cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular therapeutic strategies targeting pancreatic cancer induced cachexia

Pancreatic cancer (PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies. Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta (TGF-β), myostatin and activin, IGF-1/PI3K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting. Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon gamma (INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.
A Blueprint for Systems Biology.

Featured Article: Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, et al. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 2001;292:929–34.4 By the mid-1990s, it was clear that we would soon be able to sequence the human genome and that this would enable many other types of molecular measurements in cells and tissues. Less apparent was how these different molecular technologies and their data should be integrated to map biological structure and understand function. That is, having systematically sequenced the DNA bases in a genome, could similar systematic concepts and tools be devised to understand the rest of the human biological informational system (RNA, proteins, metabolites, lipids) and their roles in biology? Around that time, one of us (LH) had moved from Caltech to start a new department, called Molecular Biotechnology, in the medical school of the University of Washington. This department was based on the radical idea (at that time) that biology at its core was an information science, and that the path to understanding and integrating the genome and other types of biological information would be enabled only by joining the skills and expertise of biologists with those of leading investigators from engineering, chemistry, and mathematics, as well as the physical and computer sciences. This concept captured the imagination of the other of us (TI), who had studied computer …
Operational safety of an ammonia process network via model predictive control

Abstract Process safety is a crucial issue in the area of process systems engineering as accident prevention is a top priority in process operations. Operational safety needs to be directly incorporated into control system design to handle disturbances in the process. Motivated by the above considerations, this paper presents a practical application simulating multiple model predictive controllers within a multi-unit ammonia process, all of which integrate safety constraints of the process within their design. Specifically, catalytic deactivation in the shift reactor is a common and problematic disturbance that may trigger reaction thermal runaway in the methanator. Two controllers designed with the objective of improving operational safety are implemented on the ammonia plant under catalyst deactivation. Aspen Plus is a commercial process simulation software which is integrated with Matlab to run a closed-loop simulation for the ammonia process. The results demonstrate that under suitable design of the controllers, desirable closed-loop performance is achieved with high temperature extremities avoided during operation.
Fresh versus frozen embryo transfer

The fresh embryo transfer has traditionally performed in vitro fertilization (IVF) since 1978. The first pregnancy following the transfer of a frozen-thawed human embryo was reported in 1983. Since then, the clinical value of embryo cryopreservation has steadily increased over the decades. Improvements in vitrification now make frozen embryo transfer a viable alternative to fresh embryo transfer. The freeze-all strategy is a topic that has recently gained attention from clinicians and embryologists. The aim of this chapter is to provide an overview of the main cryopreservation strategies and discuss whether frozen embryo transfer is beneficial for diminished ovarian reserve patients in improving the clinical outcomes of IVF/ICSI cycles.
Environmental Effects on Aerosol-Cloud Interaction in non-precipitating MBL Clouds over the Eastern North Atlantic

Abstract. Over the eastern north Atlantic (ENA) ocean, a total of 20 non-precipitating single-layer marine boundary layer (MBL) stratus and stratocumulus cloud cases are selected in order to investigate the impacts of the environmental variables on the aerosol-cloud interaction (ACIr) using the ground-based measurements from the Department of Energy Atmospheric Radiation Measurement (ARM) facility at the ENA site during the period 2016–2018. The ACIr represents the relative change of cloud-droplet effective radius re with respect to the relative change of cloud condensation nuclei (CCN) number concentration at 0.2 % supersaturation (NCCN,0.2 %) in the water vapor stratified environment. The ACIr values vary from −0.004 to 0.207 with increasing precipitable water vapor (PWV) conditions, indicating that re is more sensitive to the CCN loading under sufficient water vapor supply, owing to the combined effect of enhanced condensational growth and coalescence processes associated with higher NC and PWV. The environmental effects on ACIr are examined by stratifying the data into different lower tropospheric stability (LTS) and vertical component of turbulence kinetic energy (TKEw) regimes. The higher LTS normally associates with a more adiabatic cloud layer and a lower boundary layer and thus results in higher CCN to cloud droplet conversion and ACIr. The ACIr values under a range of PWV double from low TKEw to high TKEw regime, indicating a strong impact of turbulence on the ACIr. The stronger boundary layer turbulence represented by higher TKEw strengthens the connection and interaction between cloud microphysical properties and the underneath CCN and moisture sources. With sufficient water vapor and low CCN loading, the active coalescence process broadens the cloud droplet size distribution spectra, and consequently results in an enlargement of re. The enhanced NC conversion and condensational growth induced by more intrusions of CCN effectively decrease re, which jointly presents as the increased ACIr. The TKEw median value of 0.08 m2 s−2 suggests a feasible way in distinguishing the turbulence-enhanced aerosol-cloud interaction in non-precipitating MBL clouds.
Cobalt Levels and Pseudotumor Characteristics Vary due to Metal Ion Source: Modular Femoral Neck vs Metal-on-Metal Articulations.

