cssi/SciSciGPT-SciSciNet huggingface dataset:
Small molecule drugs for atopic dermatitis, rheumatoid arthritis, and hereditary angioedema.

Abstract Objective To review recent trends in the development of targeted small molecule drugs (SMDs) for the treatment of immunologically driven disorders, including atopic dermatitis, rheumatoid arthritis, and hereditary angioedema. Data sources Data sources included peer-reviewed published literature from the PubMed database, published abstracts from scientific and medical meetings, and medication information from the Drugs@FDA database. Study selections Articles with primary or retrospective trial results, articles with patient or physician survey results, articles providing expert perspectives, and commentary on chronic immunologic disorders, Food and Drug Administration package inserts, and abstracts from scientific meetings were selected. Results Targeted biological therapies have greatly improved response rates and symptom relief for patients with long-term immunologically driven disorders over the past 2 decades. However, recent advances in the understanding of molecular pathways involved in the pathogenesis of these disorders have led to the development of novel targeted SMDs, such as tofacitinib and berotralstat, that can be delivered orally or topically. Few head-to-head studies that compare the safety and efficacy of biologics to SMDs in immunologically driven disorders exist, although some studies suggest that oral and topical modes of administration are preferred by patients and may improve patient quality of life over time. Conclusion Scientific advances have led to an increase in the development of targeted SMDs for the treatment of chronic immunologic disorders, which may revolutionize the management of these diseases. Head-to-head studies and real-world evidence are needed to fully compare treatment attributes between biologics and SMDs, including safety, efficacy, adherence, impact on quality of life, and cost-effectiveness.
A Review of “Historical Dictionary of Bertrand Russell's Philosophy”

“Bertrand Russell was a philosopher like few others.” So begins this fine comprehensive work on Bertrand Russell by Rosalind Carey and John Ongley. The authors are both members of the Bertrand Russ...
Distributed coordination of mobile agent teams: the advantage of planning ahead

We consider the problem of coordinating a team of agents engaged in executing a set of inter-dependent, geographically dispersed tasks in an oversubscribed and uncertain environment. In such domains, where there are sequence-dependent setup activities (e.g., travel), we argue that there is inherent leverage to having agents maintain advance schedules. In the distributed problem solving setting we consider, each agent begins with a task itinerary, and, as execution unfolds and dynamics ensue (e.g., tasks fail, new tasks are discovered, etc.), agents must coordinate to extend and revise their plans accordingly. The team objective is to maximize the utility accrued from executed actions over a given time horizon. Our approach to solving this problem is based on distributed management of agent schedules. We describe an agent architecture that uses the synergy between intra-agent scheduling and inter-agent coordination to promote task allocation decisions that minimize travel time and maximize time available for utility-acrruing activities. Experimental results are presented that compare our agent's performance to that of an agent using an intelligent dispatching strategy previously shown to outperform our approach on synthetic, stateless, utility maximization problems. Across a range of problems involving a mix of situated and non-situated tasks our advance scheduling approach dominates this same dispatch strategy. Finally, we report performance results with an extension of the system on a limited set of field test experiments.
Tectonic implications of a petrographic and geochemical characterization of the Lower to Middle Jurassic Sailor Canyon Formation, northern Sierra Nevada, California

The Lower to Middle Jurassic Sailor Canyon Formation in the northern Sierra Nevada of California consists of basinal volcaniclastic and tuffaceous sedimentary rocks. Petrographic and geochemical data from the formation provide an opportunity to assess a proposed ∼400 km of pre–Late Cretaceous dextral strike- slip displacement on the cryptic Mojave–Snow Lake fault. A corollary to the proposed displacement is that Triassic-Jurassic volcanic complexes exposed in eastern California were the source for Sailor Canyon Formation sediments. However, geochemical data derived from volcanic rocks from this area are unlike those of the volcanic provenance characterized for the Sailor Canyon Formation. Comparisons of geochemical data suggest that contemporaneous volcanic centers exposed in western Nevada north of ∼38°N may be better candidates for the source of the volcanic material in the Sailor Canyon Formation. This interpretation implies that dextral strike-slip displacement on the Mojave–Snow Lake fault may be less than ∼200 km, a value that agrees with some interpretations of Mesozoic intrabatholithic displacements in the Sierra Nevada.
PEGylated Liposomal Doxorubicin Targeted to α5β1-Expressing MDA-MB-231 Breast Cancer Cells

