cssi/SciSciGPT-SciSciNet huggingface dataset:
A low bandwidth DFB laser-based interrogator for terahertz-range fiber Bragg grating sensors

This letter reports an all-electronic, low bandwidth swept frequency laser used to interrogate terahertz-range fiber Bragg gratings (THz FBGs) for distributed strain sensing applications. A distributed feedback laser with current injection modulation was employed as the swept frequency laser source. Using the resulting narrow bandwidth (~110 GHz) laser frequency sweep, high accuracy distributed strain measurements were achieved. In order to experimentally investigate this concept, a strain test was conducted using the THz FBGs. During the test, the laser sweeping time was limited to less than 2 ms. Highly linear results were found (R 2 = 0.996), with an observed sensitivity of -0.142 GHz/μe and the standard deviation of 1.167 μe. A multiplexing test was also conducted, and no cross-talk found between sensor elements. These results demonstrate that this interrogation system holds substantial potential as a method of rapid distributed optical fiber frequency-domain sensing.
Small Molecule Inhibition of LARG/RhoA Signaling Blocks Migration of ETV6-RUNX1 Positive B-Cell Precursor Acute Lymphoblastic Leukemia

Background and Objectives Translocation t(12;21), resulting in the ETV6-RUNX1 fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite the favorable prognosis associated with ETV6-RUNX1 positive ALL, relapse and resistance to chemotherapeutics occur and treatment-induced side effects are considerable. Leukemic cells reside in the bone marrow microenvironment, where they are nurtured and protected against chemotherapy. In this study, we investigated novel ways to disrupt this leukemic niche by targeting signaling pathways contributing to the migration of ETV6-RUNX1 positive leukemic cells. Results Gene expression profiling and subsequent pathway analysis of leukemic blasts of 654 ALL patients revealed a significant enrichment of genes involved in regulation of cellular movement and cell morphology in ETV6-RUNX1 positive BCP-ALL patients compared with ETV6-RUNX1 negative BCP-ALL patients (p + ) ectopically expressing ETV6-RUNX1 (p -06 ). LARG (ARHGEF12) was identified to be the most important regulator of this pro-migratory signature. This gene encodes for the G-protein-regulated Rho Guanine Exchange Factor 12, a specific activator of the GTPase RhoA. LARG expression was 5.7-fold higher in ETV6-RUNX1 positive BCP-ALL cells than in ETV6-RUNX1 negative BCP-ALL cells (p -06 ). Similarly, LARG was upregulated 5.4-fold in CB-CD34 + cells expressing ETV6-RUNX1 compared with empty vector controls (p = 0.03). To determine the importance of the LARG/RhoA pathway in the induction of this migratory phenotype, we used two recently identified small molecule inhibitors of the LARG/RhoA pathway: Y16, a specific LARG inhibitor, and G04 (Rhosin), a specific RhoA inhibitor. Both inhibitors significantly reduced the migration of ETV6-RUNX1 positive leukemic cells towards a gradient of CXCL12 (75%, p Next, we studied the additional cellular effects of LARG/RhoA inhibition on leukemic cells. shRNA-mediated silencing of LARG modestly reduced the proliferation rate of both ETV6-RUNX1 positive and ETV6-RUNX1 negative cell lines (p LARG moderately reduced the phosphorylation level of CREB (S133, 25%, p Conclusion Together, our data indicate that small molecule inhibition of LARG/RhoA signaling affects the migration potential of ETV6-RUNX1 positive cells. In contrast to inhibition of the CXCR4/CXCL12 axis that reduces the migration of both leukemic and healthy hematopoietic cells, inhibition of the LARG/RhoA signaling pathway appears to specifically inhibit ETV6-RUNX1 positive cell migration. Our results warrant further studies to establish the clinical benefit of disrupting the leukemic niche in ETV6-RUNX1 positive BCP-ALL patients using small molecule inhibitors of LARG/RhoA signaling. Disclosures No relevant conflicts of interest to declare.
Development of a 3D matrix for modeling mammalian spinal cord injury in vitro

Spinal cord injury affects millions of people around the world, however, limited therapies are available to improve the quality of life of these patients. Spinal cord injury is usually modeled in rats and mice using contusion or complete transection models and this has led to a deeper understanding of the molecular and cellular complexities of the injury. However, it has not to date led to development of successful novel therapies, this is in part due to the complexity of the injury and the difficulty of deciphering the exact roles and interactions of different cells within this complex environment. Here we developed a collagen matrix that can be molded into the 3D tubular shape with a lumen and can hence support cell interactions in a similar architecture to a spinal cord. We show that astrocytes can be successfully grown on this matrix in vitro and when injured, the cells respond as they do in vivo and undergo reactive gliosis, one of the steps that lead to formation of a glial scar, the main barrier to spinal cord regeneration. In the future, this system can be used to quickly assess the effect of drugs on glial scar protein activity or to perform live imaging of labeled cells after exposure to drugs.
Disparities in Disability by Educational Attainment Across US States.