Abstract Background This study examines cobalt levels and pseudotumor characteristics in a non-recalled modular femoral prosthesis. We sought to determine relationships between serum cobalt levels and pseudotumors following modular and metal-on-metal (MoM) total hip arthroplasty (THA), the location and size of pseudotumors, and changes to pseudotumor grade over time. Methods We retrospectively evaluated a cohort of 190 primary THAs implanted with a dual-modular femoral stem by one surgeon from 2005 to 2013. One hundred seventeen THAs used a cobalt-chromium modular neck (CoCrMN) component and non-MoM articulation, 63 THAs had a titanium neck component and MoM articulation, and 10 had a titanium neck component and polyethylene liner. Serum ion levels were recorded for all patients. Pseudotumor grade and location were measured by musculoskeletal-trained radiologists. Results Cobalt levels did not correlate to time after index arthroplasty. In the CoCrMN group, cobalt levels were elevated in 11 of 19 (57.9%) patients with pseudotumor compared to 14 of 19 (73.7%) in the MoM group. Pseudotumors were more often located lateral to the hip joint in the CoCrMN group compared to anteromedial following MoM arthroplasty. In CoCrMN THAs, pseudotumors were visualized in 12 of 51 (23.5%) initial MARS MRIs within 40 months compared to 5 of 66 (7.6%) performed later (P = .02). Conclusion Pseudotumor characteristics differ between patients with CoCrMN designs vs those with an MoM articulation. Normal serum cobalt levels did not exclude the presence of a pseudotumor and routine MARS MRI should be included in follow-up of patients with this CoCrMN prostheses.
Pulsating Stars

Modern long-baseline interferometers are capable of resolving stellar diameters in the range of one to several milli-arcseconds with measurement precision approaching a few percent. This level of precision allows astronomers to directly resolve diameter changes associated with pulsation for various classesc of stars, including Cepheids and Miras. For several nearby Cepheids itis relatively straightforward to apply a Baade-Wesselink analysis and hence directly measure the distance to the Cepheid with a high degree of precision. This field is still quite new; I expect that in the near term several new interferometers will provide direct Cepheid distances to perhaps a few tens of Galactic Cepheids. However, equally important will be direct measurements of the atmospheric properties (in particular limb darkening) of these stars. Such measurements should help reduce the considerable systematic uncertainties that remain.
Synthesis and sintering of UN-UO2 fuel composites

Abstract The design and development of an economical, accident tolerant fuel (ATF) for use in the current light water reactor (LWR) fleet is highly desirable for the future of nuclear power. Uranium mononitride has been identified as an alternative fuel with higher uranium density and thermal conductivity when compared to the benchmark, UO2, which could also provide significant economic benefits. However, UN by itself reacts with water at reactor operating temperatures. In order to reduce its reactivity, the addition of UO2 to UN has been suggested. In order to avoid carbon impurities, UN was synthesized from elemental uranium using a hydride-dehydride-nitride thermal synthesis route prior to mixing with up to 10 wt% UO2 in a planetary ball mill. UN and UN – UO2 composite pellets were sintered in Ar – (0–1 at%) N2 to study the effects of nitrogen concentration on the evolved phases and microstructure. UN and UN-UO2 composite pellets were also sintered in Ar – 100 ppm N2 to assess the effects of temperature (1700–2000 °C) on the final grain morphology and phase concentration.
Reperfusion damage: The role of PMN Leukocytes

This chapter examines the role of polymorphonuclear (PMN) leukocytes in reperfusion damage. Central to significant focal brain injury are the molecular and cellular processes that underlie the transition from ischemia to inflammation. These include microvascular reactivity, PMN leukocyte activation and chemotaxis, endothelial cell receptor biology, cytokine synthesis and release, leukocyte transmigration and tissue invasion, and microvascular thrombosis. For PMN leukocytes to transgress the endothelial blood–brain barrier and the basal lamina, the participation of the microvascular endothelium, astrocytes, and other cells is required. PMN leukocytes contribute in part to microvascular obstruction, inflammatory tissue injury, wound repair, and hemorrhagic transformation. There is evidence that leukocytes, particularly PMN leukocytes, act within the microvascular compartment and across the microvascular wall during transmigration to promote tissue dissolution. Experimental results show that PMN leukocytes play several roles in the maturation of reperfusion injury following focal cerebral ischemia. They contribute to local “no-reflow,” edema formation, increases in postcapillary venule endothelial permeability, superoxide free radical generation, alterations in tissue integrity, and, ultimately, infarct development.
D1 Receptor in Interneurons of Macaque Prefrontal Cortex: Distribution and Subcellular Localization

