cssi/SciSciGPT-SciSciNet huggingface dataset:
The APPROACH trial: Assessing pain, patient-reported outcomes, and complementary and integrative health:

Electronic health record data can be used in multiple ways to facilitate real-world pragmatic studies. Electronic health record data can provide detailed information about utilization of treatment options to help identify appropriate comparison groups, access historical clinical characteristics of participants, and facilitate measuring longitudinal outcomes for the treatments being studied. An additional novel use of electronic health record data is to assess and understand referral pathways and other business practices that encourage or discourage patients from using different types of care. We describe an ongoing study utilizing access to real-time electronic health record data about changing patterns of complementary and integrative health services to demonstrate how electronic health record data can provide the foundation for a pragmatic study when randomization is not feasible. Conducting explanatory trials of the value of emerging therapies within a healthcare system poses ethical and pragmatic challenges, such as withholding access to specific services that are becoming widely available to patients. We describe how prospective examination of real-time electronic health record data can be used to construct and understand business practices as potential surrogates for direct randomization through an instrumental variables analytic approach. In this context, an example of a business practice is the internal hiring of acupuncturists who also provide yoga or Tai Chi classes and can offer these classes without additional cost compared to community acupuncturists. Here, the business practice of hiring internal acupuncturists is likely to encourage much higher rates of combined complementary and integrative health use compared to community referrals. We highlight the tradeoff in efficiency of this pragmatic approach and describe use of simulations to estimate the potential sample sizes needed for a variety of instrument strengths. While real-time monitoring of business practices from electronic health records provides insights into the validity of key independence assumptions associated with the instrumental variable approaches, we note that there may be some residual confounding by indication or selection bias and describe how alternative sources of electronic health record data can be used to assess the robustness of instrumental variable assumptions to address these challenges. Finally, we also highlight that while some clinical outcomes can be obtained directly from the electronic health record, such as longitudinal opioid utilization and pain intensity levels for the study of the value of complementary and integrative health, it is often critical to supplement clinical electronic health record-based measures with patient-reported outcomes. The experience of this example in evaluating complementary and integrative health demonstrates the use of electronic health record data in several novel ways that may be of use for designing future pragmatic trials.
Quantifying fascial tension in ventral hernia repair and component separation.

Excessive fascial tension is a major cause of ventral hernia recurrence. Although hernias are commonly characterized by area, the tension experienced by fascia is directly proportional to the surrounding tissue stiffness. We demonstrate an accurate and simple technique for intra-operative measurement of fascial closing tension and quantify the decrease in tension following Component Separation (CS). A tensiometer was created using a spring with a known recoil constant (k) and a surgical clamp. Using Hooke’s law (Force = kX; X = spring displacement), fascial tension was calculated. This method was first validated on a bench-top model and then applied to the anterior fascia of 4 fresh cadavers (8 hemi-abdomens) over a range of simulated hernia defect sizes. When fascia could no longer reach midline, CS was performed and measures repeated. Tissue stiffness was calculated by plotting defect size versus resulting tension. Fascial defects ranged from 1- to 18-cm wide with average midline closing tension prior to release 36.1 N (range 17–48) and 8.2 N (range 5–11) after CS, a mean 76% decrease (range 70%–85%). Mean R2 values between defect size and tension for the synthetic and cadaver models were 0.99 (p 0.95 (p < 0.01) for each hemi-abdomen, showing high precision and reproducibility. We have applied a cheap, simple, and precise method to sterilely assess fascial tension during herniorrhaphy and also quantified the decrease in tension following component separation. This technique may be rapidly translated into the operating room with minimal equipment to provide objective data critical for intraoperative decision-making.
Lead exposure and association with angiogenic factors and hypertensive disorders of pregnancy.

Abstract Objectives Lead exposure has been associated with hypertensive disorders of pregnancy. Angiogenic factors, including soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), are aberrant in preeclampsia, but have not been correlated with lead levels. We evaluated the association of lead exposure with angiogenic factors. Study design This cross sectional study utilized a convenience sample of singleton pregnancies ≥34 weeks’ gestation. Blood lead and angiogenic factors were measured before delivery; bone lead was measured postpartum. We dichotomized bone and blood lead into the top tertile versus the bottom tertiles and used log-binomial regression to assess the association between lead and a high angiogenic ratio. Main outcome measures The outcomes were high sFlt1 to PlGF ratio and development of a hypertensive disorder of pregnancy. Results We enrolled 102 participants, of whom 98 had at least one lead measurement and an angiogenic factor result. Median bone lead was 3.8 ug/g (2.0 – 6.6) and median blood lead was 0.2 ug/dL (0.2 – 0.4). Incidence of hypertensive disorders of pregnancy was 31%. When comparing the highest tertile of bone lead to the bottom two tertiles, there was no association with a high sFlt1/PlGF ratio or hypertensive disorders of pregnancy. Similar results were observed for the exposure of blood lead. Conclusions Lead exposure was not an important contributor to an elevated angiogenic factor ratio or hypertensive disorders of pregnancy in our U.S. population. However, lead exposure was modest in our population and we cannot exclude a relationship with hypertensive disorders of pregnancy.
Questioning Beliefs About Sexual Violence.

