cssi/SciSciGPT-SciSciNet huggingface dataset:
Failure to Record Delirium as a Complication of Intra-aortic Balloon Pump Treatment: A Retrospective Study

This study was conducted to determine whether or not diagnosis and treatment of delirium among patients treated with the intra-aortic balloon pump (IABP) correlates with the recording of this complication on discharge records. Since prior episodes of delirium are one of the few clear risk factors for future episodes of delirium, accurate recording of delirium on the discharge summary and list of discharge diagnoses is useful to clinicians. A retrospective review of the charts of all patients (N = 198) who underwent placement of an IABP during 1988; assessment of the type and frequency of medical and neuropsychiatric complications during IABP treatment; and comparison of chart review findings with the Massachusetts General Hospital's computer-generated lists of discharge diagnoses for the same IABP-treated patients was completed. Only 12% of patients diagnosed and treated for delirium had delirium recorded as a discharge diagnosis. In contrast, 44% and 52% of patients who had been diagnosed and treated for...
Mechanistic Investigation of the Preclinical Pharmacokinetics and Interspecies Scaling of PF-05231023, a Fibroblast Growth Factor 21–Antibody Protein Conjugate

PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analog, was generated by covalently conjugating two engineered [des-His1, Ala129Cys]FGF21 molecules to a nontargeting human IgG1 κ scaffold. The pharmacokinetics (PK) of PF-05231023 after i.v. and s.c. administration was evaluated in rats and monkeys using two enzyme-linked immunosorbent assays with high specificity for biologically relevant intact N termini (NT) and C termini (CT) of FGF21. Intact CT of FGF21 displayed approximately 5-fold faster systemic plasma clearance (CL), an approximately 2-fold lower steady-state volume of distribution, and at least 5-fold lower bioavailability compared with NT. In vitro serum stability studies in monkeys and humans suggested that the principal CL mechanism for PF-05231023 was degradation by serum proteases. Direct scaling of in vitro serum degradation rates for intact CT of FGF21 underestimated in vivo CL 5-fold, 1.4-fold, and 2-fold in rats, monkeys, and humans, respectively. The reduced steady-state volume of distribution and the bioavailability for intact CT relative to NT in rats and monkeys were compatible with proteolytic degradation occurring outside the plasma compartment via an unidentified mechanism. Human CL and PK profiles for intact NT and CT of FGF21 were well predicted using monkey single-species allometric and Dedrick scaling. Physiologically based pharmacokinetic models incorporating serum stability data and an extravascular extraction term based on differential bioavailability of intact NT and CT of FGF21 in monkeys improved accuracy of human PK predictions relative to Dedrick scaling. Mechanistic physiologically based pharmacokinetic models of this nature may be highly valuable for predicting human PK of fusion proteins, synthetically conjugated proteins, and other complex biologics.
The spatial window of the perceptual template and endogenous attention.

Abstract One primary function of spatial attention is to exclude external noise [e.g., Psychol. Sci. 11(2) (2000) 139], especially in the region of the target stimulus [J. Vis. 2(4) (2000) 312]. What is not known is the spatial profile of external noise exclusion in the vicinity of the target and how this depends upon attention. The spatial region around an oriented Gabor target was segmented into four concentric rings (R1–R4). Psychometric functions were measured for orientation discrimination with external random Gaussian noise in all combinations of rings (e.g., R1 alone; R1 + R2; etc.). Regions with larger impact on performance are weighted more heavily in the perceptual template. In an orientation discrimination task in periphery the effective noise regions aligned closely with the high contrast regions of the target Gabor, with attention reducing the effective noise across the spatial template. The combined effects of external noise regions were well-modeled by a (non-linear) perceptual template model (PTM) [Vis. Res. 38(9) (1998) 1183]. In another experiment in attended fovea, the results were similar to those in periphery, but exhibited additional ability to selectively weight clear spatial regions.
Amplified DNA in Y1 mouse adrenal tumor cells: isolation of cDNAs complementary to an amplified c-Ki- ras gene and localization of homologous sequences to mouse chromosome 6

Abstract We have isolated cDNA clones complementary to a c-Ki-ras cellular oncogene that is amplified in Y1 mouse adrenal tumor cells, with the amplified sequences located on double-minute chromatin bodies (DMs) and homogeneously staining chromosomal regions (HSRs). Characterization of the cDNAs included the isolation of corresponding genomic clones, Northern blot analysis of RNA, and DNA sequence analysis. Our studies demonstrate that the c-Ki-ras gene amplified in the Y1 cells is homologous to the human c-Ki-ras2 gene. We have also obtained evidence that, in addition to c-Ki-ras, at least one other transcription unit has been amplified in the mouse adrenal tumor cells. Moreover, by Southern blot analysis of Chinese hamster-mouse somatic cell hybrids, we have determined that the amplified DNA sequences associated with DMs and HSRs, including the c-Ki-ras gene, are present in normal mouse cells on chromosome 6.
Wide GAP a-SiC:H Alloys for Novel Photovoltaic-Electrochromic Window Coatings