Working memory performance is influenced by dopamine activation of D1 family dopamine receptors in the prefrontal cortex; working memory performance is maximal at moderate stimulation of D1 family receptors and is reduced by either higher or lower levels of D1 stimulation. The neuronal mechanisms that underlie this complex relationship are not yet understood. Previous work from this laboratory has demonstrated that the D1 family receptors, D1 and D5, are located in different compartments of pyramidal cells. Here we use an antibody specific to the D1receptor and double-label immunohistochemistry at the light and electron microscopic level to demonstrate that D1-like immunoreactivity (D1-LIR) is also present in interneurons. D1 receptor is prevalent in parvalbumin-containing interneurons and is less common in calretinin-containing interneurons. At the ultrastructural level, D1-LIR is found associated with the Golgi apparatus and endoplasmic reticulum in the soma, with the membranes of vesicles in proximal dendrites, and with the plasma membrane on distal dendrites, where it is often located near asymmetric synapses. In addition, D1-LIR is also seen in presynaptic axon terminals, which give rise to symmetric synapses onto dendritic shafts and soma. These results raise the possibility that the circuit basis of working memory in the prefrontal cortex involves a D1-mediated inhibitory component.
The diagnostic utility of nerve conduction studies and skin biopsy for diabetic neuropathy (DPN): a Bayesian analysis (S42.007)

Objective: Evaluate diagnostic utility of nerve conduction studies (NCS) and intraepidermal nerve fiber density (IENFD) for DPN using a Bayesian approach. Background: Consensus criteria require confirmatory testing for definite DPN. Bayes theorem dictates positive and negative predictive values (PPV, NPV) vary based on pretest probability (prevalence). Design/Methods: 366 diabetic patients underwent validated symptom (Michigan Neuropathy Screening Instrument) and exam (Utah Early Neuropathy Score) scales, NCS and IENFD. Receiver operating characteristic (ROC) curve analysis was performed using several gold standard definitions and sensitivity and specificity determined. PPV and NPV were modeled based on varying pretest DPN probabilities. The impact of varying cutoffs for specific NCS measures was determined. Results: Mean age was 55 years. 50[percnt] had symptoms, 21[percnt] signs, and 17[percnt] both. ROC analysis revealed similar AUC for sural sensory amplitude, peroneal motor conduction velocity and IENFD (0.769, 0.816, 0.740). NCS had low sensitivity (40[percnt]) but high specificity (95[percnt]). IENFD had high sensitivity (81[percnt]) but low specificity (41[percnt]). NCS had good NPV (90[percnt]) in low prevalence models. PPV was good (70-90[percnt]) in high prevalence models (50[percnt]) in which more stringent cutoff values further improved PPV. IENFD had a similarly high NPV in low prevalence models. The PPV of IENFD was poor (68[percnt]), even with a high prevalence. Conclusions: NCS have low sensitivity and high specificity whereas IENFD has the opposite. Both tests have good NPV (90[percnt]), particularly if the pretest probability of DPN is low (<15[percnt]) and are useful in excluding DPN. Given poor PPV, neither can reliably confirm DPN, particularly if the pretest probability is <50[percnt]. DPN diagnosis must be made using clinical judgment and confirmatory tests interpreted carefully in light of the prior probability of DPN in the population being studied. Utilization of varying cutoff values may improve diagnostic performance of specific measures. Study supported by: R01DK064814, 1ULTR001067 Disclosure: Dr. Smith has received personal compensation for activities with Pfizer and Allergan as a consultant. Dr. Smith has received research support from the NIH, the ADA, Viromed, and Impeto. Dr. Lessard has nothing to disclose. Dr. Singleton has received personal compensation for activities with Medical Review Institute.
How are they othered? Globalisation, identity and violence in an Indian city

The literature on conflict claims that there has been a resurgence of ethnic conflict in the era of globalisation. This paper attempts to investigate how local conflict may be influenced by processes of globalisation. The paper argues that in order to understand how globalisation may be implicated in local violent events, it is essential to develop a nuanced understanding of the complexities of global–local interaction in places. This paper also hopes to contribute to the analytical potency of identity-oriented explanations of conflict by explicating how identity construction has an overt spatial dimension – it is simultaneously place based and global, and how this global–local identity construction simultaneously produces socioeconomic and socio-cultural strategies of ‘othering’ that define the complexion of contemporary conflicts. Using interviews from a case study of Hindu–Muslim conflict which happened in 2002 in Ahmedabad city, India, this paper explicates how locally embedded global narratives socioeconomically and socio-culturally produce the ‘other.’
A Middle Ground Position in the Insider Trading Debate: Deregulate the Sell Side

