cssi/SciSciGPT-SciSciNet huggingface dataset:
Tuberculosis Contact Investigations Conducted in New York City Adult Day Care and Senior Centers, 2011-2018.

Objectives:Multiple tuberculosis (TB) exposures have been reported in New York City (NYC) adult day care and senior centers. Strategies to identify TB transmission at such locations are needed.Meth...
Assessment of RAS Dependency for BRAF Alterations Using Cancer Genomic Databases

Importance UnderstandingRASdependency and mechanisms ofRASactivation in non-V600BRAFvariant cancers has important clinical implications. This is the first study to date to systematically assessRASdependency ofBRAFalterations with real-world cancer genomic databases. Objective To evaluateRASdependency of individualBRAFalterations through alteration coexistence analysis using cancer genomic databases. Design and Setting A cross-sectional data analysis of 119 538 nonredundant cancer samples using cancer genomics databases including GENIE (Genomics Evidence Neoplasia Information Exchange) and databases in cBioPortal including TCGA (The Cancer Genome Atlas) (accessed March 24, 2020), in addition to 2745 cancer samples from Mayo Clinic Genomics Laboratory (January 1, 2015, to July 1, 2020). Frequencies and odds ratios of coexisting alterations ofRAS(KRAS,NRASandHRAS) andRASregulatory genes (NF1,PTPN11andCBL) were calculated for individualBRAFalterations, and compared according to the currentBRAFalteration classification; cancer type specificity of coexisting alterations ofRASorRASregulatory genes was also evaluated. Main Outcomes and Measures Primary outcome measurement is enrichment ofRAS(KRAS,NRASandHRAS) alterations inBRAFvariant cancers. Secondary outcome measurement is enrichment ofRASregulatory gene (NF1,PTPN11, andCBL) inBRAFvariant cancers. Results A total of 2745 cancer samples from 2708 patients (female/male ratio: 1.0) tested by Mayo Clinic Genomics Laboratory and 119 538 patients (female/male ratio: 1.1) from GENIE and cBioPortal database were included in the study. In 119 538 nonredundant cancer samples, class 1BRAFalterations andBRAFfusions were found to be mutually exclusive to alterations ofRASorRASregulatory genes (odds ratio range 0.03-0.13 and 0.03-0.73 respectively), confirming theirRASindependency. Both class 2 and class 3BRAFalterations show variable and overlapping levels of enrichedRASalterations (odds ratio range: 0.03-5.9 and 0.63-2.52 respectively), suggesting heterogeneity inRASdependency and a need to revisitBRAFalteration classification. ForRAS-dependentBRAFalterations, the coexisting alterations also involveRASregulatory genes by enrichment analysis (for example, S467L shows an odds ratio of 8.26 forNF1, 9.87 forPTPN11, and 15.23 forCBL) and occur in a variety of cancer types with some coalterations showing cancer type specificity (for example,HRASvariations account for 46.7% of all coexisting RAS alterations in BRAF variant bladder cancers, but 0% in non–small cell lung cancers). Variant-level assessment shows thatBRAFalterations involving the same codon may differ in RAS dependency. In addition,RASdependency of previously unclassifiedBRAFalterations could be assessed. Conclusions and Relevance CurrentBRAFalteration classification based on in vitro assays does not accurately predict RAS dependency in vivo for non-V600BRAFalterations.RAS-dependentBRAFvariant cancers with different mechanisms ofRASactivation suggest the need for different treatment strategies.
Review and Critique of PikettyS Capital in the Twenty-First Century

This essay is a comprehensive and critical review of Thomas Pikettys Capital in the Twenty-First Century. It follows the flow of Pikettys argument carefully and literally and notes his many assertions that are unsupported or contradicted by economic logic and empirical evidence, particularly in the United States. The essay particularly questions the high real interest rate needed to support Pikettys model of growth and distribution, in stark contrast with the low and even negative real interest rates the United States has been experiencing for several years. The essay also summarizes the recent critiques of Pikettys arguments by other leading economists.
Performance Analysis of Perovskite Solar Panels in Smart Grid

With an exponentially advancing world, demand for power generation is also increasing. Both public and private entities require electricity for the modern demands of today. This makes efficiency and reliable generation tantamount to the optimal use and transmission of power. Loss in power in route to customers poses a challenge to the antiquated energy infrastructure in place today. The theorized smart grid would minimize transmission and energy losses. The smart grid would also more closely tailor energy production to energy consumption. Power management techniques such as load shifting, and peak shaving can be utilized in a smart grid to manage demand and allow reliable power to customers. In parallel third generation solar energy technologies are emerging. Perovskite solar panels stand to yield high efficiency solar panels at low costs. With the dissemination of solar energy on a national scale incorporated in a smart grid, energy production can become environmentally conscious and efficient. In this paper, the use of perovskites in a solar panel array in a smart grid is simulated in a virtual environment. This work constructed a perovskite solar panel in smart grid by adapting the semiconductor characteristics and electrical properties. Furthermore, we investigated the performance of our perovskite solar array to a commercially available solar panel to assess the viability of their use by the public.
The Epidemiology of Adult Tracheostomy in the United States 2002-2017: A Serial Cross-Sectional Study.

