cssi/SciSciGPT-SciSciNet huggingface dataset:
Chemisorption and dissociation of O2 on Pd(111) studied by STM

Abstract The adsorption and dissociation of O2 on Pd(1 1 1) at low coverage was studied in a variable temperature scanning tunneling microscope (STM) in the range from 25 to 210 K. Below 60 K the diffusion rate is negligible and individual molecules appear as slightly elongated 5 pm protrusions surrounded by 10 pm depressions at low bias voltage (⪅200 mV). The molecules predominantly appear in three distinct orientations and closely resemble the peroxide species observed on Pt(1 1 1). A small fraction of the molecules occupy a second binding configuration at 25 K, appearing similar to the dominant species but with opposite orientations. No molecules resembling the superoxide precursor state on Pt(1 1 1) were observed. Both thermal activation and interaction with the STM tip induce rotation between the three orientations of each molecule, as well as displacement to adjacent sites and conversion between the two binding geometries. The molecules order in p(2 × 2) clusters, which grow in size upon annealing to 100 K. Rotational disorder is observed within the islands below 60 K, but not at higher temperature due to rapid rotation. Near 120 K, thermal O2 dissociation occurs primarily at the periphery of islands and at active sites associated with impurities beneath the Pd surface.
Measuring child, adolescent, and family service use

Currently, no method of classifying mental health services is accepted by all service sectors. Because classification is central to understanding the service delivery system for children and families, standardization of methods must be achieved.
Vascular access and increased risk of death among hemodialysis patients

Vascular access and increased risk of death among hemodialysis patients. Background Hemodialysis with a venous catheter increases the risk of infection. The extent to which venous catheters are associated with an increased risk of death among hemodialysis patients has not been extensively studied. Methods We conducted a retrospective cohort study of 7497 prevalent hemodialysis patients to assess the association between dialysis with a venous catheter and risk of death due to all causes and to infection. Results A tunneled cuffed catheter was used for access in 12% of the patients and non-cuffed, not tunneled catheter in 2%. Younger age ( P = 0.0005), black race ( P = 0.0022), female gender ( P = 0.0004), short duration since starting dialysis ( P = 0.0003) and impaired functional status ( P = 0.0001) were independently associated with increased use of catheter access. The proportion of patients who died was higher among those who were dialyzed with a non-cuffed (16.8%) or cuffed (15.2%) catheter compared to those dialyzed with either a graft (9.1%) or a fistula (7.3%; P P Conclusion Venous catheters are associated with an increased risk of all-cause and infection-related mortality among hemodialysis patients.
Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host disease: a case series of 18 patients.

Background Tacrolimus (formerly FK 506) is an immunosuppressive drug that works by inhibiting calcineurin, a calcium-dependent protein phosphatase required for immune function. Tacrolimus has been shown to be effective topically in atopic dermatitis and systemically in psoriasis and graft-vs-host disease (GVHD). However, its efficacy in treating cutaneous GVHD when applied topically has not been reported. Objective To assess the therapeutic efficacy of 0.1% tacrolimus ointment on chronic cutaneous GVHD in patients with symptoms refractory to systemic corticosteroid therapy. Results Tacrolimus ointment effectively treated pruritus and/or erythema in 13 (72%) of 18 patients with chronic GVHD. Responding patients had a rapid effect within several hours to days. Effectiveness was measured by means of patient report, results of physical examination, side-by-side comparisons of tacrolimus vs a vehicle control, and temporal flares of the cutaneous symptoms of the disease in the context of stopping tacrolimus ointment therapy. Because of the progression of GVHD and in 2 cases, loss of drug efficacy, all patients eventually went on to receive more aggressive treatment, including increases in steroid dosage, psoralen–UV-A therapy, and extracorporeal photopheresis. Conclusions This case series suggests that tacrolimus ointment has efficacy in treating the erythema and pruritus of steroid-refractory, chronic cutaneous GVHD in most patients. The rapid response of tacrolimus ointment may provide a useful therapeutic bridge to systemic therapies that have slower onset, such as psoralen–UV-A therapy or extracorporeal photopheresis.
Examination of small polystyrene latex particles using a negative staining technique

Abstract Negative staining with KPT was found to be effective in sizing latex particles as small as 20 nm. The average particle size of a polystyrene latex obtained by negative staining was found to agree very closely with that obtained by platinum/carbon shadowing. The accuracy and high resolution of the negative staining technique, coupled with its relative ease of sample preparation presents a superior, alternative method.
A model to quantify the Bullwhip Effect in systems with stochastic demand and lead time

The increase in demand variability as information flows from customers to manufacturers in a supply chain is known as the Bullwhip Effect (BE). Modeling this phenomenon is key in measuring its intensity, aiming at reducing its negative impact on both service and inventory levels in supply chains. This paper proposes a new, more precise mathematical model for quantifying the BE in systems with stochastic demand and lead time. The new model takes into account the lead time variability. In addition, the model allows a more precise assessment of the role that the demand?s coefficient of variation plays when quantifying the BE. The use of the proposed model may enable an improved management of the supply chain by attenuating the propagation of the BE.
Virial coefficients of polarizable water : Applications to thermodynamic properties and molecular clustering