Objectives. To examine how disparities in adult disability by educational attainment vary across US states.Methods. We used the nationally representative data of more than 6 million adults aged 45 to 89 years in the 2010–2014 American Community Survey. We defined disability as difficulty with activities of daily living. We categorized education as low (less than high school), mid (high school or some college), or high (bachelor’s or higher). We estimated age-standardized disability prevalence by educational attainment and state. We assessed whether the variation in disability across states occurs primarily among low-educated adults and whether it reflects the socioeconomic resources of low-educated adults and their surrounding contexts.Results. Disparities in disability by education vary markedly across states—from a 20 percentage point disparity in Massachusetts to a 12-point disparity in Wyoming. Disparities vary across states mainly because the prevalence of disability among low-educated adults varies ...
Exploration of Conceptions of Assessment within High-Stakes U.S. Culture

Past quantitative research about studentsâ€™ and faculty membersâ€™ conceptions of assessment indicates that faculty believe that one of the primary purposes of assessment is for improvement of both teaching and learning. Â Students, however, associate a primary reason for assessment in higher education for accountability of both students and the institution.Â The present study aimed to determine if beliefs were congruent between student and faculty responses to open-ended survey items.Â Using a phenomenological approach to investigate studentsâ€™ and faculty membersâ€™ conceptions of assessment, the researchers found discrepant results when qualitative data were compared to the results of past quantitative studies (Brown, 2004; DiLoreto, 2013; Fletcher, Meyer, Anderson, Johnston, & Rees, 2011). Â Additional results of this inquiry and implications of these findings for educational settings are discussed.Â Â
Visualizations of cross-cultural bibliographic classification: comparative studies of the Korean Decimal Classification and the Dewey Decimal Classification

The changes in KO systems induced by sociocultural influences may include those in both classificatory principles and cultural features. The proposed study will examine the Korean Decimal Classification (KDC)’s adaptation of the Dewey Decimal Classification (DDC) by comparing the two systems. This case manifests the sociocultural influences on KOSs in a cross-cultural context. Therefore, the study aims at an in- depth investigation of sociocultural influences by situating a KOS in a cross-cultural environment and examining the dynamics between two classification systems designed to organize information resources in two distinct sociocultural contexts. As a preceding stage of the comparison, the analysis was conducted on the changes that result from the meeting of different sociocultural feature in a descriptive method. The analysis aims to identify variations between the two schemes in comparison of the knowledge structures of the two classifications, in terms of the quantity of class numbers that represent concepts and their relationships in each of the individual main classes. The most effective analytic strategy to show the patterns of the comparison was visualizations of similarities and differences between the two systems. Increasing or decreasing tendencies in the class through various editions were analyzed. Comparing the compositions of the main classes and distributions of concepts in the KDC and DDC discloses the differences in their knowledge structures empirically. This phase of quantitative analysis and visualizing techniques generates empirical evidence leading to interpretation.
Preoperative Computed Tomography-Guided Pulmonary Lesion Marking in Preparation for Fluoroscopic Wedge Resection-Rates of Success, Complications, and Pathology Outcomes.

Purpose In this study, we describe our experience of lesion marking with fiducial markers (FM) and microcoils (MC) facilitating same-day surgical wedge resection, including success rates, pathology outcomes, and complications. We also explored patient/nodular characteristics associated with developing complications. Materials and Methods An IRB-approved single-institutional retrospective study of 136 patients who had 148 pulmonary nodules was conducted. All patients had CT-guided pulmonary nodule labeling with either FM (121) or MC (15) patients with plan for same-day fluoroscopic-guided wedge resection. Results Of 136 (98%) patients, 133 had successful same-day wedge resection as planned; 2 had delayed but successful wedge resection surgery due to complications at the time of marker placement (fiducial embolization and hemorrhage/pneumothorax, respectively). A third patient ultimately needed lobectomy due to deep lesion location. Eighty percent [118/148] of resected nodules were malignant. Further, 68% of the total group of patients [93/136] had mild complications of various types including hemorrhage [44/136, 32%], pneumothorax [35/136, 26%], a combination of both hemorrhage and pneumothorax [10/136, 7%], or migration/embolization [4/136, 3%]. Depth of nodule from skin (P = 0.011) and pleura (P = 0.027) was significantly associated with complications. Conclusion CT-guided marking of small or deep pulmonary lesions using either fiducial markers or microcoils provides an effective means to aid surgeons to accomplish minimally invasive wedge resection. The importance of the success of this technique is supported by the high incidence (80%) of malignant lesion etiology found at postresection pathology. Although complications occurred, the vast majority were mild and did not alter planned same-day resection.
Effects of Resin Architecture and Protein Size on Nanoscale Protein Distribution in Ion-Exchange Media.

