bluuebunny/crossref_metadata_2025 huggingface dataset:
Symmetrical- and Unsymmetrical Terminally Alkylated Polyamines
Authors: Woster Patrick M. , Casero, Jr Robert A.
Published: November 2011

Since their introduction in the late 1980s, analogs of the natural polyamines putrescine, spermidine and spermine have facilitated the understanding of polyamine cellular function, and in some cases have also shown promise as therapeutic agents. Early examples of these analogs include the bis(ethyl)polyamines, which were developed as potential antitumor and antidiarrheal agents. The design of these analogs was based on the simple theory that alteration of the pKa values for the terminal nitrogens of spermidine and spermine through monoalkylation would produce analogs that could disrupt polyamine metabolism. The bis(ethyl)polyamines were shown to be taken up by the polyamine transporter, which is elevated in many proliferating cells, and then to downregulate polyamine biosynthesis. However, these agents did not substitute for the cellular functions of the natural polyamines, leading to polyamine depletion and cell death. The success of the bis(ethyl)polyamines led to the synthesis of unsymmetrically substituted alkylpolyamine analogs, which provided a venue for elucidating the structure/activity relationships for terminally alkylated polyamines. Exploration of the chemical space available for the terminal alkyl substituents has resulted in the discovery of potent second-generation agents and allowed the introduction of structural diversity into the resultant molecules. Finally, compounds featuring isosteric replacements for the terminal amine moieties of the alkylpolyamines has resulted in a new class of polyamine analog that exhibits potent antitumor, antiparasitic and epigenetic activity in vitro and in vivo. In this chapter, the evolution in structure of the alkylpolyamines, as well as their development as potential drugs, will be described.
Targeting the Polyamine Catabolic Enzymes Spermine Oxidase,N1-Acetylpolyamine Oxidase and Spermidine/SpermineN1-Acetyltransferase
Authors: Goodwin Andrew C. , Murray-Stewart Tracy R. , Casero, Jr Robert A.
Published: November 2011

Three enzymes perform degradation of higher polyamines: spermine oxidase (SMO), N1-acetylpolyamine oxidase (APAO) and spermidine/spermine-N1-acetyltransferase (SSAT). This chapter will focus on the structure, function and mechanism of action of these polyamine catabolic enzymes and their role as therapeutic targets. Activation of polyamine catabolism is an encouraging strategy for the development of cytotoxic agents. However, increased levels of SMO, APAO and SSAT have been associated with the development of a number of human diseases, resulting in data suggesting that in these cases, inhibition of polyamine catabolism may represent a promising avenue for preventive or prophylactic treatment of these conditions. The chapter summarizes in vitro, in vivo and clinical research results, and offers perspectives on future attempts to develop SMO, APAO and SSAT as drug targets.
Design of Polyamine Transport Inhibitors as Therapeutics
Authors: Phanstiel IV Otto , Julian Archer Jennifer
Published: November 2011

Upregulated polyamine biosynthesis and high polyamine transport activity are hallmarks of aggressive cancers. Efforts to inhibit polyamine biosynthesis via inhibition of the proto-oncogene ornithine decarboxylase (ODC) have been disappointing in the clinic (e.g., difluoromethylornithine, DFMO) due to unforeseen compensatory mechanisms involving polyamine import. In short, DFMO-treated cells were able to meet their polyamine requirements via import of polyamines from extracellular sources. Polyamine transport inhibitors (PTIs) have been developed to work synergistically with DFMO to induce sustained polyamine depletion. The goal of this review is to summarize the efforts to develop effective PTI agents. A new terminology is introduced to better describe molecules which enter cells via a transport system (i.e., transporton) versus molecules which interact with the transport system but show no net entry into the cell (i.e., anti-transporton). Both transportons and anti-transportons will inhibit the uptake of native polyamines, and a clear distinction was necessary to properly describe this class of compounds. Molecular designs involving polycations with discrete spacing and number of charges were shown to be very effective PTI agents. Arylpolyamines, lipopolyamines, antibodies specific for heparan sulfate proteoglycans and cationic proteins have all shown activity as PTIs. Future PTI design will be shaped by the extensive structure–activity relationships developed to date.
Non-Covalent Polynuclear Platinum Compounds as Polyamine Analogs
Authors: Qu Yun , Moniodis Joseph J. , Harris Amanda L. , Yang Xiaohong , Hegmans Alex , Povirk Lawrence F. , Berners-Price Susan J. , Farrell Nicholas P.
Published: November 2011

Polynuclear platinum compounds (PPCs) represent a discrete class of antitumor agents that bear structural resemblance to polyamines. This chapter reviews developments on the chemistry and biology of polynuclear platinum drugs and especially the recognition that “non-covalent” agents based on this motif represent a further challenge to the structure-activity paradigms for platinum antitumor agents. Pt-DNA bond formation is not a strict requirement for DNA affinity leading to manifestation of promising cytotoxicity and antitumor activity. Non-covalent PPCs bind to DNA in a non-covalent manner through a novel binding motif, the phosphate clamp, analogous to the arginine fork. This binding mode is discrete from “classical” intercalation and minor groove binding. In solution, analysis of 1-D and 2-D 1HNMR data places the compounds in the minor groove of the DNA, spanning several base pairs. A melphalan protection assay indicated that the complex was at least as effective in blocking melphalan access to the minor groove as distamycin. Further biological consequences of the structure are remarkably enhanced cellular accumulation, further distinguishing the non-covalent group as a unique class of agents.
Polyamine-Based Agents for Gene and siRNA Transfer
Authors: Blagbrough Ian S. , Metwally Abdelkader A. , Ahmed Osama A. A.
Published: November 2011

