cssi/SciSciGPT-SciSciNet huggingface dataset:
Prodrug Applications for Targeted Cancer Therapy

Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant “prodrugs” such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.
Stemming the obesity-diabetes epidemic: lifestyle changes and therapeutics.

Multifactorial approaches to the treatment of type 2 diabetes mellitus have proven more effective than any individual intervention alone in reducing the risk of cardiovascular complications. As the spread of diabetes and obesity accelerates worldwide, unhindered by lifestyle modification approaches, the authors of this Viewpoint propose an aggressive multifactorial strategy for treating patients who have one or more risk factors for the metabolic syndrome in an effort to prevent or delay the onset of diabetes.
Laparoscopic Radical Nephroureterectomy for Upper Tract Transitional Cell Carcinoma: Oncological Outcomes at 7 Years

Purpose: We present long-term oncological outcomes following laparoscopic nephroureterectomy for upper tract transitional cell carcinoma.Materials and Methods: Between December 1997 and August 2005, 100 patients underwent laparoscopic nephroureterectomy for upper tract transitional cell carcinoma at our institution. Data were obtained from a prospectively maintained database, patient charts, telephone followup and a review of the Social Security Death Index.Results: Median patient age at surgery was 73 years. Final pathological stage was pTis/pTa in 28% of patients, pT1 in 31%, pT2 in 13%, pT3 in 24% and pT4 in 4%. High grade lesions were present in 58% of patients, multifocal disease was present in 23% and lymphovascular invasion was present in 9%. Positive surgical margins occurred in 7 patients (7%). Median followup was 7 years (range 2 to 10). At 2, 5 and 7 years overall survival was 81%, 59% and 50%, cancer specific survival was 91%, 77% and 72%, and recurrence-free survival was 66%, 50% and 36%, res...
Particulate transport through the mesosphere and stratosphere

THE ‘aerosol layers’ frequently observed at about 50 km altitude may be due to downward transport from above of particulates, possibly of extraterrestrial origin. This transport would be more efficient at higher altitudes (the mesosphere) than lower altitudes (the stratosphere) thus causing the layering seen in the stratopause region. The flux of particulates through the stratosphere provides a potential scavenging mechanism for pollutants and a source of condensation nucleii to the troposphere. Electric field variations, probably induced from above, can modulate this flux, providing a possible coupling mechanism between geomagnetic activity and terrestrial weather. The particulate distribution is also affected by the general circulation and atmospheric dynamics. The density of particulates is much greater than generally recognised, indicating that their role in chemical and thermal processes should be reassessed.
Cartilage oligomeric matrix protein in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and life threatening disease with median survival of 2.5–3 years. The IPF lung is characterized by abnormal lung remodeling, epithelial cell hyperplasia, myofibroblast foci formation, and extracellular matrix deposition. Analysis of gene expression microarray data revealed that cartilage oligomeric matrix protein (COMP), a non-collagenous extracellular matrix protein is among the most significantly up-regulated genes (Fold change 13, p-value <0.05) in IPF lungs. This finding was confirmed at the mRNA level by nCounter® expression analysis in additional 115 IPF lungs and 154 control lungs as well as at the protein level by western blot analysis. Immunohistochemical analysis revealed that COMP was expressed in dense fibrotic regions of IPF lungs and co-localized with vimentin and around pSMAD3 expressing cells. Stimulation of normal human lung fibroblasts with TGF-β1 induced an increase in COMP mRNA and protein expression. Silencing COMP in normal human lung fibroblasts significantly inhibited cell proliferation and negatively impacted the effects of TGF-β1 on COL1A1 and PAI1. COMP protein concentration measured by ELISA assay was significantly increased in serum of IPF patients compared to controls. Analysis of serum COMP concentrations in 23 patients who had prospective blood draws revealed that COMP levels increased in a time dependent fashion and correlated with declines in force vital capacity (FVC). Taken together, our results should encourage more research into the potential use of COMP as a biomarker for disease activity and TGF-β1 activity in patients with IPF. Hence, studies that explore modalities that affect COMP expression, alleviate extracellular matrix rigidity and lung restriction in IPF and interfere with the amplification of TGF-β1 signaling should be persuaded.
Primary anorectal lymphoma: a new manifestation of the acquired immune deficiency syndrome (AIDS)