Targeting drugs selectively to cancer cells can potentially benefit cancer patients by avoiding side effects generally associated with several cancer therapies. One of the attractive approaches to direct the drug cargo to specific sites is to incorporate ligands at the surface of the delivery systems. Integrin α(5)β(1) is overexpressed in tumor vasculature and cancer cells, thus making it an attractive target for use in drug delivery. Our group has developed a fibronectin-mimetic peptide, PR_b, which has been shown to bind specifically to integrin α(5)β(1), thereby providing a tool to target α(5)β(1)-expressing cancer cells in vitro as well as in vivo. Our current work focuses on designing modified stealth liposomes (liposomes functionalized with polyethylene glycol, PEG) for combining the benefits associated with PEGylation, as well as imparting specific targeting properties to the liposomes. We have designed PEGylated liposomes that incorporate in their bilayer the fibronectin-mimetic peptide-amphiphile PR_b that can target several cancer cells that overexpress α(5)β(1), including the MDA-MB-231 breast cancer cells used in this study. We have encapsulated doxorubicin inside the liposomes to enhance its therapeutic potential via PEGylation as well as active targeting to the cancer cells. Our results show that PR_b-functionalized stealth liposomes were able to specifically bind to MDA-MB-231 cells, and the binding could be controlled by varying the peptide concentration. The intracellular trafficking of the doxorubicin liposomes was examined, and within minutes after delivery the majority of them were found to be in the early endosomes, whereas after a longer period of time they had accumulated in the late endosomes and lysosomes. The functionalized liposomes were found to be equally cytotoxic as the free doxorubicin, especially at higher doxorubicin concentrations, and provided higher cytotoxicity than the nontargeted and GRGDSP-functionalized stealth liposomes. Thus, the PR_b-functionalized PEGylated nanoparticles examined in this study offer a promising strategy to deliver their therapeutic payload directly to the breast cancer cells, in an efficient and specific manner.
Analysis and experimental verification of a forth order plant model for manipulator force control

The analysis and experimental verification of a fourth order model of the arm/sensor/environment system plant, to be used in evaluation of force control strategies are presented. Both the undamped and underdamped eases are investigated. Approximations and qualifications, based on the reality of our experimental system, help reduce the solution to just a few dominant terms. Comparing these terms with experimental data of the system undergoing small oscillations yields approximate values for all of the parameters in the model. To justify the obtained values and thereby the approximations used, two measures are taken. First, a simulation of the fourth order model is performed, and compared against experimental data obtained from the CMU DD Arm II system. Second, a stability analysis of several force control schemes acting on the modelled plant is reviewed and compared against experimental tests of the controllers. In both cases, the simulation and analysis match closely with the experimental results, confirming the validity of the plant model. >
Sleep Duration Affects Risk for Ulcerative Colitis: A Prospective Cohort Study

Background & Aims Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. Methods We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). Results Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7–8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration 9 h/day (20/100,000 person-years) had a higher incidence of UC ( P 9 h/day, compared with sleep durations of 7–8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. Conclusions On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.
Large optical birefringence in poly(p-phenylene vinylene) films measured by optical waveguide techniques

Abstract We report here the observation of a large birefringence in an as-cast unoriented film of poly(p-phenylene vinylene), a material that has a large third-order non-linear optical susceptibility. A waveguide technique in TE and TM polarization is used to obtain in-plane and out-of-plane refractive indices at several wavelengths. At 633 nm the measured refractive index values are nTE = 2.085 and nTM = 1.612. No dependence of the in-plane refractive index on the direction of film spreading is found, indicating an in-plane isotropic behaviour. No anomalous dispersion of refractive index is found in the wavelength range 633–1064 nm.
Missions-oriented RD&D institutions in energy between 2000 and 2010: A comparative analysis of China, the United Kingdom, and the United States

Abstract In the first decade of the 21st century, governments in many countries around the world expanded or redesigned their support for the development and deployment of advanced energy-supply and energy-demand technologies. By analyzing the institutions that have been created to stimulate energy technology innovation in the United States, the United Kingdom, and China-three countries with very different sizes, political systems and cultures, natural resources, and histories of involvement in the energy sector-this paper highlights how variations in national objectives and industrial and political environments have translated into variations in policy. The analysis shows that the countries’ activities differ in terms of three general elements: whether the government's various activities are coordinated or autonomous, whether the business community is significantly involved in the design and running of the initiatives, and whether the implementing institutions focus on single or multiple missions and innovation types. These differences constitute different types of governments’ attempts to activate the state-industry innovation complex. The paper concludes with a discussion of the trade-offs involved in the design of systems for public support of energy RD&D, points to possible gaps in the government approaches to support energy RD&D, and highlights areas of future research.
Evaporative water loss from endotherms in thermally and hygrically complex environments: An empirical approach for interspecific comparisons