In this chapter, we delineate how one might design, synthesize and formulate an efficient, non-toxic, non-viral lipopolyamine vector for possible future in vivo application. This can be achieved by the ability of novel polyamine conjugates, e.g. spermine, to condense DNA, leading to the self-assembly of nanoparticles that are suitable for gene or siRNA delivery. Our focus is on the lipopolyamines synthesized by conjugation to the naturally occurring tetra-amine spermine. As the first step in gene delivery is the condensation of DNA and formation of nanoparticles, this step must be studied in detail for any understanding of rational design. The ability of lipopolyamines to condense DNA is compared and contrasted with well-known literature DNA condensing agents and with commercially available transfection agents. The transfection efficiency of these novel lipopolyamines has been investigated in cell lines and in animals. There is a tension between the cytotoxicity of these compounds and their delivery efficiency. The self-assembly of nanoparticles of genes and siRNA (lipoplexes) makes polyamine-based agents both attractive and efficient for polynucleotide transfer.
The Design and Development of Polyamine-Based Analogs with Epigenetic Targets
Authors: Huang Yi , Marton Laurence J. , Woster Patrick M.
Published: November 2011

The natural polyamines are polycationic alkylamines with multiple functions that are essential for cell growth. The association between polyamines and chromatin extends to DNA–protein interaction, particularly those interactions involving histone modifications and chromatin remodeling. The increasing knowledge of the unique role that the polyamines play in chromatin regulation has received considerable attention in recent years and led to our interest in exploiting structure-specific polyamine analogs in targeting chromatin remodeling enzymes for cancer therapy. We first designed and synthesized a series of polyaminohydroxamic acid and polyaminobenzamide compounds using various polyamine analog backbone structures combined with active site-directed inhibitor moieties of the class I/II histone deacetylases (HDACs). We then demonstrated that specific members of these analog families functionally inhibit activity of histone deacetylases and re-activate tumor-suppressor genes in cancer cells. The recent identification of flavin-dependent histone lysine-specific demethylase 1 (LSD1) demonstrated that histone methylation is a dynamic process similar to other post-translational histone modifications. LSD1 has been identified as a component of transcriptional repressor complexes that specifically catalyzes demethylation of mono- and dimethyl-lysine 4 of histone 3, key positive chromatin marks associated with transcriptional activation. Aberrant demethylation of lysine 4 of histone 3 by LSD1 may broadly repress the expression of tumor suppressor genes that are important in human cancers. Based on the structural and catalytic similarities of LSD1 and polyamine oxidases, we recently identified a group of biguanide, bisguanidine and oligoamine polyamine analogs as potent inhibitors of LSD1. Treatment with these LSD1 inhibitors leads to re-expression of aberrantly silenced genes in cancer cells. The results from these studies imply that the use of these novel polyamine-based HDAC and LSD1 inhibitors may represent a new direction for epigenetic drug development in cancer prevention and therapy.
Clinical Applications of Polyamine-Based Therapeutics
Authors: Bachmann André S. , Levin Victor A.
Published: November 2011

Polyamines are biologically important molecules in DNA and RNA function, transcription and protein synthesis, and appear to be necessary for the propagation and invasion of cancer cells, viability of parasites and, possibly, progression of neurodegenerative diseases. Ornithine decarboxylase (ODC) is a rate-limiting enzyme of polyamine biosynthesis, catalyzing the conversion of ornithine to putrescine. From here, specific synthases anabolize putrescine to spermidine and thence to spermine utilizing aminopropyl groups donated by decarboxylated S-adenosylmethionine (dcAdoMet) after conversion of S-adenosylmethionine (AdoMet) by S-adenosylmethionine decarboxylase (AdoMetDC). Together, ODC and AdoMetDC are two critical enzymes supplying the cellular polyamine pool. For these reasons, drugs that inhibit these two enzymes would be expected to have anticancer activity and an ability to inhibit survival of parasites and possibly prevent or at least delay the progression of neurodegenerative diseases. In this chapter, we discuss, in some depth, the results of anticancer trials with α-difluromethylornithine (DFMO, eflornithine, ornidyl), methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG, methyl-GAG) and SAM486A (CGP48664, free base of 4-(aminoimino-methyl)-2,3-dihydro-1H-inden-1-one-diaminomethylenehydrazone). These drugs have been shown to have variable efficacy to control leukemia and solid tumor growth. DFMO is currently evaluated in combination with etoposide in pediatric patients with neuroblastoma. In addition, DFMO has been used in colon-cancer polyp chemoprevention trials with success. DFMO has been approved for the treatment of Trypansoma brucei infection, but no polyamine synthesis inhibitor has been approved for the treatment of cancer, although DFMO and MGBG have shown good clinical activity in clinical cancer trials. In addition, polyamine inhibitors may also become of interest for the treatment of human neurodegenerative diseases, but to date, no clinical trials have been performed.
Calix[4]pyrogallolarenes as novel high temperature inhibitors of oxidative degradation of polymers
Authors: Ziaja Przemyslaw , Jodko-Piorecka Katarzyna , Kuzmicz Rafal , Litwinienko Grzegorz
Published: November 2011

