cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparing the intracellular fate of components within a noncovalent streptavidin nanoparticle with covalent conjugation

Abstract Introduction Auger radiotherapy requires adequate tumor delivery and high nuclear accumulation and retention. We hypothesize that the noncovalent nature of a streptavidin/biotin three-component nanoparticle possessing these qualities may be required for dissociation of the radiolabeled oligomer and its accumulation into the cell nucleus. Methods As a test of our hypothesis, the intracellular fate of an antisense oligomer when incubated as the nanoparticle and when incubated while covalently conjugated to the antibody was compared. The three-component noncovalent nanoparticle consisted of streptavidin linking three biotinylated components: a Cy3-labeled anti-RIα antisense phosphorodiamidate morpholino (MORF) oligomer, a tat transfecting peptide and the anti-Her2 herceptin antibody. The covalent constructs included an anti-RIα antisense DNA conjugated to a radiolabeled herceptin and a fluorescent DNA conjugated to native herceptin. Fluorescence microscopy in SK-BR-3 (Her2+) cells was used to evaluate the fate of the fluorescent Cy5.5-DNA and Cy3-MORF, while the subcellular accumulation of the 111 In-labeled herceptin and herceptin-DNA in both SK-BR-3 and MDA-MB-231 (Her2) cells was determined by isolating and counting the nuclear fractions. Results Previously, we demonstrated that when incubated as the three-component nanoparticle consisting of herceptin and streptavidin and 99m Tc-labeled antisense MORF, only the MORF accumulated in the nucleus of Her2+ cells. In this investigation, clear evidence was observed of nuclear accumulation of the antisense oligomer within the noncovalent nanoparticle as before, but when incubated as the covalent construct, by both fluorescence microscopy and nuclear counting, no evidence of nuclear accumulation was observed. Conclusion The weaker noncovalent biotin–streptavidin bond may be essential for adequate delivery of the radiolabeled antisense oligomer to the nucleus of tumor cells.
Neuron-astroglia interactions in vitro and in vivo

Abstract The role of astroglia in providing a structural framework for neuronal development has long been recognized, but the influence of neurons on astroglial development remains largely unexplored. An in-vitro model system has been devised to test the cellular and molecular mechanisms of neuronal migration. This model system has opened new possibilities for examining the effects of neurons on astroglial differentiation and proliferation, and how these effects relate to disturbances in glial morphology and neuronal migration in mutant cerebella. Although an obligatory association between growing axons and astroglia has not yet been demonstrated, the means by which glia might foster axon outgrowth, and conversely, axons might trigger glial differentiation, are discussed.
All-Arthroscopic Repair of Peripheral Triangular Fibrocartilage Complex Tears Using FasT-Fix

Injury to the triangular fibrocartilage complex (TFCC) is a major source of ulnar-sided wrist pain that results in disability with common activities of daily living involving forearm rotation, for which operative management is indicated if conservative management fails. Past results with open repairs have been successful, but recent surgical advances have allowed the development of arthroscopic management. This article describes and reviews an all-arthroscopic technique of repair of Palmer type IB TFCC injuries with FasT-Fix suture technology (Smith and Nephew, Andover, MA, USA), which is advantageous both biomechanically and in terms of decreasing risk of morbidity.
The role of the spleen in radiation injury.

Summary and ConclusionsThese hematologic and histologic data indicate that:1) Severe anemia, leucopenia, and thrombocytopenia develop in mice after a single dose of 600 r whole-body X radiation.2) Ectopic erythrocytopoiesis, in the lead-protected spleens of mice given 600 r whole-body X radiation (exclusive of spleens) compensates with such rapidity and so extensively for the destruction and interruption of this activity in the marrow spaces that no anemia of significance becomes apparent. Ectopic granulocytopoiesis and megakaryocytopoiesis in the lead-protected spleens compensates significantly but at a slower pace and less completely for the bone marrow destruction.3) A marked and sustained decrease in the amount of lymphatic tissue is produced in the lead-protected spleens of animals given 600 r whole-body X radiation. This decrease in lymphatic tissue may perhaps be a result of (a) unsuccessful competition of the lymphatic tissue with the ectopic hematopoiesis for nutritional requirements, (b) actual ...
Use of subatmospheric pressure to prevent doxorubicin extravasation ulcers in a swine model.