Evaporative water loss was measured from black-tailed prairie dogs (Cynomys ludovicianus) at eight air temperatures between 10 and 40°C, and over a broad range of humidities at each temperature. Evaporation increased, decreased, or remained constant below thermoneutrality, depending on humidity, and increased at higher temperatures indirectly with humidity. Evaporation was negatively related to humidity at different temperatures with a series of linear regressions that provided for statistical comparisons. Significantly different intercepts and slopes at different temperatures occurred for prairie dogs, and for deer mice (Peromyscus maniculatus) and house mice (Mus musculus) using published data. A general model, based on the equation for a straight line, was developed to relate evaporation to humidity; the intercept and slope were empirically derived mathematical functions of temperature. The model provided three-dimensional graphic responses for evaporation that showed different interactions between temperature and humidity for the three species.
Southern Railroad Leaders, 1865-1893: Identities and Ideologies

As the American South recovered from the Civil War, railroads and the businessmen who managed them were important ingredients in the process of economic change. But who were the railroad leaders of the first generation of the “New South” and what were their personal and corporate goals? What were the effects of their actions on the course of southern restoration? Sharply at odds with the usual “carpetbagger” demonology, Professor Klein suggests an alternative explanation and analysis.
Short photoperiod affects the responses of meadow voles to the top- and bottom-scent donors of an over-mark

Seasonally breeding animals oftentimes alter their social interactions as a result of the shift from a long-day to short-day photoperiod. When this occurs, behaviours and corresponding affiliations with conspecifics will change as well. Consequently, individuals may react differently towards signals made by conspecifics as a result of this seasonal shift. We examined the responses of short photoperiod (SP) male and female meadow voles to the over-marks of two opposite-sex conspecifics that were born and raised in the same or in a different photoperiod. We tested the hypothesis that seasonal differences exist in the responses of voles to the top- and bottom-scent donors of a same-sex over-mark. We predicted that SP voles would not spend more time investigating the mark of the top-scent donor than that of bottom-scent donor of an over-mark; a response that is different from that of long photoperiod (LP) meadow voles to the mark of the top- and bottom-scent donors of an over-mark. After exposure to various over-mark treatments, SP male subjects later spent more time investigating the mark of the SP female that provided the top-scent mark to that of the SP female that provided the bottom-scent mark and more time investigating the mark of the top-scent LP female than that of bottom-scent SP female, but they spent similar amounts of time investigating the mark of the top-scent SP female and that of the bottom-scent SP female. In contrast, SP females spent similar amounts of time investigating the mark of the top-scent LP male and that of the bottom-scent SP male, the mark of the top-scent SP male and that of the bottom-scent LP male, and the mark of the top-scent LP male and that of the bottom-scent LP male. The data provide mixed support for the hypothesis, indicating that sex differences exist in the response of SP meadow voles to the marks of the top- and bottom-scent donors of an over-mark. This suggests that the responses of voles to over-marks of donors from the same photoperiods vary seasonally for females but not for males. The sex differences in the response of voles to overmarks may depend on their reproductive state as well as the reproductive state of the donors and the position of the donor's scent marks in the over-mark.
Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Abstract This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively ( r > 0.522, P r P P r > 0.515, P r P
Estradiol esters can replace 17β-estradiol in the stimulation of DNA and esterase synthesis by MCF-7 cells: A possible role for the estrogen-sensitive MCF-7 cell esterase

Abstract In this communication we extend our earlier observations on estrogen-sensitive carboxyl esterases in MCF-7 human breast cancer cells able to hydrolyze esters of estradiol. Using either estradiol acetate or p-nitrophenyl hexanoate as substrates, esterase activity was found to increase 2–3-fold in MCF-7 cells maintained in the presence of 10−8 M estradiol. Following sucrose density centrifugation, over 85% of total esterase activity was found in the cytoplasmic fraction. No esterase activity was found in spent media from growing cells. By size exclusion chromatography, estradiol acetate esterase activity exhibited a mol. wt of 45–50 kDa. Attempts to demonstrate incorporation of [3H]estradiol into estradiol fatty acid esters by the above MCF-7 cell line (203P) were unsuccessful, although, such incorporation could be demonstrated in two other MCF-7 cell sublines. Incubation of the 203P cells with 10 nM [3H]estradiol in the presence of 0.5 mM radioinert estradiol acetate resulted in the incorporation of 35 ± 12% of the label into the estradiol acetate in 10 min. In the absence of radioinert estradiol acetate, no incorporation was observed. When MCF-7 cells were incubated with [3H]estradiol in the presence of a large excess of radioinert estradiol valerate, label was found only in estradiol valerate. Similarly, when the incubation was carried out in the presence of a mixture of radioinert estradiol acetate and estradiol valerate, label was incorporated into both esters. We conclude that the apparent formation of radiolabeled estradiol esters by MCF-7 cells incubated under the above conditions, results at least in part, from an esterase-catalyzed exchange reaction. Under conditions where no ester hydrolysis could be detected in the absence of cells, valerate and stearate esters of estradiol were found to be as effective as unesterified estradiol in stimulating esterase synthesis and the incorporation of [3H]thymidine into DNA. These results are consistent with a model in which an intracellular esterase in MCF-7 cells can generate estradiol from an exogenous lipoidal steroid and elicit an estrogen response.
Parents' reactions and recommendations after diagnosis and hearing aid fitting.