Oxidative stability of high density polyethylene containing C-alkylcalix[4]pyrogallolarenes was studied by Differential Scanning Calorimetry. The kinetic parameters of non-isothermal oxidation indicate that pyrogallolarenes are effective antioxidants at temperatures above 150 °C.
Prospects for fusion power
Authors: Post Richard F.
Published: November 2011

The quest for fusion power began some forty years ago, with the discovery of nuclear fusion reactions, followed by the theory of thermonuclear processes, which successfully explained the source of the energy of the Sun and stars. But then, apart from the musings of a perceptive few, nearly twenty years passed before heightened interest in nuclear energy sources stimulated a serious attack on the problem. By this time both the potentialities of fusion and the growing need for energy from other than fossil-fuel sources had become apparent. Here I shall try to evaluate the present state of research on controlled thermonuclear reactions in the context of the urgent need for developing new, environmentally acceptable, energy sources.
Physics Today and the spirit of the Forties
Authors: Weiner Charles
Published: November 2011

Great expectations were in the air for the future of physics when the first issue of PHYSICS TODAY appeared in May 1948. The applications of physics in World War II had created a new social environment for science in terms of public attitudes and government financial support. Among physicists themselves excitement was brewing over new experimental discoveries and theoretical interpretations in solid-state and particle phenomena. At the same time, new instruments of unprecedented power and size were offering high hopes for probing both the smallest particles of matter and the largest dimensions of the universe. The birth of PHYSICS TODAY as a communication link among physicists, and between them and the larger community, reflected these events of the postwar years. The emergence of the new magazine in May—like the dedication in June of the 200-inch Palomar telescope and the public announcement in July of the discovery of the transistor—was the culmination of a process that had been set in motion years earlier.
Macroscopic quantum phenomena from pairing in superconductors
Authors: Schrieffer J. Robert
Published: November 2011

It gives me great pleasure to have the opportunity to join my colleagues John Bardeen and Leon Cooper in discussing with you the theory of superconductivity. Since the discovery of superconductivity by H. Kamerlingh Onnes in 1911, an enormous effort has been devoted by a spectrum of outstanding scientists to understanding this phenomenon. As in most developments in our branch of science, the accomplishments honored by this Nobel prize were made possible by a large number of developments preceding them. A general understanding of these developments is important as a backdrop for our own contribution.
Electron-phonon interactions and superconductivity
Authors: Bardeen John
Published: November 2011

Our present understanding of superconductivity has arisen from a close interplay of theory and experiment. It would have been very difficult to have arrived at the theory by purely deductive reasoning from the basic equations of quantum mechanics. Even if someone had done so, no one would have believed that such remarkable properties would really occur in nature. But, as you well know, that is not the way it happened; a great deal had been learned about the experimental properties of superconductors, and phenomenological equations had been given to describe many aspects, before the microscopic theory was developed. Some of these have been discussed by Schrieffer and by Cooper in their talks.
Record superconductor at 22.3 K
Authors: Cohn Ronald J.
Published: November 2011

A new record-high superconducting transition temperature, Tc = 22.3 K for Nb3Ge, was announced recently. This temperature is, most significantly, more than two degrees above the boiling point of hydrogen; a significant step may therefore have been taken to move superconductivity applications from a technology based on liquid helium to one based on liquid hydrogen. The previous high transition temperature reported was 20.98 K for a Nb–Al–Ge pseudobinary alloy.
Hybrid magnets promise high field for low power
Authors: Saar Robert A.
Published: November 2011

Researchers at MIT's National Magnet Laboratory are employing a hybrid system to produce high magnetic fields with relatively low power consumption. A field of 195 kilogauss has been produced through the combined effect of a water-cooled magnet within a superconducting magnet.
Preparing students for physics-related jobs
Authors: Strassenburg Arnold A.
Published: November 2011

Physicists are now searching for new and alternative paths for the progress of their profession through the many problems surfacing in the 1970's. During the golden years of the last decade, we in the academic world felt secure and self-contained; we did physics and we taught physics. But the growing cutbacks in funds and in job opportunities have caused us to re-evaluate our personal goals, our responsibility to the larger society and our interactions with governmental, industrial and educational institutions. The business of training physicists is no longer a viable support for the avocation of doing physics. An obvious solution to these problems is for the academic physicist to offer his talent to a wider market, to move into physics-related fields, to engage in interdisciplinary efforts to solve current social, economic and scientific problems and to offer training that will prepare students for physics-related jobs.
Extragalactic Radio Sources
Authors: Kellerman Kenneth I.
Published: November 2011