Describe the longitudinal national epidemiology of tracheostomies performed in acute care hospitals and describe the annual rate of tracheostomy performed for patients with respiratory failure with invasive mechanical ventilation. DESIGN Serial cross-sectional study. Setting The 2002-2014 and 2016-2017 Healthcare Utilization Project's National Inpatient Sample datasets. Patients Discharges greater than or equal to 18 years old, excluding those with head and neck cancer or transferred from another hospital. We used diagnostic and procedure codes from the International Classification of Diseases, 9th and 10th revisions to define cases of respiratory failure, invasive mechanical ventilation, and tracheostomy. Interventions None. Measurements and Main Results There were an estimated 80,612 tracheostomies performed in 2002, a peak of 89,545 tracheostomies in 2008, and a nadir of 58,840 tracheostomies in 2017. The annual occurrence rate was 37.5 (95% CI, 34.7-40.4) tracheostomies per 100,000 U.S. adults in 2002, with a peak of 39.7 (95% CI, 36.5-42.9) in 2003, and with a nadir of 28.4 (95% CI, 27.2-29.6) in 2017. Specifically, among the subgroup of hospital discharges with respiratory failure with invasive mechanical ventilation, an annual average of 9.6% received tracheostomy in the hospital. This changed over the study period from 10.4% in 2002, with a peak of 10.9% in 2004, and with a nadir of 7.4% in 2017. Among respiratory failure with invasive mechanical ventilation discharges with tracheostomy, the annual proportion of patients 50-59 and 60-69 years old increased, whereas patients from 70 to 79 and greater than or equal to 80 years old decreased. The mean hospital length of stay decreased, and in-hospital mortality decreased, whereas discharge to intermediate care facilities increased. Conclusions Over the study period, there were decreases in the annual total case volume and adult occurrence rate of tracheostomy as well as decreases in the rate of tracheostomy among the subgroup with respiratory failure with invasive mechanical ventilation. There is some evidence of changing patterns of patient selection for in-hospital tracheostomy among those with respiratory failure with invasive mechanical ventilation with decreasing proportions of patients with advanced age.
The Betti numbers of Mbar_{0,n}(r,d)

We calculate the Betti numbers of the coarse moduli space of stable maps of genus 0 to projective space, using a generalization of the Legendre transform.
Observational studies of low-frequency oscillations in the Southern Hemisphere

A 40-50 day atmospheric oscillation has recently been reported in the southeastern Pacific based on analyses of satellite-derived micro­ wave brightness temperature data. Prior to this, such oscillations have not been generally recognized in this region. The purpose of this Note is to provide corroboration of the microwave analyses from an independent data set, four years of rawinsonde data from Easter Island (27®S, 109'W). Significant spectral peaks with period 45-53 days were found in the zonal wind near the jet core (300-200 mb) and in the temperature on the underside of the jet. The signal is also present in the 100 mb temperature as shown by strong coherence between 100 and 400 mb tempera­ ture perturbations. Direct comparison of the 100 mb temperature pertur­ bations and the microwave data show good agreement. There is also an indication of a lower frequency signal, about 6584 day period, in the meridional wind at 1000 mb. This signal appears to be vertically evanescent with maximum amplitude at the surface.
New Medium for Differentiation of Candida albicans from Candida stellatoidea

A simple medium effectively differentiated Candida stellatoidea from Candida albicans on the basis of a new criterion, relative sensitivity to cycloheximide.
Mycoplasmal Deoxyribonuclease Activity in Virus-infected L-Cell Cultures

Cell-free extracts of Mycoplasma hominis and medium from 72-hr broth cultures had deoxyribonuclease activity like that of deoxyribonuclease I. Mg ++ stimulated activity, and the p H optimum was between 8.0 and 9.0. Double-stranded or heatdenatured deoxyribonucleic acid (DNA) served as a substrate, and oligonucleotides were produced. Cell-free extracts of L cells infected with M. hominis or M. hominis plus equine abortion virus (equine herpes virus, EAV) had greatly increased activity over that of extracts of L cells or of L cells infected with EAV alone. In the absence of M. hominis , however, extracts had little activity, most of which was in virus-infected cell cultures. Activity was found in the culture medium only in those systems in which M. hominis was present. It is concluded that M. hominis can contribute significant deoxyribonuclease activity to virus-infected as well as virusfree cell cultures. Perhaps the most interesting question arising concerns the ability of EAV, a DNA virus, to replicate successfully despite the presence of deoxyribonuclease activity at the site of replication (the nucleus).
Late Quaternary stratigraphic charcoal records from Madagascar