This editorial is appearing in the fifth and final issue Volume 21, published in 2020, of the Journal of Trauma & Dissociation (JTD). At the time of writing this editorial (in June 2020), the world...
Decline in kidney function over the course of adulthood and cognitive function in midlife

Objective To test the hypothesis that end-stage renal disease (ESRD) risk exposure during young adulthood is related to worse cognitive performance in midlife. Methods We included 2,604 participants from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) Study (mean age 35 years, 54% women, 45% Black). Estimated glomerular filtration rate and albumin-to-creatinine ratio were measured every 5 years at year (Y) 10 through Y30. At each visit, moderate/high risk of ESRD according to the Kidney Disease: Improving Global Outcomes guidelines (estimated glomerular filtration rate 30 mg/g) was defined, totaled over examinations, and categorized into 0 episodes, 1 episode, and >1 episodes of ESRD risk. At Y30, participants underwent global and multidomain cognitive assessment. We used analysis of covariance to assess the association of ESRD risk categories with cognitive function, controlling for cardiovascular risk factors. Results Over the course of 20 years, 427 participants (16% of the study population) had ≥1 episodes of ESRD risk exposure. Individuals with more risk episodes had lower composite cognitive function (p Conclusions In this population-based longitudinal study, we show that episodes of decline in kidney function over the young-adulthood course are associated with worse cognitive performance at midlife. Preserving kidney function in young age needs to be investigated as a potential strategy to preserve cognitive function in midlife.
Venous thromboembolism in multiple myeloma is associated with increased mortality.

Background In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known. Objectives To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans. Patients/methods A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments. Results The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. VTE occurred in 327 (7.4%) patients within 1 year and occurred at a median of 77 days (interquartile range, 37-153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6 months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18-2.37). Patients in the post-lenalidomide cohort with VTE had an increased mortality at both 6 months (aHR, 2.31; 95% CI, 1.52-3.51) and 12 months (aHR, 1.66; 95% CI, 1.19-2.33) after treatment initiation. Discussion This study shows that VTE during the first 6-12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.
A basic view of stochastic integration

Outlined is a bi-measure theoretic framework, including the fundamental Grothendieck inequality and factorization theorem of which self-contained proofs are presented. Stochastic integrators have a natural description in this framework.
Lightweight Software-Defined Error Correction for Memories

Reliability of the memory subsystem is a growing concern in computer architecture and system design. From on-chip embedded memories in Internet-of-Things (IoT) devices and on-chip caches to off-chip main memories, the memory subsystems have become the limiting factor in the overall reliability of computing systems. This is because they are primarily designed to maximize bit storage density; this makes memories particularly sensitive to manufacturing process variation, environmental operating conditions, and aging-induced wearout. This chapter of the book focuses on software managed techniques and novel error correction codes to opportunistically cope with memory errors whenever they occur for improved reliability at minimal cost.
L'exemple de la doctrine du Public trust aux Etats-Unis (The Public Trust Doctrine in the United States)

French Abstract: La doctrine du public trust (« PTD » en anglais) revet des dimensions historiques, de common law et constitutionnelles. Il decoule de l’ancienne notion selon laquelle le souverain detient certaines ressources naturelles et certains objets de la nature dans l’interet des generations actuelles et futures. Le principe de la propriete publique sous-tendant la doctrine du public trust peut etre degage du droit romain en passant par la Magna Carta pour parvenir au constitutionnalisme et a la jurisprudence actuelle. Les Romains ont codifie le droit de la propriete publique sur d'importantes ressources naturelles, comme l'explique Cesar Flavius Justinien en 533 apres JC, dans son ouvrage intitule Les Institutes de Justinien. Selon la loi naturelle, ce qui appartient a l’humanite en commun ce sont l’air, l’eau courante, la mer et les rivages. Ces principes ont ensuite ete integres a la Magna Charta en 1215. La doctrine connait finalement des retombees dans le droit ecrit et dans le droit coutumier. La common law anglaise a incorpore la tradition du public trust : Blackstone notait dans ses Commentaires : « Peu de choses doivent, malgre la consecration generale et le maintien de la propriete, rester en commun. . . Tels sont, parmi d’autres, les elements de la lumiere, de l'air et de l'eau. . . » English Abstract: The public-trust doctrine has historical, common law, and constitutional dimensions. It derives from the ancient notion that the sovereign holds certain natural resources and objects of nature in trust for the benefit of current and future generations. The principle of public ownership underlying the public trust doctrine can be traced from Roman Law through the Magna Carta to present-day constitutionalism and jurisprudence. The Romans codified the right of public ownership of important natural resources. Its principles were then incorporated into the Magna Chart in 1215. There are consequences to applying the doctrine. The idea that government holds resources in trust as fiduciary for present and future generations is controversial. The idea of public trust posits that some resources are subject to a perpetual trust that forecloses private exclusion rights, a jarring exception of uncertain dimensions. For environmentalists and preservationists who view private ownership as a source of the degradation of natural and historical resources, the public trust doctrine holds out the hope of salvation through what amounts to a judicially enforced inalienability rule that locks resources into public ownership. For those who view private property as the bulwark of the free enterprise system and constitutional liberty, the doctrine looms as a vague threat. The idea that public trust principles are enforceable is of profound import to other systems that have constitutionalized the public trust obligations. Constitutionalizing the doctrine ups the stakes.
Validation of enantioseparation and quantitation of an active metabolite of abrocitinib in human plasma.