Self-powered “smart” windows utilize an electro-optic transmittance modulator based on electrochromic (EC) thin films that exhibit reversible and controlled changes in optical properties with an applied voltage between 0.7 and 2.0 V. Existing window designs require an external electrical connection, which may be economically unfeasible. This problem is solved by the tandem photovoltaic-electrochromic device, in which a wide-gap amorphous silicon-based alloy photovoltaic device is deposited together with an electrochromic optical transmittance modulator in a monolithic device on a single substrate. In this paper, we discuss our proposed monolithic photovoltaic-electrochromic device. We also present studies of transparent, wide-gap (1.8 to 2.2 eV) amorphous silicon-carbon thin films and p-i-n devices designed for use in the photovoltaic-electrochromic device. These photovoltaic cells can operate at low current ( 1.0 V) and high transparency (≈70%). We present our progress toward these design targetxxss.
North Atlantic Hurricanes Contributed by African Easterly Waves North and South of the African Easterly Jet

Abstract A majority of tropical cyclones in the North Atlantic develop from African easterly waves (AEWs), which originate along both the southern and northern flanks of the midtropospheric African easterly jet (AEWS and AEWn, respectively). The purpose of this note is to identify the contribution of AEWSs and AEWns to North Atlantic tropical cyclones that develop from AEWs. Applying a manual backtracking approach to identify the genesis locations of AEWS, it was found that the population ratio of tropical cyclones formed from AEWSs to those formed from AEWns is 1:1.2. Because the population ratio of AEWSs to AEWns is 1:2.5, the conversion rate of the former AEWS to tropical cyclones is twice as effective as the latter waves. In addition, it was found that AEWns travel farther and take longer to transform into tropical cyclones than AEWSs, which is likely because the AEWns are drier and shallower than AEWSs. An analysis of various terms in the moisture and vorticity budgets reveals that the monsoon trough...
A miniature cathode follower for single cell recording in awake, unrestrained animals.

Abstract A small, light weight cathode follower has been described which is particularly suited for studies of single cell activity in awake, unrestrained animals. It can be mounted directly on the micro-manipulator.
A neural network receiver for EM-MWD baseband communication systems

Baseband digital communication in “electromagnetic measurement while drilling” systems (EM-MWD) is often corrupted by surface noise. The conventional correlation receiver works well under the assumption of additive white Gaussian noise (AWGN); however in practice, the noise is actually non-stationary and usually contains spectral peaks in lower frequency range. In this research, a new approach based on artificial neural network is investigated. The neural network receiver has adaptive learning ability and outperforms the correlation receiver under various noise conditions, especially in the situation of non-white noise as well as the real world noise taken from actual drilling sites.
Multifusion, Multispectral, Optical Polarimetric Imaging Sensing Principles

The goal of this study is to present novel, multifusion optical imaging sensing principles, based on active-multispectral polarimetric imaging of targets surrounded by scattered media. Specifically, the novelty of this study consists in the fusion of multispectral images, with polarimetric imaging principles, forming image differences. The experimental results indicate clearly that, high-contrast multispectral Mueller polarimetric image differences, as well as Degree of Linear Polarization (DOLP) images can be obtained from transmitted or backscattered photons, from targets embedded in turbid media
Partner attachment and interpersonal characteristics.

This study investigated partner attachment and interpersonal characteristics in 134 nonclinical couples in long-term marriages. Irrespective of gender, spouses with greater anxiety over abandonment or discomfort with closeness endorsed dysfunctional relationship beliefs to a greater extent. On the anxiety over abandonment dimension, husbands with higher scores were rated less aggressive, less controlling, and more rebellious, whereas wives with higher scores were rated more dependent, more self-critical, and less competitive. Husbands higher on discomfort with closeness were rated less cooperative and responsible and were rated more aggressive and rebellious. Matched secure couples reported lower marital dissatisfaction than matched insecure or mismatched couples. Future research should contrast samples of nonclinical and clinical couples by marital duration to identify specific partner behaviors that are likely to foster marital dissatisfaction within particular attachment pairings. The authors’ findings...
A Circular Structure in the Aortic Outflow Tract During Diastole: An Unusual Complication of Cocaine Abuse

A g p n w t e o i m c a From the Departments of *Anesthesiology and †Cardiothoracic Surery, Medical College of Wisconsin and Clement J. Zablocki Veterans ffairs Medical Center, Milwaukee, WI. Address reprint requests to Paul S. Pagel, MD, PhD, FACC, Medical ollege of Wisconsin, MEB-M4280, 8701 Watertown Plank Road, ilwaukee, WI 53226. E-mail: pspagel@mcw.edu. © 2006 Elsevier Inc. All rights reserved. 1053-0770/06/2003-0030$32.00/0 doi:10.1053/j.jvca.2005.09.011
Urokinase Receptor-Deficient Mice Have Impaired Neutrophil Recruitment in Response to Pulmonary Pseudomonas aeruginosa Infection