The classic view regarding the cause of the extinction of at least 17 species of large mammals, birds, and reptiles in Madagascar during the late Holocene implicates human use of fire to modify the environment. However, analysis of the charcoal stratigraphy of three sediment cores from Madagascar shows that late Pleistocene and early- to mid-Holocene sediments deposited prior to human settlement often contain more charcoal than postsettlement and modern sediments. This observation, which is confirmed by independent measurements from direct assay and palynological counting techniques, suggests that widely held but previously untested beliefs concerning the importance of anthropogenic fires in late Holocene environmental changes and megafaunal extinctions of Madagascar may be based on an overly simplified version of actual prehistoric conditions. Moderate to low charcoal values characterized only the late Holocene millennia immediately prior to the presumed time of arrival of the first settlers. Human settlement is probably indicated in the stratigraphy by the sharp rise in charcoal content observed beginning ca. 1500 yr B.P. Fire appears to be a significant natural component of prehuman environments in Madagascar, but some factor, probably climate, has modulated the extent of natural burning.
On Hegel, imperialism, and structural stagnation

Abstract The essentials of the economic theory of imperialism a la Hobson-Luxemburg are anticipated in two paragraphs of Hegel's Philosophy of Right . Marx did not pay attention to this aspect of Hegel's thought, perhaps because it implied a longer survival probability for capitalism than Marx cared to acknowledge. The second part of the paper shows the formal similarity between the economic theory of imperialism and the theory of structural stagnation that was proposed in Latin America in the 1960s. The blindspots and early demise of that theory have the same psychological root as Marx's neglect of Hegel's insights.
The Seduction of Samuel Butler: Rhetorical Agency and the Art of Response

Using the Victorian writer Samuel Butler's response to Darwin's Origin of Species as an example, I argue for a method of reading characterized by the process of fascination and seduction. Such an antimethodical method not only requires a different kind of agency on the part of the reader, but it also resituates rhetoric as an art of response to the dynamic flux of the communicating world.
Bitumen Surface Energy Characterization by qa Inverse Gas Chromatography

Modern surface energy theory has been identified in recent years as an attractive tool by which to select compatible bitumen-aggregate combinations. In addition, this approach offers the potential to quantitatively assess moisture susceptibility of these material combinations. The success of implementing this technology depends on the availability of techniques that allow efficient and reliable surface energy characterization of the materials under consideration. This paper focuses on bitumen surface energy characterization employing inverse gas chromatography (IGC). The authors report detail column preparation and test methodologies, and provide a precision statement for this technique. Analysis procedures and results presented demonstrate successful application of this technique with modern thermodynamic theory to acquire bitumen surface energy components. The technique allows testing at different temperatures and results are in agreement with conceptual and theoretical expectations. Surface energies derived from IGC compare reasonably well with mechanical surface tension values from the literature. Results suggest that surface energies do not vary considerably between different bitumen types, indicative of the controlling role of aggregate type in bitumen-aggregate adhesion.
N-Glucuronidation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and N-hydroxy-PhIP by specific human UDP-glucuronosyltransferases

Glucuronidation is a major metabolic pathway in the biotransformation of many xenobiotics. Recent studies have shown that in humans, UDP-glucuronosyltransferase (UGT)-mediated glucuronidation plays a critical role in the detoxification of food-borne carcinogenic heterocyclic amines. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant carcinogenic heterocyclic amine found in well-cooked meats, has been shown to be extensively glucuronidated in humans. To determine which UGT isozymes are involved in the biotransformation of PhIP and the cytochrome P4501A2-mediated reactive intermediate N-hydroxy-PhIP, microsomes expressing human UGT1A1, -1A4, -1A6 or -1A9 were incubated with PhIP and N-hydroxy-PhIP and the reaction products analyzed by HPLC and ESI-MS. Incubations containing N-hydroxy-PhIP and UGT1A1 expressing microsomes, with an apparent Km of 4.58 microM and a Vmax of 4.18 pmol/min/mg protein, had the highest capacity to convert N-hydroxy-PhIP to N-hydroxy-PhIP-N2-glucuronide. Microsomes expressing UGT1A9 produced N-hydroxy-PhIP-N3-glucuronide at the highest rate with an apparent Km and Vmax of 3.73 microM and 4.07 pmol/min/mg, respectively. A third previously undefined glucuronide accounted for 31% of the total glucuronides formed from the UGT1A4 expressing microsomes. No glucuronide conjugates were detected from microsomes expressing UGT1A6. Incubations containing PhIP as substrate formed direct PhIP-glucuronides in microsomes expressing UGT1A1, UGT1A4 and UGT1A9 but at levels averaging 53-fold lower than when N-hydroxy-PhIP was used as the substrate. Knowing the glucuronidation capacity of the specific UGT isozymes involved in PhIP and N-hydroxy-PhIP glucuronidation should help in determining the individual susceptibility to the potential cancer risk from exposure to PhIP.
Metaanalysis of Survival, Complications, and Imaging Response following Chemotherapy-based Transarterial Therapy in Patients with Unresectable Intrahepatic Cholangiocarcinoma