Application of subatmospheric pressure to sites injected with doxorubicin prevented ulcer formation in treated sites (0 ulcers/16 sites) compared to control wounds (10 ulcers/16 sites) in a pig model. Background and Objectives Extravasation of doxorubicin hydrochloride (Adriamycin) frequently causes chronic ulcers, which usually progress and expose underlying structures such as tendons and bone. The exact mechanism of action that causes cell death and the chronic ulcers is unknown. Methods Eight sites were injected intradermally with doxorubicin on each of 4 pigs. Four sites on each animal served as untreated controls. The remaining four sites were exposed to 125 mm Hg subatmospheric pressure applied 1 h after injection. The sites were observed on a three times per week schedule. Sites that did not develop ulcers were re-injected up to a total of four injections. The animals were observed for 5 weeks. Results Ten of sixteen control sites developed ulcers. No subatmospheric pressure treated sites developed ulcers. The incidence of ulcer formation was significantly less for treated wounds compared to control wounds at P < 0.001 by Fisher's exact test. Conclusions This physical modality appears to successfully prevent ulcer formation after doxorubicin injection. J. Surg. Oncol. 1999;72:14–17. © 1999 Wiley-Liss, Inc.
Reactive to proactive support: a corn dance

The Linfield College support desk was disorganized and inefficient. The number of Integrated Technologies (IT) department personnel had remained static while the staff, faculty, and student populations grew. We could not keep up with the growing demand for service, our work queues grew longer, and we could not stay on top of viruses and malware. Our mission was to reinvent the support desk to meet the growing needs of the campus community but we were technicians, not managers, and this project was outside of our experience.The resources available for our reinvention project were limited. The IT staff was few in number with only a couple of student workers for assistance. Money for IT infrastructure upgrades was scarce. We spent our time in crisis management rather than preventative maintenance.The Fall 2005 Special Interest Group on University and College Computing Services (SIGUCCS) conference presented a variety of new ideas that gave us the direction we needed to make our support desk project succeed. Returning to campus, we had a fresh perspective for our IT support desk. We automated our network security with Cisco Clean Access and developed an assembly line for repair work with increased student worker technicians. TheBrain™ software centralized support desk management and helped us develop an "on demand" phone support. The campus support desk now offers increased network security, a wider range of services and faster repair times.
Limits of high frequency percutaneous transtracheal jet ventilation using a fluidic logic controlled ventilator.

A study was undertaken on dogs to find the limit of carbon dioxide exchange with high frequency jet ventilation using a fluidic logic controlled oxygen jet ventilator. Fifteen dogs were ventilated through a transtracheal catheter at respiratory rates up to 600 per minute. The following were recorded: aortic, pulmonary artery, pulmonary arterial wedge, and central venous blood pressures; intratracheal pressure; electrocardiogram; inspiratory and expiratory time of the jet; arterial and central venous blood gases; intermittent cardiac output. Normal gas exchange was found up to a respiratory rate of 400 per minute with low tidal volume and low intratracheal pressures. There were no adverse circulatory effects up to a rate of 400 per minute. At rates of 500 and 600 per minute, cardiac contractility was unaffected, but a decreased heart rate and increased peripheral resistance produced a fall in cardiac output. There was no interference with the resumption of spontaneous ventilation during weaning. In a control series of five dogs, apnoeic oxygenation was used. The PaCO2 was allowed to reach 15.96 kPa (120 torr). High frequency jet ventilation was then started at arate of 600 per minute and decreased in increments to 100 per minute. Arterial blood gases were continuously recorded through an intra-arterial catheter connected to a mass spectrometer. The PaCO2 gradually declined to normal levels as the rate decreased.
Structural characterization and photophysical properties of a luminescent trinuclear zinc(II) complex exhibiting multiple coordination geometries

A luminescent trinuclear zinc(II) complex, tris(μ-2,3-toluenedithiolato)-1:2κ2S1;1:2κ2S1′, 2:3κ2S2;3κS2′, 1:3κ2S3;3κS3′-bis(2,2′-bypyridine)-1κ2N,N′,2κ2N,N′-trizinc, containing 3,4-dimercaptotoluene (tdt) and 2,2′-bipyridine (bpy) has been synthesized and found to have the trinuclear formulation Zn3(tdt)3(bpy)2 (I). The complex crystallizes in the monoclinic space group P21/n with a = 11.7247(12), b = 20.134(2), c = 17.7376(18) A and β = 103.743(2)∘. The complex has two heteroleptic zinc(II) centers exhibiting similar distorted trigonal bipyramidal geometries with the third homoleptic zinc(II) center displaying a flattened tetrahedral geometry. Present in the solid state are both intra- and intermolecular π–π interactions. The complex is emissive at 77 K in the solid state with an emission maximum at 574± 2 nm with a luminescence lifetime of 7.4± 0.4 ns. The unstructured emission is assigned as a metal-mediated ligand-to-ligand π–π* charge transfer transition.
Postpartum aggression in mice: Experiential and environmental factors ☆

Abstract Six experiments were conducted to assess the influence of duration of lactation, the presence of young, and the stimulus characteristics of intruder animals upon postpartum aggression of mice. The first experiment showed that postpartum aggression toward conspecifics was highest between Day 3 and Day 8, declined between Day 9 and Day 14, and was present toward males but absent toward females between Day 15 and Day 21 of the lactation period. Experiment 2 showed that lactating mice rarely attacked conspecifics to which they had been previously exposed but would readily attack strangers. Experiment 3 and 4 demonstrated that lactating animals never attacked intruders when tested 5 hr after pup removal. However, placement of young behind a wire partition in the home-cage for 5 hr or replacement of the offspring for as little as 5 min following 5 hr of separation restored postpartum aggression. The fifth experiment showed that 1- and 10-day old intruders were seldom attacked while intense aggression was directed against 14- and 20-day old intruders. Finally, Experiment 6 demonstrated that 14-day old intruders whose hair was removed were rarely attacked.
Organizational patterns of economies: an ecological perspective