This study was designed to explore parent reactions to the early stages of audiologic assessment and intervention. A total of 213 parents whose children were under the age of 6 years returned a mail survey. Respondents from 45 states participated. Parents were asked to (1) report the approximate age of diagnosis and hearing aid fitting; (2) comment on reasons for any delays encountered from diagnosis to fitting; and (3) respond to questions concerning their reactions to the initial fitting of amplification. The median age of identification was earlier than some previous investigations; however, substantial delays occurred between diagnosis and hearing aid fitting. Reasons for delay included the need for further audiologic evaluation, problems obtaining return appointments, illness of the child, and difficulties obtaining adequate earmolds. Parent reactions to hearing aids, once fitted, included concerns about appearance and questions about maintenance and use, but attitudes regarding hearing aids and thei...
Application of a Latin Square Change-Over Design to Dairy Cattle Grazing Experiments

Summary A Latin square change-over design was applied to dairy cattle grazing experiments. Experimental procedure is given. Analysis of the data is presented, including the fitting of constants for nonorthogonal variables. The design gave substantial gains in efficiency over single grouping or complete randomization but required more work to analyze the data and may have led to some confounding of effects of pasture mixtures with effects of other variables.
A no-buff technique to produce surfaces that induce alignment in liquid crystals

Alignment layers for liquid crystal cells were prepared by directional deposition of high molecular weight rigid-rod ionomers on glass and indium–tin–oxide substrates. Several deposition techniques were developed and tested. Material type, concentration, temperature, and application technique were systematically varied and the resultant alignment of the liquid crystals studied. Three different methods of applying the alignment layer were investigated: directional spray deposition, brushing, and directional deposition using a squeegee (doctor bar). The application temperature ranged from 30 to 80°C. The best results were obtained using a squeegee to perform directional deposition at temperature of less than 60°C. The alignment layers obtained in this way are robust, exhibit excellent alignment, and have pretilt angles of a few degrees.
NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains

The mechanisms underlying the coupling of type I collagen and matrix metalloproteinase (MMP) expression to cell structure and adhesion are poorly understood. We propose that nuclear matrix architectural transcription factors link cell structure and transcription via their association with nuclear matrix subdomains and by their capacity for altering promoter geometry. NP/NMP4 are nuclear matrix proteins that contain from five to eight Cys2His2 zinc fingers. Some NP/NMP4 isoforms bind to the rat type I collagen α1(I) polypeptide chain promoter in the manner of architectural transcription factors and alter basal transcription in osteoblast-like cells (Thunyakitpisal et al. in review). Certain isoforms of NP/NMP4 are identical to CIZ, Cas-interacting zinc finger protein, a nucleocytoplasmic shuttling protein that associates with focal adhesions and regulates MMP expression [Nakamoto et al. (2000): Mol Cell Biol 20:1649–1658]. To better understand the role of subnuclear architecture in collagen and MMP expression, we mapped the osteoblast nuclear distribution of NP/NMP4 proteins and identified the functional motifs necessary for nuclear localization and nuclear matrix targeting. Immunofluorescence microscopy was used to determine the cellular and subnuclear distribution of native NP/NMP4 proteins and green fluorescent protein (GFP)-NP/NMP4 fusion proteins in osteoblast-like cells. All GFP-NP/NMP4 fusion proteins localized to the nucleus, but accumulated in distinct nuclear matrix subdomains. The zinc finger domain was necessary and sufficient for nuclear import and matrix targeting. We conclude that the arrangement of the NP/NMP4 zinc fingers largely determines the subnuclear location of these isoforms. J. Cell. Biochem. 79:506–517, 2000. © 2000 Wiley-Liss, Inc.
The Identification of Major Infrared Absorbing Components of Human Urine

The infrared spectra of normal and diabetic human urine were studied and the absorption peaks identified The major infrared absorbing components of normal urine were found to be urea, mono-and di-hydrogen phosphates, and sulfates Glucose absorption peaks were readily identified in the diabetic urine spectra "Synthetic" urine solutions were prepared which yielded spectra matching those of human urine samples. This infrared technique is shown to provide a basis for a simple and rapid analysis of these major components of urine.
Example of an interpolation domain

Abstract Cahen et al. (J. Algebra 225 (2000) 794), have defined a domain to be an interpolation domain if, essentially, Lagrange interpolation can be done using integer-valued polynomials. They prove results indicating that in some cases every overring of an interpolation domain is again an interpolation domain, and they ask whether the statement holds in general. In the present note, we provide a counterexample to the general statement.
The "anhedonia paradox" in schizophrenia: insights from affective neuroscience.

