cssi/SciSciGPT-SciSciNet huggingface dataset:
Validation of NGS-Based DNA Testing and Implementation of Quality Control Procedures

The rapid adoption of next-generation sequencing (NGS) (also known as massively parallel sequencing; MPS) techniques has revolutionized the way molecular diagnosis is performed in a clinical diagnostic laboratory. Hundreds to thousands of genes can be analyzed simultaneously, and samples can be multiplexed and sequenced in parallel with deep coverage. To bring such a complex technology to clinical diagnostic laboratories, limitations and challenges should be recognized when designing and implementing assays for routine clinical use. While most NGS platforms can generate enormous amount of data in a massively parallel manner, the complexities of test validation and the implementation of quality control procedures have posed tremendous challenges on quality assurance. A quality assurance program is an integral part of clinical laboratory operations, in particular for laboratories that are adopting new technologies to provide state-of-the-art genetic testing services. In this chapter, we describe the steps taken in implementation of test validation and quality control procedures in our clinical molecular diagnostic laboratory.
More Diversity Yields a Clearer Picture into the Architecture of the Protein Kinase Domain

Co-evolution analysis reveals which amino acids within the protein kinase domain are working together to mediate catalysis, regulation, and substrate binding.
Evaluation of Operating Margin and Switching Probability of Voltage- Controlled Magnetic Anisotropy Magnetic Tunnel Junctions

Voltage-controlled magnetic anisotropy (VCMA) has attracted great attention as it allows faster switching and lower energy consumption compared to traditional spin-transfer torque-based magnetization switching. In this paper, we evaluate the operating margin and switching probability of VCMA-based magnetic tunnel junctions using realistic material and device parameters. For this paper, we developed a physics-based SPICE model that incorporates various VCMA parameters such as VCMA coefficient, energy barrier, time constant, and external magnetic field. Switching probability of a VCMA device was obtained by running Monte Carlo simulations including thermal fluctuation effects. A design space exploration was performed using the proposed simulation framework. The highest switching probabilities we were able to achieve were 94.9%, 84.8%, and 53.5%, for VCMA coefficient values of 33, 105, and $290\,\,\text {fJ}\cdot \text {V}^{-1}\cdot \text {m}^{-1}$ , respectively. Our study shows that for VCMA devices to become viable, their switching probability must be improved significantly either through new physics or material innovation.
On the Effects of Active Learning Environments in Computing Education

This replication study aims at both quantifying the effects of active learning classrooms in introductory programming courses (CS1) and overcoming some design and methodological limits of prior studies on this topic. 156 students enrolled in three different sections of the same CS1 participated in this study. The three sections differed from each other either in terms of learning pedagogies (conventional lecture vs. peer instruction) or physical learning environments (lecture hall vs. active learning classroom). This study did not replicate the findings of prior studies on this topic. Instead, this study found that when learning pedagogies were controlled, learning environments did not have significant influences on student performance. On the other hand, learning pedagogies were found to have significant influences on student performance. When peer instruction is conducted other than conventional lecturing, students tended to have significantly better performance. Such findings highlight the importance of active learning in computing education, and the feasibility of conducting active learning in CS1 despite of physical environment constraints. Additionally, such findings emphasize the necessity of replication studies on the topic of active learning environments, and invite debates on the investment decisions in active learning classrooms.
CO 2 embolism can complicate transanal total mesorectal excision

Carbon dioxide (CO2) embolism is a rare but potentially devastating complication of minimally invasive abdominal and retroperitoneal surgery. Characterized by a decrease in end-tidal CO2 (ETCO2) and oxygen saturation (SpO2), CO2 emboli can cause rapid intraoperative hypotension and cardiovascular collapse. Transanal total mesorectal excision (taTME) is a novel surgical approach for rectal resection, which requires high flow CO2 insufflation in a low volume operative field. In this setting, the incidence of CO2 embolism is unknown; we evaluate three cases of intraoperative CO2 embolism that occurred during the transanal portion of the TME dissection. All taTME cases from December 2014 to March 2018 at a single institution were reviewed. Cases of CO2 embolism were identified intraoperatively and characterized using the operative reports and anesthesia records. The transanal/pelvic insufflation included a targeted pressure of 15 mm Hg, high flow and high smoke evacuation. Physiologic derangements and management of these instances were analyzed. The postoperative course was evaluated and any complications were noted. A total of 80 taTME were performed for benign and malignant disease. Three patients (4%) developed intraoperative evidence of CO2 embolism. Each instance occurred during the transanal portion of the dissection. Physiologic changes were marked by abrupt decrease in end-tidal ETCO2, SpO2, and blood pressure (BP). Management included immediate release of pneumopelvis, hemodynamic support with crystalloid or vasopressors, and placement of the patient in the Trendelenburg position with left side down. Within 10 min of the acute event, all patients had return of ETCO2, SpO2, and BP to pre-event levels. There were no intraoperative or postoperative sequelae including arrhythmia, myocardial infarction, stroke or death. No cases required conversion to open. During taTME, rare CO2 emboli may occur in the setting of venous bleeding during pneumopelvis, causing sudden, transient cardiovascular instability. Immediate recognition of rapid decrease in ETCO2, SpO2, and BP should be followed by desufflation of pneumopelvis, patient positioning in Trendelenburg and left lateral decubitus, and hemodynamic support. Increased awareness of this potential complication and maintaining a high index of suspicion will lead to preparedness of the anesthesia and surgery teams.
To Pay or Not to Pay Community Preceptors? That Is a Question …