Abstract A complex adaptive systems paradigm can be used to abridge theorizing in ecological and economic sciences. The paper discusses economic flows, connectivity and stability from the perspective of theoretical ecology. The global economy, by analogy with ecosystems, appears to self-organize as an ascendent system: most of the world trade is done among the tiny fraction of technologically advanced countries and trade interaction strength exhibits a power law with exponential decay. Small world behavior and preferential attachment characterizes interactions among economic agents. Industrial economies and the world economic system as a whole appear to evolve towards the ‘maximum power’ efficiency. Development that fosters efficiency in the maximum power sense (all the world becomes industrialized) implies a trade-off in socio-economic diversity, and may be antithetical to the stability of the global economy. If we take an ecological perspective, then the problem of global development does not reside in the realm of technology or global governance. It boils down to the question of required natural balance in living systems, the balance between organized complexity and overhead, the harmony between efficiency and adaptability.
A portable radioactive solution container

Abstract The portable lead solution container conveniently permits safe and convenient handling and transfer of radioactive solutions with minimal hazard. Its relatively light weight permits it to be manually moved or maintained in any position by use of only a clamp and a fixed ring stand. It excludes container breakage and gross contamination of working areas, and without exceeding permissible radiation exposure limits, obviates to a great extent remote handling of millicurie amounts of radioisotopes.
Immobilization and characterization of β‐galactosidase in thermally reversible hydrogel beads

Beta-Galactosidase has been immobilized within thermally reversible hydrogel beads and has been studied in batch and packed bed reactor systems. The enzyme was entrapped in a copolymer hydrogel of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) as beads were formed in an inverse suspension polymerization. A reversible deswelling and reswelling of the hydrogel matrix was induced by first warming and then cooling through 37-40 degrees C, which is the lower critical solution temperature, LCST, of the backbone copolymer. The optimum temperature for maximum activity of the immobilized enzyme-gel bead system was found to be 30-35 degrees C in a batch mode and 40 degrees C in a packed bed reactor, which were both below the 50 degrees C optimum for the free enzyme. These differences are understandable, since the mass transfer rates of substrate and product within the pores of the gel matrix are controlled mainly by the temperature, so therefore it is the temperature which governs the overall activity of the immobilized enzyme system. It was also found that when the operational temperature in the packed bed reactor was cycled between temperatures below (35 degrees C) and above (45 degrees C) the copolymer gel LCST, the activity of the immobilized enzyme almost fully recovered after each cycle. In fact, the enzyme-gel system exhibited a complete "shut-off" in activity at 50 degrees C which was the temperature where the free enzyme showed its maximum activity. The thermal cycling operation of LCST enzyme-gel beads can be used to enhance overall activity and productivity of a packed bed reactor, when compared to isothermal operation of this reactor. This is due to the thermally induced "pumping" which enhances mass transfer rates of substrate in and product out of the gel beads.
Laser-EXAFS: Fast Extended X-ray Absorption Fine Structure Spectroscopy with a Single Pulse of Laser-Produced X-rays

The extended x-ray absorption fine structure (EXAFS) spectrum of aluminum has been measured with a nanosecond pulse of soft x-rays generated by a laser-produced plasma. This technique provides a practical alternative to synchrotorn radiation for the acquisition of EXAFS data. It also provides a unique capability for the analysis of molecular structure in highly transient chemical species.
Nuclear Magnetic Resonance in Alloys

Many papers on NMR in alloys are addressed to NMR specialists rather than to metal or alloy specialists, and talk about the “potential” of NMR for application to alloys. This presentation emphasizes a review of some useful results of NMR experiments in alloys, including applications in diffusion, phase diagrams, magnetic materials, ordering in intermetallic compounds, liquid alloys and amorphous alloys.
HOST-PARASITE COEVOLUTION: EVIDENCE FOR RARE ADVANTAGE AND TIME-LAGGED SELECTION IN A NATURAL POPULATION.