Emotional disturbances, and particularly anhedonia (the loss of pleasure), occupy a prominent place in conceptualizations of schizophrenia, including early writings by Bleuler and Kraepelin. Fitting these conceptualizations, hundreds of studies using clinical measures or self-report trait questionnaires have linked schizophrenia to reduced experiences of pleasure (1). In stark contrast to these findings, laboratory studies have shown that, when exposed to pleasant stimuli across modalities (e.g., visual, auditory, gustatory), individuals with schizophrenia typically report hedonic responses similar to those of controls (2,3). These sets of findings are puzzling: why do individuals with schizophrenia typically not endorse statements such as “Beautiful scenery has been a great delight to me” but do report normative emotional experiences when exposed to pictures of attractive scenery (4)? Are in-the-moment experiences of pleasure preserved in schizophrenia, and if so, how can we reconcile these findings with clinical observations of anhedonia? Finally, can neuroimaging provide any clues that could illuminate the “anhedonia paradox” in schizophrenia?
TWO-NUCLEON CORRELATION FUNCTION AND FINAL-STATE INTERACTIONS

Abstract A triple coincidence experiment in which an inelastically scattered projectile sends off two closely correlated, high-momentum nucleons from a nucleus is proposed as a direct means of measuring the short range nuclear pair correlation function. An analysis based on potential theory shows that the Fourier transform of the correlation function is amenable to the relative momentum spectrum of the ejected nucleon pair. Final state interactions modify the low momentum components of this spectrum. However, marked characteristics of the short range effects that are not present in a pure independent particle model are expected to persist. These characteristics manifest themselves in the high Fourier components of the relative momentum spectrum.
Generation of antibody and development of an enzyme-linked immunosorbant assay for the feed additive roxarsone

Abstract Roxarsone is used in the poultry and swine industries as a feed additive to treat coccidiosis and other intestinal disorders as well as to improve feed efficiencies and weight gain. 3-Amino-4-hydroxyphenylarsonic acid (AHPA) was conjugated with keyhole limpet hemocyanin in the presence of bis-sulfosuccinimidyl-suberate for the immunogen in rabbits. The antibody has minor cross-reactivity towards 2-aminophenylarsonic acid (7.3%, n=3), arsanilic acid (5.3%, n=3), AHPA (4%, n=3), and phenylarsonic acid (3%, n=3). The mean IC50s for PBST, muscle 1:10, and muscle 1:20 were 11.7±1.50, 13.1±2.53 and 12.0±2.45 ng/mL (n=6). Using a standard curve prepared in chicken muscle extract and diluted with PBST at 1:20, muscle samples spiked with roxarsone at 2.5, 5, 10 and 25 ng/mL had recoveries of 117%, 98%, 80% and 65% having coefficients of variation of 36, 9.2, 10.2 and 11.5 respectively (n=6).
Autoradiographic localization of ornithine decar☐ylase in cerebellar cortex of the developing rat with [3H]α-difluoromethylornithine

Ornithine decarboxylase was autoradiographically localized in the developing rat cerebellar cortex after intracisternal injection of [3H]alpha-difluoromethylornithine, a specific, irreversible inhibitor of the enzyme. At nine days of age, when cerebellar ornithine decarboxylase activity is maximal, autoradiographic grains were distributed over all layers of the cerebellar cortex and throughout the brain stem. Within cerebellar folia, the highest grain density was associated with the molecular layer, whereas the internal and external granule cell layers were less densely labeled. Enhancement of ornithine decarboxylase activity by intracisternally-administered isoproterenol correspondingly increased the autoradiographic grain density over each layer. Thus much of the polyamine biosynthetic capability needed to support neuronal and/or glial differentiation appears to be associated with the developing cell processes. The combination of [3H]alpha-difluoromethylornithine autoradiography with localized injection techniques provides a potentially powerful tool for the study of the involvement of polyamine biosynthesis in brain development.
Incidence and predictors of bowel obstruction in elderly patients with stage IV colon cancer: a population-based cohort study.