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). Evidence in vitro has implicated uPAR as a modulator of beta2 integrin function, particularly CR3 (CD11b/CD18, Mac-1). Pseudomonas aeruginosa infection has been demonstrated to recruit neutrophils to the pulmonary parenchyma by a beta2 integrin-dependent mechanism. We demonstrate that mice deficient in uPAR (uPAR-/-) have profoundly diminished neutrophil recruitment in response to P. aeruginosa pneumonia compared with wild-type (WT) mice. The requirement for uPAR in neutrophil recruitment is independent of the serine protease uPA, as neutrophil recruitment in uPA-/- mice is indistinguishable from recruitment in WT mice. uPAR-/- mice have impaired clearance of P. aeruginosa compared with WT mice, as demonstrated by CFU and comparative histology. WT mice have diminished neutrophil recruitment to the lung when an anti-CD11b mAb is given before inoculation with the pathogen, while recruitment of uPAR-/- neutrophils is unaffected. We conclude that uPAR is required for the recruitment of neutrophils to the lung in response to P. aeruginosa pneumonia and that this requirement is independent of uPA. Further, we show that uPAR and CR3 act by a common mechanism during neutrophil recruitment to the lung in response to P. aeruginosa. This is the first report of a requirement for uPAR during cellular recruitment in vivo against a clinically relevant pathogen.
Analytic Reviews : State-of-the-art Management of Severe Closed-head Injury

Brain injury represents the most serious result of head trauma. In the last decade we have witnessed important advances in understanding the pathophysiological re sponses of the brain and body to severe head injury. A significant increase in good recoveries and reduction in mortality have been realized by using programs that provide rapid transport and patient triage, early diag nosis of intracranial masses and removal of large lesions, controlled positive-pressure ventilation, treatment of elevated intracranial pressure, prevention of secondary insults, and intensive management. This review empha sizes acute management of severe closed-head injury in an intensive care unit setting. Many of these same princi ples for trauma can be applied to the intensive manage ment of any brain injury, including stroke. Future ad vances are discussed.
Nitric oxide and lung surfactant

Inhalation of nitric oxide (NO) is an experimental treatment for severe pulmonary hypertension. Being rapidly metabolized by hemoglobin, inhaled NO causes selective vasodilation in the pulmonary vascular bed. In addition to the vascular smooth, muscle, other pulmonary structures are exposed to inhaled NO, resulting in suppression of NO synthesis in a variety of pulmonary cells and in potential toxicity. NO is a free radical that interacts with a number of proteins, particularly metalloproteins. Together with superoxide radical, it rapidly forms highly toxic peroxynitrite. Peroxynitrite is involved in the killing of microbes by activated phagocytosing macrophages. In severe inflammation, peroxynitrite may be responsible for damaging proteins lipids, and DNA. Peroxynitrite added to surfactant in vitro is capable of decreasing the surface activity, inducing lipid peroxidation, decreasing the function of surfactant proteins, SP-A and SP-B, and inducing protein-associated nitro-tyrosine. Exposure of animals for prolonged periods (48 to 72 hours) to inhaled NO (80 to 120 ppm) has been associated with a decrease in surface activity. This is caused by binding of surfactant to iron-proteins that are modified by NO (particularly methemoglobin), or by peroxynitrite induced damage of surfactant. In contrast, exposure of isolated surfactant complex to NO during surface cycling strikingly decreases the inactivation of surfactant, preventing the conversion of surfactant to small vesicles that are no longer surface-active, and preventing lipid peroxidation. This finding is consistent with the function of NO as a lipid-soluble chain-braking antioxidant. It is possible that this lipophilic gas has as yet undefined roles in regulation of surfactant metabolism and maintenance of surface activity. Deficiency in pulmonary NO may be present during the early neonatal period in respiratory distress syndrome and in persistent fetal circulation. The premature lung is likely to be sensitive to NO toxicity that may include lung damage, abnormal alveolarization, and mutagenicity. Defining of the indications, the dosage, and the toxicity of inhaled NO therapy remains the challenge for experimental and clinical research.
Coarctation of the aorta: outcome of pregnancy

Abstract OBJECTIVES The study sought to determine the outcome of pregnancy in women with coarctation of the thoracic aorta. BACKGROUND Patients with coarctation of the thoracic aorta are expected to reach childbearing age, but data on the outcome of pregnancy in this population are limited. METHODS The Mayo Clinic database was reviewed for women of childbearing age (≥16 years old) with a diagnosis of aortic coarctation evaluated from 1980 to 2000. Spectrum of cardiovascular disease, surgical history, and obstetrical and neonatal outcomes were determined. RESULTS Fifty women with coarctation had pregnancies: 30 had coarctation repair before pregnancy, 10 had repair after pregnancy, 4 had repair both before and after pregnancy, and 6 had no history of repair. The 50 women had 118 pregnancies resulting in 106 births. There were 11 miscarriages (9%), 4 premature deliveries (3%), and 1 early neonatal death; 38 deliveries (36%) were by cesarean section. Of the 109 offspring, 4 (4%) had congenital heart disease. A patient with Turner syndrome died of a Stanford type A dissection at 36 weeks of pregnancy. Nineteen women (38%) were known to have hemodynamically significant coarctation during pregnancy (gradient ≥20 mm Hg). Fifteen women (30%) had hypertension during their pregnancy, 11 of whom (73%) had hemodynamically significant coarctation during that time (8 with native and 3 with residual/recurrent coarctation). CONCLUSIONS Major cardiovascular complications were infrequent but continue to be a source of concern for patients with coarctation who become pregnant. Systemic hypertension during pregnancy was common and related to the presence of a significant coarctation gradient.
Functional Comparison of the α3A and α3B Cytoplasmic Domain Variants of the Chicken α3 Integrin Subunit