Knowledge of the nanoscale distribution of proteins in chromatographic resins is critical to our mechanistic understanding of separations performance. However, the nano- to mesoscale architecture of these materials is challenging to characterize using conventional techniques. Small-angle neutron scattering was used to probe (1) the nano- to mesoscale structure of chromatographic media and (2) protein sorption in these media in situ with protein-scale resolution. In particular, we characterize the effect of the architecture of cellulose-based and traditional and dextran-modified agarose-based ion-exchange resins on the nanoscale distribution of a relatively small protein (lysozyme) and two larger proteins (lactoferrin and a monoclonal antibody) at different protein loadings. Traditional agarose-based resins (SP Sepharose FF) can be envisioned as comprising long, thin strands of helical resin material around which the proteins adsorb, while higher static capacities are achieved in dextran-modified resins (S...
Neuropsychological Function in Renal Disease and Its Treatment

Our understanding of neuropsychological function in end-stage renal disease (ESRD) and chronic hemodialysis has evolved a great deal in the past 30 years. Early studies in the 1960s and 1970s documented the neurocognitive effects of uremia and chronic renal failure, while investigations in the 1970s and 1980s focused on neurocognitive outcome following initiation of hemodialysis, neuropsychological status in chronic hemodialysis and peritoneal dialysis, and correction for anemia and aluminum toxicity. In the 12 years since this chapter was first published, medical standards of dialysis adequacy have changed dramatically. Thus, many patients studied in the 1960s to 1980s may have been relatively underdialyzed at the time of assessment compared to current standards for dialysis prescription (Lowrie, Laird, Parker, & Sargent, 1981; Gotch & Sargent, 1985; National Kidney Foundation, 1997a, 1997b). Recent investigations quantifying dialysis delivery have provided new insights into the neuropsychological effects of dialysis. Several investigations into the effects of renal transplantation on cognition also have appeared within the past decade.
Engineered superparamagnetic nanomaterials for arsenic(V) and chromium(VI) sorption and separation: quantifying the role of organic surface coatings

Inorganic–organic nanoscale materials have recently received significant interest as tunable, next generation, sorbents for the separation of metal and metalloid contaminants, including arsenic (As) and chromium (Cr), among others. In this work, we have designed and synthesized IONCs coated with specific functionalized organic materials with the goal of variable explicit evaluation. Specifically, single domain, superparamagnetic, monodisperse IONCs were synthesized and transferred into water via surface functionalization by ligand exchange and encapsulation methods. The as synthesized hybrid materials showed high performance for both As(V) and Cr(VI) sorption when nanocrystals are coated with positively charged organic surface coatings such as polyethyleneimine (PEI) and cetyltrimethylammonium bromide (CTAB). IONC cores coated with negatively charged organic coating materials (polyethyleneglycol (PEG), oleic acid (OA), sodium dodecyl sulfate (SDS)) and silica (SiO2) demonstrated significantly lower sorption capacities. When silica coated IONCs (Fe3O4@SiO2, core–shell materials) were surface coated with PEI, sorption capacities for As(V) and Cr(VI) of Fe3O4@SiO2@PEI are comparable to Fe3O4@PEI, underscoring the importance of surface coating functionality. To complement these studies, real-time sorption behavior of As(V) and Cr(VI) with PEI was explored by quartz crystal microbalance with dissipation (QCM-D).
Screening Regulatory Element Function with CRISPR/Cas9-based Epigenome Editing

Genomic regulatory elements that control gene expression play an important role in many traits and diseases. Identifying the regulatory elements associated with each gene or phenotype and understanding the function of that element remain a significant challenge. To address this technological need, we developed CRISPR/Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. This protocol includes detailed instructions for design and cloning of gRNA libraries, construction of endogenous reporter cell lines via CRISPR/Cas9-mediated knock-in of fluorescent proteins, overall screen design, and recovery of the gRNA library for enrichment analysis. This protocol will be generally useful for implementing genome engineering technologies for high-throughput functional annotation of putative regulatory elements in their native chromosomal context.
Real-time interactive learning in the NERO video game

In the NeuroEvolving Robotic Operatives (NERO) video game, the player trains a team of virtual robots for combat against other players' teams. The virtual robots learn in real time through interacting with the player. Since NERO was originally released in June, 2005, it has been downloaded over 50,000 times, appeared on Slashdot, and won several honors. The real-time NeuroEvolution of Augmenting Topologies (rt-NEAT) method, which can evolve increasingly complex artificial neural networks in real time as a game is being played, drives the robots' learning, making possible this entirely new genre of video game. The live demo will show how agents in NERO adapt in real time as they interact with the player. In the future, rtNEAT may allow new kinds of educational and training applications through interactive and adapting games.
Failure mechanisms in joint replacement