Participants in the forty-year debate over whether insider trading should be liberalized have generally treated insider sales the same as insider purchases - they have argued that all such insider transactions should be either regulated or liberalized. This article contends that there is a principled basis for treating price-decreasing insider trading (e.g., insider sales) more leniently than price-increasing insider trading (e.g., insider purchases). Because equity overvaluation is more likely than equity undervaluation to occur and persist and is more likely to occasion harm to the corporate enterprise when it does occur, corporate constituents (managers and shareholders) would likely value a policy that permits price-decreasing insider trading more than a policy that permits price-increasing insider trading. Thus, the majoritarian default rule may be an asymmetric policy under which price-decreasing insider trading is generally permitted while price-increasing insider trading is generally forbidden.
Unconventional London Penetration Depth in Single-Crystal Ba ( Fe 0.93 Co 0.07 ) 2 As 2 Superconductors

The London penetration depth $\ensuremath{\lambda}(T)$ has been measured in single crystals of $\mathrm{Ba}({\mathrm{Fe}}_{0.93}{\mathrm{Co}}_{0.07}{)}_{2}{\mathrm{As}}_{2}$. The observed low-temperature variation of $\ensuremath{\lambda}(T)$ follows a power law, $\ensuremath{\Delta}\ensuremath{\lambda}(T)\ensuremath{\sim}{T}^{n}$ with $n\ensuremath{\approx}2.4\ifmmode\pm\else\textpm\fi{}0.1$, indicating the existence of normal quasiparticles down to at least $0.02{T}_{c}$. This is in contrast with previous penetration depth measurements on single crystals of ${\mathrm{NdFeAsO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}$ and ${\mathrm{SmFeAsO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}$, which indicate an anisotropic but nodeless gap. We discuss possible explanations of the observed power law behavior.
Abstract P2-10-01: onlineDeCISion.org : An interactive web-based clinical decision aid for DCIS treatment

Purpose: Treatment decisions regarding Ductal Carcinoma in Situ (DCIS) are complex, and patients often have inaccurate and incomplete understanding of the risks and benefits they face. Our objective was to create a web-based decision aid (onlineDeCISion.org) that can be used in clinical practice to guide both clinicians and their patients with these decisions. Methods: We developed a web-based clinical decision aid to provide tailored information about DCIS treatment choices including an individual patient’s risk of recurrence, likelihood of long-term breast preservation and survival outcomes following up to 6 different treatment strategies for DCIS (lumpectomy, lumpectomy with radiation, lumpectomy with tamoxifen, lumpectomy with radiation and tamoxifen, and mastectomy with or without breast reconstruction). The decision aid is populated by our previously developed simulation model of DCIS outcomes. A theoretical framework and best-practices for web-based decision tools guided the development of the decision aid including semi-structured interviews and usability testing with a diverse group of multidisciplinary clinicians and patient advocates. Results: The decision aid was designed to include these key features: 1) descriptions of treatment options; 2) ability to input patient health-adjusted age; 3) tailored likelihood of time-specific (10-year and lifetime) recurrence and survival outcomes; and 4) projections of downstream effects of each treatment. The decision aid provides default recurrence risks based on clinical trial data but allows clinicians to customize 10-year DCIS and invasive recurrence risks to retain flexibility to display expected outcomes for individual patients. These estimates can be based on the patient’s actual age, or age adjusted for health status, allowing for a more realistic expectation of the benefits each treatment holds. Conclusion: Our web-based decision aid displays tailored outcomes following different treatment strategies for DCIS, allowing patients to be better informed about the tradeoffs of treatments available to them and select treatments consonant with their personal preferences, improving the quality of decision making for DCIS. The interactive design features allow users of the decision aid the ability to address uncertainty around risks of recurrence and comorbidity risks and facilitate the use of the decision aid across diverse populations. While the decision aid warrants further evaluation, the results of our study promise to improve decision making in patients with DCIS. Citation Format: Elissa M Ozanne, Natasha K Stout, Katharine Schneider, Djora Soeteman, Deborah Schrag, Michael Fordis, Rinaa S Punglia. onlineDeCISion.org : An interactive web-based clinical decision aid for DCIS treatment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-10-01.
A Contractarian Argument Against the Death Penalty

Opponents of the death penalty typically base their opposition on contingent features of its administration, arguing that the death penalty is applied discriminatorily, that the innocent are sometimes executed, or that there is insufficient evidence of the death penalty’s deterrent efficacy. Implicit in these arguments is the suggestion that if these contingencies did not obtain, serious moral objections to the death penalty would be misplaced. In this Article, Professor Finkelstein argues that there are grounds for opposing the death penalty even in the absence of such contingent factors. She proceeds by arguing that neither of the two prevailing theories of punishment - deterrence and retributivism - is capable of justifying the death penalty. More generally, she suggests that while each theory captures an important part of the justification for punishment, each must appeal to some further limiting principle to accommodate common intuitions about appropriate punishments for crimes. Professor Finkelstein claims that contractarianism supplies this additional principle, by requiring that individuals consent to the system of punishment under whose threat they must live. Moreover, on the version of contractarianism for which she argues, they must do so based on a belief that they will benefit under the terms of that system as compared with how they would fare in its absence. While the notion of benefit is often best understood in terms of maximizing one’s expected utility, Professor Finkelstein argues that with respect to choices about the basic structure of society, rational contractors will conceive of benefit in terms of a conservative, “no-gambling” decision rule. She then argues that rational contractors applying this conception of benefit would reject any system of punishment that includes the death penalty. For while contractors would recognize the death penalty’s deterrent value, they must also consider the high cost they would pay in the event they end up subject to such a penalty. This Article presents both a significant new approach to the death penalty and a general theory of punishment, one that incorporates the central intuitions about deterrence and desert that have made competing theories of punishment seem compelling.
Tomographic separation of composite spectra - The components of the O-star spectroscopic binary AO Cassiopeiae