In theory, parasites can create time-lagged, frequency-dependent selection in their hosts, resulting in oscillatory gene-frequency dynamics in both the host and the parasite (the Red Queen hypothesis). However, oscillatory dynamics have not been observed in natural populations. In the present study, we evaluated the dynamics of asexual clones of a New Zealand snail, Potamopyrgus antipodarum, and its trematode parasites over a five-year period. During the summer of each year, we determined host-clone frequencies in random samples of the snail to track genetic changes in the snail population. Similarly, we monitored changes in the parasite population, focusing on the dominant parasite, Microphallus sp., by calculating the frequency of clones in samples of infected individuals from the same collections. We then compared these results to the results of a computer model that was designed to examine clone frequency dynamics for various levels of parasite virulence. Consistent with these simulations and with ideas regarding dynamic coevolution, parasites responded to common clones in a time-lagged fashion. Finally, in a laboratory experiment, we found that clones that had been rare during the previous five years were significantly less infectible by Microphallus when compared to the common clones. Taken together, these results confirm that rare host genotypes are more likely to escape infection by parasites; they also show that host-parasite interactions produce, in a natural population, some of the dynamics anticipated by the Red Queen hypothesis.
Patterning of Narrow Au Nanocluster Lines Using V2O5 Nanowire Masks and Ion-Beam Milling

A shadow mask technique employing V2O5 nanowires and ion-beam milling is used to define narrow lines of monolayer-encapsulated Au nanoclusters. When positioned between electrodes these lines are shown to be conducting and to have nonlinear I−V characteristics with nonzero threshold voltages consistent with Coulomb blockade.
Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth

The IGF axis is important for long bone development, homeostasis and disease. The activities of IGF-I and IGF-II are regulated by IGF binding proteins (IGFBPs). IGF-I and IGFBP2 are co-expressed in dynamic fashions in the developing long bones of the chick wing, and we have found that IGF-II is present in the cartilage model and surrounding perichondrium, proliferative and hypertrophic chondrocytes and developing periosteum. To gain insight into endogenous roles of IGF-I, IGF-II and IGFBP2 in long bone development, we have overexpressed IGFBP2 in the developing skeletal elements of the embryonic chick wing in vivo, using an RCAS retroviral vector. IGFBP2 overexpression led to an obvious shortening of the long bones of the wing. We have investigated, at the cellular and molecular levels, the mechanism of action whereby IGFBP2 overexpression impairs long bone development in vivo. At an early stage, IGFBP2 excess dramatically inhibits proliferation by the chondrocytes of the cartilage models that prefigure the developing long bones. Later, IGFBP2 excess also reduces proliferation of the maturing chondrocytes and attenuates proliferation by the perichondrium/developing periosteum. IGFBP2 excess does not affect morphological or molecular indicators of chondrocyte maturation, osteoblast differentiation or cell/matrix turnover, such as expression of Ihh, PTHrP, type X collagen and osteopontin, or distribution and relative abundance of putative clast cells. We also have found that IGFBP2 blocks the ability of IGF-I and IGF-II to promote proliferation and matrix synthesis by wing chondrocytes in vitro. Together, our results suggest that the mechanism of action whereby IGFBP2 excess impairs long bone development is to inhibit IGF-mediated proliferation and matrix synthesis by the cartilage model; reduce the proliferation and progression to hypertrophy by the maturing chondrocytes; and attenuate proliferation and formation of the periosteal bony collar. These actions retard the growth and longitudinal expansion of the developing long bones, resulting in shortened wing skeletal elements. Our results emphasize the importance of a balance of IGF/IGFBP2 action at several stages during normal long bone development.
Empirical tests of philosophical intuitions

Experimental philosophy seeks to examine empirically various factual issues that, either explicitly or implicitly, lie at the foundations of philosophical positions. A study of this genre (Miller & Feltz, 2011) was critiqued. Questions about the study were raised and broader issues pertaining to the field of experimental philosophy were discussed.
Repositioning of the basilic vein and superficial femoral artery for chronic hemodialysis.

Suitable access to the circulation for chronic hemodialysis is usually provided by the external silastic shunt [1] or the subcutaneous arterio-venous fistula [2].Occasionally autologous saphenous vein grafts [3] or repositioning of the superficial femoral artery have been used [4–6].We now present an additional technique: superficializing the basilic vein for use as a return site.This method can be used in combination with repositioning of the femoral artery to provide both "pull" and "return" access to the circulation.Chronic hemodialysis is thus made possible in a patient who lacks major accessible veins and who has a small superficial femoral artery. Under general anesthesia, a 13cm incision is made in the medial groove between biceps and triceps muscles.The basilic vein is dissected free, tributaries are ligated, and the vein is raised to a superficial position one cm lateral to the incision.Subcutaneous tissue is then closed beneath the vein using interrupted catgut sutures and the skin is approximated with fine wire.
Transient analysis of a capillary pumped loop heat pipe

A bench-top Capillary Pumped Loop (CPL) test system has been developed and tested to investigate the transient mode operation of this system by applying a step power input to the evaporators. Tests were conducted at several power input and evaporator inlet subcooling combinations. In addition, a lumped-heat-capacity model of the CPL test system has been presented which is used for predicting qualitatively the transient operation characteristics. Good agreement has been obtained between the predicted and the measured temperature variations. A simple evaporator inlet subcooler model has also been developed to study effects of inlet subcooling on the steady-state evaporator wall temperature. Results were compared with the test data collected.
Glaciated appalachian plateau: till shadows on hills.