Phenomenon: Pairing medical students with community-based preceptors has provided unique medical education advantages. However, due to an increase in the number of M.D.-granting medical schools and medical school class sizes, academic medical institutions have struggled to recruit community preceptors to teach their students. This task has been made more difficult due to rising pressures upon institutions and clinicians-for example, increased productivity demands, greater volume and oversight of electronic health record documentation, and competition for community preceptors from both D.O. and non-U.S.-based medical schools. Although academic institutions have historically relied largely on altruistic motives and intrinsic rewards to actively engage and retain community-based preceptors, alternative models have arisen, chiefly those in which community-based preceptors are explicitly compensated for teaching. Approach: To study this phenomenon, representatives of the Alliance for Clinical Education developed and deployed a 31-item survey accompanied with a subset of free text questions to the collective membership of its 8-member constituent organizations. Survey questions explored if community preceptors were compensated indirectly or directly and what types of compensation were provided, if any. There were 188 surveys analyzed, with an estimated response rate of 18.2%. Findings: Twenty-six percent of respondents indicated they compensate community preceptors directly and/or indirectly. Respondents discussed their motivations for payment (or nonpayment), mechanisms for paying, aspirations to pay, and expectations of the recipient. No statistically significant association was found when comparing responses of paid versus not paid by region. Free text responses provided additional insight regarding payment considerations, institutional competition, recruitment/retention, recognition, and education issues. Insights: Increasingly, medical schools are finding it necessary to provide funding for community preceptors in order to retain them. New creative forms of compensation to community preceptors may prove important in the future for this vital aspect of medical student education.
Review: The Dysfunctional Library, Challenges and Solutions to Workplace Relationships

When nonlibrarians ask what you do, and you respond that you work in a library, a frequent comment heard is that it must be a fun place to work, surrounded by so many books, getting to read all day...
Identification of IGF binding proteins in bovine milk and the demonstration of IGFBP-3 synthesis and release by bovine mammary epithelial cells.

Insulin-like growth factor system components are synthesized and secreted by mammary epithelial cells and multiple IGF binding proteins (IGFBP) are found in milk of various species. This study was conducted to identify the IGFBP in bovine milk, to compare them with those found in blood, and to identify the cell(s) responsible for mammary IGFBP synthesis. Bovine blood, milk, and cell culture-conditioned media were analyzed and characterized with Western ligand blot procedures for specific IGFBP. Electrophoresis and [ 125 I]IGF-II ligand blot analyses of the samples indicated that, unlike serum and mammary primary cell culture-conditioned media, milk required removal of casein in order to accurately disclose all IGFBP. Immunoprecipitation studies identified IGFBP-2, -3, -4, and -5 in blood, milk, and primary cell culture conditioned media. The IGFBP were present at higher concentrations in serum than in milk, and milk concentrations were greater than that shown in conditioned media from primary cultures of bovine mammary cells. Northern analysis detected IGFBP-3 messenger RNA in extracts from fresh tissue and cells in culture, and in situ hybridization studies with fresh tissue utilizing probes for IGFBP-3 and αS 1 -casein showed that the mRNA for IGFBP-3 is predominant in the secretory epithelial cells, when compared to other tissue cell types.
MOTOR VEHICLES AND TRAFFIC Drivers' Licenses, Uniform Rules of the Road: Modify Procedures and Penalties Relating to Driving Under the Influence of Drugs or Alcohol

SB 489 initiates administrative suspension of drivers'; licenses for second time DUI violators. SB 487 increases penalties for habitual DUI violators and creates a crime of endangering a child by driving under the influence of alcohol or drugs. HB 451 defines traffic accident which resulted in serious injuries or fatalities.; SB 579 allows a driver to reduce points on her license by taking a corrective course before eight points are accumulated. HB 1508 directs the Department of Public Safety to accept driver correction courses certified by other states. SB 524 adds an additional monetary penalty onto a conviction for DUI to help fund the Georgia Crime Victims Emergency Fund.
Compressed hyperspectral Raman microscope for imaging tissues and cellular structures