Aims: A chiral HPLC–MS/MS method for quantitation of an active metabolite (M2) of abrocitinib was validated in human plasma. Methods: Protein precipitation extraction and normal phase LC with basel...
Some fear, more loathing? Threats and anxieties shaping protective gun ownership and gun carry in the U.S.

Given notable recent spikes in gun purchases in the U.S., we revisit the ‘fear and loathing’ hypothesis of firearm demand by (1) establishing how crime/victimization fears are shaped by broader eco...
A Consistency Analysis of the FEM: Application to Primitive and Wave Equations

Publisher Summary This chapter discusses application to primitive and wave equations. The order of consistency is a direct measure of the speed at which a model converges to the exact solution as the elements become finer. As such, consistency unveils the behavior of the numerical solution, in the limit, where the grid spacing is reduced to zero. Here, the analysis is restricted to the spatial semi-discretization. Often, one may establish the consistency of an approximation by proving that the local truncation error goes to zero in the limit as the grid size is reduced to zero. When the solution is well-behaved, the natural tool for such an analysis is the Taylor series expansion. Then, the approximation is expanded around a point. This leads to an expression containing the exact differential equation plus some error terms. Because, the order of consistency represents the rate at which the approximate solution approaches the exact solution as the mesh is refined, it is desirable to build models with a high order of consistency. For finite element method (FEM), a definition of consistency in a global sense is more appropriate.
Constraints on the depths of origin of peak rings on the Moon from Moon Mineralogy Mapper data

Abstract Important to understanding the process of basin formation on planetary bodies are constraints on the mineralogy and depths of origin of interior ring structures. We summarize previous analyses of the mineralogy of basin materials on the Moon and use hyperspectral image-cubes from the Chandrayaan-1’s Moon Mineralogy Mapper (M 3 ) to determine the mineralogy of interior rings in lunar protobasins and peak-ring basins. Nearly all peak rings outside of South Pole-Aitken (SPA) basin have extensive outcrops of pure anorthosite (⩾99% plagioclase) on the order of several square kilometers in areal dimensions. No obvious mantle components were identified. Outcrops spectrally dominated by pyroxene occur within SPA and other areas of thinner crust, such as regions within large ancient impact basins. In addition, many outcrops of candidate shocked plagioclase are observed within the same peak rings containing crystalline plagioclase. These spectral observations strongly support a crustal origin for peak rings on the Moon. Recent analyses of the Orientale basin and other lunar basins show that the inner rings of multi-ring basins are also anorthosite-rich and therefore derived from the lunar crust. To further constrain the depths of origin of materials forming peak rings, we compare the pre-impact crustal thickness for each basin with calculated vertical reference points, including: (1) maximum depth of excavation, which is the deepest point at which the crater will excavate material, (2) maximum depth of melting, which is deeper than the maximum depth of excavation and represents the maximum extent of impact-induced melting beneath the sub-impact point, and (3) maximum depth of the transient cavity, which is deepest part of the growing transient cavity that is formed of both excavated and displaced target material. Taken together with the observed mineralogy, the origin of peak-ring lithologies is constrained to stratigraphic levels near the maximum depth of excavation and likely shallower than this if the lower crust is comprised of noritic materials. The maximum depth of melting for peak-ring basins extends far into the mantle and is therefore not a valid proxy for estimating the depth of origin of materials forming peak rings. We find that our estimates of the depths of origin of peak-ring materials are consistent with current models of peak-ring formation, including predictions by hydrocode simulations and conceptual models emphasizing the role of interior impact melting and centro-symmetric collapse of the walls of the transient cavity. Firmer constraints on the depths of origin of peak rings on the Moon await an improved understanding of the crustal compositional structure, particularly that of the lower crust, and improved model predictions on the sampling depths and shock pressures experienced by uplifted peak-ring materials.
A Dynamic Test Method for Determining Transfer Function Coefficients for a Wall Specimen Using a Calibrated Hot Box

This paper describes a dynamic test method for determining transfer function coefficients (TFCs) for a wall specimen using a calibrated hot box (CHB). In this method, a wall specimen is installed between the climatic and metering chambers of a CHB. After a steady specimen heat transfer rate is attained, the air temperature in the climatic chamber is quickly ramped from an initial to a final temperature level in a linear manner. The final temperature level is maintained until a new steady specimen heat transfer rate is attained. The metering chamber is maintained at a steady indoor condition and is used as a calorimeter. The transient heat transfer rate at the inside surface of the wall specimen is determined at hourly time steps from an energy balance of the metering chamber. The poles and residues for a ramp analytical solution are derived by analyzing the measured specimen heat transfer response. The ramp analytical solution is subsequently used to form a triangular pulse from which TFCs are derived. The dynamic test method was conducted on a masonry wall. Empirical TFCs derived by the test method predicted the diurnal performance of the wall specimen with good agreement. In fact, the results predicted by empirical TFCs tracked the measured results as closely as an analytical model.
Tumors of the Central Nervous System