Abstract Integrin α3β1 can be alternatively spliced to generate α3A and α3B cytoplasmic domain variants that are conserved among vertebrates. To identify distinct functions of these variants, we transfected cells with intact α3 integrins or chimeric receptors. α3Aβ1 and α3Bβ1 each localized to focal contacts in keratinocytes on an extracellular matrix rich in laminin-5, to which both are known to bind with high affinity. However, α3B accumulated intracellularly in keratinocytes on collagen, suggesting that laminin binding may stabilize α3Bβ1 surface expression. Neither α3 cytoplasmic domain affected recruitment of chimeric α5 integrins to fibronectin-induced focal contacts, and either substituted for the α5 cytoplasmic domain in α5β1-mediated cell migration. However, the α5/α3B chimera localized to cell–cell borders in MDCK or CHO cells to a lesser extent than did the α5/α3A chimera. To determine whether the α3 cytoplasmic domains conferred distinct localization to a nonintegrin protein, we transfected cells with interleukin-2 receptor (IL-2R) chimeras containing the α3 cytoplasmic domains. The IL-2R/α3A chimera was expressed efficiently on the cell surface, while the IL-2R/α3B chimera accumulated intracellularly. Our findings suggest that the α3B cytoplasmic domain harbors a retention signal that is regulated in an intact integrin and can alter cell surface expression and distribution of α3β1.
Forecasting the professional profile of technology students

Issues pertaining to initial placement and future career development for students in technology degree programs are discussed. It is argued that the success of technologist careers depends to a large degree on their own planning and initiative. Career development plans and programs need to be implemented by employers to facilitate the growth and professional development of technologists. Companies also have to identify technology positions clearly and work with recruiters and graduates in improving the career match between the technologies and the job positions available. Faculty can contribute to the professional growth of technology by accurately portraying the profession and working to improve student written and oral communications skills. >
The Association of Tobacco mosaic virus with Green Spot of Cured Wrapper Tobacco Leaves

LaMondia, J. A. 2008. The association of Tobacco mosaic virus with green spot of cured wrapper tobacco leaves. Plant Dis. 92:37-41. Near-isogenic lines of cigar wrapper tobacco resistant or susceptible to Tobacco mosaic virus (TMV) were used to evaluate the association of TMV infection with green spot symptoms in cured leaves. TMV infection, as determined by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), was detected on susceptible but not resistant plants in field experiments. Green spot severity on cured leaves was greater for susceptible than resistant plants, even when symptoms of TMV were not evident in the field. Some green spots were present on resistant leaves despite the fact that the virus was not detected by ELISA. Resistant and susceptible plants had similar responses to virus infection and similar ELISA detection of TMV when plants were held at continuous temperatures over 28°C in growth chambers. Plant resistance was not compromised in the field in cloth-covered shade tents even when 33.5 of the 96 h immediately following inoculation were above 28°C. Green spot of cured leaves was strongly associated with TMV infection in susceptible plants, even when plants were infected after leaf expansion and mosaic symptoms were not present. Green spot also occurred to a lesser extent and for a limited time in inoculated resistant plants. The development of green spot symptoms on cured leaves may be the result of either systemic infection of TMV-susceptible plants or associated with the systemic resistance response to TMV inoculation of resistant plants. Additional keyword: N-gene
A new mutually reinforcing network node and link ranking algorithm

This study proposes a novel Normalized Wide network Ranking algorithm (NWRank) that has the advantage of ranking nodes and links of a network simultaneously. This algorithm combines the mutual reinforcement feature of Hypertext Induced Topic Selection (HITS) and the weight normalization feature of PageRank. Relative weights are assigned to links based on the degree of the adjacent neighbors and the Betweenness Centrality instead of assigning the same weight to every link as assumed in PageRank. Numerical experiment results show that NWRank performs consistently better than HITS, PageRank, eigenvector centrality, and edge betweenness from the perspective of network connectivity and approximate network flow, which is also supported by comparisons with the expensive N-1 benchmark removal criteria based on network efficiency. Furthermore, it can avoid some problems, such as the Tightly Knit Community effect, which exists in HITS. NWRank provides a new inexpensive way to rank nodes and links of a network, which has practical applications, particularly to prioritize resource allocation for upgrade of hierarchical and distributed networks, as well as to support decision making in the design of networks, where node and link importance depend on a balance of local and global integrity.
The Effect of Short-Term Hyperglycemia on the Innate Immune System