Radio astronomers have recently begun to harvest a wealth of data using instruments with greatly improved sensitivity and resolution. They are now mapping the internal structure of galaxies and quasars over a wide range of the radio spectrum. Variations in the structure as well as in the intensity of these sources are being observed on time scales ranging from a few days to a few years. The velocities of the component parts of some of the sources have been measured, and they apparently exceed the velocity of light—only one of the many problems that the new data present to astrophysicists.
Auroral effects seen in laboratory vortexes
Authors: Saar Robert A.
Published: November 2011

An explanation of the aurora's undulating folds and rays may come from models of instabilities, some of which were developed to explain effects seen in the laboratory. The folds and rays appear to be vortexes of charge density that occur when the aurora charge sheet becomes unstable above a certain charge density. Work reported by Harold F. Webster (General Electric) and Thomas J. Hallinan (University of Alaska) has centered on the analysis of charge distribution in current sheets and charge sheets in the presence of a magnetic field and its possible usefulness as an auroral model.
Research with the space shuttle
Authors: Naugle John E.
Published: November 2011

The new space transportation system based on a reusable space shuttle, currently under development, will substantially change our traditional methods of space research that have been based on a ballistic-missile technology and its reliance on expensive expendable components. The shuttle will not become operational until 1979, but the time is ripe now for planning the space-exploration and space-science programs for the period 1978–85.
Introducing the AAPM
Authors: Karzmark C. J. , O'Foghludha Fearghus
Published: November 2011

The American Association of Physicists in Medicine, affiliated with AIP since 1968, recently became a full member of the Institute. Though the AAPM is one of the smaller member societies, it may be the fastest growing. Founded in 1958, its membership is now close to 1000. This growth reflects the burgeoning interest of physicists in the social applications of their science and may be related also to the somewhat restricted opportunities in the more traditional branches of physics. Whatever the reasons, AIP members are likely to become increasingly aware of AAPM as this active society works to strengthen the substantial links it has already forged between the physics and medical communities.
Many models proposed to explain cosmic gamma-ray bursts
Authors: Scott John T.
Published: November 2011

The various wavelength regimes of observational astronomy seem to generate their maximum excitement when rapid time-varying phenomena are first observed. For example, radioastronomy gave us pulsars; x-ray astronomy has its flares and pulsating sources. Now it is the turn of gamma-ray astronomy. Ray Klebesadel, Ian Strong and Roy Olson (Los Alamos) recently reported finding 16 short bursts of cosmic gamma radiation in three-years-worth of data from the Vela satellite program.
Advances in light-emitting diodes
Authors: Duke C. B. , Holonyak N.
Published: November 2011

The bright future of semiconductor lamps, especially “light-emitting diodes,” is by now widely recognized. This recognition is fairly recent even though the existence of light emission from semiconductor junctions has been known for almost twenty years. The transformation of LED's from laboratory devices to commercial products constitutes a good example of the effective interaction between solid-state materials technology and the quantum theory of condensed matter. Moreover, this interaction continues to generate changes in the materials, fabrication techniques and cost of LED's. In this article we will examine the influence of the fundamental principles of the quantum theory of solids on the design of semiconductor light emitters. Emphasis is placed on some of the more recently recognized consequences of these principles for tunable solid-state light sources. In particular, we describe how breakdowns of momentum conservation caused by the presence of neutral impurities in semiconductors has exerted a profound influence on the materials used to construct solid-state lamps.
VLF emissions from the magnetosphere
Authors: Sudan Ravindra Nath , Denavit Jacques
Published: November 2011

From the earliest days of radio experimentation, various kinds of very-low-frequency electromagnetic radiation have intrigued those who heard the strange mixture of glissandi whistles, hisses, chirps and warbling sounds on their headphones. One common type sounds like birds awakening in the morning and was appropriately named the “dawn chorus.” Confined usually to an audiofrequency range of 200 to 30 000 Hz, these emissions appeared to be distinct from other forms of “static”—locally initiated noise due to nearby lightning strokes, precipitation, or man-made electrical interference. The observational equipment required for the study of such emissions is comparatively simple—a single-turn loop antenna connected to a high-gain, lownoise, wide-band audio amplifier. If the output is recorded on magnetic tape, spectrograms can be produced by standard techniques. Time markers can be added either from a local clock or from a radio station.
Geophysics—an overview
Authors: Spilhaus Athelstan F.
Published: November 2011

Understanding the Earth and its environment in space is a broad challenge that has been accepted by a variety of physicists, chemists, mathematicians, engineers, geologists and biologists. While many of these studied aspects of geophysics at the graduate level, many others became geophysicists without being conscious of the transition. A physicist studying phase equilibria at high pressure learns one day that he is working with materials possibly similar to the composition of the interior of the Earth. As he works with geologists and geophysicists to develop models of what we have not yet sampled, he is continuously drawn by the fascination of Earth's secrets into a total commitment to geoscience, a commitment that will not change his tools or methods of research but will necessitate constant interaction with colleagues, in a variety of disciplines, who are addressing themselves to parts of the solution for the same problem. This need for collaboration among individuals, among disciplines and among countries is a fundamental characteristic of geophysics that in a sense sets it above the basic sciences and gives it a unique flavor of excitement through accomplishment even when progress appears stalled.
The interior of the Moon
Authors: Anderson Don L.
Published: November 2011