Importance Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking. Objective To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer. Design and Setting Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005. Patients Patients 65 years or older with stage IV colon cancer (n = 12 553). Main Outcomes and Measures Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features. Results We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07-1.40]), high tumor grade (1.34 [1.16-1.55]), mucinous histological type (1.27 [1.08-1.50]), and nodal stage N2 (1.52 [1.26-1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47-2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72-0.98]). Conclusions and Relevance In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and outcomes in this serious, common complication.
The Aspiration Hazard and Toxicity of a Homologous Series of Alcohols

(1966). The Aspiration Hazard and Toxicity of a Homologous Series of Alcohols. Archives of Environmental Health: An International Journal: Vol. 13, No. 4, pp. 457-461.
Application of the pople-santry-segal CNDO method to the cyclopropylcarbinyl and cyclobutyl cation and to bicyclobutane

Abstract The CNDO method has been applied to the cyclopropylcarbinyl and cyclobutyl cations, and has given results which are in very good accord with experimental data. A cross-ring interaction is calculated to be of importance with cyclobutyl derivatives, and agrees with the large difference in rate observed with equatorial and axial leaving groups. Some properties of bicyclobutane as well as the relative energies for some models of the activated complex for the thermal rearrangement of bicyclobutane have also been calculated and compared with experimental data. The CNDO method appears to have considerable promise in the investigation of the organic chemical phenomena.
Direct and mediational links between parental bonds and neglect, antisocial personality, reasons for drinking, alcohol use, and alcohol problems.

Objective:The self-medication model suggests that some individuals may use alcohol as a means to cope with their negative experiences. Antisocial personality reflects a lack of concern for others and is often linked to alcohol use disorders. The aim of this investigation was to examine potential parental influences to both pathological reasons for drinking and antisocial personality as pathways to alcohol use and problems. Method:Direct and indirect links between parental bond (care, rejection, overprotection, autonomy, and neglect) and antisocial personality, pathological reasons for drinking, alcohol use, and alcohol-related problems were investigated. A two-group SEM path model with college students (164 female, 240 male) was examined. Results:In general, the overall patterns among male and female respondents were distinct. Among women, perceptions of having a caring mother lowered the likelihood of having antisocial tendencies, and perceptions of being rejected by one's father were directly linked to ...
How Salmonella became a pathogen

In many pathogens, virulence can be conferred by a single region of the genome. In contrast, the facultative intracellular lifestyle of Salmonella demands a large number of genes distributed around the chromosome. The evolution of Salmonella has been marked by the acquisition of several 'pathogenicity islands', each contributing to the unique virulence properties of this microorganism.
Effect of β-Alkylthioethyl Substitution in 1,3-Dithianes: Quasianchimeric Assistance in Photoinduced Electron Transfer?

Nanosecond laser flash photolysis (LFP) experiments show that the rates of ET quenching of triplet benzophenone by 2-alkyldithianes significantly decrease with bulkier substitution. Introduction of sulfur at the β-position of the flexible alkyl chain reverses this trend, whereas such substitution at the α-position has negligible effect. This is rationalized in terms of the three electron two center bonds, favorable due to the formation of five-membered cyclic radical cations in the case of β-substitution, which is supported by DFT computations.
Psychosocial correlates of dyslexia across the life span

This series of four studies examined the psychosocial functioning of children, adolescents, and adults with developmental dyslexia. One sample of nonreferred dyslexic and nondyslexic men, and three different samples of dyslexic and normally achieving control children and adolescents were studied. The child samples included both clinic-referred and nonreferred populations, and sibling and nonsibling control designs. Variables assessed included depressive and ADHD symptomatology, self-concept and, in the adult sample, socioeconomic status and other life adjustment variables.We found that, across three samples, children and adolescents report lower global self-worth and lower perceived competence in scholastic domains, more depressive symptomatology, and (both by self- and parent report) more ADHD symptomatology than normal achievers. In contrast, adult dyslexic men, while also perceiving themselves as less intelligent than their peers, reporting more generalized psychological distress, and showing less social mobility, were nonetheless comparable to their peers in terms of global self-worth, depressive symptomatology, and other indices of adult adjustment and satisfaction. Results are discussed in terms of a developmental “niche-finding” model, in which the shift into adult life may foster more constructive experiences and internal processes.
Laparoscopic donor nephrectomy 1997 to 2003: lessons learned with 500 cases at a single institution.