Abstract Purpose Unresectable intrahepatic cholangiocarcinoma represents a devastating illness with poor outcomes when treated with standard systemic therapies. Several smaller nonrandomized outcomes studies have been reported for such patients undergoing transarterial therapies. A metaanalysis was performed to assess primary clinical and imaging outcomes, as well as complication rates, following transarterial interventions in this patient population. Materials and Methods By using standard search techniques and metaanalysis methodology, published reports (published in 2012 and before) evaluating survival, complications, and imaging response following transarterial treatments for patients with unresectable intrahepatic cholangiocarcinoma were identified and evaluated. Results A total of 16 articles (N = 542 subjects) met the inclusion criteria and are included. Overall survival times were 15.7 months±5.8 and 13.4 months±6.7 from the time of diagnosis and time of first treatment, respectively. The overall weighted 1-year survival rate was 58.0%±14.5. More than three fourths of all subjects (76.8%) exhibited a response or stable disease on postprocedure imaging; 18.9% of all subjects experienced severe toxicities (National Cancer Institute/World Health Organization grade≥3), and most experienced some form of postembolization syndrome. Overall 30-day mortality rate was 0.7%. Conclusions As demonstrated by this metaanalysis, transarterial chemotherapy-based treatments for cholangiocarcinoma appears to confer a survival benefit of 2–7 months compared with systemic therapies, demonstrate a favorable response by imaging criteria, and have an acceptable postprocedural complication profile. Such therapies should be strongly considered in the treatment of patients with this devastating illness.
Hyper-spectral content aware resizing

Image resizing is performed for many reasons in image processing. Often, it is done to reduce or enlarge an image for display. It is also done to reduce the bandwidth needed to transmit an image. Most image resizing algorithms work based on principles of spatial or spatial frequency interpolation. One drawback to these algorithms is that they are not image content aware and can fail to preserve relevant features in an image, especially during size reduction. Recently, a content aware image resizing algorithm, called seam carving, was developed. In this paper we discuss an extension of the seam carving algorithm to hyper-spectral imagery. For a hyper-spectral image with an MxN field of view and with P spectral layers, our algorithm identifies a one pixel wide path through the image field of view containing a minimum of information and then removes it. This process is repeated until the image size is reduced to the desired dimension. Information content is assessed using normalized spatial power metrics. Several such metrics have been tested with varying results. The resulting carved hyper-spectral image has the minimum reduction in information for the resizing based upon energy metrics used to quantify information. We will present the results of seam carving applied to imagery sets of: three spectra RGB imagery from a standard still camera, two spectra imagery generated synthetically, and three spectra imagery captured with VNIR, SWIR, and LWIR cameras.
Load sharing among converters in an autonomous microgrid in presence of wind and PV sources

Power sources in a microgrid must be controlled in coordination with each other in order to meet optimization requirements and satisfy the operating criteria of the microgrid as a whole. Droop control is a distributed control method for sharing current components of the load between interface converters, where output voltage of each converter is controlled according to droop characteristics, to provide the proper sharing of any of load current components. As for wind and PV sources, active current reference is provided by MPPT1 system. If interface converters of these sources are controlled in a current-controlled mode to generate the desired active current, they will not be able to contribute to providing the other components of the load current with share factors that are determined by the objective function. This paper proposes a control scheme that allows the interface converters of wind and PV sources to generate active current according to the output of MPPT system and at the same time contribute to providing the other components with the share factors calculated by the objective function.
Patterns of resemblance of order 2

Abstract We will investigate patterns of resemblance of order 2 over a family of arithmetic structures on the ordinals. In particular, we will show that they determine a computable well ordering under appropriate assumptions.
Clinical challenges associated with incorporation of nonradiology images into the electronic medical record

To date, the majority of Picture Archival and Communication Systems (PACS) have been utilized only for capture, storage, and display of radiology and in some cases, nuclear medicine images. Medical images for other subspecialty areas are currently stored in local, independent systems, which typically are not accessible throughout the healthcare enterprise and do not communicate with other hospital information or image management systems. It is likely that during the next few years, healthcare centers will expand PAC system capability to incorporate these multimedia data or alternatively, hospital-wide electronic patient record systems will be able to provide this function.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Joule heating patterns as a function of polar cap index

[1] Previous work by Chun et al. [1999] has shown that the polar cap (PC) index can be used as a proxy indicator of the integrated Joule heating rate in the Northern Hemisphere. However, knowledge of the spatial distribution of Joule heating is also important. The PC index is a single magnetometer station-derived index which measures the level of geomagnetic activity in the polar cap. A negative PC index corresponds to a condition related to lobe-merging convection conditions in the polar cap, near-zero PC indicates a quiet polar cap, and a positive PC indicates geomagnetically active periods. In this study we developed average patterns of Joule heating as a function of PC using 56 days (∼12,800 individual patterns) of Assimilative Mapping of Ionospheric Electrodynamics data from various case studies. With PC ranging from −3 to 8, we divide the Joule heating patterns into PC bins of 1.0, finding that there is a clear spatial evolution of Joule heating from negative PC to positive PC. When PC is negative, Joule heating on average is constrained to the high-latitude dayside. As PC goes to zero, Joule heating disappears. When PC increases in the positive direction, Joule heating intensifies throughout the auroral oval, with primary heating occurring along the dawn/dusk flanks. Further analysis reveals that it is primarily changes in the electric potential and not the Pedersen conductance that accounts for Joule heating shifting from the auroral zone to the high-latitude dayside when PC goes negative. We also find that the cross polar cap potential is linearly proportional to the PC index, consistent with previous studies. Finally, we compare the hemispheric energy budget between Joule heating and electron particle energy. We find that globally, Joule heating is roughly 4 times that of particle energy during geomagnetically active times (positive PC). During quiet times (zero PC), Joule heating and particle energy are equal contributors. When lobe-merging conditions occur (negative PC), Joule heating again dominates over particle energy except during the winter season, when polar cap conductivity is driven more by particle precipitation.
The role of an epithelial occlusion zone in the termination of vitellogenesis in Hyalophora cecropia ovarian follicles