Publisher Summary Joint replacement has revolutionised the treatment of arthritic disorders of the hip, knee, shoulder, and other articulations in the body. Total joint replacement is changing. No longer is a “one size fits all― mentality pervasive. The options for joint replacement are individualised for each patient. This has lead to concepts such as choosing the most functional, least expensive prosthesis for the level of activity of the patient to Minimally Invasive Surgery [“MIS―] in which incisions and surgical dissections are kept to those that are necessary to accomplish the procedure only. The concept of MIS would facilitate a quicker rehabilitation, early discharge and return to normal activities, but it has not yet been conclusively shown. Modularity of implants would provide the surgeon with a host of options to reconstruct normal biomechanics on the spot. Newer bearing surfaces employing highly cross-linked polyethylene, metal-on-metal and ceramic-on-ceramic articulations might allow a wider range of activities. However, enthusiasm should be tempered by the unavailability of long-term follow-up. Computer-assisted surgery has the potential to improve implant alignment with online feedback in the operating room, but this concept is still in its infancy and multi-plane alignment cannot easily be assessed.
Creating an Efficient Learning Model: Students’ Perceptions and Outcomes of an Active Learning Fixed Prosthodontics Course

With the extensive amount of learning required in dental schools, educators are constantly seeking more efficient learning models. The aim of this retrospective study was to evaluate a fixed prosthodontics course after its curriculum transitioned from a traditional lecture format to an active learning structure over the course of five years. In this retrospective, mono-centered study completed in 2018 at a U.S. dental school, data from the school's fixed prosthodontics course exams, National Board Dental Examination Part II (NBDE II), and the operative portion of the Western Regional Examining Board (WREB) licensure exam were collected for 381 students from the inaugural Class of 2015 to the Class of 2019. Data were evaluated for two groups based on method of instruction: the Classes of 2015 and 2016 were taught in a traditional model, and the Classes of 2017-19 were taught in the modified learning model. The data showed a 30% reduction in time students spent in the classroom and simulation clinic as compared to the previous model. The modified learning model reduced time spent in lecture, length of the course, and number of projects needed, while student performance remained consistent. Students in the active learning classes were able to pass all assessments including practical examinations at the same rate as previous classes using traditional learning methods. Students' performance on standardized national exams (NBDE II and WREB licensure exams) remained consistent among the graduating classes, and scores were comparable to the national average. Although limited in scope, this study suggests that it is possible to reduce contact time in fixed prosthodontics and maintain performance by increasing student engagement through active learning techniques.
Quantifying spatial uncertainty in rock through geostatistical integration of borehole data and a geologist's cross-section

Abstract In order to increase understanding of spatial uncertainty in subsurface conditions for problems in geological and geotechnical engineering, this study develops a geostatistical approach for incorporating a geologist's interpreted cross-section to quantify spatial uncertainty of lithology. In this work, the Sequential Indicator Cosimulation (COSISM) algorithm and the information theory concept of entropy are utilized to generate uncertainty models. A sensitivity analysis is used to study how both borehole data and the cross-section are incorporated into the algorithm, which is quantified using entropy as a metric for uncertainty in geologic unit boundary locations. A verification methodology is then developed to identify the most appropriate combination of input parameters for combining these two data types; recommendations from the verification methodology are made by comparing the calculated entropy to accuracy at the global scale on a point-by-point basis. This methodology is then used to investigate how calibrated input parameters vary due to differences in the input cross-section based on different levels of understanding of the subsurface geology by iteratively providing a geologist with additional borehole data after a cross-section is developed. Results show that two of the parameters, variogram range and the number of conditioning data, can be used to most directly reflect geologist understanding in the simulations. Finally, this study provides guidelines for incorporating a geologist's understanding of a geological environment into this modeling framework, as results show cross-sections that are locally accurate are better represented by different parameters than cross-sections that are not locally accurate but are globally accurate. These guidelines are intended to aid geologists and engineers in understanding how to incorporate a geologist's interpretation of the subsurface lithology or categorical geotechnical parameters at a particular worksite into a structured geostatistical framework.
Two-Carbon Ring Expansion of 1-Indanones via Insertion of Ethylene into Carbon-Carbon Bonds.

A rhodium-catalyzed direct insertion of ethylene into a relatively unstrained carbon–carbon bond in 1-indanones is reported, which provides a two-carbon ring expansion strategy for preparing seven-membered cyclic ketones. As many 1-indanones are commercially available and ethylene is inexpensive, this strategy simplifies synthesis of benzocycloheptenones that are valuable synthetic intermediates for bioactive compounds but challenging to prepare otherwise. In addition, the reaction is byproduct-free, redox neutral, and tolerant of a wide range of functional groups, which may have implications on unconventional strategic bond disconnections for preparing complex cyclic molecules.
Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II.

An autosomal recessive deficiency of acid {alpha}-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients - two infants and and adult - provided a rare opportunity to analyze the effect of the second mutation in patients who displayed dramatically different phenotypes. A deletion of Lys-903 in one patient and a substitution of Arg for Leu-299 in another resulted in the fatal infantile form. In the adult, a T-to-G base change at position-13 of intron 1 resulted in alternatively spliced transcripts with deletion of exon 2, the location of the start codon. The low level of active enzyme (12% of normal) generated from the leakage of normally spliced mRNA sustained the patient to adult life. 61 refs., 9 figs., 3 tabs.
Most pediatric transplant centers are low volume, adult-focused, and in proximity to higher volume pediatric centers.