Non-Hodgkin's lymphomas with particular clinicopathologic features occur with a high incidence in homosexual men affected by AIDS. More frequently than in the general population, these lymphomas have an extranodal location including the gastrointestinal tract. We have recently observed four cases of AIDS-associated lymphomas whose primary location is in the lower rectum and anus. The patients were 27 to 44 years of age, had greatly depressed helper-suppressor T-cell ratios, and antibodies to human immunodeficiency virus (HIV). All four presented with anorectal symptoms and originally had surgery for anorectal fistulas or tumor masses. When staged, three patients had no other organ involvement, the fourth only had lymphoma in an axillary lymph node, and all four had large tumor masses confined within the rectum. In terms of histology, the lymphomas were of undifferentiated or of large cell type and of B-cell phenotype. Lymphomas with primary or major location in the rectum are a rare occurrence in the general population, and until recently, are rare even among the lymphomas associated with the immune deficiency syndrome. At the Lenox Hill Hospital in New York City, no rectal lymphoma among the 58 cases of AIDS-related lymphoma diagnosed during the past 4 years was recorded until 10 months ago. The recognition of the new feature in presentation, a neoplasm associated with AIDS, is obviously important for its early diagnosis and treatment. Its unusual occurrence at the suspected portal of entry of the HIV infection is of interest because it may provide new clues to the association between AIDS and neoplasia.
Edge-flame structure and oscillations for unit Lewis numbers in a non-premixed counterflow

We examine the structure and oscillatory instability of low Peclet number, non-premixed edge-flames in a fixed rectangular channel, closed at one end, with constant side-wall mass injection, one su...
K -Series X-Ray Energies and Intensities for Curium, Berkelium, Californium, and Einsteinium

The energies of the $K{\ensuremath{\alpha}}_{1}$, $K{\ensuremath{\alpha}}_{2}$, $K{\ensuremath{\beta}}_{1}$, and $K{\ensuremath{\beta}}_{3}$ x rays of Cm, Bk, Cf, and Es, arising in the decay of suitable parent radioactivities, have been measured with a high-resolution Ge(Li) photon detector. The $K$-shell binding energies of Cm, Bk, and Cf have been determined using previously published values for the ${L}_{\mathrm{II}}$-, ${L}_{\mathrm{III}}$-, ${M}_{\mathrm{II}}$-, and ${M}_{\mathrm{III}}$-shell binding energies. The relative transition probabilities ($K{\ensuremath{\alpha}}_{1}=1000$) of the $K$-series lines have been determined for Cm, Bk, Cf, and Es. The measured energies and relative transition probatilities agree well with recent theoretical predictions.
The determinants of industrial-sector earnings in Senegal

Abstract The paper presents an econometric framework for testing the determinants of the industrial-sector earnings in Senegal. Using relatively rich data from the 1976 Industrial Census it is possible to test several hypotheses and generate estimates, some of which could not be obtained within the context of developing countries before. The main results relate to the earnings effects of sex, ethnic background, occupational attainment, and industry characteristics.
Ductility in boron-doped, nickel-base L12 alloys processed by rapid solidification

Etude de la ductilite dans les composes intermetalliques de type Ni 3 X (ou X=Al, Ga, Si, Ge) de structure ordonnee L1 2 en fonction de la teneur en bore (0,1 a 1% at.)
Polarization of the Energy Beam in Perkin-Elmer Infrared Grating Spectrophotometers

An account is given of the polarization occuring within the Perkin-Elmer models 421 and 521 infrared grating spectrophotometers. It is shown that the use of gratings in these instruments results in considerable polarization of the energy beam. The efficiency curves and the degree of polarization curves for the two components of polarization are given as a function of frequency. The polarization properties of the microsampling unit and the attenuated total reflectance accessory are also investigated.
The use of injections for treating childhood diseases: determinants and consequences for preventive health care in developing countries.

Abstract This paper examines the extent of injection use among children as well as the factors that influence the use of injections for treating childhood diseases in four sub-Saharan African countries. Employing the Andersen Behavioral framework of predisposing, enabling and need factors, data from the Demographic and Health Surveys (DHS) were examined. About 30 percent of children with fever, and about 20 percent of children with respiratory problems were treated with injections. Multivariate analyses showed that the effects of the predisposing and enabling characteristics upon use of injections were consistently higher than those of the need component, suggesting the existence of great inequities in the health care system. Implications for preventive health care are examined.
The Carathéodory and Kobayashi/Royden metrics by way of dual extremal problems

We study the Caratheodory and Kobayashi metrics by way of the method of dual extremal problems in functional analysis. Particularly, incisive results are obtained for convex domains.
Heart rate derived from blood pressure and other physiological signals.