We determine the second and third virial coefficients B2 and B3 for the Gaussian charge polarizable model (GCPM) as a function of temperature over the range 210−723 K. The overlap sampling implementation of Mayer sampling molecular simulation is applied to calculate the values, obtaining results to a precision that ranges from 0.1% for B2 to an average of 1% for B3. These calculated values compare very well with known values of B2 and B3 for real water and outperform both pairwise models and other polarizable models in describing experimental virial-coefficient data. We examine these coefficients in the context of the equation of state and molecular clustering. Comparisons are made to established molecular simulation data, quantum chemical calculations, and experimental data for real water. Under both saturated-vapor and supercritical conditions, the virial series up to B3 describes the equation of state quite well. The virial coefficients are used to characterize molecular clusters (dimers and trimers) i...
Voluntary intake of low-protien diets by ruminants: I. Intake of food by cattle

1. A study was made of the voluntary intake hay, of low nutritive value, by heifers of two breeds of African cattle when given four different amounts concentrate foods (9, 18, 27 and 36 g/kg W0.73/day) each providing three levels of protein (1·3, 2·6 and 3·9 g DCP kg W0.73/day). The trial was designed two incomplete Latin squares, one for each breed, with thirteen treatments, thirteen heifers and four replicates.2. Voluntary intakes of low-protein hay by Africander and Mashona heifers were similar and these increased as levels of supplementary protein were raised and intakes of hay were reduced amounts of concentrate provided to them became more liberal. Inter-relationships of food intake and dietary composition were, however, very complex.3. Increased allowances of dietary protein and concentrate generally corresponded with higher intakes of total food and digestible energy. But this was not true at the lower levels of protein input where there was evidence that food and digestible nutritient intakes were depressed when liberal amounts of concentrate were fed to the cattle.
Stereoelectronic control in addition of nucleophiles to an amidinium ion.

Nucleophilic addition to 1,3-dimethyl-5-phenyl-1,4,5,6-tetrahydropyrimidinium ion provides a quantitative measure of stereoelectronic control. This amidinium ion presents the nucleophile with two distinct paths for attack. Axial attack is favored by interaction between the orbital of the developing bond and antiperiplanar lone pairs on the nitrogens. Reaction of the amidinium salt with diverse nucleophiles (D-, H3C-, n-Bu-, PhCH2-, allyl-, Ph-, C5F6-, CH2CH-, HC⋮C-, PhC⋮C-, CN-) produces mixtures of cis and trans stereoisomers. Both kinetic and thermodynamic product distributions were measured by 1H NMR, before and after acid-catalyzed equilibration. The values provide insight into the roles of steric and stereoelectronic forces at the transition state and in products. Stereoelectronic effects on reactivity are found to be weak (ca. 1 kcal/mol).
Prostaglandin E2-protein kinase a signaling and protein phosphatases-1 and -2A regulate human head and neck squamous cell carcinoma motility, adherence, and cytoskeletal organization

Human head and neck squamous cell carcinoma (HNSCC) cultures were established from cancers of two patients. These cells were used to study if phosphorylation reactions by protein kinase A (PKA) and dephosphorylation reactions by protein phosphatases-1 and -2A (PP-1/2A) regulate tumor motility and adhesion to extracellular matrix components, and if this might be associated with cytoskeletal reorganization. Both cultures were motile and adherent to collagen I, fibronectin, vitronectin and laminin. Motility and adhesiveness was dependent on production of prostaglandin E2 PGE2 and on PKA activation. Blocking PP-1/2A activity with okadaic acid resulted in a PKA-dependent increase in m otility and, in some instances, adhesiveness by the HNSCC cells. The okadaic acid-induced increase in motility and adhesiveness coincided with a reduction in filamentous actin. These data suggest PKA and PP-1/2A have opposing effects in regulating the motility, adherence, and actin polymerization.
Graphene nanoribbon Schottky-barrier FETs for end-of-the-roadmap CMOS: Challenges and opportunities

On the ITRS roadmap [1], the physical gate length, L G , has been rapidly scaling down, and will reach values below ∼ 10nm beyond 2020 (see Table I, shaded region). The single-gate (SG) extremely thin SOI (ETSOI) MOSFET, the double-gate (DG) FinFET, and the gate-all-around (GAA) Si nanowire (SiNW) MOSFET geometries may facilitate such scaling [2–4]. Nevertheless, sub-10nm L G scaling will be a great challenge because of the significant mobility degradation [5] and channel thickness variations [2] in the aforementioned geometries with a few-nanometer body thicknesses as required by electrostatic short-channel considerations. Therefore, new device geometries and technologies are required that could simultaneously maintain the electrostatic integrity and the superior transport properties for sub-10nm L G scaling. It has been recently shown that the atomic-thin- body (ATB) geometry can meet the electrostatic requirements for L G ≤ 10nm [6]. At the ATB limit, carbon electronics based on graphene nanoribbons (GNRs) with tunable band gaps [7] have been widely considered for high-performance digital electronics [8–10]. Here, ballistic transport of GNR Schottky-barrier (SB) FETs is simulated self-consistently [6], including both thermionic emission and tunneling. We show the better gate length scalability of GNRs compared to Si MOSFETs, even though significant material related challenges will have to be overcome. L G scaling below 10nm is mainly limited by direct source-to-drain tunneling and the ambipolar effect in the off-state, which can be suppressed by narrower ribbon widths (of the order ∼ 1nm), and larger effective masses obtained from bandstructure engineering. If a negative metal-graphene SB-height could be achieved, the GNR SB-FET could operate without significant series resistance effects, and deliver high on-current (ION ) [11]. The performance of the ultimate GNR SB-FETs is comparable to the MOSFET targets of the ITRS roadmap [1].
Shining new light on 3D cell motility and the metastatic process