The UV photospheric lines of the short-period, double-lined O-star spectroscopic binary AO Cas are analyzed. Archival data from IUE (16 spectra uniformly distributed in orbital phase) were analyzed with a tomography algorithm to produce the separate spectra of the two stars in six spectral regions. The spectral classifications of the primary and secondary, O9.5 III and O8 V, respectively, were estimated through a comparison of UV line ratios with those in spectral standard stars. An intensity ratio of 0.5-0.7 (primary brighter) at 1600 A is compatible with the data.
Modeling the effects of anomalous diffusion on synaptic plasticity

The diffusion of cytosolic intracellular signals in spiny dendrites is anomalous due to spine trapping [1]. During anomalous diffusion the mean square displacement (MSD) of diffusing molecules follows a power law, MSD ~ tα, with α called the anomalous exponent. We have shown that α depends on the density and structure of spines and could be a general property of all spiny dendrites [2]. Anomalous diffusion affects the spatial spread and temporal concentration profiles of cytosolic molecules, thus potentially affecting the specificity and reliability of synaptic plasticity. Here we study the effect of anomalous diffusion on the spatial and the temporal distribution of signals involved in the expression of long term depression (LTD) in Purkinje cells (PCs). LTD depends on the PKC-MAPK positive feedback cascade. Increased [Ca2+] activates PKC, which in turn activates MAPK. Activated MAPK and [Ca2+] results in production of arachidonic acid which then activates PKC. The activated PKC either further activates MAPK or phosphorylates AMPARs, which are then removed from the synapse [3]. We use the fractional diffusion formulation of anomalous diffusion. In such a framework the diffusion-reaction equation for a given reactant is: ∂αCRi∂tα=γ∇2CRi+fCRi,CRj where α depends on the spine density along the dendrite, γ(t) is the generalized transport coefficient, CRi(t) is the concentration of the reactant Ri and f(CRi, CRj) defines the reaction terms of the specific biochemical reaction. Solving a system of coupled fractional diffusion-reaction equations for [Ca2+], PKC and MAPK is computationally expensive. To address this problem we recently developed a Fractional Integration Toolbox (FIT) [4]. We have solved a simplified LTD model. In this model [Ca2+] does not undergo anomalous diffusion [1]. However, since PKC and MAPK are large proteins, they are susceptible to molecular trapping by spines resulting in anomalous diffusion. Our results show that in spiny dendrites (α < 1) the diffusion of either PKC or MAPK is slower than in the case of diffusion in spineless dendrites (α = 1) (Figure ​(Figure1A).1A). Under anomalous diffusion there is a longer activation of the PKC-MAPK positive feedback loop. Once activated, PKC and MAPK stay activated longer (Figure ​(Figure1B),1B), implying a lower [Ca2+] activation threshold. Thus, anomalous diffusion affects not only the spatial spread of molecules produced during LTD but also the activation threshold of the synaptic plasticity process. Figure 1 Diffusion of PKC along a dendrite with no spines (α = 1) or high spine density (α = 0.4). (A) Spatial profile of PKC at t = 1 sec after release at × = 0, the anomalous diffusing PKC remains longer and with higher amplitude than ...
Amortized analysis of algorithms for set union with backtracking

Mannila and Ukkonen [Lecture Notes in Computer Science 225, Springer-Verlag, New York, 1986, pp. 236–243] have studied a variant of the classical disjoint set union (equivalence) problem in which an extra operation, called de-union, can undo the most recently performed union operation not yet undone. They proposed a way to modify standard set union algorithms to handle de-union operations. In this paper several algorithms are analyzed based on their approach. The most efficient such algorithms have an amortized running time of $O({{\log n} / {\log \log n}})$ per operation, where n is the total number of elements in all the sets. These algorithms use $O(n\log n)$ space, but the space usage can be reduced to $O(n)$ by a simple change. The authors prove that any separable pointer-based algorithm for the problem requires $\Omega ({{\log n} / {\log \log n}})$ time per operation, thus showing that our upper bound on amortized time is tight.
Acetazolamide Attenuates Hunter-Cheyne-Stokes Breathing but Augments the Hypercapnic Ventilatory Response in Patients with Heart Failure