The Moon is one of the more obvious of our neighbors in space and is certainly the most accessible. In spite of intensive analysis and probing by virtually every conceivable chemical and physical technique, the maneuvering room for speculation on lunar origin has scarcely diminished as a result of the Apollo program. This is not primarily due to lack of information but to the unexpected and confusing nature of the newly acquired data, most of which is open to multiple interpretations.
Daresbury builds a 30-MV electrostatic accelerator
Authors: Lubkin Gloria B.
Published: November 2011

By far the highest voltage tandem electrostatic accelerator is now under construction at the Daresbury Laboratory in England. It is a 30-MV terminal voltage machine that is expected to produce 60-MeV protons and heavy ions up to about 800 MeV. The accelerator is being built by the laboratory itself, rather than being purchased from one of the two leading suppliers of electrostatic accelerators, High Voltage Engineering Corp and National Electrostatics Corp, although formal agreement has been signed with the former encompassing joint R&D activities. The Daresbury Nuclear Structure Facility (whose abbreviation unfortunately leads to confusion with a venerable American institution) is expected to be finished by the end of 1978.
Proposals for PEP and ISABELLE submitted
Authors: Saar Robert A.
Published: November 2011

Two proposals for major high-energy physics research installations were received by the Atomic Energy Commission this Spring. A 30-GeV center-of-mass energy electron–positron colliding-beam facility is the subject of a joint Stanford University and University of California proposal submitted in April. The other proposal, submitted in May, comes from Brookhaven National Laboratory and spells out the particulars of ISABELLE, a proton–proton intersecting storage accelerator where center-of-mass energies of up to 400 GeV would be available.
Storing ions for collision studies
Authors: Walls Fred L. , Dunn Gordon H.
Published: November 2011

A static trap capable of storing ions for many hours—electrons for over a month—bids fair to bring the convenience of the chemist's reagent shelf to the study of ions and their interactions. The trap to store heavy ions developed at the Joint Institute of Laboratory Astrophysics, shown on the cover and in figure 1, is preferable for our work to its older cousin, the radiofrequency trap, in that it does not feed energy into the system it contains. Its usefulness is further enhanced by a nondestructive detection technique. Thus ends the era when our knowledge of ions and their interactions depended exclusively on analysis of plasmas, laboratory and natural, or the cleaner method of colliding beams.
Maybe the Sun is round after all
Authors: Levi Barbara G.
Published: November 2011

Many ears pricked up at two recent conferences when Henry Hill of the University of Arizona reported that he and his colleagues had looked for but not found any oblateness in the mass distribution of the sun. Hill announced these results at both the Fifth Cambridge Conference on Relativity held at Cambridge, Mass. on 10 June and the Seventh International Conference on Gravitation and Relativity held at Tel Aviv, Israel from 24 to 28 June. Hill and his colleagues—Paul D. Clayton, Doug L. Patz and Alfred W. Healy of the University of Arizona, Robin L. Stebbins of the High Altitude Observatory and James R. Oleson and Carl A. Zanoni of Wesleyan University—made their measurements at the Santa Catalina Laboratory for Experimental Relativity by Astrometry (SCLERA), a facility near Tucson that is jointly operated by the University of Arizona and Wesleyan University.
Table of fundamental constants is updated
Authors: Rothenberg Marian S.
Published: November 2011

An adjusted set of values for the fundamental constants has been recommended for international adoption by E. Richard Cohen and Barry N. Taylor. These values were worked out under the auspices of the International Council of Scientific Union's CODATA Task Group on Fundamental Constants; they therefore represent the first internationally “official” adjustment ever carried out. The complete Taylor–Cohen report appears in the Journal of Physical and Chemical Reference Data; a card listing the recommended values may be found opposite page 81. Both Cohen (Rockwell International, Thousand Oaks, California) and Taylor (US National Bureau of Standards, Gaithersburg, Maryland) have previously done semiofficial and widely used adjustments; the most recent work of Cohen and Jesse W. M. DuMond appeared in 1963 and that of Taylor, William H. Parker and Donald N. Langenberg in 1969.
The urinary drop spectrometer
Authors: Aiello Gerald , Lafrance Pierre , Ritter Rogers C. , Trefil James S.
Published: November 2011

A new diagnostic instrument that can potentially affect the lives of hundreds of thousands of people has resulted from a collaboration among physicians, physicists, engineers and mathematicians. This article is the case history of the interdisciplinary study which culminated in the development of the urinary drop spectrometer, a painless instrument, now in clinical use, for the early detection of lower-urinary-tract abnormalities. As the name implies, this instrument analyzes the spectrum of drops into which the urinary stream breaks up. As the drop spectra carry a “memory” of the passage the fluid has traversed, their statistics may be used to map the delicate tubes of the urinary system. Figure 1 shows how the output of the spectrometer clearly distinguished output from patients suffering from two different disease conditions from each other and from that of a normal individual. We will see how these clearly distinguishable differences arise, and how they form the basis for medical diagnosis.
Designing shape-memory Heusler alloys from first-principles
Authors: Siewert M. , Gruner M. E. , Dannenberg A. , Chakrabarti A. , Herper H. C. , Wuttig M. , Barman S. R. , Singh S. , Al-Zubi A. , Hickel T. , Neugebauer J. , Gillessen M. , Dronskowski R. , Entel P.
Published: November 2011