Raman imaging continues to grow in popularity as a label-free technique for characterizing the underlying chemical structure of biological materials, both in-vitro and in-vivo. While Raman spectra demonstrate high chemical specificity, spontaneous Raman scattering is an inherently weak process and requires prohibitively long acquisition times. When Raman is utilized to image highly scattering cellular environments, integration times can be on the order of several minutes to hours. Recently developed compressed sensing techniques can greatly improve hyperspectral Raman acquisition times by randomly under-sampling the spatial dimensions. A digital micromirror device (DMD) is used to spatially encode the image plane. The encoded image is then propagated to a spectrometer where the spectral components are produced by shearing one spatial dimension. Several reconstruction algorithms have been developed that can then be used to return the original. Here, we will present single-shot, 2D Raman imaging of CHO cells using compressed hyperspectral Raman microscope. This system provides an order of magnitude improvement on traditional hyperspectral acquisition rates. Single-shot compressed hyperspectral Raman images can reveal biochemical changes due to short lifetime dynamic processes. These improvements will allow imaging of samples that metabolize quickly, rapidly oxidize, or are physically altered under experimental conditions.
Irrigation rate and timing effects on Arizona cotton yield, water productivity, and fiber quality

Abstract Irrigated agriculture in the Arizona low desert faces multiple threats, including drought in the Colorado River basin, depletion of reservoirs supplying water to irrigation districts, competition from growing municipal and industrial sectors, and climate uncertainty. Improving irrigation water productivity is imperative for sustaining agricultural production in the region. The objective of the study was to measure responses of cotton yield, water productivity, and fiber quality to variable irrigation rates and timings for the 2016, 2017, and 2018 cotton growing seasons at Maricopa, Arizona. Four irrigation rates were used, including 60%, 80%, 100%, and 120% of recommended amounts from a scheduling tool. The four rates were administered differentially during two time periods: (1) squaring to peak bloom and (2) peak bloom to 90% open boll. The experimental design incorporated 16 irrigation treatments in a randomized block design with four replications, and irrigation was applied via an overhead lateral-move sprinkler system with commercial site-specific irrigation equipment. Linear mixed models could estimate cotton fiber yield, seasonal evapotranspiration, fiber micronaire, and fiber strength with root mean squared errors of cross validation (RMSECV) of 11.9%, 1.8%, 6.4%, and 3.6%, respectively. Variation in irrigation water productivity and several fiber quality metrics could be explained by water applied in the second irrigation period but not in the first, suggesting more opportunity in the early season for improving water productivity without sacrificing yield or fiber quality. Irrigation rates in the first period could be reduced up to 70 mm (6% of total water applied to the 100%–100% treatment) without sacrificing yield. During the second irrigation period, full irrigation was required to prevent yield losses and maintain high fiber quality. This study provides valuable guidance on opportunities for using sprinkler irrigation to improve water productivity while maintaining acceptable cotton yield and fiber quality in the Arizona low desert. Further effort is needed to clarify requirements for pre-plant irrigation, incorporate plant feedback data into in-season irrigation scheduling algorithms, and identify metrics to guide irrigation termination decisions.
Machine learning for extracting target electrical parameters from qualitative inverse scattering imagery

The Linear Sampling Method is an imaging technique that reconstructs target shape via a series of beamforming operations without using linear scattering assumptions. The norm of the solution is typically used to determine which pixels are inside the target support. There has not been much study of how to use the phase of the solution to aid in target identification. In this study, we explore using the solution phase to classify targets according to their electrical properties via a machine learning approach. We implement a support vector machine, apply it to imagery from simulated target data, and quantify classification accuracy.
Characteristics of Children’s Media Use and Gains in Language and Literacy Skills

Media use could be detrimental to children's language and literacy skills because it may displace other language-enhancing activities like shared reading and caregiver-child interactions. Furthermore, the extent to which children use media with adults (joint media engagement), the extent to which they use interactive media (apps/games), and the time of the day and week during which media use occurs may attenuate any negative effects. The current study examines the relation between characteristics of children's media use and gains in first graders' language and literacy skills. Children (N = 488) completed direct assessments of language and literacy skills in the spring of kindergarten and the spring of first grade. Parents reported how many hours children used both interactive and non-interactive media during different times of the day on the most recent weekday and weekend day and responded to items about the extent to which they engage with their children during media use. A quadratic relationship between media use and language gains showed that a moderate amount of media use was related to larger language gains, whereas high use was related to smaller gains. For literacy, an interaction between media use and joint media engagement showed a small negative effect of media use at low levels of joint media engagement and little to no relation between media use and literacy gains at higher levels of joint media engagement. Children's language and literacy skills were not predicted by either the proportion of media time that was spent with apps/games or morning and weekday media use. These results show that moderate amounts of media use may not be a negative influence on children's developing language skills, whereas high levels may displace other language-enhancing activities. Additionally, joint media engagement may play an important buffering role in the relation between media use and early literacy skills, aligned with current recommendations encouraging co-viewing.
Variations in Schedule III Prescription Patterns in a Medicaid Population Pre- and Post-Policy