A device for providing a continuous on-line output of beat-by-beat HR in physiologic studies is described. The circuit eliminates the need for obtaining an EKG signal since it uses other vascular phenomena such as blood pressure, blood flow, or plethysmograph to produce an index of heart action to provide subsequent rate phenomena. Signal conditioning to produce the electrical analog of the vascular change is derived from either a pressure transducer, flow probe, plethysmograph, or other transducing device connected to the input of a Beckman-Offner, or Grass (Model 6) polygraph recorder. The output is in the form of a relay closure to provide initiating action to such devices as cardiotachometers, integrators, printers, counters, and many other instruments used in physiological studies.
EU Counterterrorism Policy: A Paper Tiger?

ABSTRACT Following the September 11, 2001 terrorist attacks on the United States, the European Union has acted on several fronts to reinforce its existing and nascent capabilities to combat terrorism. The European Council adopted a comprehensive Plan of Action and reached political agreement on a number of important counterterrorism initiatives, including the introduction of a European Arrest Warrant; strengthening of Europol and Eurojust; the drafting of a common EU definition of terrorism; and freezing of terrorist finances. This article provides a critical analysis of all these measures and reveals that the EU counterterrorism policy suffers from an implementation deficit, in large part due to the absence of genuine pro-integration thinking in the area of Justice and Home Affairs. The March 11, 2004 terrorist attacks in Madrid provided fresh impetus for enhancing the EU counterterrorism capabilities but a multitude of political, legal, and cultural challenges still need to be overcome in order to make ...
Coupling osteological development of the feeding apparatus with feeding performance in common snook, Centropomus undecimalis, larvae: identifying morphological constraints to feeding.

article i nfo Identifying bottlenecks to feeding in marine finfish larvae is becoming a dominant theme as commercially important fish stocks collapse worldwide. The transition from endogenous yolk reserves to feeding exogenously is perhaps the largest constraint to developing aquaculture technologies in closed systems. Mass mortality during early larval development is generally attributed to a lack of suitable prey during the first feeding stage, however, empirical evidence identifying a causal link between morphology and performance remains scarce. In this study, we examined the link between osteological development of the feeding apparatus and feeding performance, expressed as (1) the median number of prey consumed by larvae and (2) the median size of prey consumed by larvae, during larval development of the common snook, Centro- pomus undecimalis. Cluster analysis, nMDS, and SIMPER analysis allowed us to identify functional intervals of the feeding apparatus through larval development. Results revealed that first feeding larvae exhibited rudimentary skeletal elements and selected only one or two of the prey types available relative to older larvae, which included more and larger prey types in their diet. Upon complete formation of the hyoid apparatus, around 8 dph, a dietary shift to rotifers was observed suggesting that high rates of mortality observed in closed culture systems may be attributed to the absence of a suitable small, non-elusive food organism during the first feeding stage. First feeding larvae exhibit a poorly developed feeding apparatus that may constrain their ability to consume elusive prey as an initial diet. Based on the association between stage- specific characteristics of the feeding apparatus and corresponding stage-specific metrics of feeding performance established in this study, we propose a stage-specific feeding-management scheme for snook hatchery aquaculture.
Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor

Replacement of the central, para-substituted fluorophenyl ring in the γ-secretase inhibitor 1 (BMS-708,163) withthe bicyclo[1.1.1]pentane motif led to the discovery of compound 3, an equipotent enzyme inhibitor with significant improvements in passive permeability and aqueous solubility. The modified biopharmaceutical properties of 3 translated into excellent oral absorption characteristics (∼4-fold ↑ Cmax and AUC values relative to 1) in a mouse model of γ-secretase inhibition. In addition, SAR studies into other fluorophenyl replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane moiety over conventional phenyl ring replacements with respect to achieving an optimal balance of properties (e.g., γ-secretase inhibition, aqueous solubility/permeability, in vitro metabolic stability). Overall, this work enhances the scope of the [1.1.1]-bicycle beyond that of a mere “spacer” unit and presents a compelling case for its broader application as a phenyl group replacement in scenarios where th...
Analysis of structural reliability under parameter uncertainties

Abstract Formulation of structural reliability requires selection of probabilistic or physical models, which usually involve parameters to be estimated through statistical inference — a process that invariably introduces uncertainties in parameter estimates. The measure of reliability that incorporates these parameter uncertainties is termed the predictive reliability index. Methods for computing this measure and the corresponding failure probability are introduced. A simple approximate formula is derived for the predictive reliability index, which requires a single solution of the reliability problem together with parameter sensitivities with respect to mean parameter values. The approach also provides measures of the uncertainties inherent in the estimates of the reliability index and the failure probability, which arise from parameter uncertainties. An illustrative example involving component and system problems demonstrates the influence of parameter uncertainties on the predictive reliability index and the accuracy of the simple approximation formula.
Automated feature extraction in brain tumor by magnetic resonance imaging using Gaussian mixture models