Abstract Background Diabetes mellitus increases the susceptibility to infection by altering both the innate and the adaptive immune systems. Hyperglycemia has been associated with adverse outcomes in hospitalized patients, especially critically ill patients; these poor outcomes are explained in part by hospital-associated infections. Materials and Methods PubMed, EMBASE and Google Scholar were searched to identify studies published between 1970 and 2014 reporting short-term effects of hyperglycemia on the innate immune system. MeSH database search terms included hyperglycemia, immune system, inflammation, inflammation mediators, neutrophils, endothelial dysfunction, complement system proteins and diabetes. Pertinent articles reported studies in healthy volunteers and diabetic patients, using in vitro laboratory experiments, and with animal models. Results Hyperglycemia activates protein kinase C, and this inhibits neutrophil migration, phagocytosis, superoxide production and microbial killing. High glucose concentrations decrease the formation of neutrophil extracellular traps. Hyperglycemia can also induce Toll-like receptor expression and inhibit neutrophil function and apoptosis. High glucose concentrations decrease vascular dilation and increase permeability during the initial inflammatory responses, possibly through protein kinase C activation. Hyperglycemia can cause direct glycosylation of proteins and alter the tertiary structure of complement; these changes inhibit immunoglobulin-mediated opsonization of bacteria and complement fixation to bacteria and decreases phagocytosis. Hyperglycemia also stimulates the production and release of cytokines. Several trials have demonstrated that better glycemic control reduces nosocomial infections in critically ill patients and surgical site infections. Conclusions In summary, acute hyperglycemia can significantly alter innate immune responses to infection, and this potentially explains some of the poor outcomes in hospitalized patients who develop hyperglycemia.
Recent advances in mathematical programming techniques for the optimization of process systems under uncertainty

Abstract Optimization under uncertainty has been an active area of research for many years. However, its application in Process Systems Engineering has faced a number of important barriers that have prevented its effective application. Barriers include availability of information on the uncertainty of the data (ad-hoc or historical), determination of the nature of the uncertainties (exogenous vs. endogenous), selection of an appropriate strategy for hedging against uncertainty (robust/chance constrained optimization vs. stochastic programming), large computational expense (often orders of magnitude larger than deterministic models), and difficulty of interpretation of the results by non-expert users. In this paper, we describe recent advances that have addressed some of these barriers for mostly linear models.
Tolerance Specification and Related Issues for Additively Manufactured Products

Additive manufacturing (AM) has gained increased attention in the last decade as a versatile manufacturing process for customized products. AM processes can create complex free-form shapes, introducing features such as internal cavities and lattices. These complex geometries are either not feasible or very costly with traditional manufacturing processes. This creates new challenges in maintaining and communicating dimensional and geometric accuracy of parts produced. In order to manufacture a product that meets functional needs, the specification of those needs through geometry, material and tolerances is necessary. This paper surveys the current state and needs of geometry related accuracy specification mechanisms for AM, including a review of specification standards such as ASME Y14.5 and ISO 1101. Emerging AM-related tolerancing challenges are identified, and a potential plan of action is put forth for addressing those challenges.Various issues highlighted in this paper are classified as (a) AM-driven specification issues and (b) specification issues highlighted by the versatility of AM processes. AM-driven specification issues include build direction, layer thickness, support structure related specification, and scan/track direction. Specification issues highlighted by the versatility of AM processes include, region-based tolerances for complex freeform surfaces, tolerancing internal functional features, tolerancing lattice and infills. Basic methods of solving these specification issues are also highlighted.© 2015 ASME
Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients

Capecitabine is commonly used in treating breast cancer; however, therapeutic response varies among patients and there is no clinically validated model to predict individual outcomes. Here, we investigated whether drug sensitivity quantified in ex vivo patients' blood-derived cell lines can predict response to capecitabine in vivo. Lymphoblastoid cell lines (LCLs) were established from a cohort of metastatic breast cancer patients (n = 53) who were prospectively monitored during treatment with single agent capecitabine at 2000 mg/m2/day. LCLs were treated with increasing concentrations of 5'-DFUR, a major capecitabine metabolite, to assess patients' ex vivo sensitivity to this drug. Subsequently, ex vivo phenotype was compared to observed patient disease response and drug induced-toxicities. We acquired an independent cohort of breast cancer cell lines and LCLs derived from the same donors from ATCC, compared their sensitivity to 5'-DFUR. As seen in the patient population, we observed large inter-individual variability in response to 5'-DFUR treatment in patient-derived LCLs. Patients whose LCLs were more sensitive to 5'-DFUR had a significantly longer median progression free survival (9-month vs 6-month, log rank p-value = 0.017). In addition, this significant positive correlation for 5'-DFUR sensitivity was replicated in an independent cohort of 8 breast cancer cell lines and LCLs derived from the same donor. Our data suggests that at least a portion of the individual sensitivity to capecitabine is shared between germline tissue and tumor tissue. It also supports the utility of patient-derived LCLs as a predictive model for capecitabine treatment efficacy in breast cancer patients.
Anti-Herpetic Activity of (±)-(1α, 2β, 3α)-9-[2-Hydroxy-3-(Hydroxymethyl)Cyclobutyl]Guanine and Inhibition of HSV-1 DNA Polymerase