Brain tumors are the most common solid tumor in childhood. For example, there are approximately 2000 brain tumors diagnosed in children each year in the United States. The incidence of brain tumors is higher among males than females, and higher among white children than any other group. While the incidence of reported pediatric brain tumors has been increasing over the past few decades, this is probably because of improvements in diagnostic capabilities and reporting. Recent advances in diagnostic capabilities, aggressive surgical techniques, and multimodal therapy, including radiation and/or chemotherapy, have lead to longer survival and even cure of some classifications of pediatric brain tumors [17].
The Resurgence of Nativism in California? The Case of Proposition 187 and Illegal Immigration

Objective. We propose a new explanation for the appeal of Proposition 187 to California voters during the 1994 election and offer a new approach to studying the political context in which it gained voter approval. We argue that support for this proposition was an example of cyclical nativism, which was provoked primarily by California's economic downturn during the early 1990s. We also argue that the issue of illegal immigration was politicized during the election by the gubernatorial and senatorial candidates and that this endogeneity must be considered in any analysis of voter support for this proposition. Methods. To test this theory, we develop hypotheses about how nativist attitudes might be reflected in the voting behavior of specific groups based on economic perceptions, race, education, and area of residence. We test these hypotheses using Voter News Service (VNS) exitpoll data from the 1994 California election. We formulate a two-stage probit model to allow for the endogeneity. Results. We find support for our nativist theory and our endogeneity argument in the data. Voters who perceived the economy as poor, perceived themselves as threatened financially by illegal immigrants, or who lived closer to the immigrant source were more likely to support the measure. We also find that voters were relying on candidate endorsements, rather than on party identification or political ideology, in making their vote choice. Conclusions. These findings cause us to conclude, specifically, that nativism, fueled by economic conditions, was a salient factor leading many Californians to support Proposition 187 and, generally, that it is necessary to consider the effects of candidate endorsements on proposition voting.
Microhardness and Strain Field Characterization of Self-Reacting Friction Stir and Plug Welds of Dissimilar Aluminum Alloys

Friction stir welding (FSW) is a solid state welding process with potential advantages for aerospace and automotive industries dealing with light alloys. Self-reacting friction stir welding (SR-FSW) is one variation of the FSW process being developed at the National Aeronautics and Space Administration (NASA) for use in the fabrication of propellant tanks. Friction plug welding is used to seal the exit hole that remains in a circumferential SR-FSW. This work reports on material properties and strain patterns developed in a SR-FSW with a friction plug weld. Specifically, this study examines the behavior of a SR-FSW formed between an AA 2014-T6 plate on the advancing side and an AA 2219-T87 plate on the retreating side and a SR-FSW (AA 2014-T6 to AA 2219-T87) with a 2219-T87 plug weld. This study presents the results of a characterization of the micro-hardness, joint strength, and strain field characterization of SR-FSW and FPW joints tested at room temperature and cryogenic temperatures.
Biochemical studies on adenovirus multiplication: XIV. Macromolecule and enzyme synthesis in cells replicating oncogenic and nononcogenic human adenovirus

Abstract Exponentially growing KB cells infected with nononcogenic Ad 2 and oncogenic Ad 12 and 31 stopped dividing but continued to synthesize and accumulate protein, DNA, and RNA. The protein and DNA content per infected cell was twice that of uninfected cells at 36 hours after infection and the RNA content increased by 30–80% until 20 hours after infection and then sharply decreased to the initial levels. The rate of synthesis of protein, DNA, and RNA per cell increased initially and then decreased in cells infected with Ad 2, 12, and 31 as determined by pulse labeling with radioactive valine, thymidine, and uridine. Stimulation and inhibition occurred later after infection with oncogenic adenoviruses. Infected cells incorporated two to three times more valine, thymidine, and uridine into the acid-soluble fraction than did uninfected cells. The species of DNA synthesized at different times after infection were identified by density gradient centrifugation and by DNA-DNA hybridization. Host cell DNA synthesis was blocked completely at 24 to 36 hours after infection with Ad 2, 7, 12, 18, and 31. DNA polymerase activity did not increase after infection of exponentially growing KB cells with Ad 2, 12, or 31. Thymidine kinase activity was increased 2- to 3-fold in cells infected with Ad 12 and 31, but not in cells infected with Ad 2. Stimulation of enzyme activity in adenovirus-infected cells may depend upon the base level of enzyme activity in the uninfected host cell and the growth rate of the virus.
Differences in activities of murine retroviral long terminal repeats in cytotoxic T lymphocytes and T-lymphoma cells