Rationale: Acetazolamide has been used to attenuate Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) associated with heart failure. However, the mechanisms underlying this improvement remain to be fully elucidated.Objectives: We hypothesized that acetazolamide stabilizes CSA by attenuating the ventilatory sensitivity to CO2, which is increased in patients with heart failure and is thought to be the major mechanism mediating CSA.Methods: Six consecutive male patients with stable systolic heart failure and CSA (apnea-hypopnea index [AHI] ≥ 15 episodes/h) were randomized to a double-blind crossover protocol with acetazolamide or placebo received 1 hour before bedtime for six nights with 2 weeks of wash-out. Under both conditions, we measured the hypercapnic ventilatory response (HCVR), arterial blood Pco2, steady-state metabolic CO2 production, overnight attended polysomnography, and also assessed cardiac and pulmonary function.Measurements and Main Results: Compared with placebo, acetazolamide ...
Reversible renal failure in a patient with the hypereosinophilia syndrome during therapy with alpha interferon

Human recombinant interferon (IFN)-alpha (alpha)-2b was given to a 57-year-old man with hypereosinophilia syndrome refractory to prednisone and hydroxyurea. One year later, he developed progressive renal failure and nephrotic-range proteinuria. Percutaneous kidney biopsy showed focal and segmental glomerular and mesangial sclerosis, chronic interstitial nephritis, and focal tubular necrosis. Discontinuation of cytokine therapy led to marked improvement in renal function and significant reduction in proteinuria. The potential role of IFN-alpha as the cause of renal failure and nephrotic-range proteinuria is discussed. The spectrum of renal disease attributed to IFN-alpha and the proposed pathogenic mechanisms are reviewed.
Right ventricular aneurysm following modified Norwood-Sano operation for hypoplastic left heart syndrome

Hypoplastic left heart syndrome is a rare congenital heart defect characterized by underdevelopment of left-sided heart structures, including the aortic arch. The contemporary surgical management of this anomaly includes the Norwood procedure and provision of pulmonary blood flow by either a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery (RV-PA) conduit, commonly referred to as the Sano shunt. We report on an unusual complication of the Sano shunt, that of a giant right ventricular pseudoaneurysm occurring at the shunt insertion site.
Chemistry Development of a Convergent Route to Trecetilide Hemi-Fumarate

A novel, efficient, stereoselective synthetic route for N-(4-{4-[ethyl(6-fluoro-6-methylheptyl)amino]-1-(S)-hydroxybutyl}phenyl)methanesulfonamide hemi-fumaric acid salt (trecetilide hemi-fumarate, Figure 1) has been developed. The process features a convergent approach, which assembles two key intermediates in the last step to form the final molecule, which is then isolated by pH-controlled extraction. The new route offers significant yield and purity advantages over the previous route. However, the solvent volume and cycle time were not fully optimized due to the termination of the project.
Target specific differentiation of peripheral trigeminal axons in rat-chick chimeric explant cocultures.

Avian and rodent trigeminal ganglion (TG) neurons share common features in their neurotrophin requirements and axonal projections between the sensory periphery and the brainstem. In rodents, the whisker pad (WP) is a major peripheral target of the infraorbital (IO) nerve component of the TG. The chick IO nerve is much smaller and innervates the maxillary process (MP). In the embryonic WP, IO axons course in fascicles from a caudal to rostral direction and form terminal plexuses around follicles. In the chick, IO axons travel as a thin bundle to the MP and branch out with no specific patterning. We cocultured E15 rat TG with E5–6 chick MP or chick TG with rat WP explants to examine target influences on trigeminal axon growth patterns as visualized with DiI labeling or neurofilament immunohistochemistry. Chick TG axons showed robust growth into WP explants, and the ganglion increased in size. Thick bundles of axons traveled between rows of follicles and formed a distinct pattern as they developed terminal arbors around individual follicles. In contrast, rat TG axon growth was sparse in chick MP explants and the ganglion size reduced over time. Furthermore, rat TG axons did not show any patterning in the chick MP. Similar target-specific growth patterns were observed when TG explants were given a choice between chick MP and rat WP explants. Collectively these results indicate that both the chick and rat TG cells respond to similar target-specific peripheral cues in the establishment of innervation density and patterning in peripheral orofacial targets.
The murine Sm-D autoantigen: multiple genes, genetic polymorphism, evolutionary conservation and lack of intervening sequences in the coding region.