Background Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open nephrectomy that has several potential advantages. However, there have been few large series reports describing the complications of LDN and the details of their management. Methods We performed a retrospective review of 500 LDNs performed at our center between October 1997 and September 2003. We evaluated preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. A modification of the Clavien classification was developed and used to grade the severity of all complications. Results The overall rate of intraoperative complications was 2.8%. There were 9 open conversions (1.8%), of which 6 were in the first 100 cases. Six of the 9 open conversions were for management of complications; 3 were elective. Seven renovascular incidents (1.4%) all required open conversion except one. The overall rate of postoperative complications was 3.4%. Thirty of 500 patients in our LDN series experienced an intraoperative or procedure-related complication (6.0%). When graded by severity, 18 of 31 (58.1%) of all complications were grade 1, 11 of 31 (35.4%) grade 2, and 2 of 31 (6.5%) grade 3. Only 1 recipient experienced delayed graft function, and only 1 recipient had a urologic complication. Conclusions Our series supports the safety and efficacy of LDN with very low intraoperative complication and conversion rates. Most of the intraoperative complications can be managed laparoscopically. Readmissions are extremely rare (1.5%). Aberrant vascular anatomy and obesity are not contraindications to LDN, but they require experience. With careful surgical technique, delayed graft function and urologic complications in recipients can be avoided. A graded classification scheme for reporting complications of donor nephrectomy might be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.
Predicting short circuit power from timing models

Power dissipation is becoming a major show stopper for integrated circuit design especially in the server and pervasive computing technologies. Careful consideration of power requirements is expected to bring major changes in the way we design and analyze integrated circuit performance. This paper proposes a practical methodology to evaluate the short-circuit power of static CMOS gates via effective use of timing information from timing analysis. We introduce three methods to estimate short-circuit power of a static CMOS circuit without requiring explicit circuit simulation. Our proposed methodology offers practical advantages over previous approaches, which heavily rely on simple special device models. Proposed approach is experimented with an extensive set of benchmark examples and several device models and found very accurate.
Polarization and effective Mueller matrix for multiple scattering of light by nonspherical ice crystals

We investigated the errors associated with the scalar approximation (i.e., an approach that neglects polarization effects) for simulating the intensity of the radiation reflected by an ice cloud. In a case for an optical thickness of τ=1, the relative errors of the scalar approximation are typically between -0.5% and 0.1%. We also investigated the effect of the order of scattering on the degree of linear polarization. It is shown that substantial errors can be introduced by the first-order scattering approximation, and thus, the multiple-scattering effect is essential to an accurate simulation of the polarization configuration of a radiation field. Furthermore, we investigate the effective Mueller matrix pertaining to multiple scattering of light by ice clouds. The effective Mueller matrix is a 4×4 matrix that relates the incident and scattered Stokes parameters. This matrix implicitly contains the effects of all orders of scattering and absorbing events in the entire radiation transfer process. The sensitivity of the (2,1) and (3,1) elements of the effective Mueller matrix to ice crystal shape and size indicates that polarimetric information may be useful for inferring the microphysical properties of ice crystals within ice clouds.
HIV-1 infection inhibits cytokine production in human thymic macrophages.

Objective The thymus serves as a critical site of T-lymphocyte ontogeny and selection. Thymic infection by HIV-1 is known to disrupt thymocyte maturation by both direct and indirect means; however, the mechanism behind these effects remains poorly defined. Macrophages represent one of the most important peripheral targets of HIV-1 infection, are resident in the thymic stroma, and play a central role in thymocyte maturation. Materials and Methods Studies presented here define three primary features and outcomes of thymic macrophages (TM) and HIV-1 infection: (1) The distinctive TM phenotype (surface markers and cytokine production measured by immunofluorescence, fluorescence-activated cell sorting, and reverse transcriptase polymerase chain reaction) relative to macrophages from other sources (blood [monocyte-derived macrophages] and bone marrow); (2) infection of TM by different HIV-1 subtypes (X4, R5, and X4/R5) measured by enzyme-linked immunosorbent assay and polymerase chain reaction; and (3) consequences of HIV-1 infection on cytokine production by TM measured by reverse transcriptase polymerase chain reaction. Results The results demonstrate that TM display a distinctive phenotype of HIV-1 receptors (CD4 lo , CXCR4 lo , CCR5 med , CCR3 hi ), chemokine production (macrophage inflammatory protein−1α + ; regulated on activation, normal T expressed and secreted + ; macrophage inflammatory protein−1b − ; stromal cell−derived factor -1 − ); and cytokine production (tumor necrosis factor−α + , interleukin-8 + , macrophage colony-stimulating factor + , interleukin-6 − ) relative to either monocyte-derived macrophages or bone marrow. TM were infected in vitro with R5 and X4/R5-tropic HIV-1 subtypes, and developed syncytia formation during long-term X4/R5 culture. In contrast, TM supported only transient replication of X4-tropic HIV-1. Lastly, infection of TM with HIV-1 abolished the production of all cytokines tested in long-term in vitro cultures. Conclusions Taken together, these results indicate that TM are a potential direct target of in situ HIV-1 infection, and that this infection may result in the disruption of macrophage functions that govern normal thymocyte maturation.
Euthanasia, Ethics and Public Policy: An Argument Against Legislation

(2003). Euthanasia, Ethics and Public Policy: An Argument Against Legislation. Journal of Legal Medicine: Vol. 24, No. 3, pp. 395-405.
Mucolytic enzyme systems. XVII. Purification of the nonspecific hyaluronidase inhibitor in human blood.