Abstract Background Independent studies provide evidence that low volume pediatric solid organ transplant centers have inferior outcomes compared to high volume pediatric centers. The study assessed whether patients treated at low volume pediatric centers have access to higher volume pediatric centers, which offer potentially better outcomes. Methods We analyzed center specific data on 467 pediatric solid organ transplant centers in the U.S using the Organ Procurement and Transplantation Network database from 2002 to 2014. The proximities of low volume pediatric centers to high volume pediatric centers were determined using Maptive, a tool based on Google Maps. Results Most low volume pediatric transplant centers focused on transplantation of adults (84% heart, 83% liver, and 93% kidney programs). A majority of low volume pediatric centers (77% for heart, 53% for lung, 68% for liver and 90% for kidney) were within 150 miles of high volume centers. Among all children listed for transplantation, 30.7% were listed in low volume pediatric centers. Most low volume pediatric centers are adult focused and near high volume pediatric centers. Conclusion We need greater scrutiny of outcomes, particularly waitlist outcomes, of low volume pediatric solid organ transplant centers located close to high volume pediatric solid organ transplant centers. Type of Study and Level of Evidence Retrospective Comparative Study, Level III.
Aging, Vision, and Work:

Older people who lose their vision often do not return to competitive employment. Work, however, meets important, financial, psychological, and social needs. This article explores the variety of re...
Chapter 4 – Authentication Servers

Publisher Summary This chapter discusses Authentication and Authorization/Directory server configuration. The Instant Virtual Extranet (IVE) supports several different types of authentication servers with which to integrate, including local authentication, Lightweight Directory Access Protocol (LDAP), Network Information Service (NIS), ACE, Remote Authentication Dial-In User Service (RADIUS), Active Directory/NT, anonymous, SiteMinder, certificate, and Security Assertion Markup Language (SAML) authentication. The IVE can integrate with most common LDAP servers, including Active Directory, Sun ONE (iPlanet), Novell eDirectory, and generic LDAP servers, such as OpenLDAP. The IVE can authenticate natively to a Unix NIS server. It is observed that the IVE can authenticate natively to an RSA/ACE server, allowing users with hardware or software one-time password tokens. The IVE can use a RADIUS server to authenticate users and perform role-mapping rules based on RADIUS attributes. It is found that SAML authentication allows the IVE to pass user and session state information to an external system that supports SAML, and prevents the need to enter usernames and passwords multiple times.
Radiation Safety Concerns Related to PET/Computed Tomography Imaging for Assessing Pediatric Diseases and Disorders

The Image Gently Nuclear Medicine Working Group published a 10-year update in 2019. One of the future goals of this working group is to continue the efforts started in 2014 to harmonize the North American guidelines with the European Association of Nuclear Medicine pediatric dosing guidelines, continuing to publicize the use of the North American guidelines. The update also acknowledged the need for standardization of CT parameters in hybrid imaging and also will seek to tackle this issue as one of its future goals.
Leveraging spatial textures, through machine learning, to identify aerosols and distinct cloud types from multispectral observations

Abstract. Current cloud and aerosol identification methods for multispectral radiometers, such as the Moderate Resolution Imaging Spectroradiometer (MODIS) and Visible Infrared Imaging Radiometer Suite (VIIRS), employ multichannel spectral tests on individual pixels (i.e., fields of view). The use of the spatial information in cloud and aerosol algorithms has been primarily through statistical parameters such as nonuniformity tests of surrounding pixels with cloud classification provided by the multispectral microphysical retrievals such as phase and cloud top height. With these methodologies there is uncertainty in identifying optically thick aerosols, since aerosols and clouds have similar spectral properties in coarse-spectral-resolution measurements. Furthermore, identifying clouds regimes (e.g., stratiform, cumuliform) from just spectral measurements is difficult, since low-altitude cloud regimes have similar spectral properties. Recent advances in computer vision using deep neural networks provide a new opportunity to better leverage the coherent spatial information in multispectral imagery. Using a combination of machine learning techniques combined with a new methodology to create the necessary training data, we demonstrate improvements in the discrimination between cloud and severe aerosols and an expanded capability to classify cloud types. The labeled training dataset was created from an adapted NASA Worldview platform that provides an efficient user interface to assemble a human-labeled database of cloud and aerosol types. The convolutional neural network (CNN) labeling accuracy of aerosols and cloud types was quantified using independent Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and MODIS cloud and aerosol products. By harnessing CNNs with a unique labeled dataset, we demonstrate the improvement of the identification of aerosols and distinct cloud types from MODIS and VIIRS images compared to a per-pixel spectral and standard deviation thresholding method. The paper concludes with case studies that compare the CNN methodology results with the MODIS cloud and aerosol products.
Regulatory Reform and Bureaucratic Responsiveness to Firms: TheImpact of User Fees in the FDA