This paper presents a novel method for Glioblastoma (GBM) feature extraction based on Gaussian mixture model (GMM) features using MRI. We addressed the task of the new features to identify GBM using T1 and T2 weighted images (T1-WI, T2-WI) and Fluid-Attenuated Inversion Recovery (FLAIR) MR images. A pathologic area was detected using multithresholding segmentation with morphological operations of MR images. Multiclassifier techniques were considered to evaluate the performance of the feature based scheme in terms of its capability to discriminate GBM and normal tissue. GMM features demonstrated the best performance by the comparative study using principal component analysis (PCA) and wavelet based features. For the T1-WI, the accuracy performance was 97.05% (AUC = 92.73%) with 0.00% missed detection and 2.95% false alarm. In the T2-WI, the same accuracy (97.05%, AUC = 91.70%) value was achieved with 2.95% missed detection and 0.00% false alarm. In FLAIR mode the accuracy decreased to 94.11% (AUC = 95.85%) with 0.00% missed detection and 5.89% false alarm. These experimental results are promising to enhance the characteristics of heterogeneity and hence early treatment of GBM.
Direct activation of sparse, distributed populations of cortical neurons by electrical microstimulation

For over a century, electrical microstimulation has been the most direct method for causally linking brain function with behavior. Despite this long history, it is still unclear how the activity of neural populations is affected by stimulation. For example, there is still no consensus on where activated cells lie or on the extent to which neural processes such as passing axons near the electrode are also activated. Past studies of this question have proven difficult because microstimulation interferes with electrophysiological recordings, which in any case provide only coarse information about the location of activated cells. We used two-photon calcium imaging, an optical method, to circumvent these hurdles. We found that microstimulation sparsely activates neurons around the electrode, sometimes as far as millimeters away, even at low currents. Our results indicate that the pattern of activated neurons likely arises from the direct activation of axons in a volume tens of microns in diameter.
Comparison of configuration interaction expansions based on different orbital transformations

The characteristics of CI expansions based on different types of orbitals (all obtained from the same basis set) are compared in a series of calculations on the water molecule. The orbitals compared include canonical SCF molecular orbitals, natural orbitals, and two other types related to these. The comparisons include energy and property convergence and the distribution of magnitudes of the off-diagonal elements of the Hamiltonian matrix and of the eigenvector components. The implications of the results are discussed.
Reversal of sexual induction in Volvox carteri by ultraviolet irradiation and removal of sexual pheromone

Washing in fresh culture medium or short exposure to ultraviolet irradiation (UV) was found to reverse the action of the sexual pheromone produced by the green alga Volvox carteri. Induced gonidia which would normally form egg-bearing females formed mainly asexual individuals in response to these treatments. The UV effect is strongly dependent on the stage of the life cycle at which exposure is given. Sexual induction in this organism requires early and continuous exposure to the sexual pheromone. The mechanism by which UV reverses sexual induction is not understood, but it could be caused by inactivation of the pheromone or by inactivation of a pheromone-induced repressor of asexual characters.
Dealiased spectral images from aliased Fizeau Fourier transform spectroscopy measurements

Fizeau Fourier transform imaging spectroscopy (FTIS) is a technique for collecting both spatial and spectral information about an object with a Fizeau imaging interferometer and postprocessing. The technique possesses unconventional imaging properties due to the fact that the system transfer functions, including the imaging and spectral postprocessing operations, are given by cross correlations between subapertures of the optical system, in comparison with the conventional optical transfer function, which is given by the autocorrelation of the entire aperture of the system. The unconventional imaging properties of Fizeau FTIS can be exploited to form spatially dealiased spectral images from undersampled intensity measurements (obtain superresolution relative to the detector pixel spacing). We demonstrate this dealiasing technique through computer simulations and discuss the associated design and operational trade-offs.
Turbulence Measurements In Liquids Using An Improved Total Pressure Probe

(1970). Turbulence Measurements In Liquids Using An Improved Total Pressure Probe. Journal of Hydraulic Research: Vol. 8, No. 2, pp. 131-158.
Val64Ile Polymorphism in the C-C Chemokine Receptor 2 Is Associated With Reduced Coronary Artery Calcification

Objective— Studies in mice have shown that genetic disruption of monocyte chemotactic protein-1 or its receptor, the C-C chemokine receptor 2 (CCR2), inhibits atherosclerosis, but few data exist in humans to suggest that the monocyte chemotactic protein-1—CCR2 interaction is important in atherogenesis. A common polymorphism in the human CCR2 gene resulting in a substitution of isoleucine for valine (Val64Ile) has been associated with other disease phenotypes in humans. Methods and Results— A cohort of first-degree relatives of persons with premature coronary artery disease was recruited and quantitatively phenotyped for the extent of CAC, a marker of coronary atherosclerosis, by using electron beam CT. The extent of CAC was significantly lower in subjects with the CCR2-Ile64 variant (Val/Ile and Ile/Ile genotypes) than in subjects carrying 2 Val64 alleles, even after adjustment for traditional risk factors. Conclusions— This study provides genetic evidence linking CCR2 with coronary atherosclerosis in humans.
Birth Plans: The Good, the Bad, and the Future