Abstract At the end of vitellogenesis, the follicular epithelium of Hyalophora cecropia follicles forms an occlusion zone that can halt the access of horseradish peroxidase to the oocyte surface in living follicles, and of lanthanum nitrate in fixed preparations. It is proposed that this barrier is responsible for terminating the uptake of blood proteins by the oocyte. Although three types of interfollicle cell junctions were observed, only tight junctions appeared to be responsible for the observed impermeability. Sodium dodecyl sulfate-acrylamide gel electrophoresis of [3H]leucinelabeled proteins revealed no change in the protein synthetic pattern during the transformation of follicles from vitellogenesis to the subsequent terminal growth period; in addition, pinocytotic figures continued to be formed in the postvitellogenic oocyte. These findings suggest that the epithelial secretion which the oocyte is known to deposit in yolk during vitellogenesis continues to be sequestered in the absence of blood proteins after occlusion zone formation. The proposal explains the origin of a layer of membrane-limited bodies which occupy the cortex of the oocyte in mature silkworm eggs, and which differ markedly in appearance from the protein yolk spheres assembled earlier.
Coated Transjugular Intrahepatic Portosystemic Shunt Does Not Improve Thrombocytopenia in Patients with Liver Cirrhosis

Background/Aim Thrombocytopenia is a common complication of chronic liver disease. The theory of portal decompression to improve thrombocytopenia due to hypersplenism has led to the study of transjugular intrahepatic portosystemic shunt (TIPS) as a potential therapy. However, there is a paucity of data and results have been conflicting. The aim of this study was to determine whether platelet counts improved in cirrhotic patients after placement of the new polytetrafluoroethylene (PTFE)-coated TIPS, developed in 2004.
Dynamics of a stratified shear layer with horizontal shear

The evolution of a stratified shear layer with mean shear in the horizontal direction, orthogonal to gravity, is numerically investigated with focus on the structural organization of the vorticity and density fields. Although the Reynolds number of the flow increases with time, facilitating instabilities and turbulence, the bulk Richardson number signifying the level of stratification also increases. Remarkably rich dynamics is found: turbulence; the emergence of coherent core/braid regions from turbulence; formation of a lattice of dislocated vortex cores connected by thin horizontal sheets of collapsed density and vorticity; density-driven intrusions at the edges of the shear layer; and internal wave generation and propagation. Stratification introduces significant vertical variability although it inhibits the vertical velocity. The molecular dissipation of turbulent kinetic energy and of turbulent potential energy are both found to be substantial even in the case with highest stratification, and primarily concentrated in thin horizontal sheets. The simulation data are used to help explain how buoyancy induces the emergence of columnar vortex cores from turbulence and then dislocates these cores to eventually form a lattice of ‘pancake’ eddies connected by thin sheets with large vertical shear (horizontal vorticity) and density gradient.
Development and application of BioFeed model for optimization of herbaceous biomass feedstock production

Abstract An efficient and sustainable biomass feedstock production system is critical for the success of the biomass based energy sector. An integrated systems analysis framework to coordinate various feedstock production related activities is, therefore, highly desirable. This article presents research conducted towards the creation of such a framework. A breadth level mixed integer linear programming model, named BioFeed, is proposed that simulates different feedstock production operations such as harvesting, packing, storage, handling and transportation, with the objective of determining the optimal system level configuration on a regional basis. The decision variables include the design/planning as well as management level decisions. The model was applied to a case study of switchgrass production as an energy crop in southern Illinois. The results illustrated that the total cost varied between 45 and 49 $ Mg −1 depending on the collection area and the sustainable biorefinery capacity was about 1.4 Gg d −1 . The transportation fleet consisted of 66 trucks and the average utilization of the fleet was 86%. On-farm covered storage of biomass was highly beneficial for the system. Lack of on-farm open storage and centralized storage reduced the system profit by 17% and 5%, respectively. Increase in the fraction of larger farms within the system reduced the cost and increased the biorefinery capacity, suggesting that co-operative farming is beneficial. The optimization of the harvesting schedule led to 30% increase in the total profit. Sensitivity analysis showed that the reduction in truck idling time as well as increase in baling throughput and output density significantly increased the profit.
On the detection of homotropic effects in enzymes of low co-operativity. Application to modified aspartate transcarbamoylase.