Antibodies to the Sm nuclear antigen are diagnostic of systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr mice develop a similar illness, and a proportion also develop anti-Sm. To understand better anti-Sm reactivity in this murine model, we have cloned the murine Sm-D autoantigen. One cDNA clone was 517 bp long with an open reading frame of 357 nucleotides, encoding a 13.3 kDa protein of 119 amino acids. At the nucleotide level, the murine Sm-D cDNA was 89.8% homologous with human Sm-D (94% in the coding region), yet there was identity at the protein level, including a Gly-Arg nine-fold repeated C-terminus motif. Southern blot analysis of FstI-digested genomic DNA from seven mouse strains demonstrated a 7.8 kb band in every strain; in addition, a 2.8 kb band was seen in AKR/J, LG/J and MRL/Mp-lpr/lpr. PCR amplification of genomic DNA showed a single Sm-D gene product of 360 bp, which indicated a lack of intervening sequences. The Sm-D protein is thus highly conserved in evolution, probably owing to its essential role in the physiology of the cell.
Saturation behavior of cascade damage production using fission fragment and ion irradiations

Abstract The saturation of electrical-resistivity changes, which were induced by various types of irradiations at liquid helium temperatures, was studied as a function of the primary recoil energy in copper and silver. For both copper and silver, the saturation resistivity was observed to decrease as the primary recoil spectrum was shifted to higher energies. For copper, the saturation resistivity varied from 6.5 nΩ · m for a 150-keV H + irradiation to 4.4 nΩ · m for a 600-keV Bi ++ irradiation. For silver, the saturation resistivity varied from 6.1 nΩ · m for a 150-keV H + irradiation to 4.7 nΩ · m for a 235 U fission-fragment irradiation. The saturation resistivity was also determined for 235 U fragment damage in aluminum, nickel, gold and vanadium.
Structural features of δ-crystallin of turtle lens

1. δ-Crystallin was characterized from the 1-day-old lens of the red-eared turtle, Pseudemys scripta. δ-Crystallin was identified by crossreaction with antiserum against chicken δ-crystallin and was purified from a lens homogenate by isoelectric focusing in a sucrose density gradient. The δ-crystallin isoelectrically focused at a pH of about 5.8. It had an apparent native molecular weight near 180000 as judged by gel filtration. The δ-crystallin polypeptides contained a predominant band near 48 kDa and a very minor band just larger than 48 kDa when examined by sodium dodecyl sulfate (SDS)-urea-polyacrylamide gel electrophoresis. This is consistent with a tetrameric structure for the native protein. The turtle lens also contained a prominent band of polypeptides of about 46 kDa. These did not immunoprecipitate with anti-chicken δ-crystallin antiserum (or with anti-calf α-, β- or γ-crystallin antisera) and differed from δ-crystallin with respect to isoelectric point (near 6.2) and pattern of Staphylococcus aureus V8 protease peptides on an SDS-polyacrylamide gel. Both the 48 kDa and 46 kDa polypeptides were synthesized in a rabbit reticulocyte lysate supplemented with turtle lens RNA. 2. Far-ultraviolet circular dichroism (CD) spectroscopy showed that the turtle δ-crystallin had considerable α-helical content (57%), like other δ-crystallins. In contrast to δ-crystallins of other species, turtle δ-crystallin had a positive (instead of negative) near-ultraviolet CD spectrum and had a fluorescence emission maximum at 326 nm (instead of 315 nm) after excitation at 280 nm, suggesting unique microenvironments for the aromatic amino acids (especially tryptophan) in turtle native δ-crystallin. 3. These results indicate conservation of subunit and secondary structure, with some change in tertiary structure during the evolution of δ-crystallin. The data also provide evidence for the existence of a new crystallin with a polypeptide molecular weight near 46000.
A new technique for the measurement of ternary molecular diffusion coefficients in liquid systems

A double Savart plate birefringent interferometer was used to study the diffusional behavior of the ternary system. Acetone (1) – Benzene (2) – Methanol (3). The ternary diffusion coefficients were measured at 9 composition points covering the entire ternary diagram. The binaries forming the borders of the ternary diagram were also studied. The ternary diffusion coefficients at one composition point of the ternary system Actone (1) – Benzene (2) – Carbon tetrachloride (3) were measured and compared with previously reported data of Cullinan and Toor(18), obtained by diaphragm cell method. Validity of the birefringent interferometric measurements when applied to the ternary liquid systems was confirmed through this comparison. On a employe un interferometre birefringent a deux plateaux de Savart pour etudier le comportement a la diffusion du systeme ternaire forme de l'acetone, du benzene et du methanol. On a mesure les coefficients de diffusion ternaire a 9 points de composition embrassant tout le diagramme ternaire; on a aussi etudie les points de composition binaire qui constituent les limites du diagramme ternaire. On a mesure les coefficients de diffusion ternaire a un seul point du systeme ternaire forme d'acetone, de benzene et de tetrachlorure de carbone et les a compares aux resultats prealablement obtenus par Cullinan et Toor(18) au moyen de la methode de cellules a diaphragme. Ladite comparaison a permis de confirmer la validite des mesures faites par l'interferometre birefringent et appliquees aux systemes ternaires de liquides.
Dendritic Cell-Induced Th1 and Th17 Cell Differentiation for Cancer Therapy.