This paper examines the impact of user fees on the speed of new drug review and on the responsiveness of FDA reviewers to pharmaceutical firms. User fees are expected to alter FDA behavior and responsiveness to pharmaceutical firms because they give regulators a financial incentive to process more new drug applications and because they convey information to regulators that may reduce type I error. The analysis examines the variation in FDA review times for new drugs approved between 1990-1995 as a function of differences that exist among firms and drugs. Specifically, it compares estimates of regulator responsiveness to several firm and drug characteristics before and after the introduction of user fees. The results show that user fees produced a significant change in FDA behavior. Regulators have become less responsive to the differences among firms after the introduction user fees which suggests that the reform has led to more equity in the new drug review process. In addition, the FDA has expedited the review of new drugs, especially the most therapeutically novel drugs which suggests that politicians have been relatively successful in designing a reform to realign regulatory incentives in the FDA.
How many students could continue learning during COVID-19-caused school closures? Introducing a new reachability indicator for measuring equity of remote learning

Abstract This paper proposes a new reachability indicator to analyze the effectiveness of remote learning policies adopted by ministries of education in response to school closures caused by the COVID-19 pandemic. The indicator provides the share of students that can potentially be reached by remote learning policies given the availability of necessary household assets such as radios, televisions, computers and internet access. The results of this analysis outline the stark inequities in access to remote learning, suggesting that at a minimum, more than 30 % of schoolchildren globally cannot be reached by remote learning policies due to the high variation in access to assets for remote learning that exists within and between the world regions. The analysis finds that wealth and area of residence are key factors affecting the reachability of remote learning policies, suggesting that children who reside in rural areas and/or belong to the poorest households in their country are at the greatest risk of being left behind.
One-Pot Synthesis of Carbon Nanofibers from CO2

Carbon nanofibers, CNFs, due to their superior strength, conductivity, flexibility, and durability have great potential as a material resource but still have limited use due to the cost intensive complexities of their synthesis. Herein, we report the high-yield and scalable electrolytic conversion of atmospheric CO2 dissolved in molten carbonates into CNFs. It is demonstrated that the conversion of CO2 → CCNF + O2 can be driven by efficient solar, as well as conventional, energy at inexpensive steel or nickel electrodes. The structure is tuned by controlling the electrolysis conditions, such as the addition of trace transition metals to act as CNF nucleation sites, the addition of zinc as an initiator and the control of current density. A less expensive source of CNFs will facilitate its adoption as a societal resource, and using carbon dioxide as a reactant to generate a value added product such as CNFs provides impetus to consume this greenhouse gas to mitigate climate change.
Economic evaluation of environmental health interventions to support decision making.

Environmental burden of disease represents one quarter of overall disease burden, hence necessitating greater attention from decision makers both inside and outside the health sector. Economic eval...
Spatiotemporal Access Control Enforcement under Uncertain Location Estimates

In a mobile environment, user's physical location plays an important role in determining access to resources. However, because current moving object databases do not keep the exact location of the moving objects, but rather maintain their approximate location for reasons of minimizing the updates, the access request evaluation cannot always guarantee the intended access control policy requirements. This may be risky to the system's security, especially for the highly sensitive resources. In this paper, we introduce an authorization model that takes the uncertainty of location measures into consideration for specifying and evaluating access control policies. An access request is granted only if the confidence level of the location predicate exceeds the predefined uncertainty threshold level specified in the policy. However, this access request evaluation is computationally expensive as it requires to evaluate a location predicate condition and may also require evaluating the entire moving object database. For reducing the cost of evaluation, in this paper, we compute lower and upper bounds (R min and R max ) on the region that minimize the region to be evaluated thereby allowing unneeded moving objects to be discarded from evaluation. We show how R min and R max can be computed and maintained, and provide algorithms to process access requests.
Coordinated regulation of cardiac Na(+)/Ca (2+) exchanger and Na (+)-K (+)-ATPase by phospholemman (FXYD1).

Phospholemman (PLM) is the founding member of the FXYD family of regulators of ion transport. PLM is a 72-amino acid protein consisting of the signature PFXYD motif in the extracellular N terminus, a single transmembrane (TM) domain, and a C-terminal cytoplasmic tail containing three phosphorylation sites. In the heart, PLM co-localizes and co-immunoprecipitates with Na+-K+-ATPase, Na+/Ca2+ exchanger, and L-type Ca2+ channel. The TM domain of PLM interacts with TM9 of the α-subunit of Na+-K+-ATPase, while its cytoplasmic tail interacts with two small regions (spanning residues 248–252 and 300–304) of the proximal intracellular loop of Na+/Ca2+ exchanger. Under stress, catecholamine stimulation phosphorylates PLM at serine68, resulting in relief of inhibition of Na+-K+-ATPase by decreasing Km for Na+ and increasing Vmax, and simultaneous inhibition of Na+/Ca2+ exchanger. Enhanced Na+-K+-ATPase activity lowers intracellular Na+, thereby minimizing Ca2+ overload and risks of arrhythmias. Inhibition of Na+/Ca2+ exchanger reduces Ca2+ efflux, thereby preserving contractility. Thus, the coordinated actions of PLM during stress serve to minimize arrhythmogenesis and maintain inotropy. In acute cardiac ischemia and chronic heart failure, either expression or phosphorylation of PLM or both are altered. PLM regulates important ion transporters in the heart and offers a tempting target for development of drugs to treat heart failure.
Expression Profile and Genome Location of cDNA Clones from an Infant Human Trabecular Meshwork Cell Library