A written birth plan encourages women to clarify desires and expectations and communicate with their providers to make a realistic plan for care during labor. Tension between health professionals and patients caused by birth plans reflects the larger problems with contemporary maternity care: conflicting beliefs about birth, what constitutes safe, effective care, and ethical issues related to informed consent and informed refusal. The focus of birth plans should be to answer three patient-focused questions: What will I do to stay confident and feel safe? What will I do to find comfort in response to my contractions? Who will support me through labor, and what will I need from them? In this article, the history and purposes of birth plans and approaches to resolving tensions will be discussed.
The Adipocyte as an Endocrine Cell

Adipose tissue contains many cell types. Among the more abundant are adipocytes, preadipocytes, immune cells, and endothelial cells. During times of excess caloric intake, these cells have to adjust and remodel to accommodate the increased demand for triglyceride storage. Based on a comprehensive analysis of the total adipose tissue secretome, this article focuses on three areas of adipokine biology: (1) How does the adipocyte interact with the extracellular matrix over the course of obestiy? (2) Does the adipocyte, per se, play a role in the innate immune response? (3) How is the angiogenic profile of adipose tissue linked to the development of insulin resistance? The authors present a comprehensive overview of all of the currently available secreted adipose tissue products that have been identified at the protein level.
Historia, mito e imaginación constructiva en los dramas históricos de Emilio Carballido

En Mexico, donde la retorica historica es el sine qua non del discurso politico y donde abundan los monumentos a los heros de ayer, la historia y sus consecuencias son aspectos -aspectos ubicuos- de la sociedad.
Delay in blood glucose monitoring during an insulin infusion protocol is associated with increased risk of hypoglycemia in intensive care units.

BACKGROUND: Hypoglycemia during insulin infusion therapy is a major problem. We investigated whether a delay in blood glucose (BG) monitoring during an insulin infusion protocol (IIP) in the intensive care unit (ICU) is associated with hypoglycemia. METHODS: Data were collected for 50 consecutive patients treated with Brigham and Women's Hospital's IIP. Point-of-care BG values were obtained from the bedside paper flow sheets and the exact times of individual measurements were ascertained from an internet-based glucose meter download program. Data were carefully studied for protocol time violations, defined as a delay of >10 minutes after the recommended time for BG measurement. RESULTS: A total of 2309 BG values were evaluated for time violation. A total of 1474 (63.9%) measurements had been obtained at the recommended time or earlier; 835 (36.1%) measurements had been obtained >10 minutes after the recommended time for measurement. There were a significantly higher proportion of BG values <80 mg/dL following the time violation as compared to no time violation (17.8% versus 11.6%; P < 0.001). CONCLUSION: We conclude that the risk of hypoglycemia during insulin infusion therapy is higher after a delay in BG measurement. Journal of Hospital Medicine 2009;4:E5–E7. © 2009 Society of Hospital Medicine.
Functional Morphology of the Testis

graded series of ethanol, cleared in propylene oxide and embedded in Epon. Onesections were cut with glass knives, mounted on slides, stained with 1% toluidine blue and examined with the light micro- scope. These sections were used to identify the stages of the cycle of the seminiferous epithelium in the monkey as described by Clermont (1969). Adjacent thin sections, showing silver to pale gold interference colors, were cut with a diamond knife, mounted on uncoated copper grids and stained with lead citrate and uranyl acetate (Reynolds, 1963). The preparations were examined and photographed on a Philips 200 or JEM 100 S electron microscope. The techniques utilizing intercellular tracer compounds such as lan- thanum nitrate and horseradish peroxidase have been described previously (Dym and Fawcett, 1970; Dym,
Evolution of Human Immunodeficiency Virus Type 1 Coreceptor Usage during Antiretroviral Therapy: a Bayesian Approach