The present study investigated variations in patient movement patterns between prescribers before and after House Bill 1 (HB1) implementation in Kentucky using network abstractions (PPN: prescriber-prescriber networks) from a one-month cross-sectional Schedule III prescription data in a Medicaid population. Network characteristics such as degree centrality distribution of PPN was positively skewed and revealed Dental Practitioners to be the highly connected specialty with opioid analgesic hydrocodone-acetaminophen to be the most commonly prescribed drug. Taxonomy enrichment of the prescriber specialties in PPN using chi-square test revealed a reduction in the enriched taxonomies Post-HB1 compared to Pre-HB1 with Dental practitioners being constitutively enriched (p < 0.05). PPNs were also found to exhibit rich community structure revealing inherent clustering of prescribers as a result of patient movement, and were markedly different from those generated by random graph models. The magnitude of deviation from random graphs decreased Post-HB1 relative to Pre-HB1. The proposed network approach provides system-level insights into prescribers with potential to complement classical reductionist approaches and aggregate statistical measures used in assessing changes in prescription patterns pre- and post- policy implementation. It can provide preliminary cues into drug seeking behavior, and facilitate targeted surveillance of prescriber communities.
Development of Metal-Supported Proton-Conducting Solid Oxide Cells Via Co-Sintering

Metal-supported solid oxide cells with P434L stainless steel support and BZCYYb-4411 electrode backbone and electrolyte layers are fabricated. Sintering aids for the ceramic layer are optimized. LiF is found to lower the ceramic sintering temperature too much. Manganese oxide enhances sintering and densification without dramatically reducing the sintering onset temperature. The impact of metal particle size on sintering is assessed. A symmetric structure helps to prevent warping or cracking arising from residual mis-match between the metal and ceramic sintering shrinkage. Intact cell structures are successfully prepared with <15 μm stainless steel particles and 2 wt% manganese oxide added to the BZCYYb-4411 layers.
Cooper, Darius. Aavaan Javaan: Arriving at and Departing from. Authorspress, 2018

Review of: Cooper, Darius. Aavaan Javaan: Arriving at and Departing from. Authorspress, 2018. Reviewed by Mitali P. Wong.
Reachability Analysis for FollowerStopper: Safety Analysis and Experimental Results

Motivated by earlier work and the developer of a new algorithm, the FollowerStopper, this article uses reachability analysis to verify the safety of the FollowerStopper algorithm, which is a controller designed for dampening stop-and-go traffic waves. With more than 1100 miles of driving data collected by our physical platform, we validate our analysis results by comparing it to human driving behaviors. The FollowerStopper controller has been demonstrated to dampen stop-and-go traffic waves at low speed, but previous analysis on its relative safety has been limited to upper and lower bounds of acceleration. To expand upon previous analysis, reachability analysis is used to investigate the safety at the speeds it was originally tested and also at higher speeds. Two formulations of safety analysis with different criteria are shown: distance-based and time headway-based. The FollowerStopper is considered safe with distance-based criterion. However, simulation results demonstrate that the FollowerStopper is not representative of human drivers - it follows too closely behind vehicles, specifically at a distance human would deem as unsafe. On the other hand, under the time headway-based safety analysis, the FollowerStopper is not considered safe anymore. A modified FollowerStopper is proposed to satisfy time-based safety criterion. Simulation results of the proposed FollowerStopper shows that its response represents human driver behavior better.
Structural analysis of the ITER EDA magnet system

The most recent design of the ITER magnet system is easier to assemble and is expected to be more conventionally manufactured. A stainless steel case with pancake wound plates replaces the earlier poloidally wrapped plate toroidal Field (TF) coil design. The number of TF coils has been reduced from 24 to 20 to ease access. The price for these improvements has been an increase in radial build of the TF coil, and a reallocation of space within the reactor. The TF and central solenoid (CS) are still bucked, making their interface an important area to simulate in structural models. Out-of-plane (OOP) forces are no longer supported by keys between TF legs. The TF case is strong enough to support most of the load when, it in turn, is supported by additional external structures. The most significant of these structures are the upper and lower crowns. A fluted torque shell on the outside of the CS provides a bearing surface for the TF and this along with the CS, and the TF inner legs, takes the global twist applied to the central column of the machine. A US Home team contribution has been a large scale global finite element model which addresses details of construction, and results of this model are presented. Cyclic case bending, torque shell shear, CS shear, the effects of assembly gaps, are presented. The case supports a large portion of the OOP loading, and the possibility of removal or simplifications in the OOP structures is discussed. CS shear stresses from local conductor behavior are combined with the shears from the global behavior and the total shear is compared with the insulation shear allowable used in the ITER EDA. A smaller structural model has been used to simulate multiple pulse, frictional effects, and results of this model are shown.
Aeroengine deviation parameters nonlinear estimation using improved Quantum-behaved PSO algorithm

Estimation of aeroengine deviation parameters (EDPs) is one of the key technologies of performance seeking control (PSC). The estimation errors may be great using traditional linear estimation algorithm, so nonlinear estimation model is established. The problem of nonlinear estimation is conversed to a problem of optimization. Mutation Quantum-behaved PSO (QPSO) algorithm is used to estimate EDPs. Take the given turbofan engine as an example, the feasibility of using Mutation QPSO (MQPSO) to estimate EDPs is validated by simulation.
A relatedness analysis approach for regulation comparison and e-rulemaking applications