North slopes are twice as steep as south slopes on the hills of central New York. This asymmetry is caused by unequal till thickness—3.6 meters on north slopes and 27.6 meters on south slopes. Previous workers interpreted the hills as being of bedrock sculptured by glacial erosion, with till 0.9 to 3 meters thick.
Phonetic correlates of tongue root vowel contrasts in Maa

Maa, a Nilo-Saharan language, exhibits a cross-height vowel harmony system known as 'tongue root harmony'. The high and mid vowels participate in this system, but the low vowel does not. The Maa harmony system is briefly described, followed by an investigation into the phonetic properties of the vowels. Five Maa speakers were recorded producing 100 example words three times each. The [+ATR] vowels were found to have consistently lower first formant values and relatively less energy in the higher frequency regions than their [-ATR] counterparts. An investigation of the differences between the auditorily quite similar [-ATR] high and [+ATR] mid vowels revealed durational differences for the back vowels and much inter-speaker variation for the front vowels. Electroglottographic data obtained from one speaker indicated a slightly less constricted glottis for [+ATR] than [-ATR] vowels. This phonation difference is not readily detectable auditorily in the current data, but has been reported previously for Maa. The results contribute to typological knowledge about the phonetics of tongue root vowel contrasts, as very little data is currently available for Nilo-Saharan languages. A possible origin of stronger voice quality distinctions common to other tongue root harmony languages is offered from the theory of Auditory Enhancement.
Phytoplankton response to natural and experimental iron addition

Primary production, chlorophyll biomass, and the maximum quantum yield of photosynthesis were measured during a survey around the Galapagos Islands and during an open-ocean iron addition experiment. Dissolved iron concentrations exceeded 1 nmol kg-1 over the Galapagos shelf, and a plume of chlorophyll was observed to the west of the islands. The quantum yield of photosynthesis was greater than 0.02 mol C mol photons-1 at the surface in the base of the plume, and less than 0.01 mol C mol photons-1 outside the plume. Primary production was two-fold higher at the base of the plume relative to surrounding waters. The distributions of quantum yield, primary production and chlorophyll are consistent with a direct effect of iron on phytoplankton growth rate. The experimental iron addition was performed 300 km south of the Galapagos and raised surface water dissolved iron concentrations from 0.05 to approximately 3 nmol kg-1. Quantum yield increased from less than 0.008 to 0.015 mol C mol photons-1 within 24 h of the addition, and remained elevated throughout the experiment. Chlorophyll concentrations were initially near 0.2 mg m-3, and reached 0.8 mg m-3 in the iron-enriched waters. Primary production increased from 2.0 to 3.1 mmol C m-3 d-1. These results show that iron directly regulates photosynthesis of the dominant phytoplankton in surface waters of the high-nutrient, low-chlorophyll eastern equatorial Pacific. It appears, however, that the dominant phytoplankton were unable to escape grazing control, limiting the impact of a transient increase in iron availability on surface water nutrient concentrations.
Medical dissolution of gallstones by oral bile acid therapy

The rationale, safety, and efficacy of cholesterol gallstone dissolution by orally administered ursodiol, chenodiol, or a combination of the two agents are summarized herein. Bile must be supersaturated in cholesterol for gallstones to form, and desaturation of bile by orally administered bile acids induces gradual stone dissolution. The mechanism of action of the two agents differs, but both cause a decreased input of cholesterol into the metabolic pool. Ursodiol is free of side effects, and the combination with chenodiol is equally efficacious and also has few side effects. Chenodiol, although an effective desaturation agent, causes diarrhea, mild reversible hepatic injury, and a small increase in the plasma cholesterol level. Extracorporeal shock-wave lithotripsy decreases gallstone size markedly and thereby increases the speed of dissolution by orally administered bile acids. Medical therapy with oral bile acids is appropriate for patients who present with small cholesterol stones and for patients with larger cholesterol gallstones who cannot or will not have surgery. Oral bile acids may also be valuable in the treatment of gallstone recurrence before it has become symptomatic or to prevent recurrence after prior successful dissolution of recurrent stones.
Sudden acquired retinal degeneration syndrome (SARDS)

Sudden acquired retinal degeneration syndrome (SARDS) is a disease of dogs causing sudden onset blindness. There is no treatment and it causes permanent blindness. This article aims to give an overview of the disease and its diagnosis.
Eltrombopag: An Oral Thrombopoietin Receptor Agonist for the Treatment of Idiopathic Thrombocytopenic Purpura