PURPOSE To delineate the profile of genes expressed in infant human trabecular meshwork and identify candidate genes for glaucoma. METHODS Human trabecular meshwork cell cultures were established from six young donors. A cDNA library was made from the combined trabecular meshwork mRNA. The end-sequence of random clones was determined by direct sequencing. These sequences were then analyzed by a National Center for Biotechnology Information (NCBI, Bethesda, MD) database search. Nucleotide searches were performed using the BLASTN (ver. 2.1.3; against the nonredundant nucleic acid sequence) and dbEST databases (both provided by NCBI in the public domain at www.ncbi.nlm.nih.gov). RESULTS Sequences from 1118 clones from this nonamplified trabecular meshwork cDNA library were categorized. Of these, 877 expressed sequence tags (ESTs) (78.7%) were known genes. One hundred thirty-nine ESTs (12.5%) showed close identity to EST sequences reported in the public domain database (dbEST). Thirteen ESTs (1.2%) showed no significant similarity to known genes or ESTs in the public databases and were thus defined as novel ESTs. The most abundant genes expressed by the human trabecular meshwork included ferritin H, eukaryotic translation elongation factor 1-alpha, ferritin L, fibronectin, and TIMP-1. Ferritin H was the most abundant transcript, making up more than 4% of the genes expressed by the human trabecular meshwork. Extracellular matrix proteins were also highly expressed. The chromosome location of the trabecular meshwork ESTs is reported. CONCLUSIONS A profile of genes expressed by human trabecular meshwork is presented. Thirteen novel ESTs were identified. The combined information obtained from expression analysis and chromosomal localization of trabecular meshwork cDNAs should be valuable in identifying candidate genes for glaucoma.
Hemorrhage into hydatid of morgagni simulating acute appendicitis

Abstract These cases illustrate the similarity of the clinical picture of twisted hemorrhagic hydatid of Morgagni to that of an acute appendiceal lesion. The former however gives a history of a menstrual irregularity and dysmenorrhea (our attack occurred before the onset of menstruation), with only a few of the signs of an acute abdomen.
Induction of chicken ovalbumin upstream promoter‐transcription factor I (COUP‐TFI ) gene expression is mediated by ETS factor binding sites

Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI, or NR2F1) is an orphan nuclear receptor that plays a major role in the development of the nervous system. We show here that three ETS response elements in the COUP-TFI promoter mediate its transcription. A reporter gene containing these ETS binding sites is activated by Ets-1, while the same reporter with point mutations on all three ETS response elements is not. We also show that Ets-1 binds to these response elements and that other ETS factors also transactivate the COUP-TFI promoter. In addition, COUP-TFI is coexpressed with some ETS factors in the mouse embryo. These results indicate that members of the ETS family can activate COUP-TFI gene expression.
Reaction of the α Subunit of the Escherichia coli Tryptophan Synthetase with 1,5-Difluoro-2,4-dinitrobenzene

1,5-Difluoro-2,4-dinitrobenzene introduces an intramolecular cross-linkage into the Escherichia coli tryptophan synthetase α subunit between residues cysteine 80 and lysine 108, concomitant with a loss of its aldolytic activity on indoleglycerol phosphate. The stereochemical relationship of these residues and other residue pairs cross-linked by other bifunctional reagents to the activity of the enzyme is discussed.
Alternative splicing in humans

Alternative pre-mRNA splicing is the mechanism by which a cell fine-tunes gene expression, by deciding what discrete segments of a gene's total coding information should be selected for expression in a specific cell type. The phenomenon of multiple alternative splicing pathways in the human genome, and the opportunity to regulate these pathways during development, allows a relatively small number of genes to encode a complex proteome in tissue-specific patterns. Individual splicing decisions are controlled by interplay among splicing regulatory proteins, acting at specific enhancer and silencer sequences in the pre-mRNA, and the catalytic machinery known as the spliceosome. Proper splicing regulation is a critical aspect of gene expression during normal human development, and derangements in this process are responsible for many human diseases. Recent advances in genome sequencing, gene expression profiling, bioinformatics, and biochemical analysis of the splicing machinery give hope that the rules by which splicing regulatory networks govern alternative splicing in humans will be deduced. Keywords: alternative splicing; regulation; splicing enhancer; silence; disease
Leiomyosarcoma of the gastrointestinal tract.