Understanding tissue architecture and physical and chemical reciprocity between cells and their microenvironment provides vital insights into key events in cancer metastasis, such as cell migration through three-dimensional (3D) extracellular matrices. Yet, many mechanistic details associated with metastasis remain elusive due to the difficulty of studying cancer cells in relevant 3D microenvironments. Recently, optical imaging has facilitated the direct observation of single cells as they undertake fundamental steps in the metastatic processes. Optical imaging is also providing novel 'optical biomarkers' with diagnostic potential that are linked to cell-motility pathways associated with metastasis, and these can to help guide new approaches to cancer diagnosis and therapy. Here we present recent advances in one subclass of optical imaging of particular promise for cellular imaging - multiphoton microscopy - that can be used to improve the detection of malignant cells as well as advance our understanding of the cell biology of cancer metastasis.
Dynamically generating problems on static scope

Solving problems is an integral part of learning in Computer Science. In order to provide students with a vast supply of problems with which to practice, we propose to use applets that automatically generate problems. In this paper, we first discuss the capabilities required of such applets, and then, present the design and features of an applet we have developed to automatically generate problems on static scope in Pascal.
Oral hairy leukoplakia: Diagnosis and management

Oral hairy leukoplakia (HL) is a remarkable lesion associated with Epstein-Barr virus (EBV) found in persons infected with the human immunodeficiency virus. The clinical and histologic features of HL are characteristic and distinctive. However, none of these features are entirely specific for HL, and we consider that the presence of EBV is required for diagnosis in questionable cases. EBV can be demonstrated by means of electron microscopy, immunocytochemistry, or molecular biologic techniques. Therapy directed toward the HL lesion is sometimes indicated; acyclovir is the current drug of preference in such cases.
Metabolic Profiling of Human Blood Serum from Treated Patients with Bipolar Disorder Employing 1H NMR Spectroscopy and Chemometrics

Metabolic profiling employing hydrogen nuclear magnetic resonance (1H NMR) spectroscopy and chemometric analysis of human blood serum samples taken from the control group (n = 25) and patients with bipolar disorder (n = 25) was performed to identify molecular changes related to the disorder and to different drug treatments: lithium (n = 15) versus other medications (n = 10). This strategy showed significant potential for exploring pathophysiological and toxicological features involved in bipolar disorder. The investigated groups (control and patients with bipolar disorder under different treatments) could be distinguished according to their metabolic profiles, and the main differential metabolites found were lipids, lipid-metabolism-related molecules (acetate, choline, and myo-inositol), and some key amino acids (glutamate, glutamine). Our results suggest that some of the 24 identified metabolites may be linked to lithium- and other-medication-provoked metabolic changes or may even be directly related to ...
Coset decomposition of positively self-conjugate inverse submonoids of polycyclic monoids

We obtain several new results about the coding of a monoid by an appropriate submonoid of a polycyclic monoid. In particular, we characterize groups, periodic monoids, and right cancellative monoids in terms of the coset decomposition of positively self-conjugate inverse submonoids of polycyclic monoids.
Removal of a sewing needle from an occult esophageal ingestion in a 9-month-old

A healthy 9-month-old boy presented with a 1-month history of cough. A chest x-ray showed a linear metallic foreign body (FB) lying transversely in the posterior mediastinum. Computed tomographic scan confirmed the location and size of the metallic FB and also revealed a large pericardial effusion that was corroborated by echocardiogram. The patient underwent a right thoracotomy revealing a normal esophagus without mediastinitis and a 12-mm needle in the posterior mediastinum embedded in the pericardium with the sharp end abutting the left atrium. The needle was extracted uneventfully, and his postoperative course was unremarkable. The diagnosis and treatment for this case are discussed along with a review of the literature.
C5a delays apoptosis of human neutrophils via an extracellular signal‐regulated kinase and Bad‐mediated signalling pathway