The phase diagrams of magnetic shape-memory Heusler alloys, in particular, ternary Ni-Mn-Z and quarternary (Pt, Ni)-Mn-Z alloys with Z = Ga, Sn, have been addressed by density functional theory and Monte Carlo simulations. Finite temperature free energy calculations show that the phonon contribution stabilizes the high-temperature austenite structure while at low temperatures magnetism and the band Jahn-Teller effect favor the modulated monoclinic 14M or the nonmodulated tetragonal structure. The substitution of Ni by Pt leads to a series of magnetic shape-memory alloys with very similar properties to Ni-Mn-Ga but with a maximal eigenstrain of 14%.
Alternating current susceptibility study on the cluster glass behavior in disordered β-LiFeO2
Authors: Liu Lina , Bie Xiaofei , Ehrenberg Helmut , Wang Chunzhong , Wei Yingjin , Chen Gang , Du Fei
Published: November 2011

The static and dynamic magnetic behavior of β-LiFeO2 has been investigated by measuring dc and ac susceptibilities. The zero-field-cooled (ZFC) and field-cooled (FC) curves reveal an irreversibility behavior at about 156 K and a broad peak at 129 K, indicating a spin glass transition. However, the dc susceptibility of β-LiFeO2 in FC mode differs from a flat curve as expected for a homogeneous spin glass by an increase below Tirr, which is the characteristic magnetic behavior of a cluster spin glass. The real part of the ac susceptibility shows a broad maximum at 135 K, which shifts to higher temperatures and becomes less pronounced with increasing frequency. The corresponding parameter δ=ΔTf/TfΔlogω = 0.005 is calculated for β-LiFeO2, suggesting a spin glass state rather than superparamagnetism. In addition, three models (the Néel–Arrhenius law, the Vogel–Fulcher law, and the power law) have also been employed to analyze the frequency dependence of Tf, which confirm a cluster spin glass state in β-LiFeO2.
Dynamics of photothermally driven VO2-coated microcantilevers
Authors: Cabrera Rafmag , Merced Emmanuelle , Sepúlveda Nelson , Fernández Félix E.
Published: November 2011

The dynamic response of VO2-coated silicon microcantilevers thermally driven over the film’s insulator-to-metal transition was studied using laser light pulses directly incident on the cantilevers. The measured photothermal response revealed very high curvature changes of approximately 2500 m−1 up to pulse frequencies greater than 100 Hz and readily observable vibrations up to frequencies of a few kHz with no amplitude degradation after tens of thousands of pulses. Maximum tip amplitudes for 300-μm-long, 1-μm-thick cantilevers used in these experiments were nearly 120 μm and correspondingly less for 2-μm-thick cantilevers. The main mechanism limiting oscillation amplitude was found to be heat transport response during heating and cooling, which depends mainly on thermal conduction through the cantilever itself to the massive anchor and chip body, which acted as a heat sink at room temperature. For the laser-driven oscillations studied, damping by the surrounding air is unimportant in the range of frequencies probed. Large-curvature response is expected to extend to higher pulse frequencies for cantilevers with smaller dimensions.
Noise reduction by signal combination in Fourier space applied to drift correction in optical tweezers
Authors: Mashaghi Alireza , Vach Peter J. , Tans Sander J.
Published: November 2011

A general method is proposed to reduce noise by combining signals. Different measurements of the same physical quantity often exhibit different noise levels in different frequency ranges. Hence, a single high-fidelity signal can be constructed by combining the low-noise parts of the signals in Fourier space. We demonstrate this method by reducing noise in the measured bead-to-bead distance in an optical tweezers setup.
Comparative investigation on the 2.7 μm emission in Er3+/Ho3+ codoped fluorophosphate glass
Authors: Zhang Liyan , Yang Zhonghua , Tian Ying , Zhang Junjie , Hu Lili
Published: November 2011

104 times higher Er3+:2.7 μm fluorescence was observed when Ho3+ was added into an Er3+ doped fluorophosphate glass under 976 nm excitation. Obviously changed J-O parameters and the calculated spectroscopic properties of Er3+ prove that Ho3+ influences the local environment of Er3+ greatly. Increased upconversion luminescence around 550 nm and 658 nm shows that heat generation rises with Ho3+ introduction. Complicated energy transfer processes exist in this codoping situation and interactions among the excessive Ho3+ ions are considered as the dominant energy loss mechanisms, otherwise, the sensitizing effect from Ho3+ to Er3+ is very high if Ho3+:Er3+ ratio below 4. All the calculated results coincide well with the measured ones. Excellent 2.7 μm spectroscopic property, Raman analysis, together with the outstanding glass forming ability identify that this Er3+/Ho3+ codoped fluorophosphate glass can be effectively used for Er3+:2.7 μm fiber laser.
The persistent charge and spin currents in topological insulator Bi2Se3 nanowires
Authors: Lou Wen-Kai , Cheng Fang , Li Jun
Published: November 2011