A novel nucleoside analogue, (±)-(1α, 2β, 3α)-9-[2-hydroxy -3-(hydroxymethyl)cyclobutyl]guanine [(±)-HHCG] was synthesized and has antiviral activity against herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus (HCMV) and varicella-zoster virus (VZV) in plaque reduction assays. The antiviral activity of (±)-HHCG against HSV-2 shows a 10-40-fold dependence on the presence of a virally encoded thymidine kinase. (±)-HHCG is a substrate for HSV-1 thymidine kinase with a phosphorylation rate of 28 μm h−1 compared to 15 μm h−1 for acyclovir under identical conditions. Enzymatically prepared HHCG-triphosphate is a competitive inhibitor of dGTP incorporation into DNA by HSV-1 DNA polymerase with an inhibition constant corresponding to 0.0077 μm. Hybridization studies using an HSV-1-specific DNA probe indicated that DNA synthesis is reduced in HSV-1-infected WI-38 cells treated with (±)-HHCG, with an ED50 comparable to that of acyclovir. These results suggest that the antiviral activity of (±)-HHCG is d...
Substrate Ubiquitination Controls the Unfolding Ability of the Proteasome

In eukaryotic cells, proteins are targeted to the proteasome for degradation by polyubiquitination. These proteins bind to ubiquitin receptors, are engaged and unfolded by proteasomal ATPases, and are processively degraded. The factors determining to what extent the proteasome can successfully unfold and degrade a substrate are still poorly understood. We find that the architecture of polyubiquitin chains attached to a substrate affects the ability of the proteasome to unfold and degrade the substrate, with K48- or mixed-linkage chains leading to greater processivity than K63-linked chains. Ubiquitin-independent targeting of substrates to the proteasome gave substantially lower processivity of degradation than ubiquitin-dependent targeting. Thus, even though ubiquitin chains are removed early in degradation, during substrate engagement, remarkably they dramatically affect the later unfolding of a protein domain. Our work supports a model in which a polyubiquitin chain associated with a substrate switches the proteasome into an activated state that persists throughout the degradation process.
Decoupling and Police Organizational Structure

The paradox of police organization structure is that while the high-risk environment demands strict bureaucratic control, the devolution of authority and response to environmental changes necessary for street-level decision-making is counter to the rational bureaucracy. This article posits that loose coupling is both a beneficial and a healthy attribute for police organizations in that it allows for greater devolution of authority and supports the level of discretion that is placed at the street level. Loose coupling maintains ties between the primary organization and the subunit, while also supporting an organic connection that allows for street-level decision-making. However, loose coupling is tenuous, and, if not strictly maintained, can lead to a decoupled state. Through the process of decoupling, members of the police organization can exist without proper supervision, form deviant subcultures, or develop a separate suborganization. This article examines the theoretical foundations of coupling theory ...
The Ethic of Rights and the Ethic of Duties

My discussion so far of social justice (especially in Chapter 4) should have shown us that, at its heart, it is liberal in conception. Liberals of various persuasions may disagree about some of the details, but what they all agree on is the primacy of justice among virtues; that is to say that, among other things, justice, fairness and individual rights play a commanding role in the organization and functioning of a liberal society. Equally importantly, in a liberal social order there are no a priori ends, but only those that individuals constituting it freely choose to pursue. The tacit social contract that it presupposes is that any individual is free to pursue his/her own personal interests, as long as, and to the extent that, it does not unduly obstruct the personal interests pursued by all the others in this society. It, therefore, does not legislate what interests individuals might pursue but only how the interests of all are to be regulated. It is for this reason that liberal theories tend to concentrate on procedural justice - namely, rules and principles whose adoption would be most likely to enable each member of society to get the maximum possible satisfaction of his/her interests, consistent with a similar outcome for all. There is a clear sense in which such liberalism provides the ideal framework for capitalist free enterprise, that is, the pursuit of private profit and wealth. And this has not been the least of the merits sustaining it in its dominant social role in Western democracies, since its emergence in the doctrines and ideas of Hobbes, Locke and others. But it would be wrong to think that its main intellectual or moral appeal rests in its ability to buttress capitalism.
Inherent functional dependence among cochlear dose surrogates for stereotactic radiosurgery of vestibular schwannomas

Abstract Purpose Various cochlear dose surrogates have been reported as associated with hearing outcome in studies of stereotactic radiosurgery (SRS) for vestibular schwannomas. In this study, we investigated whether an inherent functional relationship exists among these reported surrogates. Methods and materials A cohort of 85 serial patient cases treated with single-fraction stereotactic radiosurgery from 1997 through 2013 at our institution was analyzed. For all the cases, the mean prescription dose was 12.5 ± 0.3 Gy (range, 12-13 Gy) and mean target volume 1.32 ± 1.51 mL (range, 0.80-8.77 mL). The mean cochlea volume was 0.078 ± 0.016 mL (range, 0.048-0.131 mL; median, 0.076 mL). Correlation analysis among mean cochlear dose, point maximum dose and modiolus dose was performed and also parameterized with new variables such as the effective dose radius (EDR) as derived from a general dose fall-off model. Results Weak correlation via linear regression was found between the point maximum dose and the mean cochlear dose (R 2 = 0.719) as well as the modiolus dose (R 2 = 0.568). However, when parameterized with EDR, a near-perfect correlation ( P 2 = 0.996), and with the EDR for the modiolus dose (R 2 = 0.993). Such a result led to a functional formula relating these dose surrogates, yielding dose equivalence results such as: 12-Gy point maximum dose is equivalent to mean cochlear dose of 5.6 ± 0.1 Gy (95% confidence level), or modiolus dose of 6.0 ± 0.2 Gy (95% confidence level). Conclusions An inherent functional relationship was found among point maximum, modiolus, and mean cochlear doses for SRS of vestibular schwannomas. As such, clinical hearing outcome can be interchangeably analyzed or reported via any of these dose surrogates.
The Transformed Library: E-Books, Expertise, and Evolution by Jeannette Woodward