Aims We recently demonstrated that complement fragment C5a delays apoptosis of human neutrophils via induction of the phosphatidylinositol-3 kinase (PI 3-K) pathway. In the present study, we examined whether C5a modulates neutrophil survival through the extracellular signal-regulated kinase (ERK) and Bad-mediated signalling pathway. Methods Human neutrophils were isolated by percoll gradient and preincubated for 1 h with or without PD98059 (20 µM), a specific ERK inhibitor, followed by incubation with C5a (1 µg mL−1) for 24 h. Apoptosis was quantified by flow cytometry, using propidium iodide nuclear staining. Extracellular signal-regulated kinase downstream signalling events were evaluated by measuring the expression of cytosolic total and phosphorylated p44/p42 proteins, and Bad phosphorylation using immunoblot analyses. These time-dependent analyses were performed over a brief exposure to C5a (0–30 min). Modulation of cytosolic caspase-9 and caspase-3 activity was measured by Western blot analyses. Results C5a inhibited neutrophil apoptosis (P = 0·04), which was abrogated in the presence of PD98059 (P = 0·04). Time-dependent effect of C5a on p44/p42 phosphorylation was rapid, peaked at 5 min, and was abrogated by the ERK inhibitor (P = 0·04). In addition, brief stimulation of neutrophils with C5a induced phosphorylation of Bad, which was inhibited by the ERK inhibitor (P = 0·03). Further, C5a suppressed the proteolytic cleavage of caspase-9 and caspase-3, which was reversed by ERK inhibition. Finally, blockade of both the ERK (with PD98059) and PI 3-K (with wortmannin) pathways did not induce additive inhibition of neutrophil apoptosis by C5a. Conclusion This study demonstrates that in addition to the PI 3-K pathway, C5a also inhibits neutrophil apoptosis via an ERK-signalling pathway, resulting in phosphorylation of Bad and blockade of proteolytic cleavage of caspases. The activation of this additional survival-signalling pathway may be another important cellular mechanism that enhances neutrophil survival in inflammatory states.
‘Partist’Resistance to the Many*

We are confronted by a metaphysical problem and discover, to our dismay, that standard proposals for its resolution have strongly counterintuitive corollaries. That naturally encourages consideration of previously overlooked or neglected ways out of the problem. As it turns out, one of these unorthodox proposals has a leg up on the various standard ways out of our problem. Metaphysical progress. This is the general line pursued by Hud Hudson. The seemingly intractable problem that is Hudson's primary concern emerges from a set of assumption suggesting that a great many people are located more or less where each of us is located. Many people exist where, as we normally would judge, only a single person is located! We are confronted by the dreaded Problem of the Many, and told that "every out seems to involve some severe embarrassment or other" (pp. 16-17). There is reason to turn attention to unorthodox previously ignored or neglected "outs". Much of Hudson's book is devoted to the task of arguing that one such proposal Partism, as Hudson names it offers the best resolution of the Problem of the Many (PM hereafter). Hudson's defense of Partism rests largely with the conviction that standard treatments of PM are "overwhelmingly unattractive" (p. 45). We might agree with that and also have grave misgivings about Partism. On such a conception of the situation, PM has yet to be resolved. Although I have a number of reservations about claims defended by Hudson, I think this is a marvelous book that is worthy of close attention. In Chapter 1, Hudson argues against ten proposed resolutions of PM. His own Partist approach to PM is presented in Chapter 2. Chapter 3 defends both an epistemic approach to vagueness and the thesis of (compositional) Universalism. Chapters 4 6 address the subject of personal identity and various moral questions concerning pre-persons and post-persons. Chapter 7 is devoted to a defense of the view that Christian Materialism allows for bodily resurrection.
Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis

Selenoprotein K (SelK) is an 11-kDa endoplasmic reticulum (ER) protein of unknown function. Herein, we defined a new eukaryotic protein family that includes SelK, selenoprotein S (SelS), and distantly related proteins. Comparative genomics analyses indicate that this family is the most widespread eukaryotic selenoprotein family. A biochemical search for proteins that interact with SelK revealed ER-associated degradation (ERAD) components (p97 ATPase, Derlins, and SelS). In this complex, SelK showed higher affinity for Derlin-1, whereas SelS had higher affinity for Derlin-2, suggesting that these selenoproteins could determine the nature of the substrate translocated through the Derlin channel. SelK co-precipitated with soluble glycosylated ERAD substrates and was involved in their degradation. Its gene contained a functional ER stress response element, and its expression was up-regulated by conditions that induce the accumulation of misfolded proteins in the ER. Components of the oligosaccharyltransferase complex (ribophorins, OST48, and STT3A) and an ER chaperone, calnexin, were found to bind SelK. A glycosylated form of SelK was also detected, reflecting its association with the oligosaccharyltransferase complex. These data suggest that SelK is involved in the Derlin-dependent ERAD of glycosylated misfolded proteins and that the function defined by the prototypic SelK is the widespread function of selenium in eukaryotes.
Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells.