We investigate theoretically the surface states of three-dimensional topological insulator cylinder nanowires analytically and numerically. In contrast to the conventional semiconductor cylinder nanowires, these surface states exhibit unique massless Dirac dispersion and interesting transport properties. We find that the persistent charge current and persistent spin current, i.e., the Aharonov-Bohm oscillation, can be induced by the driven magnetic flux. The amplitude of persistent charge current shows an oscillating behavior with increasing the electron density.
Enhanced transmission in rolled-up hyperlenses utilizing Fabry-Pérot resonances
Authors: Kerbst Jochen , Schwaiger Stephan , Rottler Andreas , Koitmäe Aune , Bröll Markus , Ehlermann Jens , Stemmann Andrea , Heyn Christian , Heitmann Detlef , Mendach Stefan
Published: November 2011

We experimentally demonstrate that the transmission through rolled-up metal/semiconductor hyperlenses can be enhanced at desired frequencies utilizing Fabry-Pérot resonances. By means of finite difference time domain simulations, we prove that hyperlensing occurs at frequencies of high transmission.
Lateral imaging of the superconducting vortex lattice using Doppler-modulated scanning tunneling microscopy
Authors: Fridman I. , Kloc C. , Petrovic C. , Wei J. Y. T.
Published: November 2011

By spatially mapping the Doppler effect of an in-plane magnetic field on the quasiparticle tunneling spectrum, we have laterally imaged the vortex lattice in superconducting 2H-NbSe2. Cryomagnetic scanning tunneling spectroscopy was performed at 300 mK on the ab-surface, which was oriented parallel to the field H. Conductance images at zero bias show stripe patterns running along H, with the stripe separation varying as H−0.5. Regions of higher zero-bias conductance show lower gap-edge conductance, consistent with spectral redistribution by a spatially modulated superfluid momentum. Our results are interpreted in terms of the interaction between vortical and screening currents, and demonstrate a general method for probing subsurface vortices.
Study on transport pathway in oxide nanowire growth by using spacing-controlled regular array
Authors: Klamchuen Annop , Yanagida Takeshi , Kanai Masaki , Nagashima Kazuki , Oka Keisuke , Rahong Sakon , Gang Meng , Horprathum Mati , Suzuki Masaru , Hidaka Yoshiki , Kai Shoichi , Kawai Tomoji
Published: November 2011

Metal oxide nanowires formed via vapor-liquid-solid (VLS) process are promising nanoscale building blocks. Although understanding material transport pathways across three phases is crucial to realize well-defined oxide nanowires, such knowledge is unfortunately far from comprehensive. Here we investigate the material transport pathway in VLS grown MgO nanowires by utilizing spacing-controlled regular array. Defining the regular spacing of catalysts allows us to extract the information of transport pathway for each catalyst. We found the significant contribution of vapor phase transport pathway rather than the surface diffusion transport. This result highlights the critical role of re-evaporation process on VLS oxide nanowires.
Citizens without Nations
Authors: Isin Engin F
Published: November 2011

To broach the question of whether citizenship could exist without (or beyond) community, this paper discusses genealogies of citizenship as membership that binds an individual to the community of birth (of the self or a parent). It is birthright as fraternity that blurs the boundary between citizenship and nationality. After briefly discussing recent critical studies on birthright citizenship (whether it is civic or ethnic or blood or soil) by Ayelet Shachar and Jacqueline Stevens, the paper discusses three critical genealogies of the relationship between birthright and citizenship by Max Weber, Hannah Arendt, and Michel Foucault. Although each provides a critical perspective into the question, Weber reduces citizenship to fraternity with nation and Arendt reduces citizenship to fraternity with the state. It is Foucault who illustrates racialization of fraternity as the connection between citizenship and nationality. Yet, since Foucault limits his genealogical investigations to the 18th and 19th centuries, a genealogy of fraternity of what he calls an immense biblical and Greek tradition remains for Derrida to articulate as a question of citizenship.
Comorbidities and depression in older adults with HIV
Authors: Havlik Richard J. , Brennan Mark , Karpiak Stephen E.
Published: November 2011