The process of e-rulemaking with participation from the public involves a non-trivial task of sorting through and organizing a massive volume of electronically submitted comments. This research proposes to make use of available Information and Communication Technology (ICT) to help describe the relationship of public comments to policy drafts and deliberations. Based on previous work on regulatory management and comparisons, a relatedness analysis tool has been prototyped and applied to compare drafted regulations with the associated public comments. An example using a drafted regulation on rights-of-way access and the comments received by the Access Board is employed to illustrate the prototyped analysis tool. The drafted regulation and public comments are compared using not only a traditional term match but also a combination of feature matches, and not only content comparison but also structural analysis. This comparison framework helps review of comments with respect to provisions in the draft. Examples of results are shown to illustrate the use and limitations of ICT to support policy making.
Perception of weight status in children and adolescents: findings from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 (811.3)

Weight misperception in children and adolescents may lead to unhealthy or excessive weight control practices among overweight, underweight or normal weight individuals. Accurate self-perception of weight status has been linked to appropriate weight control behaviors in youth. The objective of this study was to examine gender and racial/ethnic differences in prevalence of weight misperception among children and adolescents. We used data from 4355 children and adolescents aged 8-15 years who participated in NHANES 2005-2010. Accuracy of weight perception status was determined by comparing self-reported weight status (overweight, about right and underweight) to actual weight status based on measured height and weight. The weight misperception prevalence was estimated and compared among age, gender and race/ethnic groups. Nearly, 29% of children and adolescents have misperception of their weight status. Weight misperception is more common among boys than girls and among children than adolescents. The prevalen...
The effect of down regulation of protein kinase C on the inhibitory modulation of dorsal root ganglion neuron Ca2+ currents by neuropeptide Y.

Dorsal root ganglion (DRG) neurons cultured from neonatal rats contained high concentrations of protein kinase C (PKC). Normally, the majority of the enzyme activity was found in the cytosol and considerably less was associated with the membrane fraction. Upon incubation with the phorbol ester phorbol dibutyrate (PDBu, 10(-6) M) for 20 min, PKC activity increased in the membrane-associated fraction and decreased in the cytoplasmic fraction. Longer incubations with phorbol ester also induced a decline in membrane-associated PKC activity. If incubations were continued for periods of over 10 hr, both membrane and cytosolic PKC activity declined essentially to zero. Down- regulation of PKC had no effect on the number or affinity of 125I- neuropeptide Y (NPY) binding sites on DRG cells or on the absolute magnitude of the DRG Ca2+ current. However, the ability of NPY to inhibit the DRG Ca2+ current was greatly reduced. When sustained Ca2+ currents were evoked from depolarized holding potentials (-40 mV), all concentrations of NPY (10(-10)-10(-7) M) were less effective. In contrast, higher concentrations of NPY still blocked the transient portion of the DRG Ca2+ current evoked from hyperpolarized holding potentials. These results support the suggestion that PKC is involved in the inhibitory modulation of DRG Ca2+ currents by neurotransmitters. The precise role of PKC may vary depending on the type of Ca2+ channel involved.
Functional Responses and Costimulator Dependence of Memory CD4+ T Cells

To examine the functional characteristics of memory CD4+ T cells, we used an adoptive transfer system to generate a stable population of Ag-specific memory cells in vivo and compared their responses to Ag with those of a similar population of Ag-specific naive cells. Memory cells localized to the spleen and lymph nodes of mice and exhibited extremely rapid recall responses to Ag in vivo, leaving the spleen within 3-5 days of Ag encounter. Unlike their naive counterparts, memory cells produced effector cytokines (IFN-gamma, IL-4, IL-5) within 12-24 h of Ag exposure and did not require multiple cycles of cell division to do so. Memory cells proliferated at lower Ag concentrations than did naive cells, were less dependent on costimulation by B7 molecules, and independent of costimulation by CD40. Furthermore, effector cytokine production by memory cells also occurred in the absence of either B7 or CD40 costimulation. Lastly, memory cells were resistant to tolerance induction. Together, these findings suggest that the threshold for activation of memory CD4+ cells is lower than that of naive cells. This would permit memory cells to rapidly express their effector functions in vivo earlier in the course of a secondary immune response, when the levels of Ag and the availability of costimulation may be relatively low.
Amniotic fluid cortisol in normal and diabetic pregnant women and its relation to respiratory disease in the neonate

Abstract One hundred and thirty samples of amniotic fluid from normal and diabetic pregnant women were analyzed for cortisol concentration. In normal pregnancies, cortisol was present in low concentrations until 35 weeks' gestation, followed by a sharp rise at 36 weeks and a continued upward trend to 39 weeks. The rise after 35 weeks was delayed or absent in many patients with diabetes. In the combined population, the incidence of respiratory disease with a lecithin/sphingomyelin ratio ≥ 2 was 26 per cent if the amniotic fluid cortisol was
A neuronal cell-based assay for highly sensitive detection of pharmaceutical preparations of BONT/A and patient neutralizing serum antibodies