Abstract In contrast with the ease of observing heterotropic effects in allosteric enzymes of low co-operativity, the detection of homotropic effects is often difficult. As a consequence, erroneous conclusions about the uncoupling of homotropic and heterotropic effects can result unless sensitive techniques are used for analyzing the kinetic data. Simulations of experiments as well as actual measurements on the allosteric enzyme, aspartate transcarbamoylase, of Escherichia coli and some of its modified forms, were performed in attempts to develop stringent diagnostic procedures for the detection of homotropic effects in enzymes of low co-operativity. The analyses show that direct saturation plots (velocity versus substrate concentration), double reciprocal plots, and Hill plots yield misleading results in that the co-operativity known to be present is not observed. In contrast, Eadie plots (velocity/substrate concentration versus velocity) are much more sensitive in revealing homotropic effects. Since the observed co-operativity depends on both the allosteric equilibrium constant, L , and the number of active sites, n , simulations were performed on the effect of those parameters. The maxima in the Eadie plots increased as L was lowered and conversely the maxima decreased as n was reduced. These changes were confirmed with a mutant aspartate transcarbamoylase which had the same specific activity as the wild-type enzyme and a lower value of L , and also with a hybrid enzyme containing fewer active sites and the same L value. Analogous experiments on nitrated aspartate transcarbamoylase derivatives of decreasing activity showed that Eadie plots were of value in distinguishing between the changes in L and n values resulting from the inactivation. Data from the literature were analyzed in the form of Eadie plots and in all cases homotropic effects were readily detectable for aspartate transcarbamoylase derivatives previously claimed to be devoid of co-operativity.
Chemical Tools to Monitor and Manipulate the Adaptive Immune System

The ability to monitor and manipulate antigen-specific immune responses would have a major impact on several areas of biology and medicine. In this perspective, I consider pharmacological methods to do this, with a focus on the development of abiological "antigen surrogates" capable of binding to the antigen-binding sites of antibodies and B cell receptors with high affinity and selectivity. I describe the application of combinatorial library screening to identify antigen surrogates for monoclonal antibodies of therapeutic interest using chronic lymphocytic leukemia as an example. Furthermore, I discuss the use of multiplexed assays for the quantification of antigen surrogate-antibody complexes as diagnostic tools and antigen surrogate discovery via serum screening. Although antigen surrogates are a fairly new concept, I argue that they will open new avenues for both basic and clinical research and that major advances can be expected over the next few years.
Middle East Respiratory Syndrome: What Clinicians Need to Know

A severe viral illness caused by a newly discovered coronavirus was first reported in the Middle East in 2012. The virus has since been named the Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV cases have been reported in several countries around the world in travelers from the Middle East. The illness has a high mortality rate. Limited human-to-human transmission has occurred including transmission to health care workers. The source of the virus remains unclear, but camels are a possible source. Two unrelated imported cases of MERS-CoV have been reported in the United States. Neither a vaccine nor effective therapy against the virus is available. International cooperation and information sharing will be key to understanding and ending the MERS-CoV outbreak.
The limitations of salt cryoscopy for the study of complex species in aqueous solution

Abstract The implications and the validity of the tacit assumptions made in the theory and in the application of the salt cryoscopic method as used for the study of charged poly- and mononuclear complexes have been examined. Data obtained from salt cryoscopy are compared with results obtained from different experimental methods. On the basis of this information, it appears that the method has limited value for the study of polynuclear complexes containing more than 3 or 4 metal atoms or for the study of systems containing a series of stepwise mononuclear complexes. Results in these cases should be considered indicative rather than conclusive. The conditions necessary for the interpretation of cryoscopic and e.m.f. data are compared, particularly for the case of polynuclear complexes, and it is seen that the conditions are much better satisfied in the case of the e.m.f. measurements.
Confronting Alzheimer's Disease

As the number of Americans with Alzheimer's disease increases, efforts to achieve earlier and better diagnosis of dementia have become key components of state plans for confronting the epidemic and will probably figure into a mandated national Alzheimer's plan.
Phase II Trial of Pegylated Interferon-α2b in Patients with Advanced Renal Cell Carcinoma

Abstract Background Pegylated interferon (IFN) has a longer serum half-life compared with standard IFN, and this allows for weekly dosing. In this study, the efficacy and toxicity of pegylated IFN was assessed in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Thirty-two patients with previously untreated mRCC were treated with pegylated IFN-α2b in a prospective, single-arm phase II trial. Pegylated IFN was given by subcutaneous administration on a weekly schedule at a dose of 4.5 μg/kg. Results Of the 32 assessable patients, 29 (91%) had a nephrectomy previously, and none had been treated previously with systemic therapy. Forty-one percent had good-risk, 53% had intermediate-risk, and 6% had poor-risk features per Memorial Sloan-Kettering Cancer Center risk criteria. The best response was a complete response (CR) in 1 patient (3%). Nine patients (28%) had a partial response. Fifteen patients (47%) had stable disease. The median progression-free survival (PFS) was 5 months (95% CI, 3-7 months), and median overall survival was 31 months (95% CI, 18 months to not reached). Five patients had a prolonged PFS of ≤ 17 months, 1 of whom achieved a CR. There were no grade 4 toxicities; primary grade 3 toxicities were hematologic (11 of 32 patients; 34%) and fatigue (4 of 32 patients; 13%). Conclusion Pegylated IFN administered weekly has antitumor activity in patients with mRCC with predominantly good- and intermediate-risk features. This study suggests comparable efficacy and safety comparerd with standard IFN-α.
Impaired left ventricular function, one- or two-vessel coronary artery disease, and severe ischemia: outcome with medical therapy versus revascularization.