Summary Two principal methods were described for the purification of the nonspecific hyaluronidase inhibitor in blood. The first, which gave a purification of 60 times, involved precipitation of the inhibitor by protamine sulfate and selective extraction with acetate buffer (pH 5.2). The second, which gave a purification of 130 times, depended on initial precipitation at pH 5.4, followed by ethanol fractionation. With increasing purification, an increase in concentration of metachromatic material was found, suggesting that the inhibitor contains an acid polysaccharide, possibly heparin. Eighty-five per cent of the material in preparations of purified inhibitor in solution of 0.1 ionic strength and pH 8.6 (veronal buffer) migrated electrophoretically as a single component with a mobility of approximately 6.6×10 −5 cm. 2 /sec./v. The remaining material migrated at a slightly slower rate. The final purified inhibitor extract contained small amounts of prothrombin, thrombin, and caeruloplasmin. The former two were shown to have no effect on hyaluronidase inhibitor activity. A lack of parallelism between caeruloplasmin concentration, as determined by its blue color, and inhibitor activity has been demonstrated, but present evidence does not justify dismissal of the possibility that this substance is in some way related to inhibitor activity.
The molecular structure of B2O2(g), B2Ss(g), Al2O2(g) and a number of the aluminum family chalcogenides as determined from thermochemical considerations

Abstract The structures of B2O2(g), B2S2(g), Al2O2(g) and other aluminum family chalcogenides of the M2X2 species (X  S, Se, Te), have been investigated on the basis of thermochemical considerations. Contrary to previous postulations, the preponderance of thermochemical evidence suggest a bent M-X-M-X configuration for these gaseous species. The fundamental frequencies and free energy functions for B2O2(g) and Al2O2(g) are calculated and the atomization energy of Al2O2(g) is estimated to be less than 484 kcal mole−1.
Making tea in India: Chai, capitalism, culture

This essay examines the process by which tea, a plant and product introduced into the Indian subcontinent in the early 19th century as a colonial cash crop, became indigenized and popularized as chai, often regarded today as India’s ‘national drink’. This process mainly occurred during the 20th century and involved aggressive and innovative marketing by both British and Indian commercial interests, advances in the technology of processing Assam tea, and changes in social space and practice, especially in urban areas.
Chromatography of phenolic compounds on borate impregnated paper

Abstract 1. The influence of sodium phosphate (Na 2 HPO 4 ) and sodium borate (NaBO 3 ) on the ionization of phenols has been determined spectrophotometrically. Na 2 HPO 4 ionizes only strongly acidic phenolic hydroxyl groups whereas sodium borate ionizes most phenolic groups. Lower R F values on borate impregnated paper, therefore, are not necessarily due to the presence of ortho -dihydroxyl groups but may arise from ionization of individual hydroxyl groups. 2. Phenolic hydroxyl groups are not ionized by a mixture of boric acid—sodium acetate. Phenols containing ortho -dihydroxyl groupings may be detected chromatographically by their lower R F values on boric acid—sodium acetate impregnated paper as compared with plain paper.
Economies of scale in bus transit service in the USA: How does cost efficiency vary by agency size and level of contracting?

Abstract Past studies of economies of scale in transit have tended to treat the transit industry as a set of similar agencies that have the same cost structure, and have conducted an analysis for the entire range of agency size using a single regression function. This may have caused problems in the interpretation of analysis results because agencies of different sizes that may have different cost structures are treated as a homogeneous data set. In this paper, I examine the issues of economies of scale in the provision of fixed-route bus transit service in the USA, using level of contracting as a variable to classify agencies into three different size groups. In this analysis, using a significantly larger pooled data set (compared to previous studies) constructed from the National Transit Database of the US Federal Transit Administration from 1992 to 2000, I found that agencies with different levels of contracting exhibit very different relationships between cost per vehicle hour and agency size. Applying the observed range of agency size, I also found diseconomies of scale for all agency sizes with all levels of contracting, even when I utilized a quadratic function for the regression equation. While the analysis is limited since the model did not control for many other explanatory variables, the findings suggest that the level of contracting is possibly an important variable, among many attributes of transit systems, with which to classify agencies into different size groups, each of which has a different transit cost structure.