Clostridium botulinum neurotoxins (BoNTs) A and B are widely used as pharmaceuticals to treat various neurologic disorders and in cosmetic applications. The mouse lethality method is widely accepted for assay of therapeutic preparations of BoNTs, but it has well-known drawbacks including wide variability, the need for a large number of animals, and 2–4 days time requirements. We present a primary neuronal spinal cord assay that is capable of detection of BoNT with a sensitivity of less than 0.1 U. The neuronal assay is shown to be highly sensitive and specific for detection and quantitation of BoNT in pharmaceutical toxin preparations (Mentor Biologics). The assay measures the ratio of cleaved compared to full-length SNAP-25 by Western blot and densitometry analyses. Another development of the assay is the detection of neutralizing serum antibodies, since an adverse effect of clinical treatments of patients with BoNT has been resistance to treatment after multiple injections. In a double-blinded analysis, sera were evaluated from approximately 40 patients, and SNAP-25 cleavage was inhibited in the cohort of non-responders but not in the controls. Currently, patients receiving BoNT therapies and patients enrolled in clinical trials for new applications and/or new formulations of BoNTs are not routinely monitored for the formation of neutralizing antibodies, since no assay other than the mouse protection assay is scientifically accepted that reliably tests for the presence of such antibodies. We present results that highlight the utility of the neuronal assay for highly sensitive and specific detection of neutralizing antibodies to BoNT/A in patient sera. New assay platforms for detection of BoNT and antibodies in neuronal cells are also being investigated and are described.
TESTING GENERAL RELATIVITY WITH LASER RANGING TO THE MOON.

This paper assesses some possibilities inherent in precise laser ranging to the moon for testing Einstein's theory of gravitation. The anticipated accuracy of the determination of the light transit time for a laser pulse returned by an optical corner reflector on the lunar surface is about two parts in ${10}^{10}$. Such high precision opens the possibility of detecting general relativistic effects in both the light propagation itself and in the lunar motion. The detailed analysis presented here indicates that, although the effects on light propagation are probably not detectable, there are general relativistic effects in the lunar motion which appear to be observationally accessible with the expected laser-ranging data. Observation of the dominant effect would provide a significant test of the correctness of the geodesic equation, to $O(\frac{1}{{c}^{2}})$ beyond the Newtonian approximation, for describing the motion of bodies in a gravitational field.
Complications of Continuous Ambulatory Peritoneal Dialysis: Diagnostic Value of Peritoneal Scintigraphy

Eighteen patients with complications secondary to continuous ambulatory peritoneal dialysis underwent peritoneal scintigraphy utilizing Technetium-99m sulfur colloid. Patients were divided into three groups. Group 1 patients (11) had dialysate leaks leading to abdominal-wall edema, genital edema, or exit-site drainage. Scintigrams were abnormal in nine patients in this group and frequently provided localizing information that aided in the management of leaks. Group 2 patients (five) had recurrent peritonitis. Two of these patients had abnormal scintigrams. In one instance, scintigraphy detected multiple abdominal-wall hernias that may have been responsible for recurrent peritonitis, which resolved following corrective surgery. Group 3 patients (two) had inadequate ultrafiltration but no clinical evidence of a dialysate leak. Scintigrams were negative in this group, eliminating consideration of an underlying structural defect in the peritoneum. Scintigraphic imaging is possible for several hours following instillation of labeled dialysate. This capability is important, since scintigrams that were initially negative frequently became positive after several hours of ambulation. Postdrainage images were also helpful in confirming extraperitoneal leakage. This study demonstrates that peritoneal scintigraphy is a useful diagnostic tool in the management of complications of continuous ambulatory peritoneal dialysis.
Dickens and Modernity: The English Association. Essays and Studies 2012

“How modern was Dickens?” Juliet John asks in her introduction to Dickens and Modernity, posing a question well suited to 2012 and the revaluations of the novelist that marked the bicentenary of hi...
Humanized TLR7/8 Expression Drives Proliferative Multisystemic Histiocytosis in C57BL/6 Mice

A humanized TLR7/TLR8 transgenic mouse line was engineered for studies using TLR7/8 ligands as vaccine adjuvants. The mice developed a spontaneous immune-mediated phenotype prior to six months of age characterized by runting, lethargy, blepharitis, and corneal ulceration. Histological examination revealed a marked, multisystemic histiocytic infiltrate that effaced normal architecture. The histological changes were distinct from those previously reported in mouse models of systemic lupus erythematosus. When the mice were crossed with MyD88−/− mice, which prevented toll-like receptor signaling, the inflammatory phenotype resolved. Illness may be caused by constitutive activation of human TLR7 or TLR8 in the bacterial artificial chromosome positive mice as increased TLR7 and TLR8 expression or activation has previously been implicated in autoimmune disease.
Picosecond–milliångström lattice dynamics measured by ultrafast X-ray diffraction