Objective To determine whether patients with impaired left ventricular function and one- or two-vessel coronary artery disease who manifest severe ischemia during exercise radionuclide angiography have a lower rate of subsequent cardiac events when initial management is revascularization rather than medical therapy. Design During a median follow-up of 100 months, we compared the outcome between 37 patients who underwent a revascularization procedure and 22 who received medical therapy at the Mayo Clinic between September 1980 and December 1985. Material and Methods The revascularization therapy consisted of coronary artery bypass grafting in 31 patients and coronary angioplasty in 6. Overall survival and survival free of initial cardiac events were compared statistically for the medically and surgically treated patients. Results Eleven deaths occurred in the patients who received medical therapy and 9 in the revascularization group. Five-year overall survival was 58% in the medically treated patients versus 84% in the revascularization group. A significant association was noted between type of treatment and overall survival (adjusted χ 2 = 6.20; P = 0.013). Twenty patients had initial cardiac events—7 in the medically treated group (3 cardiac deaths and 4 nonfatal myocardial infarctions) and 13 in the revascularization group (3 cardiac deaths, 3 out-of-hospital cardiac arrests, and 7 nonfatal myocardial infarctions). Survival free of cardiac events at 5 years was 72% in the medically treated patients and 66% in those who underwent revascularization. No association was detected between type of treatment and survival free of cardiac events. Conclusion These nonrandomized data suggest that overall survival for patients with one- or two-vessel coronary artery disease, impaired left ventricular function, and severe exercise-induced ischemia may be improved by revascularization, but the subsequent cardiac event rates are not.
posaconazole for the Treatment of Oropharyngeal candidiasis, Including Triazole-Resistant Disease, in HIV-positive patients

Oropharyngeal candidiasis is a common affliction in HIV-positive patients worldwide. Although the incidence has decreased with the advent of potent antiviral combinations, it continues to be a cause of significant morbidity. Historically, fluconazole or itraconazole was the treatment of choice for oropharyngeal candidiasis, but increasing incidence of resistance and high recurrence rates mandate the use of alternative therapies. Posaconazole, a broad-spectrum second-generation triazole antifungal agent, has been studied in both first-line and salvage settings for treatment of oropharyngeal candidiasis. Posaconazole is well-tolerated, yields high response rates and demonstrates durable response rates with long-term use. This review will provide state-of-the-art knowledge of pharmacology and therapeutics of posaconazole focusing on the indication for oropharyngeal candidiasis in HIV-positive patients.
Absolute protein-protein association rate constants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association.

Abstract Theory and computation have long been used to rationalize the experimental association rate constants of protein-protein complexes, and Brownian dynamics (BD) simulations, in particular, have been successful in reproducing the relative rate constants of wild-type and mutant protein pairs. Missing from previous BD studies of association kinetics, however, has been the description of hydrodynamic interactions (HIs) between, and within, the diffusing proteins. Here we address this issue by rigorously including HIs in BD simulations of the barnase-barstar association reaction. We first show that even very simplified representations of the proteins—involving approximately one pseudoatom for every three residues in the protein—can provide excellent reproduction of the absolute association rate constants of wild-type and mutant protein pairs. We then show that simulations that include intermolecular HIs also produce excellent estimates of association rate constants, but, for a given reaction criterion, yield values that are decreased by ∼35–80% relative to those obtained in the absence of intermolecular HIs. The neglect of intermolecular HIs in previous BD simulation studies, therefore, is likely to have contributed to the somewhat overestimated absolute rate constants previously obtained. Consequently, intermolecular HIs could be an important component to include in accurate modeling of the kinetics of macromolecular association events.
13C relaxation in cyclopentadienyliron dicarbonyl acyl compounds

T1 values for the protonated carbons of four acyl compounds, all possible combinations of methylpropanoyl and 2-ethylbutanoyl groups with cyclopentadienyl- and methylcyclopentadienyl-iron dicarbonyl, were determined at ambient temperature. Carbon-13 T1 ratios for the acyl group relative to the ring system indicate relative differences in motion when obtained in the two solvents, CDCl3 and CD2 Cl2 . T1 values at -10°C, relative to 24°C, give further insight into motional modes. Carbon-13 and proton NMR chemical shift values for all compounds and the NOE for one compound are reported.
A New Paradigm of Organized Crime in the United States: Criminal Syndicates, Cyber‐gangs, and the Worldwide Web