Background & Aims: Cholangiocarcinomas often arise within a background of chronic inflammation suggesting that inflammation imparts survival signals to this cancer. Previous studies have also shown that the inflammatory cytokine interleukin (interleukin [IL]-6) contributes to survival signals in an autocrine fashion and that myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell leukemia-2 family, is an important participant in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in this neoplasm. The present study evaluated the possibility that IL-6 signaling contributes to Mcl-1 up-regulation in cholangiocarcinoma. Methods: Protein kinase B (Akt) and Mcl-1 expression in human tissue was assessed by immunohistochemistry. The relationship between IL-6 signaling, Akt activity, and Mcl-1 expression was examined in cell lines. Results: Immunohistochemistry showed that the serine/threonine kinase Akt and Mcl-1 are strongly expressed in the preneoplastic bile duct inflammatory disease primary sclerosing cholangitis and in human cholangiocarcinoma specimens. Immunoblotting showed that Akt is expressed and constitutively phosphorylated in 3 human cholangiocarcinoma lines. Further analysis showed that treatment with anti-IL-6-neutralizing antiserum led to reduced Akt phosphorylation, diminished Mcl-1 expression, and enhanced TRAIL sensitivity. Likewise, the Akt inhibitor A443654.3 led to diminished signaling through the Akt pathway, decreased Mcl-1 expression, and enhanced TRAIL-mediated apoptosis. Conclusions: These findings not only show that an autocrine IL-6/Akt signaling pathway enhances Mcl-1 expression in cholangiocarcinoma but also suggest a strategy for overcoming the resulting apoptosis resistance.
Single layer of Mn in a GaAs quantum well: A ferromagnet with quantum fluctuations

Some of the highest transition temperatures achieved for Mn-doped GaAs have been in $\ensuremath{\delta}$-doped heterostructures with well-separated planes of Mn. In the absence of magnetic anisotropy, the Mermin-Wagner theorem implies that a single plane of magnetic ions cannot be ferromagnetic. Using a Heisenberg model, we show that the same mechanism that produces magnetic frustration and suppresses the transition temperature in bulk Mn-doped GaAs, due to the difference between the light and heavy band masses, can stabilize ferromagnetic order for a single layer of Mn in a GaAs quantum well. This comes at the price of quantum fluctuations that suppress the ordered moment from that of a fully saturated ferromagnet. By comparing the predictions of Heisenberg and Kohn-Luttinger models, we conclude that the Heisenberg description of a Mn-doped GaAs quantum well breaks down when the Mn concentration becomes large, but works quite well in the weak-coupling limit of small Mn concentrations. This comparison allows us to estimate the size of the quantum fluctuations in the quantum well.
Design and application of a GaAs digital RF memory chip

The design and performance of a GaAs integrated memory/logic chip designed for digital RF memory (DRFM) applications is described. This chip, called a programmable delay-line element (PDLE), implements the basic DRFM storage and delay functions. The RAM-with-logic configuration combines a 4-kb static RAM with 750 logic gates, providing on a single chip the components for storage, address generation, demultiplexing, multiplexing, and control functions normally provided by a variety of separate chips. A distributed control organization, where the chip is configured to provide as outputs all the signals required as inputs to another identical chip, is used. Chips cascaded into strings implement the programmable delay lines required for DRFM systems. Problems associated with complex signal distribution networks are avoided since, within a string, signal distribution requires only local interconnections between adjacent chips. Correct operation of all functions was demonstrated in a four-chip string which provides a total memory capacity of 16 kb. The maximum sampling rate was 800 MHz, and power dissipation was approximately 2 W per chip. >
Structural Basis of Smad1 Activation by Receptor Kinase Phosphorylation

Phosphorylation of Smad1 at the conserved carboxyl terminal SVS sequence activates BMP signaling. Here we report the crystal structure of the Smad1 MH2 domain in a conformation that reveals the structural effects of phosphorylation and a molecular mechanism for activation. Within a trimeric subunit assembly, the SVS sequence docks near two putative phosphoserine binding pockets of the neighboring molecule, in a position ready to interact upon phosphorylation. The MH2 domain undergoes concerted conformational changes upon activation, which signal Smad1 dissociation from the receptor kinase for subsequent heteromeric assembly with Smad4. Biochemical and modeling studies reveal unique favorable interactions within the Smad1/Smad4 heteromeric interface, providing a structural basis for their association in signaling.
The Ethics of Care: Personal, Political, and Global

The Ethics of Care: Personal, Political, and Global. By Virginia Held. New York: Oxford University Press, 2005. 220p. $45. In her latest book, Virginia Held elaborates on themes from previously published articles to explicate and defend the ethics of care. For those unfamiliar with this well-developed tendency of feminist thought, she reviews its evolution from the 1980s writings of Sara Ruddick, Carol Gilligan, and Nel Noddings to the more recent work of theorists including, among many others, Eva Kittay, Annette Baier, Joan Tronto, and Selma Sevenhuijsen. Held also underlines the differences between the ethics of care and dominant moral and political perspectives, including Kantian universalism, utilitarianism, liberal contract theory, and virtue theory. She proposes that care is, compared with justice, the more basic value, on the grounds that society can exist without the latter but not without the former. She recommends that men and women participate equally in care activities; that care infuse citizen as well as familial relations; and that society beat back the imperializing thrust of the market ethos and the conflict-mongering thrust of the militarized state to improve the well-being of children, the elderly, the sick and disabled, the community, culture, the environment, and deprived regions of the world.
Gene therapy: clinical considerations.