Abstract Background Idiopathic thrombocytopenic purpura (ITP) is a relatively rare acquired autoimmune disease characterized by either decreased platelet production or increased platelet destruction leading to reduced platelet counts and increased risk of bleeding. Immune modulators have been used in treatment; however, a novel class of thrombopoietin mimetics has recently been developed. Eltrombopag is approved for patients with chronic ITP who have failed initial treatments with traditional immune modulators or splenectomy. Objectives The goals of this review were to summarize the pharmacology, pharmacokinetic properties, efficacy, and tolerability of eltrombopag and review the approved and investigational uses of this drug. Methods A search of Cochrane Central Register of Clinical Trials and clinicaltrials.gov was conducted using the terms eltrombopag or SB-497115-GR. In addition, all reviews and preclinical and clinical studies published in English between January 1980 and January 2011 were identified in PubMed and Cochrane Database of Systemic Reviews using the same terms. Results A total of 153 publications and 13 clinical trials were identified; 14 publications were excluded because they were not published in English. A Phase III trial randomized 114 patients with ITP 2:1 to eltrombopag 50 mg or placebo and demonstrated by day 43 a significantly greater proportion of patients responding in the eltrombopag group than in the placebo group (59% vs 16%, odds ratio [OR] = 9.61; 95% CI, 3.31–27.86; P Conclusion Eltrombopag is well tolerated and effective in raising platelet counts in patients with chronic ITP.
Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis.

M-type K+ channels, consisting of KCNQ1–5 (Kv7.1–7.5) subunits, form a variety of homomeric and heteromeric channels. Whereas all the subunits can assemble into homomeric channels, the ability of the subunits to assemble into heteromultimers is highly variable. KCNQ3 is widely thought to co-assemble with several other KCNQ subtypes, whereas KCNQ1 and KCNQ2 do not. However, the existence of other subunit assemblies is not well studied. To systematically explore the heteromeric assembly of KCNQ channels in individual living cells, we performed fluorescence resonance energy transfer (FRET) between cyan fluorescent protein- and yellow fluorescent protein-tagged KCNQ subunits expressed in Chinese hamster ovary cells under total internal reflection fluorescence microscopy in which excitation light only penetrates several hundred nanometers into the cell, thus isolating membrane events. We found significant FRET between homomeric subunits as expected from their functional expression in heterologous expression systems. Also as expected from previous work, robust FRET was observed between KCNQ2 and KCNQ3. KCNQ3 and KCNQ4 also showed substantial FRET as did KCNQ4 and KCNQ5. To determine functional assembly of KCNQ4/KCNQ5 heteromers, we performed two types of experiments. In the first, we constructed a mutant tetraethylammonium ion-sensitive KCNQ4 subunit and tested its assembly with KCNQ5 by patch clamp analysis of the tetraethylammonium ion sensitivity of the resulting current; however, those data were not conclusive. In the second, we co-expressed a KCNQ4 (G285S) pore mutant with KCNQ5 and found the former to act as a dominant negative, suggesting co-assembly of the two types of subunits. These data confirm that among the allowed assembly conformations are KCNQ3/4 and KCNQ4/5 heteromers.
Possible convexity of the indirect utility function due to nonlinear budget constraints

Abstract A concave utility function coupled with a nonlinear budget constraint can lead to a convex indirect utility function given sufficient complementarity between products. Hence, the principle of diminishing marginal returns to income need not hold.
Photoinitiated predissociation of the NO dimer in the region of the second and third NO stretch overtones.

Photofragment yield spectra and NO(X2Π1/2,3/2; v = 1, 2, 3) product vibrational, rotational, and spin−orbit state distributions were measured following NO dimer excitation in the 4000−7400 cm-1 region in a molecular beam. Photofragment yield spectra were obtained by monitoring NO(X2Π; v = 1, 2, 3) dissociation products via resonance-enhanced multiphoton ionization. New bands that include the symmetric ν1 and asymmetric ν5 NO stretch modes were observed and assigned as 3ν5, 2ν1 + ν5, ν1 + 3ν5, and 3ν1 + ν5. Dissociation occurs primarily via Δv = −1 processes with vibrational energy confined preferentially to one of the two NO fragments. The vibrationally excited fragments are born with less rotational energy than predicted statistically, and fragments formed via Δv = −2 processes have a higher rotational temperature than those produced via Δv = −1 processes. The rotational excitation likely derives from the transformation of low-lying bending and torsional vibrational levels in the dimer into product rotat...
Aging and neuropathic pain.

Although chronic neuropathic pain disorders are more prevalent in the senescent population, little is known about how the aging process alters the thermal hyperalgesic sensitivity to peripheral nerve injury. In this study, neuropathic pain was induced in young, mature and aged FBNF1 hybrid rats via unilateral ligation of the left sciatic nerve. The extent to which the aging process affects the thermal hyperalgesic responsiveness of these animals was investigated. The results demonstrate that the aging process differentially alters nociceptive processing.
Long throw linear magnetic actuators stackable to one millimeter of structural height

Magnetic micro-actuators fabricated using LIGA-like processing and an aligned stacking technique have obtained structural heights of greater than one millimeter with structure aspect ratios greater than 100 to 1. Actuator displacements approaching 500 μm have been obtained under DC drive conditions with minimal input power. The actuator produces large output force and large sensitivity of inductance with respect to displacement. Inductance changes of ∼50 μH/μm are ideal for position sensing and closed loop actuator control.
Predictive performance of missing data methods for logistic regression, classification trees and neural networks