Transcriptional activities of the long terminal repeats (LTRs) of various murine leukemia viruses were tested in the cytotoxic T-cell lines CTLL-1 and CTLL-2. In contrast to T-lymphoma cells, in which the LTRs of T-lymphomagenic virus SL3-3 and Moloney murine leukemia virus are more active than those of other viruses, transcriptional activity in these mature, interleukin-2-dependent cells is not correlated with the specificity of viral leukemogenicity. Several approaches were used to investigate the molecular basis for LTR activity differences in lymphoma cells and mature cytotoxic T cells. Deletion analysis of the Moloney virus LTR showed that the direct repeats associated with enhancer activity have, at most, a slight effect on expression in CTLL-1 cells, whereas they stimulate expression six- to eightfold in T-lymphoma cells. This suggests that the mature T-cell line lacks one or more factors present in T-lymphoma cells that function to augment transcription from the Moloney murine leukemia virus LTR. We also used recombinant viral LTRs to investigate the role of the enhancer core element of SL3-3 in CTLL-1 and CTLL-2 cells. A one-base-pair difference between the core sequences of SL3-3 and nonleukemogenic Akv virus, which is important for SL3-3 activity in T-lymphoma cells, had no effect in these cells. The inability to distinguish the single-base-pair difference in expression assays was correlated with the absence of binding of a cellular factor, S-CBF, to the SL3-3 enhancer core in extracts of CTLL-1 and CTLL-2 nuclei. These studies may have implications for identification of the target cells for viral leukemogenesis, as well as for tracing of changes in the transcriptional machinery during T-lymphocyte differentiation.
Catalysis by Supported Size-Selected Clusters

The use of size-selected metal clusters as model catalysts opens up many exciting new possibilities for the study of size-dependent catalysis. By supporting these size-selected clusters on planar thin-film or single-crystal metal oxide substrates, a variety of analysis techniques can be employed to examine them in detail in an effort to understand how and why these clusters exhibit unique reactivity. In this review, we focus on examples involving CO oxidation by gold clusters, NO reduction and the cycloisomerization of acetylene with Pd clusters, and hydrazine decomposition over Ir clusters. We conclude with some thoughts about in situ reaction probes and the potential of atom-by-atom design of bimetallic clusters with regard to size and composition.
Pressure Swing Reforming: A novel process to improve cost an efficiency of CO2 capture in power generation

Abstract We present a novel method of hydrogen production - applicable to gaseous and distillate fuels - that integrates with a gas turbine and has the potential to reduce the cost and energy required for CO 2 capture. The Pressure Swing Reformer (PSR) process yields syngas at high efficiency and with the compactness of an autothermal reformer. PSR is a cyclic, reverse-flow reactor that alternates combustion steps to heat the catalyst bed with reforming steps that cool the bed. During these steps the center of the catalyst bed remains at temperatures approaching 1200 ∘ C, enabling rapid and high conversion. Heat exchange within the packed-bed results in relatively cool products, resulting in high efficiency. The debits of conventional hydrogen manufacture, such as air separation or high-temperature furnaces, are completely eliminated. As applied to CO 2 capture, PSR’s syngas product is shifted and separated to yield hydrogen and a sequesterable CO 2 stream. The hydrogen is used to fuel a gas turbine for power generation, and is also used to fuel the PSR. The power turbine is further integrated by borrowing compressed air from the turbine to use as a combustion source within the PSR. Recovering CO 2 from high pressure syngas can reduce separation cost, just as in IGCC. But unlike IGCC, PSR is a low-cost reactor system that uses air at the conditions provided by the GT compressor and returns air at conditions appropriate for the expander. Integrated as such, the PSR enables lower cost production of power with CO 2 capture.
Recent hypotheses regarding the phosphatidylinositol effect.

Abstract In 1975, Michell first proposed that activation of phosphatidylinositol turnover provided a direct link between surface receptors and membrane Ca gates. Subsequently, a number of laboratories have begun to re-investigate this phenomenon first described by Hokin and Hokin some twenty years earlier. As would be expected, some new hypothesis have emerged, most being extensions or revisions of Michell's original concept. Despite difficulties in obtaining direct proof, indirect evidence suggests that the plasma membrane is the primary locus of receptor-activated phosphatidylinositol turnover, at least for phosphatidylinositol breakdown and phosphatidic acid synthesis. The presence or absence of Na + can markedly affect labelling of phosphatidylinositol by radioactive precursors but there is no compelling evidence that the initial events are mediated by Na + . Prostaglandins are apparently formed in some tissues on receptor activation, but in most instances the evidence suggests that these compounds are not obligatory intermediates in tissues that show the phosphatidylinositol effect. Several laboratories have obtained evidence that phosphatidic acid newly synthesized following phosphatidylinositol breakdown, may function as an endogenous Ca ionophore under neurohumoral control.
The global distribution of total ozone: TOMS satellite measurements