Fundamental processes on the molecular level, such as vibrations and rotations in single molecules, liquids or crystal lattices and the breaking and formation of chemical bonds, occur on timescales of femtoseconds to picoseconds. The electronic changes associated with such processes can be monitored in a time-resolved manner by ultrafast optical spectroscopic techniques1, but the accompanying structural rearrangements have proved more difficult to observe. Time-resolved X-ray diffraction has the potential to probe fast, atomic-scale motions2,3,4,5. This is made possible by the generation of ultrashort X-ray pulses6,7,8,9,10, and several X-ray studies of fast dynamics have been reported6,7,8,11,12,13,14,15. Here we report the direct observation of coherent acoustic phonon propagation in crystalline gallium arsenide using a non-thermal, ultrafast-laser-driven plasma — a high-brightness, laboratory-scale source of subpicosecond X-ray pulses16,17,18,19. We are able to follow a 100-ps coherent acoustic pulse, generated through optical excitation of the crystal surface, as it propagates through the X-ray penetration depth. The time-resolved diffraction data are in excellent agreement with theoretical predictions for coherent phonon excitation20 in solids, demonstrating that it is possible to obtain quantitative information on atomic motions in bulk media during picosecond-scale lattice dynamics.
Preliminary risk assessment database and risk ranking of pharmaceuticals in the environment

There is increasing concern about pharmaceuticals entering surface waters and the impacts these compounds may have on aquatic organisms. Many contaminants, including pharmaceuticals, are not completely removed by wastewater treatment. Discharge of effluent into surface waters results in chronic low-concentration exposure of aquatic organisms to these compounds, with unknown impacts. Exposure of virulent bacteria in wastewater to antibiotic residues may also induce resistance, which could threaten human health. The purpose of this study was to provide information on pharmaceutical threats to the environment. A preliminary risk assessment database for common pharmaceuticals was created and put into a web-accessible database named "Pharmaceuticals in the Environment, Information for Assessing Risk" (PEIAR) to help others evaluate potential risks of pharmaceutical contaminants in the environment. Information from PEIAR was used to prioritize compounds that may threaten the environment, with a focus on marine and estuarine environments. The pharmaceuticals were ranked using five different combinations of physical-chemical and toxicological data, which emphasized different risks. The results of the ranking methods differed in the compounds identified as high risk; however, drugs from the central nervous system, cardiovascular, and anti-infective classes were heavily represented within the top 100 drugs in all rankings. Anti-infectives may pose the greatest overall risk based upon our results using a combination of factors that measure environmental transport, fate, and aquatic toxicity. The dataset is also useful for highlighting information that is still needed to assuredly assess risk.
Desacetyl vinblastine amide sulfate induced ineffective erythropoiesis

Ineffective erythropoiesis occurred during desacetyl vinblastine amide sulfate (VDS) therapy of a patient with metastatic Ewing's sarcoma. The peripheral blood was characterized by anisocytosis, poikilocytosis and reticulocytopenia. Bone marrow showed megaloblastic red cell hyperplasia with nuclear fragmentation, binuclearity and abnormal metaphases. Radioiron incorporation into red cells was markedly decreased. Electron microscopy showed red cell surface changes previously called ropalocytosis. Normal erythropoiesis promptly resumed when VDS treatment was withheld. Although less common than leukopenia, red cell abnormalities are part of the spectrum of vinca alkaloid toxicity.
Heterostructure barrier varactor (HBV) frequency multipliers for terahertz application

Two heterostructure barrier varactor (HBV) frequency multipliers, a 300 GHz tripler and a 210 GHz quintupler, are designed, fabricated, and tested. The frequency tripler is fabricated with integrated technology, and the quintupler uses flip-chip mounted HBV diodes. The 210 GHz frequency quintupler shows record output power and efficiency. Moreover, the agreement between the simulation and measurement results validates our design methodology. The frequency tripler exhibits a measured output power of 4 mW and efficiency of 5% at 300 GHz. The 210 GHz frequency quintupler also achieves 5% conversion efficiency with 100 mW of input power. With an input E-H tuner, it can provide over 2 mW output power with over 10% bandwidth. Design, modeling and testing of these frequency multipliers are described and presented in this paper. Some possible methods to improve these frequency multipliers are addressed.
On being a pharmacy resident

As I woke up and fumbled for the light switch, I realized the time. It was 2:10 a.m. and my first night of inhouse call as a pharmacy practice resident (postgraduate year 1). I was being paged by one of the neurosurgery residents, requesting that I come to the intensive care unit to calculate a
Cluster size effects on hydrazine decomposition on Irn/Al2O3/NiAl(1 1 0)

Abstract A series of planar model catalysts were prepared by deposition of size-selected Ir n + on Al 2 O 3 /NiAl(1 1 0), and hydrazine decomposition chemistry was used to probe their size-dependent chemical properties. Small Ir n ( n ⩽ 15) on Al 2 O 3 /NiAl(1 1 0) are able to induce hydrazine decomposition at temperatures well below room temperature, with significant activity first appearing at Ir 7 . Both activity and product branching are strongly dependent on deposited cluster size, with these small clusters supporting only the simplest decomposition mechanism: dehydrogenation and N 2 desorption at low temperatures, followed by H 2 recombinative desorption at temperatures above 300 K. For Ir 15 , we begin to see ammonia production, signaling the onset of a transition to clusters able to support more complex chemistry.
Collaborative destination marketing: A case study of Elkhart county, Indiana