Although the effect of missing data on regression estimates has received considerable attention, their effect on predictive performance has been neglected. We studied the performance of three missing data strategies—omission of records with missing values, replacement with a mean and imputation based on regression—on the predictive performance of logistic regression (LR), classification tree (CT) and neural network (NN) models in the presence of data missing completely at random (MCAR). Models were constructed using datasets of size 500 simulated from a joint distribution of binary and continuous predictors including nonlinearities, collinearity and interactions between variables. Though omission produced models that fit better on the data from which the models were developed, imputation was superior on average to omission for all models when evaluating the receiver operating characteristic (ROC) curve area, mean squared error (MSE), pooled variance across outcome categories and calibration X 2 on an inde...
Annular keratotomy for the treatment of painful bullous keratopathy.

Purpose To determine whether annular keratotomy can relieve pain associated with bullous keratopathy. Methods Three patients with painful bullous keratopathy and poor visual potential underwent partial-thickness (0.30 to 0.42 mm) trephination of the cornea under local anesthesia. Results All patients reported an absence of pain and foreign body sensation during an average follow-up interval of six months. The surgical procedure was uncomplicated; however, two eyes developed increased central corneal stromal edema. Conclusions Annular keratotomy appears to be a relatively safe and simple surgical procedure that may be useful in managing pain in eyes with painful cornea edema and poor visual potential.
Sequential Framework for Short-Term Passenger Flow Prediction at Bus Stop

Short-term prediction of passenger flow plays an important role in real-time bus dispatching. Such prediction is also useful in diagnosing bus operation problems, such as forecasting bus bunching. A novel framework is proposed in this paper to predict the passenger flow at bus stops. The framework consists of three sequential stages. In the first stage, a seasonal ARIMA-based method is used to predict the arrival passenger count and empty space on a bus when the bus reaches a bus stop. The historical passenger arrivals at the bus stop can be obtained from the corresponding boarding count data by an allocation approach. In the second stage, an event-based method is developed to predict the departure passenger counts from the stop. The proposed method iteratively forecasts the bus arrival events and consequently updates the passenger flow. In the third stage, a Kalman filter-based method is proposed to predict the waiting passenger counts at the stop according to results from the first and second stages. Th...
Does Outreach Impact Choices of Major for Underrepresented Undergraduate Students

Over the last decade, there has been a concerted effort to bring more diverse voices to the technology field, with much of this being done through outreach activities to girls and boys. Unfortunately, data demonstrating the long-term impact of outreach activities remains rare. To contribute to knowledge on the longitudinal effect of outreach programs, we used a quantitative methodology that followed a descriptive design approach to explore the impact of participation in outreach activities on the choice of undergraduate major. Of those surveyed, 45.3% of the 770 respondents recalled participating in these activities. The results indicate that these activities had a more positive impact on Asians and more negative impact on Hispanics. Blacks/African Americans were more likely to voluntarily participate in outreach activities than Hispanics, and whites were more likely to feel that they were a welcome part of the group than non-whites. The results also may indicate that when outreach programs are available in earlier grades, they are not reaching non-white participants to the same extent as white participants.
Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus

Abstract Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro . After incubation of slices of ductus arteriousus in Krebs' solution with (1- 14 C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguisable from 6 keto-PGF 1α as determined by its chromatographic mobility and resistance to alkaline conversion to PGB. The PGI 2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF 1α , suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.
A polymorphism in the α4 nicotinic receptor gene (chrna4) modulates enhancement of nicotinic receptor function by ethanol

Background: Several studies indicate that ethanol enhances the activity of 42 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the 4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the 4 protein. Mouse strains expressing the A variant have, in general, greater nAChR-mediated 86 Rb efflux in response to nicotine than strains with the T variant. However, the possibility of the polymorphism modulating the effects of ethanol on the 86 Rb efflux response has not been investigated. Methods: We have used the 86 Rb efflux method to study the acute effects of ethanol on the function of the 42 nAChR in the thalamus in six different mouse strains. Experiments were also performed on tissue samples taken from F2 intercross animals. The F2 animals were derived from A/J mice crossed with a substrain of C57BL/6J mice that carried a null mutation for the gene encoding the 2 nAChR subunit. Results: In strains carrying the A polymorphism (A/J, AKR/J, C3H/Ibg), coapplication of ethanol (10 –100 mM) with nicotine (0.03–300 M) increased maximal ion flux when compared with nicotine alone with no effect on agonist potency. In contrast, ethanol had little effect on the nicotine concentrationresponse curve in tissue prepared from strains carrying the T polymorphism (Balb/Ibg, C57BL/6J, C58/J). Experiments with the F2 hybrids demonstrated that one copy of the A polymorphism was sufficient to produce a significant enhancement of nAChR function by ethanol (50 mM) in animals that were also 2 /. Ethanol had no effect on nicotine concentration-response curves in T/T 2 / animals. Conclusions: The results suggest that the A/T polymorphism influences the initial sensitivity of the 42 nAChR to ethanol.
Community–Labor Coalitions for Progressive Change