Summary 1.Twelve cases of leiomyosarcoma of the gastrointestinal tract are reported. Locations of the tumors were: stomach, 3 cases; duodenum 3 cases; jejunum 2 cases; ileum 3 cases, and cecum 1 case. 2.The principle clinical features of these tumors are blood loss and subsequent weakness. The bleeding may be into the lumen of the bowel but may also occur into the peritoneal cavity or within the tumor itself. 3.The relatively low grade malignancy of these neoplasms is confirmed by the absence of distant metastases despite the long duration of symptoms. 4.It is important to keep the diagnosis of leiomyosarcoma of the intestinal tract in mind because with early radical surgery the prognosis in these lesions is excellent.
Maternal-fetal interactions and the maintenance of HLA polymorphism

There is some empirical evidence that a fetus with an HLA antigen not present in its mother has a higher survival than a fetus sharing antigens with its mother. We have developed both single locus and two-locus theoretical models to examine this mode of selection. First, this immunologically based model appears to have the potential to maintain many alleles at a single locus and to result in an excess of heterozygotes when selection is strong. Second, substantial gametic disequilibrium is maintained between alleles at two loci for this selection mode when recombination is that observed between HLA loci A, B, and DR. Overall, it appears that this mode of selection has the potential to strongly affect genetic variation in the HLA region.
The Effect of Antivascular Endothelial Growth Factor Therapy on the Development of Neovascular Glaucoma after Central Retinal Vein Occlusion: A Retrospective Analysis

Purpose. Ischemic central retinal vein occlusion (CRVO) eyes are at high risk of developing neovascular glaucoma (NVG). Our purpose is to investigate the effect of anti-VEGF therapy for macular edema after CRVO on the development of neovascular glaucoma (NVG) in ischemic CRVO eyes. Methods. This is a retrospective case series of 44 eyes from 44 patients with CRVO treated with anti-VEGF therapy for macular edema. The primary outcome was the development of NVG. Results. Of the 44 eyes, 14 eyes had ischemic CRVO, and 30 eyes had nonischemic CRVO. Nonischemic eyes received a mean of 8.4 anti-VEGF doses, over mean follow-up of 24 months. One nonischemic eye (3.3%) developed NVD but not NVG. The 14 ischemic eyes received a mean of 5.6 anti-VEGF doses, with mean follow-up of 23 months. Of these 14 ischemic eyes, two eyes (14%) developed iris neovascularization and 3 eyes (21%) developed posterior neovascularization. Three of these 5 eyes with neovascularization progressed to NVG, at 19.7 months after symptom onset, on average. Conclusion. Anti-VEGF therapy for macular edema may delay, but does not prevent, the development of ocular NV in ischemic CRVO. Significant risk of NVG still exists for ischemic CRVO eyes.
Continuous time and communication in a public-goods experiment

Abstract We investigate the nature of continuous time strategic interaction in public-goods games. In one set of treatments, four subjects make contribution decisions in continuous time during a 10-min interval while in another they make them only at 10 discrete points of time during this interval. The effect of continuous time is muted in public-goods games compared to simpler social dilemmas and the data suggest that widespread coordination problems are to blame. When we add a rich communication protocol, these coordination problems largely disappear and the median subject contributes completely to the public good with no sign of decay over time. At the median, the same communication protocol is less than half as effective in discrete time.
Hog thyroid peroxidase: Physical, chemical, and catalytic properties of the highly purified enzyme☆

Abstract Studies are reported on the purity and on the physical, chemical, and catalytic properties of a highly purified, stable, thyroid peroxidase (TPO). The enzyme was solubilized by treatment with deoxycholate and trypsin, and it was purified by a series of column treatments, including ion-exchange chromatography on DEAE-cellulose, gel filtration through Bio-Gel P-100, and hydroxylapatite chromatography. The final product, designated TPO VII, had a value for A 410 /A 280 of 0.54, and its specific activity based on the guaiacol assay (794 μmol of guaiacol oxidized/min/mg) was considerably greater than that of any previously described TPO. Specific activity values based on other peroxidase-catalyzed reactions were also higher for TPO VII than for previous TPO preparations. Purity estimates for TPO VII, based on polyacrylamide disc gel electrophoresis and on isoelectric focusing in polyacrylamide gels, ranged from 80 to 95%. The molecular weight, determined by sedimentation equilibrium, was 93,000. Results of sodium dodecyl sulfate-gel electrophoresis also indicated a molecular weight of approximately 90,000. Sodium dodecyl sulfate-gel electrophoresis under reducing conditions indicated that TPO VII is composed of two peptide chains of unequal size, with the larger about 2.5-fold the size of the smaller. Carbohydrate analysis revealed that TPO is a glycoprotein containing about 10% by weight of carbohydrate. The predominant sugars were mannose and N -acetyl glucosamine. A significant amount of glucose was also found, along with small amounts of galactose, fucose, and xylose. The amino acid composition of TPO VII showed a high proline content, a predominance of arginine over lysine, and a ratio of [Asp] plus [Glu] to [Lys] plus [Arg] of over 2. Isoelectric focusing in polyacrylamide gels indicated an isoelectric pH of 5.75. In agreement with observations made on earlier preparations of TPO, heme spectral data showed significant differences between the pyridine hemochromogens of TPO VII and horseradish peroxidase, suggesting that the heme in TPO is not ferriprotoporphyrin IX. Circular dichroism measurements indicated that approximately 40% of TPO VII involves α helix or β structure.