This paper explores the creation and evolution of organized crime as a concept within the United States. The paper argues that traditional definitions are both incomplete and inaccurate due primarily to their reliance on La Cosa Nostra (i.e. Italian mafia) models and inflexibility. The author proposes the introduction of a new definition, and distinguishes between computer crime committed by organized crime groups and organized criminal activity in a technological environment. In addition, a distinction is made between organized crime and cyber-gangs. Finally, the author discusses specific examples of computer crime committed by criminal syndicates.
Microbial communities and enzyme activities in soils under alternative crop rotations compared to wheat–fallow for the Central Great Plains

Winter wheat–fallow (W–F) rotation is the predominant cropping system in the Central Great Plains. However, other cropping systems are being suggested because reduced tillage and fallow can provide more residues that can increase soil organic carbon (SOC) content and other parameters related to soil quality and functioning. This study compared the microbial biomass and community composition and enzyme activities under native pasture and research plots under grass and different crop intensities (CI) established for 15 years in Akron, CO. The soil (Weld loam; fine, smectitic, mesic Aridic Paleustolls) was under alternative CI rotations (100 and 67%) of winter wheat (Triticum aestivum L.) (W), corn (Zea mays L.) (C), proso millet (Panicum miliaceum L.) (M), and fallow (F) under no-tillage (nt) compared to the typical 50% CI rotation (W–F) under either conventional tillage (ct) and nt. Relative to F–Wct, the 100% (C–M–W) and 67% (C–F–W) CI rotations increased soil microbial biomass C (MBC) and N (MBN) but only at the 0–5 cm depth. Native pasture and 15 years of undisturbed grass plots showed higher soil MBC up to 2–5-fold and 1.4–3-fold when compared to the cropping systems at 0–5 cm, respectively. Similar trends were found for MBN and several enzyme activities. Enzyme activities of C (β-glucosaminidase, β-glucosidase, and α-galactosidase) and P cycling (alkaline phosphatase, acid phosphatase and phosphodiesterase) as a group separated the 100 and 67% CI rotations from the 50% CI rotation (W–Fct) at 0–5 and 5–15 cm of soil. Separation in these enzyme activities was observed for rotations sampled under a crop (W–C–F) compared to when sampled under fallow (F–W–C). Principal component analyses (PCA) of fatty acids methyl esters (FAME) suggested a shift in the microbial community structure with greater fungal populations in pasture, grass, and CI rotations of 100 and 67% compared to W–Fct. The sum of fungal indicators (18:2ω6c, 18:3ω6c, 18:1ω9c, 16:1ω5c) was significantly correlated (r > 0.60; P < 0.05) to β-glucosaminidase, β-glucosidase, acid phosphatase and α-galactosidase activities. After 15 years, our results show that the combination of no-tillage and continuous cropping with reduced fallow frequency in two alternative (100 and 67% CI) rotations for the Central Great Plains have had a positive effect on soil quality parameters such as the microbial populations and community composition but only at 0–5 cm depth, and in several enzyme activities at both 0–5 and 5–15 cm.
Interleukin-6 is linked to longitudinal rates of cortical thinning in aging

Interleukin-6 (IL-6) is a pro-inflammatory cytokine produced by immune cells and other cell types such as microglia throughout the brain. Higher levels of IL-6 in older adults have been cross-sectionally and longitudinally associated with physical and cognitive impairment, as well as increased dementia risk. The association between IL-6 levels and structural and functional brain changes is less clear. In the present study, we investigated the relationship between IL-6 concentrations and cortical thinning with aging. Magnetic Resonance Imaging (MRI) scans from the Baltimore Longitudinal Study of Aging were analyzed for 121 older subjects (M = 69.3; SD = 7.3; range = 56.1 - 85.9 yrs) who were repeatedly tested over an average period of 7.5 yrs, and who remained non-demented for the entire follow-up period. The Freesurfer longitudinal processing stream was utilized for image processing, and IL-6 measures were based on serum ELISA assays averaged across time points. Results showed that higher mean IL-6 concentrations were associated with accelerated annual rates of cortical thinning in the inferior temporal poles bilaterally. Additional pronounced regions of IL-6 -accelerated thinning included the transverse frontopolar gyri within the left hemisphere, and subcentral gyrus and sulcus within the right hemisphere. Our results indicate that sustained high levels of the inflammatory biomarker IL-6 are associated with regionally increased rates of age-related cortical thinning. These data build on previous findings that link IL-6 to chronic disease and demonstrate one mechanism through which high levels of inflammation may have adverse effects on physical and cognitive function.
Type II collagen autoimmunity in otosclerosis and Meniere's Disease

Antibodies to collagen types I, II, and IV were measured in patients with otosclerosis and patients with Meniere's disease. Levels of antibodies to type II collagen were significantly higher in these patients than in control subjects, while no differences were found among levels of antibodies to collagen type I or type IV. These observations suggest a possible role for type II collagen autoimmunity in the etiology of otosclerosis and Meniere's disease.
Bridgeport Center: Re-Minding Richard Meier

(1990). Bridgeport Center: Re-Minding Richard Meier. Journal of Architectural Education: Vol. 44, No. 1, pp. 33-36.