This book is a cornucopia of thoughts, opinions, experiences, and suggestions to libraries and librarians struggling to find their way in the new digital environment, one in which access to informa...
Profiles, harmonics, and transient analysis of 240 V air conditioning load during peak demand

This paper provides 240 V ac air conditioning load data collected during summer peak heat load in Austin, TX. Air conditioning load profiles are studied in high, one-minute data resolution over the course of a typical, representative work-week where both electrical power and power factor are displayed. While THDv is 3.35%, TDDI is more concerning at 11.17% due to odd harmonics out to the 9th order. Load harmonics are tabulated, along with a discussion as it relates to IEEE Std 519–2014 harmonic limits. Lastly, the cyclical nature of air conditioning cycling is captured during a turn-on transient state so inrush current, voltage fluctuations, and electrical system parameters may be viewed. Voltage dips to 0.062 pu for 5 cycles while inrush current and power draw increase nearly 6 fold.
Kinetics of Multicomponent Nucleation in Gas Phase

Kinetics of n-component nucleation is considered as the Brownian diffusion in the size and (n�1) composition spaces. The formula for nucleation rate is obtained, which has correct transitions to all possible unary cases.
Irradiation effects on thermal properties of LWR hydride fuel

Abstract Three hydride mini-fuel rods were fabricated and irradiated at the MIT nuclear reactor with a maximum burnup of 0.31% FIMA or ∼5 MWd/kgU equivalent oxide fuel burnup. Fuel rods consisted of uranium-zirconium hydride (U (30 wt%)ZrH1.6) pellets clad inside a LWR Zircaloy-2 tubing. The gap between the fuel and the cladding was filled with lead-bismuth eutectic alloy to eliminate the gas gap and the large temperature drop across it. Each mini-fuel rod was instrumented with two thermocouples with tips that are axially located halfway through the fuel centerline and cladding surface. In-pile temperature measurements enabled calculation of thermal conductivity in this fuel as a function of temperature and burnup. In-pile thermal conductivity at the beginning of test agreed well with out-of-pile measurements on unirradiated fuel and decreased rapidly with burnup.
Abstract 199: Anticoagulant Heparan Sulfate Conveys Anti-Inflammatory Activity of Antithrombin

Antithrombin (AT) therapy reduces morbidity/mortality in systemic inflammatory response syndromes, such as septic shock. These effects stem from the ability of AT to directly initiate cell signaling, which requires AT engagement with heparan sulfate proteoglycans. It is presently unclear if this process involves anticoagulant heparan sulfate (HS AT+ ), a specific motif with high affinity for AT that is produced by endothelial cells. If HS AT+ regulates anti-inflammatory signaling, then Hs3st1 -/- mice, which lack endothelial HS AT+ , should exhibit a proinflammatory state and should not benefit from AT treatment. We tested these hypotheses using a mouse model of lipopolysaccharide (LPS)-induced septic shock. Hemodynamics were monitored with a left ventricle pressure-volume catheter. Both Hs3st1 +/+ and Hs3st1 -/- mice die of cardiogenic shock. However, Hs3st1 -/- , compared to Hs3st1 +/+ , mice exhibited a much more rapid onset of death. Left ventricular gene expression profiles of mice with systemic LPS challenge showed enhanced expression of leukocyte recruitment genes (P-selectin, Cxcl10) in Hs3st1 -/- mice. Consistent with these data, LPS-treated Hs3st1 -/- mice, compared to Hs3st1 +/+ , exhibited enhanced leukocyte rolling flux within cremaster muscle venules. Thus, mice lacking HS AT+ exhibit a proinflammatory phenotype. AT treatment of Hs3st1 +/+ mice reduced both LPS-induced lethality and leukocyte-endothelial interactions. Conversely AT treatment of Hs3st1 -/- mice enhanced both LPS-induced lethality and leukocyte-endothelial interactions. Thus, AT failed to elicit anti-inflammatory effects in mice lacking HS AT+ . Our results indicate that endothelial HS AT+ is one component that mediates AT’s anti-inflammatory activity. These findings provide an initial step towards elucidating the role of HS AT+ and AT in a novel natural anti-inflammatory pathway of the blood vessel wall. This pathway is an ideal target for developing therapeutics to combat the devastating outcomes of septic shock.
Losing or choosing faith : mother loss and religious change.