Objective
To investigate whether the high rates of depression found in older adults living with HIV are associated with the number and types of comorbidities. Methods: The Research on Older Adults with HIV (ROAH) study collected self-reported health data on ~1000 New York City HIV-positive men and women aged 50 years and older. Participants provided data on health problems experienced in the past year and depressive symptomatology (Center for Epidemiological Studies Depression Scale (CES-D)). Data were analysed using a non-parametric test of association and multiple regression analysis. Results: The correlation between CES-D scores and number of comorbidities was significant (r = 0.24). In multivariate analyses, depression remained a significant covariate of the number of comorbid conditions, in addition to female gender, inadequate income, history of drug and alcohol use, AIDS diagnosis and self-rated health. Correlations of depression with specific comorbidities varied. Significant correlations with sensory loss and dermatological problems were observed. Significant correlations existed with heart and respiratory conditions as well as fractures, but the directionality of these cross-sectional relationships is uncertain. Conclusions: The findings suggest the need for further longitudinal research to understand how high rates of depressive symptoms are related to comorbidities. Focussed clinical care that strives to prevent the collapse of the immune system must evolve into an effective treatment strategy for multimorbidities, where HIV is but one of many other chronic illnesses. If the management of depression continues to be a low priority, the older person with HIV may experience an avoidable reduction in life expectancy.
Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth
Authors: Steketee Michael B. , Moysidis Stavros N. , Jin Xiao-Lu , Weinstein Jessica E. , Pita-Thomas Wolfgang , Raju Hemalatha B. , Iqbal Siraj , Goldberg Jeffrey L.
Published: November 2011

Understanding neurite growth regulation remains a seminal problem in neurobiology. During development and regeneration, neurite growth is modulated by neurotrophin-activated signaling endosomes that transmit regulatory signals between soma and growth cones. After injury, delivering neurotrophic therapeutics to injured neurons is limited by our understanding of how signaling endosome localization in the growth cone affects neurite growth. Nanobiotechnology is providing new tools to answer previously inaccessible questions. Here, we show superparamagnetic nanoparticles (MNPs) functionalized with TrkB agonist antibodies are endocytosed into signaling endosomes by primary neurons that activate TrkB-dependent signaling, gene expression and promote neurite growth. These MNP signaling endosomes are trafficked into nascent and existing neurites and transported between somas and growth cones in vitro and in vivo. Manipulating MNP-signaling endosomes by a focal magnetic field alters growth cone motility and halts neurite growth in both peripheral and central nervous system neurons, demonstrating signaling endosome localization in the growth cone regulates motility and neurite growth. These data suggest functionalized MNPs may be used as a platform to study subcellular organelle localization and to deliver nanotherapeutics to treat injury or disease in the central nervous system.
Hypo- and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms
Authors: Landor Sebastian K.-J. , Mutvei Anders P. , Mamaeva Veronika , Jin Shaobo , Busk Morten , Borra Ronald , Grönroos Tove J. , Kronqvist Pauliina , Lendahl Urban , Sahlgren Cecilia Maria
Published: November 2011

A switch from oxidative phosphorylation to glycolysis is frequently observed in cancer cells and is linked to tumor growth and invasion, but the underpinning molecular mechanisms controlling the switch are poorly understood. In this report we show that Notch signaling is a key regulator of cellular metabolism. Both hyper- and hypoactivated Notch induce a glycolytic phenotype in breast tumor cells, although by distinct mechanisms: hyperactivated Notch signaling leads to increased glycolysis through activation of the phosphatidylinositol 3-kinase/AKT serine/threonine kinase pathway, whereas hypoactivated Notch signaling attenuates mitochondrial activity and induces glycolysis in a p53-dependent manner. Despite the fact that cells with both hyper- and hypoactivated Notch signaling showed enhanced glycolysis, only cells with hyperactivated Notch promoted aggressive tumor growth in a xenograft mouse model. This phenomenon may be explained by that only Notch-hyperactivated, but not -hypoactivated, cells retained the capacity to switch back to oxidative phosphorylation. In conclusion, our data reveal a role for Notch in cellular energy homeostasis, and show that Notch signaling is required for metabolic flexibility.
Role of type 2 deiodinase in response to acute lung injury (ALI) in mice
Authors: Barca-Mayo Olga , Liao Xiao-Hui , DiCosmo Caterina , Dumitrescu Alexandra , Moreno-Vinasco Liliana , Wade Michael S. , Sammani Saad , Mirzapoiazova Tamara , Garcia Joe G. N. , Refetoff Samuel , Weiss Roy E.
Published: November 2011

Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3′-triiodothyronine (T
3
) and thyroid-stimulating hormone and an increase in reverse T
3
. Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serum TH levels were observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroid WT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T
3
reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T
3
in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue.
Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation
Authors: Shin Sejeong , Wolgamott Laura , Yu Yonghao , Blenis John , Yoon Sang-Oh
Published: November 2011

The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, protein synthesis, and cell cycle. Thus, deregulation of S6K contributes to the progression of type 2 diabetes, obesity, aging, and cancer. Considering the biological and clinical importance of S6K1, a complete understanding of its regulation is critical. One of the key motifs in the activation of S6K1 is a turn motif, but its regulation is not well understood. Here we provide evidence for two mechanisms of modulating turn motif phosphorylation and S6K1 activity. First, mammalian target of rapamycin regulates turn motif phosphorylation by inhibiting its dephosphorylation. Second, we unexpectedly found that glycogen synthase kinase (GSK)-3 promotes turn motif phosphorylation. Our studies show that mammalian target of rapamycin and GSK-3 cooperate to control the activity of S6K1, an important regulator of cell proliferation and growth. Our unexpected results provide a clear rationale for the development and use of drugs targeting GSK-3 to treat diseases such as diabetes, cancer, and age-related diseases that are linked to improper regulation of S6K1.