There is substantial evidence for ongoing replication and evolution of human immunodeficiency virus type 1 (HIV-1), even in individuals receiving highly active antiretroviral therapy. Viral evolution in the presence of antiviral therapy needs to be considered when developing new therapeutic strategies. Phylogenetic analyses of HIV-1 sequences can be used for this purpose but may give rise to misleading results if rates of intrapatient evolution differ significantly. To improve analyses of HIV-1 evolution relevant to studies of pathogenesis and treatment, we developed a Bayesian hierarchical model that incorporates all available sequence data while simultaneously allowing the phylogenetic parameters of each patient to vary. We used this method to examine evolutionary changes in HIV-1 coreceptor usage in response to treatment. We examined patients whose viral populations exhibited a shift in coreceptor utilization in response to therapy. CXCR4 (X4) strains emerged in each patient but were suppressed following initiation of new antiretroviral regimens, so that CCR5-utilizing (R5) strains predominated. By phylogenetically reconstructing the evolutionary relationship of HIV-1 obtained longitudinally from each patient, it was possible to examine the origin of the reemergent R5 virus. Using our Bayesian hierarchical approach, we found that the reemergent R5 virus detectable after therapy was more closely related to the predecessor R5 virus than to the X4 strains. The Bayesian hierarchical approach, unlike more traditional methods, makes it possible to evaluate competing hypotheses across patients. This model is not limited to analyses of HIV-1 but can be used to elucidate evolutionary processes for other organisms as well.
Peripheral Pain Mechanisms in Chronic Widespread Pain

Clinical symptoms of chronic widespread pain (CWP) conditions like fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalised tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli, which can be either noxious (hyperalgesia) or non-noxious (allodynia). For example, patients with muscle hyperalgesia will rate painful muscle stimuli higher than normal controls, whereas patients with allodynia may perceive light touch as painful, something that a ‘normal' individual will never describe as painful. The pathogenesis of such peripheral and/or central nervous system changes in CWP is unclear, but peripheral soft tissue changes have been implicated. Indirect evidence from interventions that attenuate tonic peripheral nociceptive impulses in patients with CWP syndromes like FM suggest that overall FM pain is dependent on peripheral input. More importantly, allodynia and hyperalgesia can be improved or abolished by removal of peripheral impulse input. Another potential mechanism for CWP pain is central disinhibition. However, this pain mechanism also depends on tonic impulse input, even if only inadequately inhibited. Thus, a promising approach to understanding CWP is to determine whether abnormal activity of receptors in deep tissues is fundamental to the development and maintenance of this chronic pain disorder. Conclusions Most CWP patients present with focal tissue abnormalities including myofascial trigger points, ligamentous trigger points or osteoarthritis of the joints and spine. While not predictive for the development of CWP, these changes nevertheless represent important pain generators that may initiate or perpetuate chronic pain. Local chemical mediators, including lactic acid, adenosine triphosphate (ATP) and cytokines, seem to play an important role in sensitising deep tissue nociceptors of CWP patients. Thus, the combination of peripheral impulse input and increased central pain sensitivity may be responsible for widespread chronic pain disorders including FM.
Long noncoding RNA in genome regulation: prospects and mechanisms.

Long noncoding RNAs (lncRNAs) are pervasively transcribed and critical regulators of the epigenome[1, 2]. These long, polyadenylated RNAs do not code for proteins, but function directly as RNAs, recruiting chromatin modifiers to mediate transcriptional changes in processes ranging from X-inactivation (XIST) to imprinting (H19)[3]. The recent discovery that lncRNA HOTAIR can link chromatin changes to cancer metastasis[4] furthers the relevance of lncRNAs to human disease. Here, we discuss lncRNAs as regulatory modules and explore the implications for disease pathogenesis. Although large-scale analyses of mammalian transcriptomes have revealed that more than 50% of transcripts have no protein coding potential[2, 5, 6], the functions of these putative transcripts are largely unknown. A subset of these noncoding transcripts are termed long noncoding RNAs (lncRNAs), based on an arbitrary minimum length of 200 nucleotides. LncRNAs are roughly classified based on their position relative to protein-coding genes: ...
Filming France's colonial past: Women ‘wearing the pants’ in Outremer and Indochine

ABSTRACTReleased when France had to deal with the aftermath of immigration (mainly from its former colonies) and its long overdue coming-to-terms with its colonial past, as well as gender parity in the workforce and politics, Outremer/Overseas (Rouan, 1990) and Indochine (Wargnier, 1992) provide views on the status of women during the colonial era. Each film portrays a strong female colonizer torn between her contrasting roles as wife/lover/mother and domain manager. Placed in a position of relative power between the colonized and the male colonizer, these women venture out of the private sphere (women's traditional space) to enter a public sphere that was expanded when colonisation stretched the boundaries of nation and pitted the notion of national identity against that of race and culture. By examining and comparing the representations of these two female characters who assume men's roles, the article aims to show how their characterizations can participate in the discourse on gender roles that informe...
Designing High-Efficiency Interference Coatings With Atomic Layer Deposited TiO 2 Layers

