an arousal-bias competition model [Mather and Sutherland (Perspectives in Psychological Sciences 6:114-133, 2011)], suggesting that emotional arousal modulates top-down attentional control settings (emotional regulation) with age.