Abstract The fragmented nature of the tourism industry requires a substantial degree of coordination and collaboration among the variety of different players in destination marketing. However, the studies on partnerships and collaboration have taken very narrow perspectives of cooperation relationships and therefore, none of them individually can explain the nature of marketing alliances and networks among tourism organizations. Based upon the results of previous research and a case study of Elkhart County, Indiana, this paper proposes a more integrative theoretical framework in an attempt to better describe and explain the nature and dynamism of collaborative destination marketing. The implications of this framework are provided from both practical and theoretical perspectives.
Iodine metabolism in goitrous cretins.

ABSTRACT The iodine metabolism of 6 sporadic goitrous cretins was studied by determinations of stable and radioactive iodine. The 6 patients were placed in 3 groups on the basis of the level and type of metabolic block in the chain of events leading to the elaboration of thyroid hormone. The 3 patients in Group 1 were able to trap iodide without being able to bind it to protein, although in 1 patient minute amounts of monoiodotyrosine were found in the thyroid gland. The 2 patients in Group 2 could trap iodide and totally bind it to protein, but the resulting iodotyrosines were converted to only a small amount of thyroxine. Radioiodinated tyrosines were present in the serum and urine of these 2 patients. The single patient in Group 3 was able to trap iodide but, unlike those in Group 2, could bind only part of it to protein. The resulting thyroidal iodotyrosines were associated with only a small amount of thyroxine in the thyroid gland and with iodotyrosines in the urine.
Masking patterns in the bullfrog (Rana catesbeiana). I: Behavioral effects

A psychophysical technique based on reflex modification was used to measure masked auditory thresholds in the bullfrog (Rana catesbeiana). Masked thresholds were converted to critical ratios to describe the frequency selectivity of the bullfrog’s hearing. The bullfrog’s critical ratio function is complex. At low frequencies (100–600 Hz), it increases gradually with tone frequency at a rate of about 4 dB/octave. At high frequencies (1000–2500 Hz), the rate of increase with tone frequency is steeper (9 dB/octave). Critical ratios are lowest at frequencies around 1000 Hz (about 18 dB). Unlike effects previously reported in another anuran species, the green treefrog, the bullfrog’s critical ratio function is not parallel to its pure‐tone audiogram. Moreover, the relationship of the bullfrog’s critical ratio function to the spectral composition of its species‐specific vocalizations is not as compelling as in the green treefrog.
Infertility and Multiples

Abstract Infertility and its treatments can present highly complex medical and/or surgical problems accompanied by emotional turmoil for individuals, couples, and families. On a societal and global level, infertility treatments can include costly interventions that result in questions of priority, access, and payment. Infertility technologies also raise moral and ethical dilemmas in areas where the interventions have yet to be matched with shared ethical guidelines.
Recruiting the Next Generation of Fisheries Professionals

Fishes are an invaluable resource for myriad reasons. In the United States, they support important commercial (National Marine Fisheries Service [NMFS] 2011), recreational (Southwick Associates 200...
Delay-time statistics of cooperative emission in the presence of homogeneous line broadening.

We have developed a theoretical model that allows us to study the delay-time statistics of superfluorescent pulses for the case of collisional broadening with a Lorentzian line shape. Our model is based upon a more robust definition of delay time, based upon an energy rather than an intensity reference. We calculate the probability distribution of delay times in the initiation regime of superfluorescence, where the inversion is essentially constant. We find that, as the collisional dephasing rate is increased, the mean delay time increases and the distribution broadens. We compare our results with those for the case of inhomogeneous broadening with a Lorentzian line shape and find the unexpected result that the statistical behavior is identical.
Exact solution of the scalar wave equation with focused Gaussian gain

An exact analytic solution of the scalar wave equation in a rotationally symmetric focused-Gaussian-amplifying medium is constructed from coupled Gaussian-Laguerre solutions of the free-space wave equation. The solution allows for the analytic construction of the characteristic eigenmodes of the system and has direct application to Raman, dye, and free-electron lasers.
Effect of hydrogen peroxide, periodate and persulfate on photocatalysis of 2-chlorobiphenyl in aqueous TiO2 suspensions

Abstract Decomposition of 2-chlorobiphenyl (2-CB) in the systems of UV/TiO 2 , UV/oxidant and UV/TiO 2 /oxidant (i.e. H 2 O 2 , S 2 O 8 2− and IO 4 − ), were investigated. The addition of inorganic oxidants to the UV/TiO 2 system showed no rate-enhancing effects for the degradation of 2-CB with oxidant concentration of 10 −3 and 10 −2 M and TiO 2 concentration of 25 mg/l. The negative effect of oxidants on the heterogeneous oxidation was demonstrated. Homogeneous photooxidation seems to dominate over the parallel heterogeneous process when both TiO 2 and oxidants are present.