Atomic Layer Deposition (ALD) has enabled the manufacturing of high-efficiency optical interference coatings. This paper reviews the interference coating designing methodology necessary to use TiO2 as an optical material when deposited using ALD.
Passive optical sensing of atmospheric polarization for GPS denied operations

There is a rapidly growing need for position, navigation, and timing (PNT) capability that remains effective when GPS is degraded or denied. Naturally occurring sky polarization was used as long ago as the Vikings for navigation purposes. With current polarimetric sensors, the additional polarization information measured by these sensors can be used to increase the accuracy and the availability of this technique. The Sky Polarization Azimuth Sensing System (SkyPASS) sensor measures this naturally occurring sky polarization to give absolute heading information to less than 0.1° and offers significant performance enhancement over digital compasses and sun sensors. SkyPASS has been under development for some time for terrestrial applications, but use above the atmosphere may be possible and the performance specifications and SWAP are attractive for use as an additional pose sensor on a satellite. In this paper, we will describe the phenomenology, the sensor performance, and the latest test results of terrestrial SkyPASS; we will also discuss the potential for use above the atmosphere and the expected benefits and limitations.
Changes of Glucocorticoids Therapy on Hematological Indices in Patients with Inflammatory Demyelinating Disease

Objective To investigate the changes of glucocorticoids therapy on hematological indices in patients with inflammatory demyelinating disease.Methods Total of 15 patients with inflammatory demyelinating disease were divided into two groups.Ten cases received treatment with methylprednisolone(group M),The other 5 cases received treatment with dexamethasone(group D).All the patients received prednisone with intravenous dripping(i.v.) then changed to oral administration with different dosage and extenuated gradually in these two treatment teams.Results (1)Blood glucose:The fasting plasma glucose(FPG) of patients in group M increased significantly on the first and the 2nd day after the treatment(P0.01) and on the third day after the treatment the increasing was less(P0.05);The 2 h postprandial plasma glucose(2hPG) increased(P0.01) from the 1st to the 3rd day after treatment and the 2hPG(lunch,supper) still increased on the 7th day after treatment(P0.01),and less increased on the 14th day(P0.05).The 2hPG(lunch) of patients in group D increased on the 2nd day after the treatment(P0.05).(2)Leukocytes:the white blood cell count(WBC) and neutrophils(NEUT) of the patients in group M increased significantly(P0.01) on the 7th and the 14th day after treatment and those of the patients in group D increased significantly(P0.01) on the 7th day after treatment.(3) High density lipoproteins(HDL): the HDL of the patients in group M increased more significantly(P0.01) than group D(P0.05) on the 14th day after treatment.(4)Others: Compared to prior treatment,blood pressure,blood calcium,phosphorus,alanine amino transferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN) and creatinine(CRE) didn't change significantly(P0.05).Conclusions Methylprednisolone could make patients blood glucose increase more significantly than dexamethasone.Both methylprednisolone and dexamethasone could cause HDL,WBC and NEUT increase,but bring little influence on blood pressure,blood calcium,phosphorus,ALT,AST,BUN and CRE.Since the sample capacity was limited,some conclusions should be confirmed by another study with more sample capacity.
Late Quaternary sedimentological characteristics and sedimentary environment evolution in sea area between Nan'ao and Chenghai,eastern Guangdong

The sedimentological characteristics and sedimentary environment evolution in the Late Quaternary in the sea area between Nan'ao and Chenghai of eastern Guangdong province are studied based on the analysis on 12 boreholes and chronological researches.Three sedimentary cycles were identified according to the borehole data.Each cycle shows a feature of upward-fining sequence,normally starting with coarse-medium sand and ending with silt or clay.Chronological data were obtained by 14C dating with the samples from the beds of difference cycles.It is demonstrated that the Quaternary sediments started depositing in the Late Pleistocene,which was coeval with the deposits of the Hanjiang River Delta.The dating results also indicate that the first two cycles were formed in the Late Pleistocene,while the last one was in the Holocene.The influence of sea level change on this sea area since the Holocene was relatively minor compared with the inner plain where two transgression/regression sequences were recorded,indicating that the sedimentary environment in the research area has been relatively stable since the Holocene.
DIRECT AND INDIRECT EFFECTS OF PEREGRINE FALCON PREDATION ON SEABIRD ABUNDANCE