The general behavior of total ozone by season and latitude was known before 1930 through the pioneering observations by Dobson. The ozone record at Oxford and other European stations was dominated by an annual cycle and by irregular short term fluctuations. The amplitude and phase of the annual cycle were determined at representative latitudes in both hemispheres. However, the short term variations appeared to be meteorological origin, although the specific cause could not be identified. Data from the Total Ozone Mapping Spectrometer (TOMS) on the Nimbus 7 spacecraft, with global coverage at an average spatial resolution of 66 km, can now be used to completely map the total ozone field. These maps demonstrate that troughs and ridges in the upper troposphere are responsible for the large, short term ozone variations found at middle latitudes, while in the tropics, the steady, low ozone levels show broad scale structure associated with the Hadley circulation.
Stereospecificity for the zinc borohydride reduction of alpha-aryloxy-beta-hydroxy ketones

Abstract Several lignin model precursors have been submitted to zinc borohydride reductions and their resultant stereochemistries determined by NMR spectroscopy. Benzoyl carbonyls of α-aryloxy-β-hydroxy systems were reduced without significant stereoselectivity to produce both threo and erythro isomers. However, protection of the β-hydroxyl with either an acyl, alkyl, or silyl group and subsequent reduction gave erythzro-specificities of up to 97%. A mechanism where competition for zinc cation complexation between the β-hydroxyl and the α-aryloxy substituent is invoked to explain the observed results. Protection of the β-hydroxyl prevents its complexation with the zinc cation; complexation occurs solely with the α-aryloxy substituent, affording the erythro-isomers.
Estimates of the cost of equity for public utilities, 1961–1976

Abstract Using a simple version of the dividend cash flow (DCF) model of stock valuation, the cost of equity for public utilities is often inferred to be equal to the sum of the dividend yield and the expected rate of growth in dividends. Witnesses who employ this approach generally extrapolate past growth patterns into the future and then assume that investors expect these trends to continue; no effort is made to actually assess the expectations of investors. This approach to estimating the cost of equity for public utilities is criticized for the failure to develop testable hypotheses as an inferential basis for testing the statistical reliability of estimates of the cost of equity. This article demonstrates an alternative to the traditional approach, based on the premise that reliable estimates of the cost of equity are derived only within a methodological framework that produces testable hypotheses. The Gordon model of share valuation is formulated in such a way as to show that there is a systematic and predictable relationship between the ratio of market price to book value of common stock and a firm's normal or expected return on equity. This relationship suggests an econometric model that not only tests the Gordon model of share valuation but produces at the same time, inferences concerning the cost of equity. Using this approach, year-end estimates of the cost of equity for electric utilities are determined for the 16-yr period from 1961 to 1976.
Augmentation of human and rat lenticular glutathione in vitro by prodrugs of γ-L-glutamyl-L-cysteine

A marked age-related decrease in glutathione (GSH) levels as well as depression of gamma-glutamylcysteine synthetase activity are factors that are believed to render the aged lens more susceptible to oxidative stress and, therefore, to cataractogenesis. Providing gamma-L-glutamyl-L-cysteine, the dipeptide precursor of GSH, would effectively bypass the compromised first step in its biosynthesis and should protect the lens from GSH depletion. Accordingly, some bioreversible sulfhydryl-, amino-, and C-terminal carboxyl-protected prodrug forms of this dipeptide were prepared. Sulfhydryl protection was in the form of an acetyl thioester, while the carboxyl group was protected as the ethyl ester. These prodrugs were evaluated for their GSH-enhancing activity in cultured human and rat lenses in vitro using an assay that measured the incorporation of [14C]glycine into lens GSH. Ethyl S-acetyl-gamma-L-glutamyl-L-cysteinate (2) raised GSH levels in human lenses by 25% and in rat lenses by >150%. These data suggest that 2 may have potential as an anticataract agent since ethyl gamma-L-glutamyl-L-cysteinate (1a), the des-S-acetyl analog of 2, had been shown (by others) to protect against experimental rodent cataracts. GSH augmentation by 1a was 2% in human lenses and 25% in rat lenses, considerably less than that shown by 2.
Hepatic-Specific Disruption of SIRT6 in Mice Results in Fatty Liver Formation Due to Enhanced Glycolysis and Triglyceride Synthesis

Under various conditions, mammals have the ability to maintain serum glucose concentration within a narrow range. SIRT1 plays an important role in regulating gluconeogenesis and fat metabolism; however, the underlying mechanisms remain elusive. Here, we show that SIRT1 forms a complex with FOXO3a and NRF1 on the SIRT6 promoter and positively regulates expression of SIRT6, which, in turn, negatively regulates glycolysis, triglyceride synthesis, and fat metabolism by deacetylating histone H3 lysine 9 in the promoter of many genes involved in these processes. Liver-specific deletion of SIRT6 in mice causes profound alterations in gene expression, leading to increased glycolysis, triglyceride synthesis, reduced beta oxidation, and fatty liver formation. Human fatty liver samples exhibited significantly lower levels of SIRT6 than did normal controls. Thus, SIRT6 plays a critical role in fat metabolism and may serve as a therapeutic target for treating fatty liver disease, the most common cause of liver dysfunction in humans.
Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors

We have recently identified several novel ATP-independent inhibitors that target the extracellular signal-regulated kinase-2 (ERK2) protein and inhibit substrate phosphorylation. To further characterize these compounds, we describe the use of C. elegans as a model organism. C. elegans is recognized as a versatile and cost effective model for use in drug development. These studies take advantage of the well characterized process of vulva development and egg laying, which requires MPK-1, the homolog to human ERK2. It is shown that treatment of C. elegans eggs or larvae prior to vulva formation with a previously identified lead compound (76) caused up to 50% reduction in the number of eggs produced from the adult worm. In contrast, compound 76 had no effect on egg laying in young adult or adult worms with fully formed vulva. The reduction in egg laying by the test compound was not due to effects on C. elegans life span, general toxicity, or non-specific stress. However, compound 76 did show selective inhibition of phosphorylation of LIN-1, a MPK-1 substrate essential for vulva precursor cell formation. Moreover, compound 76 inhibited cell fusion necessary for vulva maturation and reduced the multivulva phenotype in LET-60 (Ras) mutant worms that have constitutive activation of MPK-1. These findings support the use of C. elegans as a model organism to evaluate the selectivity and specificity of novel ERK targeted compounds.
Comparison of testicular volume differential calculations in adolescents with varicoceles.

Abstract Purpose We aimed to develop a conversion formula between different calculations for testicular volume asymmetry. Materials and methods Male adolescents with varicoceles who underwent scrotal ultrasound were studied. Two formulas were analyzed: (1) testicular volume differential, TVDiff = (RTV – LTV)/(TTV), and (2) atrophy index, AI = (RTV – LTV)/(RTV). RTV, LTV, and TTV represent the right, left, and total testicular volume. Through transformations and regression a conversion formula between the calculations was derived. Results Based on 248 ultrasounds, a clear relationship between the two formulas was demonstrated: AI = ln[(1.97 × TVDiff) + 1], (p Conclusions Differential testicular volumes can easily be converted from one formula to another with near-perfect accuracy. The formulas are essentially identical and interchangeable.
High-ductility magnesium–zinc–cerium extrusion alloys

A previous paper (Mishra et al., 2008 [1] ) showed that the ductility of extruded Mg–0.2% Ce alloy is higher than that of magnesium and other conventional magnesium alloys. However, the strength of the Mg–0.2% Ce alloy was low. This study shows that a small addition of zinc (about 2%) can significantly improve the strength of the Mg–0.2% Ce alloy. The results showed that Zn increased strength through solid solution strengthening, and the Ce addition increased the ductility by providing a random texture in the extrusion.
Comparative study of different pancreas transplantation modalities: Islet cell vs organ pancreas transplantation in pancreatectomized dogs

Abstract This report confirms the satisfactory results obtained with splenic autotransplantation of islet cells or organ pancreas transplantation. When the allotransplantation technique was utilized, the islet cells rejected significantly faster than the organ pancreas grafts. Rejection in the allotransplant model was correlated with high levels of glucose and amylase at the onset of this phenomenon in the organ graft group and only elevation of glucose in the islet cell group. A progressive increase of these levels was continued after the first rejection was established and this persisted until death. Our data in the dog appear to indicate that islet cell allotransplantation is not justified clinically until better methods to control rejection are introduced. However, islet cell autotransplantation appears to be a good technical advancement in cases with pancreatitis undergoing total or near total pancreatectomy. Organ pancreas transplantation appears to be a good technique for allotransplantation in virtue of our results observed in the dog that has been moderately immunosuppressed.
Structural analyses of gp45 sliding clamp interactions during assembly of the bacteriophage T4 DNA polymerase holoenzyme. III. The Gp43 DNA polymerase binds to the same face of the sliding clamp as the clamp loader.

In the preceding paper (Latham, G. J., Bacheller, D. J., Pietroni, P. , and von Hippel, P. H. (1997) J. Biol. Chem. 272, 31677-31684), we demonstrated that the T4 gp44/62-ATP clamp loader binds to the C-terminal face of the gp45 sliding clamp. Here we extend these results by exploring the structural relationship between the gp43 polymerase and the gp45 sliding clamp. Using fluorescence intensity and polarization techniques, as well as photo-cross-linking methods, we present evidence that gp43, like gp44/62, binds to the C-terminal face of gp45. In addition, we show that g43 binds to the gp45 clamp in two distinct interaction modes, depending on the presence or absence of template-primer DNA. When template-primer DNA is present, gp43 binds tightly to gp45 to form the highly processive DNA polymerase holoenzyme. Gp43 also binds to gp45 in the absence of template-primer DNA, but this interaction is more than 100 times weaker than gp43-gp45 binding on DNA. Specific interactions between gp43 and the C-terminal face of gp45 are maintained in both modes of binding. These results underscore the pivotal role of template-primer DNA in modulating the strength of protein-protein interactions during DNA synthesis and provide additional insight into the structural requirements of the replication process.
The Patient with Daily Headaches