Maternal religiosity is often associated with children's religiosity even as children grow into adulthood. However, experiencing the death of one's mother during adolescence or young adulthood may modify the transmission of maternal religiosity across the life course. Drawing on national data on young adults in the United States (1994-1995 and 2008 National Longitudinal Study of Adolescent to Adult Health; Add Health), I find the relationship between maternal religiosity and child religiosity is negative among those whose mother has died. Longitudinal models of child religiosity across more than a decade show that when maternal religiosity is high or strong, mother loss leads to lower predicted levels of child religiosity. When maternal religiosity is low or nonexistent, mother loss leads to higher predicted levels of child religiosity. In total, these findings direct attention to the interaction of mother loss and maternal religiosity as important factors for the transmission of religiosity across generations.
Methods for Monitoring Multiple Proportions When Inspecting Continuously

This paper proposes a multinomial cumulative sum (CUSUM) chart for monitoring when there is a specifiable direction for out-of-control shift, items can be classified into more than two categories, and the items are not put into subgroups. Examples demonstrate that multinomial CUSUM charts can detect shifts in category probabilities as fast or faster than multiple Bernoulli CUSUM charts. The authors recommend using multiple Bernoulli CUSUM charts if the direction of the out-of-control shift in the parameter vector cannot be specified.
Fiber Optic Assessment of Damage in FRP Strengthened Structures

Publisher Summary Fiber-reinforced plastics have been increasingly used in conjunction with civil structural materials, either as reinforcement for concrete structures or repair and strengthening of existing structural elements. A distributed fiber optic sensor is developed for condition monitoring of civil infrastructure systems. The fiber optic sensor is especially useful in applications involving structures strengthened by fiber reinforced polymer composites. Five types of failure modes can be expected when reinforced concrete beams are strengthened with carbon fiber reinforced polymer (CFRP) fabrics. These failure modes include laminate rupture, crushing of concrete in compression, yielding of steel rebar, shear failure of the beam, and peeling of CFRP fabric. The sensor principles are simple and, therefore, practical for detection of cracks, debonding, and deformation measurements. Structural monitoring capability of the sensor is evaluated through experiments with cracked reinforced concrete beams strengthened by way of CFRP fabrics. Sensor principle and experimental results are also discussed in this chapter.
Diel behavior in moths and butterflies: a synthesis of data illuminates the evolution of temporal activity

Lepidoptera (butterflies and moths) are one of the most taxonomically diverse insect orders with nearly 160,000 described species. They have been studied extensively for centuries and are found on nearly all continents and in many environments. It is often assumed that adult butterflies are strictly diurnal and adult moths are strictly nocturnal, but there are many exceptions. Despite the broad interest in butterflies and moths, a comprehensive review of diel (day-night) activity has not been conducted. Here, we synthesize existing data on diel activity in Lepidoptera, trace its evolutionary history on a phylogeny, and show where gaps lie in our knowledge. Diurnality was likely the ancestral condition in Lepidoptera, the ancestral heteroneuran was likely nocturnal, and more than 40 transitions to diurnality subsequently occurred. Using species diversity estimates across the order, we predict that roughly 75-85% of Lepidoptera are nocturnal. We also define the three frequently used terms for activity in animals (diurnal, nocturnal, crepuscular), and show that literature on the activity of micro-moths is significantly lacking. Ecological factors leading to nocturnality/diurnality is a compelling area of research and should be the focus of future studies.
The Problem of Truth in the ‘Critique of Pure Reason’

At first sight it appears that Kant might be contradicting himself by asserting, in the course of his theoretically critical philosophy, that truth is the agreement of being and thought; for he dismissed that definition, in the introduction to transcendental logic, as peripheral and insufficient. It is our intention to examine whether in fact Kant contradicts himself, and at the same time to point up the place occupied by the problem of truth in Kant’s transcendental philosophy as we encounter it in the Critique of Pure Reason.
Inheritance of Hypoxic Exercise Tolerance in Mice

All mammals tested, when exposed acutely to a degree of hypoxia above some threshold, exhibit a reduced capacity to perform work. Chronic hypoxic exposure is usually associated with some degree of acclimation resulting in partial recovery of the preexposure work capacity. The present study reports that, among mice, interindividual variability in recovery of ability to tolerate a standardized hypoxic exercise [tet; time elapsed in treadmill exercise in hypoxia until 4-s failure to avoid a grid configured to deliver a mild aversive current (0.15 mA)], after 8 weeks' exposure to half-atmospheric pressure, is influenced predominantly by two unlinked genes of major effect. Two approaches were taken toward genetic characterization. In one, a maximum-likelihood procedure was applied to 11 models of genetic determinacy in the tet distributions of BALB/cBy (C) and C57BL/6By (B6) parental inbred strains, their F1 hybrid, and the backcross (BC) generations. Breeding tests of the resulting candidate “best-fit” major locus inheritance models involved repeated cycles of selecting, as the progenitor of a new BC generation, the male with the highest value of the test variable in the previous BC generation, and breeding him to C females. Mice from each of four distinct phenotypes appearing in BC3 were bred to C mice, producing distributions expected from two-locus segregation. The second approach was based upon CXB/By RI strain distribution pattern and derivative breeding tests to reveal phenotypic distributions consistent with two-locus inheritance of tet. Melding these results with a positional cloning strategy may permit relating a behavioral difference to specific heritable elements and identifying their products as the (partial) physiological substrata of the behavior.