ABsTP, ACT.--Peregrine Falcons (Falco peregrinus) have become conspicuous members of the bird assemblage at Tatoosh Island, Washington, since 1983. We have sufficient before and after observations and data to conclude that two species of storm-petrel (Oceanodroma spp.) show no significant population trends (as based on catch per hour in standardized mist nets from 1978-1988) and that numbers of both Cassin's (Ptychoramphus aleuticus) and Rhinoceros (Cerorhinca monocerata) auklets, the primary falcon prey, are probably declining. An important effect of falcons is their consumption of Northwestern Crows (Corvus caurinus) or simply restriction of crow activities. The numbers of Common Murres (Uria aalge) and Pelagic Cormorants (Phalacrocorax pelagicus) that inhabit Tatoosh have increased markedly, probably due to significantly decreased crow-related egg predation. The fledging rate of Black Oystercatchers (Haematopus bachmani) approximately doubled in 1987, when one falcon routinely ate crows. These relationships appear to be independent of the locally abundant Glaucous-winged Gulls (Larus glaucescens). We conclude that the indirect, positive effects are at least as important to seabird abundance patterns as are direct, negative effects. We suggest that more attention be paid to corvid activities near seabird colonies and, especially, that the impact on populations of small alcids or other prey be considered when planning conservation efforts to augment the population of an effective avian predator. Received 9 January 1989, accepted 13 September 1989.
Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ

Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6 months after primary cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67–94 years diagnosed with DCIS during 2004–2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p < .001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR = 0.90; p = .71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4 %, p < .001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3 %, p = .04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident.
Effects of Selective M1 Muscarinic Receptor Activation on Hippocampal Spatial Representations and Neuronal Oscillations.

The muscarinic M1 acetylcholine receptor is a key target for drugs aimed at treating cognitive dysfunction, including the memory impairment in Alzheimer’s disease. The overall question of the current study was to ask how systemic administration of the bitopic M1 agonist VU0364572, the M1 positive allosteric modulator BQCA, and the acetylcholinesterase inhibitor donepezil (current standard of care for Alzheimer’s disease), would impact spatial memory-related hippocampal function in rats. Hippocampal pyramidal neuron spiking and local field potentials were recorded from regions CA1 and CA3 as rats freely foraged in a recording enclosure. To assess the relative stability versus flexibility of the rats’ spatial representations, the walls of the recording enclosure were reshaped in 15-m intervals. As compared to the control condition, systemic administration of VU0364572 increased spatial correlations of CA1 and CA3 pyramidal neuron spiking across all enclosure shape comparisons, whereas BQCA and donepezil app...
Entering the Metals Zone

Publisher Summary This chapter focuses on the metal zone. Metals are found everywhere in the Materials World, and a world without any metals are unimaginable. Some objects, such as forks, could be made of plastics rather than sterling silver, however, some applications like skyscrapers or jet planes would never exist without metals. The chapter explores metals across several length scales, from the atomic level up to the bulk, and establishes how the properties are a direct outcome of the structure. Different schemes or frameworks of how to think about some of the concepts are presented. Certain phrases that are descriptive of “concepts” are used to help understand the “effects” or behavior of metals. The lists of the effects, concepts, and constructs are presented in this chapter. Metals are primarily made up of metallic elements. A quick scan of the Periodic Table reveals that most elements are metals. The metallic elements are electropositive and are quite willing to give up or share their valence electrons.
Assessing photograph aesthetic quality with color based descriptor

Assessing photograph aesthetic quality is an interesting and important problem of computer vision. The understanding of how to classify photographs based on their aesthetic value not only provides us with important knowledge about effective methods and techniques of summarizing information embedded in digital images, but also has numerous practical applications in photo management systems, image search engines, photo library optimization processes, and smart cameras. Previous work has explored the method of using generic local descriptors extracted from gray-scale photographs to assess the aesthetic quality. In our work, we designed an aesthetic descriptor based on color information of local patches to asses the aesthetic quality of photographs. We employed the Bag of Words (BOW) model to describe our data. The BOW model is widely used in text analysis tasks due to its good performance. This model can also be adopted by computer vision tasks to classify and categorize images. With such a model, every photograph in our dataset was represented as a vector of visual words derived from the color descriptors. A Gaussian mixture model was used to cluster and verbalize photographs, which is proven to be highly effective in our classification task. The best performance we achieved in our experiments was 72.9% AUC.
Incorporating Patient Preferences and Quality of Life

In slowly progressive cancers such as lentigo maligna and lentigo maligna melanoma (LM/LMM), the optimal management may vary widely among different patients. Comorbidity and patient preference should be addressed when discussing treatment options, notably in the elderly population that is often affected, as most cases of LM/LMM are nonfatal. While health related quality of life has not been well-studied in regards to facial LM/LMM and its treatment, this area of research may lend important insights into optimizing disease management. An individualized plan accounting for patient comorbidities, social support, and aesthetic concerns should be developed using a model of shared decision-making.