Gene therapy can be defined as the introduction of nucleic acid into cells to ameliorate a disease process. To date there have been more than 313 trials with more than 2000 patients enrolled. The majority of these trials are Phase I or Phase II and have target diseases of either cancer or acquired immunodeficiency syndrome using retroviral and retroviral vectors. The choice of molecular target and the means of delivery have varied and chosen on the basis of the specific indication. Until recently the risks associated with treatment had been under appreciated. The first fatality associated with gene therapy occurred in September 1999 in which an adenoviral vector was used in the treatment of a patient with orthnithine transcarbamylase deficiency. Subsequent to this report, other reports have surfaced suggesting that reporting of previous non-fatal reactions may have been minimized. Safety must be considered in relation to the disease process and to alternative treatments available. It may be easier to rationalize placing patients at risk who are facing a fatal disease process without effective alternative therapies. The ultimate goal of gene therapy will be the injection of a vector that has a specific target cell and that will be regulated by physiologic signals. Such a goal will require major improvements in the currently available delivery systems or the development of novel vectors.
Who wants to walk? Preferences for recovery after SCI: a longitudinal and cross-sectional study.

Cross-sectional and longitudinal direct observation of a constrained consensus-building process in nine consumer panels and three rehabilitation professional panels. To illustrate differences among consumer and clinician preferences for the restoration of walking function based on severity of injury, time of injury and age of the individual. Regional Spinal Cord Center in Philadelphia, USA. Twelve panels (consumer and clinical) came to independent consensus using the features–resource trade-off game. The procedure involves trading imagined levels of independence (resources) across different functional items (features) at different stages of recovery. Walking is given priority early in the game by eight out of nine consumer panels and by two out of three professional panels. The exception consumer panel (ISCI<50) moved walking later in the game, whereas the exception professional panel (rehRx) moved wheelchair early but walking much delayed. Bowel and Bladder was given primary importance in all panels. Walking is a high priority for recovery among consumers with spinal cord injury irrespective of severity of injury, time of injury and age at time of injury. Among professional staff, walking is also of high priority except in rehabilitation professionals.
Glass half empty: the Eurozone and internal market overshadow the health effects of Maastricht

In the past 20 years, the European Union (EU) has become part of health policymaking to an extent that few commentators would have predicted. But the EU’s positive contributions as an advocate for public health have been overshadowed by the effects of its internal market regulation and centralized fiscal governance on the health of Europeans. Three things happened in Maastricht 20 years ago. European heads of state met to celebrate the completion of the internal market as prefigured in the Single Europe Act, agreed to create a common currency and added the first clear and positive words about health to the Treaties. This first mention of health was the harbinger of more effective promotion of health issues within EU policymaking.1 In time, however, the internal market and the single currency have had the biggest health consequences of the three.2 Putting aside some specific areas of EU competency created under the public health power, such as blood safety, the public health language in the treaties as they stand authorizes EU action, obliges the EU to take health into account and clarifies that it does not have a role in the organization and finance of health care services. Within this framework, most of EU public health policy is expenditure. This means it is limited. EU expenditures as a percentage of gross domestic product (GDP) are nowhere near as much as a member state health system spends, and health is a tiny share of EU expenditures (the EU member states’ average expenditure on health in 2012 was 9% of GDP, according to …
STRUCTURE AND TOTAL SYNTHESIS OF HF-7, A NEUROACTIVE GLYCONUCLEOSIDE DISULFATE FROM THE FUNNEL-WEB SPIDER HOLOLENA CURTA

Spider venom toxins have attracted considerable attention for their ability to block the action of excitatory amino acids such as glutamate and aspartate. A new neuroactive compound designated HF-7 was isolated in 1993 from the venom of a funnel-web spider, Hololena curta. HF-7 was shown to block kainate receptors and, albeit weakly, L-type calcium channels. Spectroscopic analysis established the structure of HF-7 as an unusual acetylated, disulfated fucopyranosyl guanosine, with the acetate ester attached at the 4-position of an α-linked fucose ring and two sulfates attached to the ribose ring. Because insufficient quantities of natural HF-7 were available for chemical degradation or X-ray diffraction analysis, total synthesis of three candidate structures was used to establish the identity of HF-7. Once HF-7 was fully characterized as 3‘-O-(4‘ ‘-O-acetyl-α-l-fucopyranosyl)guanosine-2‘,5‘-disulfate, an improved, targeted synthesis of the natural product was developed.
A Theoretical Heterogeneous Model of Wood Pyrolysis

Abstract A model is developed for the pyrolysis and combustion of wood, explicitly including the fibrous heterogeneity of the substance. The heterogeneity enters the equations through the fiber diameter and the interfiber material treated as undergoing charring. The emphasis is on the condensed phase. The vapor phase details are not included in this paper. The energy flux needed to drive the pyrolysis is externally prescribed; an externally heated slab or a slab burning under its own flame resulting from the products of pyrolysis mixing with an oxidizer (air) provide two examples. The method of matched asymptotic expansions is used to analytically derive a closed form expression for the time independent rate of regression of the charring plane, including the nonlinear Arrhenius degradation term for the pyrolysis. The differences between predictions from previous homogeneous models and this heterogeneous model are discussed. Some remarks concerning the apparent negative temperature rate region indicated by...
Fifth-order aberration theory of gradient-index optics