The success of cellular immunotherapies against cancer requires the generation of activated CD4+ and CD8+ T-cells. The type of T-cell response generated (e.g., Th1 or Th2) will determine the efficacy of the therapy, and it is generally assumed that a type-1 response is needed for optimal cancer treatment. IL-17 producing T-cells (Th17/Tc17) play an important role in autoimmune diseases, but their function in cancer is more controversial. While some studies have shown a pro-cancerous role for IL-17, other studies have shown an anti-tumor function. The induction of polarized T-cell responses can be regulated by dendritic cells (DCs). DCs are key regulators of the immune system with the ability to affect both innate and adaptive immune responses. These properties have led many researchers to study the use of ex vivo manipulated DCs for the treatment of various diseases, such as cancer and autoimmune diseases. While Th1/Tc1 cells are traditionally used for their potent anti-tumor responses, mounting evidence suggests Th17/Tc17 cells should be utilized by themselves or for the induction of optimal Th1 responses. It is therefore important to understand the factors involved in the induction of both type-1 and type-17 T-cell responses by DCs.
Equity sharing in international joint ventures: an empirical analysis of strategic and environmental determinants

Abstract Equity sharing in international joint ventures (IJVs) is a critical issue with implications for risk sharing, resource allocation, knowledge commitment, and organizational control. As a departure from previous research, this study aims to explore strategic antecedents and environmental dimensions underlying sharing arrangements. It argues that the structure of equity sharing controls the ex post degree of economic exposure or risk propensity, and boosts risk-adjusted returns earned from strategic resources or global integration. Analysis of data collected from IJVs in China suggests that strategic orientation, resource dependence, knowledge protection, and global integration as sought by MNEs are important antecedents of equity sharing. Equity sharing is an inverse function of host-country environmental complexity and hostility as perceived by MNE managers.
Content-preserving warps for 3D video stabilization

We describe a technique that transforms a video from a hand-held video camera so that it appears as if it were taken with a directed camera motion. Our method adjusts the video to appear as if it were taken from nearby viewpoints, allowing 3D camera movements to be simulated. By aiming only for perceptual plausibility, rather than accurate reconstruction, we are able to develop algorithms that can effectively recreate dynamic scenes from a single source video. Our technique first recovers the original 3D camera motion and a sparse set of 3D, static scene points using an off-the-shelf structure-from-motion system. Then, a desired camera path is computed either automatically (e.g., by fitting a linear or quadratic path) or interactively. Finally, our technique performs a least-squares optimization that computes a spatially-varying warp from each input video frame into an output frame. The warp is computed to both follow the sparse displacements suggested by the recovered 3D structure, and avoid deforming the content in the video frame. Our experiments on stabilizing challenging videos of dynamic scenes demonstrate the effectiveness of our technique.
A non-negative matrix factorization algorithm for the detection of chemicals from an incomplete Raman library

Raman spectroscopy has proven to be a powerful technique for the standoff identification of surface-deposited chemical agents. In the supervised detection framework, the measured Raman spectrum is compared to a reference library of known spectra. A well-known shortcoming of the supervised approach is that no comprehensive library exists, and when chemicals are present that are not contained in the reference library, the supervised algorithms may confuse those chemicals with library members. One way to deal with this problem is to use an unsupervised method such as nonnegative matrix factorization (NMF) to estimate both the constituent spectra and their relative quantities directly from a block of measured spectra. Chemical identification may then be performed by associating the extracted spectra with the reference library spectra. This two-stage NMF approach often fails because knowledge of the reference library was not used in extracting the spectra. We present a novel modification of NMF in which a subset of the extracted spectra are constrained to be equal to the known reference library. This method is shown to outperform the standard NMF approach and the common supervised identification algorithms when there are chemicals present that are not in the library. This algorithm is applicable to any problem in which a target is identified by comparing a block of measured data to a library of known constituent signatures.
In vitro sporulation of Frankia strain HFPCcI3 from Casuarina cunninghamiana

Optimization of the in vitro sporulation of Frankia is a prerequisite for the development of spore preparations as a practical inoculum for actinorhizal plants. The in vitro sporulation of Frankia strain HFPCcI3 previously isolated from Casuarina cunninghamiana was increased from 0 to 12 million spores per millilitre of culture medium when nitrogen and phosphorus were excluded from a defined nutrient medium. The same medium did not increase sporulation of Frankia isolates HFPArI3 from Alnus rubra and HFPCpI1 from Comptonia peregrina. The addition of 10 mM aliphatic L amino acids increased the in vitro sporulation of HFPCcI3 by as much as 39% when grown in a defined nutrient medium with 1 mM potassium phosphate lacking ammonium chloride, whereas the addition of 10 mM acidic, basic, aromatic, and sulfur amino acids decreased sporulation. The in vitro sporulation of HFPCcI3 was inhibited by culture at 33°C relative to culture at 23 and 28°C. Rotary shaking at 100 rpm increased sporulation at the low culture temperatures. (Less)