The term “chronic daily headache” (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose a...
Outdoor air pollution in close proximity to a continuous point source

Abstract Data are lacking on human exposure to air pollutants occurring in ground-level outdoor environments within a few meters of point sources. To better understand outdoor exposure to tobacco smoke from cigarettes or cigars, and exposure to other types of outdoor point sources, we performed more than 100 controlled outdoor monitoring experiments on a backyard residential patio in which we released pure carbon monoxide (CO) as a tracer gas for continuous time periods lasting 0.5–2 h. The CO was emitted from a single outlet at a fixed per-experiment rate of 120–400 cc min−1 (∼140–450 mg min−1). We measured CO concentrations every 15 s at up to 36 points around the source along orthogonal axes. The CO sensors were positioned at standing or sitting breathing heights of 2–5 ft (up to 1.5 ft above and below the source) and at horizontal distances of 0.25–2 m. We simultaneously measured real-time air speed, wind direction, relative humidity, and temperature at single points on the patio. The ground-level air speeds on the patio were similar to those we measured during a survey of 26 outdoor patio locations in 5 nearby towns. The CO data exhibited a well-defined proximity effect similar to the indoor proximity effect reported in the literature. Average concentrations were approximately inversely proportional to distance. Average CO levels were approximately proportional to source strength, supporting generalization of our results to different source strengths. For example, we predict a cigarette smoker would cause average fine particle levels of approximately 70–110 μg m−3 at horizontal distances of 0.25–0.5 m. We also found that average CO concentrations rose significantly as average air speed decreased. We fit a multiplicative regression model to the empirical data that predicts outdoor concentrations as a function of source emission rate, source–receptor distance, air speed and wind direction. The model described the data reasonably well, accounting for ∼50% of the log-CO variability in 5-min CO concentrations.
Fluorescence-enhanced absorption and lifetime imaging

Near-IR biomedical optical imaging consists of imaging interior volumes on the basis of optical property contrast from measurement conducted at the air-tissue interface. However, the ability to optically image or detect diseased tissue volumes located deep within tissues depends upon the contrast provided by differences in absorption and scattering. The exogenous contrast offered by fluorescent contrast agents may be superior to that provided by nonfluorescing, light-absorbing compounds, when the optical measurement are conducted with frequency-domain techniques. However, the reconstruction of internal fluorescent properties of quantum efficiency and lifetime has been difficult, especially when the finite partitioning of fluorescent compounds takes place between normal and diseased tissues. Also, the correct absorption coefficient map is required for the successful reconstruction of lifetime. Herein we present a novel fluorescence-enhanced imaging algorithm for frequency-domain photon migration measurements imaging differs in that it utilizes measurements of generated fluorescent wave instead of scattered excitation wave. Using synthetic data sets, we demonstrate fluorescence-enhanced imaging using FDA approved fluorescent agent. Indocyanine Green. Our results show the fluorescence-enhanced imaging algorithm works well up to 10:1 dye uptake ratio, and it is relatively insensitive to measurement noise. In addition, we present the lifetime reconstruction with a modified fluorescence-enhanced imaging technique.
Synthesis of methyl 3-O-α-d-mannopyranosyl-α-d-talopyranoside and methyl 3-O-α-d-talopyranosyl-α-d-talopyranoside

Abstract Methyl 2- O -benzyl-3- O -(2,3,4,6-tetra- O -acetyl-α- d -mannopyranosyl)-α- d -mannopyranoside ( 4 ) and methyl 2- O -benzyl-3- O -α- d -mannopyranosyl-α- d -mannopyranoside ( 6 ) were prepared form a common intermediate, namely, methyl 2- O -benzyl-4,6- O -benzylidene-3- O -(2,3,4,6-tetra- O -acetyl-α- d -mannopyranosyl)-α- d -mannopyranoside. On treatment with tert -butylchlorodiphenylsilane, in N,N -dimethylformamide in the presence of imidazole, 4 and 6 afforded methyl 2- O -benzyl-6- O - tert -butyldiphenylsilyl-3- O -(2,3,4,6-tetra- O -acetyl-α- d -mannopyranosyl)-α- d -mannopyranoside ( 7 ), and methyl 2- O -benzyl-6- O - tert -butyldiphenylsilyl-3- O -(6- O - tert -butyldiphenylsilyl-α- d -mannopyranosyl)-α- d -mannopyranoside ( 8 ), respectively. Compound 8 was converted into its 2,3- O -isopropylidene derivative ( 9 ), and oxidation of 7 and 9 with pyridinium chlorochromate, and reduction of the resulting carbonyl intermediates gave methyl 2- O -benzyl-6- O - tert -butyldiphenylsilyl-3- O -(2,3,4,6-tetra- O -acetyl-α- d -mannopyranosyl)-α- d -talopyranoside and methyl 2- O -benzyl-6- O - tert -butyldiphenylsilyl-3- O -(6- O - tert -butyldiphenylsilyl-2,3- O -isopropylidene-α- d - talopyranosyl)-α- d -talopyranoside, respective. Removal of the protecting groups furnished the title disaccharides.