The fifth-order aberration coefficients for gradient-index lenses are presented. A procedure for calculation is outlined.
Multiple layer data hiding scheme for medical images

Nowadays, the transmission of digitized medical information has become very convenient due to the generality of Internet. Regardless of the prevention of medical fault, the real-time detection of abnormal event, the support of clinical decision, even the model developing of medical service based on patient, Internet has created the biggest benefit to achieve the goals of promoting patient safety and medicine quality. However, it is easier that the hackers can grab or duplicate the digitized information on the Internet. This will cause following problems of medical security and copyright protection. Therefore, the information hiding techniques are developed for protection of medical information and copyright. This paper proposes a multiple-layer data hiding technique in spatial domain. It utilizes a reduced difference expansion method to embed the bitstream in the least significant bits (LSBs) of the expanded differences. By using the reduced difference expansion method, we can embed a large amount of data in a medical image whose quality can also be maintained. Moreover, the original image can be restored after extracting the hidden data from the stego-image. Experimental results show that the proposed scheme provides higher embedding capacity at the same level image quality compared with Tian's difference expansion method.
Boundary Crossings: Oral History of Nazi Germany and Apartheid South Africa – a Comparative Perspective

Oral history can reveal how memory and imagination generate historical knowledge in an effort to make sense of the personal experience of historical events. Many things shape memory: for instance the circumstances of the remembering, the time between the event and the telling, and the age of the narrator both then and now. Another influence on memory, less well understood, is the socio-political context of experience, in particular the way in which revisions of a nation's historical memory may compel individuals to repress or alter their private memories. Using oral narratives of the Nazi period in Germany and the Apartheid era in South Africa respectively, we tried to recover the subjective popular experiences of social change wrought within living memory.1 The stories we heard during our research were filtered through the past and present experiences of their narrators. They turned around silences and censorship, around minute, almost insignificant episodes, and around decisive experiences. We were struck by the tension that emerged between the present and past historical political context in which these stories are embedded and the private personal experiences of our respondents. As we compared our fieldwork notes, it became apparent that for both of us there were disturbing moments in the interviews, when tensions arose from something uncomfortable, shocking, or offensive. Although the interviews followed common lines, some were more marked by their narrators' obvious attempts to manipulate them. Beyond this, in some the normal narrative broke down, a boundary was crossed and the narrative ruptured into something atypical. The significance of such moments, however rare, continued to puzzle us as we wrestled with the challenge of transforming the stories we were told into history. Despite the narrators' active part in telling and remembering their life histories,2 what we found then seemed to go beyond the narrator's conventional story, beyond what the narrator thought she was telling us, and beyond the questions set by our research agendas. We believe that such moments in the interview process itself, which we will call boundary crossings or ruptures in the narrative, reveal oral history's potential to
CD8+ T-cell interaction with HCV replicon cells: evidence for both cytokine- and cell-mediated antiviral activity.

Abstract The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or in vitro model has hindered our understanding of the host T-cell/HCV interaction. Our aim was to develop an in vitro model to study the mechanisms of HCV-specific T-cell-mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I-matched subject. CD8 + T cells were expanded with 2 HCV-specific/HLA-restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with 51 Cr. After a 48-hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti-interferon gamma (IFN-γ), anti-tumor necrosis factor α (TNF-α), and anti-FasL. Cytolytic activity was measured by 51 Cr release. HCV replicon cells express homozygous HLA-A11 alleles and present HCV nonstructural proteins. HCV-specific expansion of CD8 + cells led to a 10-fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T-cell binding, suggesting cytokine-mediated antiviral activity. The CD8 + antiviral effect was markedly reduced by blocking either IFN-γ or FasL but was unaffected by blocking TNF-α. In conclusion, HCV-specific CD8 + cells inhibit viral RNA replication by cytokine-mediated and direct cytolytic effects. This T-cell/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV-infected hepatocytes. (H epatology 2003;37:1335-1342.)
Engaging the Periphery for Visual Communication on Mobile Phones

While mobile phones have become ubiquitous instruments of communication and social interaction, they still require explicit interaction, placing high demands on attention. Engaging the periphery of users' attention offers opportunities for awareness and interaction while reducing demands on attention and risks of disruption. We explore the mobile peripheral design space with Emotipix, an application for camera phones that turns the background of the phone's display into a place for visual conversations. We conducted an exploratory 2-week user study with 6 pairs and one 4-person group, and found that Emotipix facilitated ongoing social practices. Our study shows that there is an unexploited opportunity to use mobile phones for peripheral awareness. We provide recommendations for managing users' expectations, desires for control, and privacy in mobile peripheral display design.
A role for TBP dimerization in preventing unregulated gene expression.

Abstract The recruitment of the TATA box–binding protein (TBP) to promoters in vivo is often rate limiting in gene expression. We present evidence that TBP negatively autoregulates its accessibility to promoter DNA in yeast through dimerization. The crystal structure of TBP dimers was used to design point mutations in the dimer interface. These mutants are impaired for dimerization in vitro, and in vivo they generate large increases in activator-independent gene expression. Overexpression of wild-type TBP suppresses these mutants, possibly by heterodimerizing with them. In addition to loss of autorepression, dimerization-defective TBPs are rapidly degraded in vivo. Direct detection of TBP dimers in vivo was achieved through chemical cross-linking. Taken together, the data suggest that TBP dimerization prevents unregulated gene expression and its own degradation.
Electromagnetic and ultrasonic induction of hyperthermia in tissue-like substances

The potential of electromagnetic radiation and ultrasound for generating hyperthermia in tissues is discussed. Electrical properties, propagation parameters for electromagnetic and ultrasonic radiation and reflection problems yield limitations on most suitable frequency choices. Considerable insight has been gained in electromagnetic induced heat deposition patterns for the case of whole body irradiation and for local irradiations which can cause hot spot type of heating patterns. Pertinent results are compared and indicate that frequencies near 1000 MHz may be optimal for the electromagnetic case. But RF-frequencies using frequencies sufficiently low to reduce the magnetically induced term provide probably greater reproducibility. Finally recent work on mm-wave therapy and diagnosis is indicated. Emphasis is on the comparative merits of the various possible approaches.
Regional Distribution of Catalase in the Adult Rat Brain

: Catalase activity was measured in 11 areas of perfused adult rat brain. The hypothalamus and substantia nigra contained the highest activities. The corpus callosum. a white-matter structure, contained intermediate activity. The caudate-putamen and frontal cortex contained the lowest activities. Regional catalase bears some relationship to the reported distribution of microperoxisomes, but considerable activity is present in areas with few microperoxisomes. Catalase may function as one of the systems detoxifying H2O2 formed in CNS amine metabolism.
Mislocalization to the nuclear envelope: An effect of the dystonia-causing torsinA mutation

Primary dystonia is a disease characterized by involuntary twisting movements caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a form of primary dystonia caused by an in-frame GAG deletion (ΔE302/3) in the TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We show that torsinA is also present in the nuclear envelope (NE), where it appears to interact with substrate, and that the ΔE302/3 mutation causes a striking redistribution of torsinA from the endoplasmic reticulum to the NE. In addition, ΔE302/3-torsinA recruits WT torsinA to the NE, potentially providing insight into an understanding of the dominant inheritance of the disease. DYT1 dystonia appears to be a previously uncharacterized NE disease and the first, to our knowledge, to selectively affect CNS function.
A prediction rule to identify low-risk patients with heart failure

Objectives: To derive a prediction rule using data available in the emergency department (ED) to identify a group of patients hospitalized for the treatment of heart failure who are at low risk of death and serious complications. Methods: The authors analyzed data for all 33,533 patients with a primary hospital discharge diagnosis of heart failure in 1999 who were admitted from EDs in Pennsylvania. Candidate predictors were demographic and medical history variables and the most abnormal examination or diagnostic test values measured in the ED (vital signs only) or on the first day of hospitalization. The authors constructed classification trees to identify a subgroup of patients with an observed rate of death or serious medical complications before discharge < 2%; the tree that identified the subgroup with the lowest rate of this outcome and an inpatient mortality rate < 1% was chosen. Results: Within the entire cohort, 4.5% of patients died and 6.8% survived to hospital discharge after experiencing a serious medical complication. The prediction rule used 21 prognostic factors to classify 17.2% of patients as low risk; 19 (0.3%) died and 59 (1.0%) survived to hospital discharge after experiencing a serious medical complication. Conclusions: This clinical prediction rule identified a group of patients hospitalized from the ED for the treatment of heart failure who were at low risk of adverse inpatient outcomes. Model performance needs to be examined in a cohort of patients with an ED diagnosis of heart failure and treated as outpatients or hospitalized.
Calorimetric enthalpies of formation and decomposition of hydrides of ZrMn2, ZrCr2, and related systems☆

Abstract Integral enthalpies of absorption and desorption of hydrogen by hyperstoichiometric ZrMn2T0.8 (T = Mn, Fe, Co, Ni, and Cu) and stoichiometric ZrMn2- and ZrCr2-based alloys have been determined. The measured enthalpies range from ∼24 to ∼41 kJ/mole H2. The ΔH values for hydrides formed by the series of metallic hosts ZrMn2T0.8 are smaller than that for ZrMn2, accounting for the enhanced dissociation pressures of the ZrMn2T0.8 hydrides. In the series of ZrMn2T0.8 hydrides there is a pronounced minimum for hydride of ZrMn2Co0.8, accounting for the extraordinarily high decomposition pressure of this system. Site occupancies, provided by published neutron diffraction studies, were used to calculate configurational entropies of ZrCr2 hydrides and related systems. Results obtained were in fair agreement with experiment.