In the current neo-liberal economic and political climate, the labor movement faces immense challenges for survival and efficacy. As a massive redistribution of wealth upward has occurred, poverty is growing along with low-wage and insecure employment. The labor movement is developing new strategies that incorporate community organizing and local community issues into its issues as it organizes low-wage workers, often urban residents. Among these are living wage campaigns, community benefits agreements, and building regional progressive power. Many opportunities for collaboration with social work and involvement by social workers, particularly community practitioners, exist in these developments.
Rethinking Governmentality: Towards Genealogies of Governance

Foucault introduced the concept ‘governmentality’ to refer to the conduct of conduct, and especially the technologies that govern individuals. He adopted the concept after his shift from structuralist archaeology to historicist genealogy. But some commentators suggest governmentality remains entangled with structuralist themes. This article offers a resolutely genealogical theory of govermentality that: echoes Foucault on genealogy, critique, and technologies of power; suggests resolutions to problems in Foucault’s work; introduces concepts that are clearly historicist, not structuralist; and opens new areas of empirical research. The resulting genealogical theory of governmentality emphasizes nominalism, contingency, situated agency, and historicist explanations referring to traditions and dilemmas. It decenters governance by highlighting diverse elite narratives, technologies of power, and traditions of popular resistance.
Effectiveness of Wildlife Underpasses and Fencing to Reduce Wildlife–Vehicle Collisions

Abstract Transportation planners are increasingly incorporating roadway design features to mitigate impacts of highways on wildlife and to increase driver safety. We used camera and track surveys to evaluate wildlife use before and after construction of 3 wildlife underpasses and associated fencing on a new section of United States Highway 64 in Washington County, North Carolina, USA. We recorded 242 occasions of white-tailed deer (Odocoileus virginianus) use of underpass areas before highway construction began. Following completion of the highway, we collected 2,433 photographs of 9 species with deer representing 93% of all crossings. Adjusting for differences in number of monitoring days, white-tailed deer use of underpass areas averaged 6.7 times greater after the new highway and underpasses were completed. We recorded 3,614 wildlife crossings of ≥20 species based on track counts, representing most medium and large mammals known to occur in the area and several reptiles and birds. After completion of t...
Global Dynamics of an Autoparametric System With Multiple Pendulums

The Hamiltonian dynamics of a resonantly excited linear spring-mass-damper system coupled to an array of pendulums is investigated in this study under 1:1:1:...:2 internal resonance between the pendulums and the linear oscillator. To study the small-amplitude global dynamics, a Hamiltonian formulation is introduced using generalized coordinates and momenta, and action-angle coordinates. The Hamilton's equations are averaged to obtain equations for the first-order approximations to free and forced response of the system. Equilibrium solutions of the averaged Hamilton's equations in action-angle or comoving variables are determined and studied for their stability characteristics. The system with one pendulum is known to be integrable in the absence of damping and external excitation. Exciting the system with even a small harmonic forcing near a saddle point leads to stochastic response, as clearly demonstrated by the Poincare sections of motion. Poincare sections are also computed for motions started with initial conditions near center-center, center-saddle and saddle-saddle-type equilibria for systems with two, three and four pendulums. In case of the system with more than one pendulum, even the free undamped dynamics exhibits irregular exchange of energy between the pendulums and the block. The increase in complexity is also demonstrated as the number of pendulums is increased, and when external excitation is present.
Epidemiologic evidence for multiple sclerosis as an infection.

The worldwide distribution of multiple sclerosis (MS) can be described within three zones of frequency: high, medium, and low. The disease has a predilection for white races and for women. Migration studies show that changing residence changes MS risk. Studies of persons moving from high- to low-risk areas indicate that in the high-risk areas, MS is acquired by about age 15. Moves from low- to high-risk areas suggest that susceptibility is limited to persons between about ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics beginning in 1943. The disease appears to have been introduced by British troops who occupied the islands for 5 years from 1940, and it has remained geographically localized within the Faroes for half a century. What was introduced must have been an infection, called the primary MS affection (PMSA), that was spread to and from successive cohorts of Faroese. In this concept, PMSA is a single widespread systemic infectious disease (perhaps asymptomatic) that only seldom leads to clinical neurologic MS. PMSA is also characterized by a need for prolonged exposure, limited age of susceptibility, and prolonged incubation. I believe that clinical MS is the rare late outcome of a specific, but unknown, infectious disease of adolescence and young adulthood and that this infection could well be caused by a thus-far-unidentified (retro)virus. Images
Constructing lower and upper bounded delay routing trees using linear programming

This paper presents a new approach for solving the Lower and Upper Bounded delay routing Tree (LUBT) problem using linear programming. LUBT is a Steiner tree rooted at the source node such that delays from the source to sink nodes lie between the given lower and upper bounds. We show that our proposed method produces minimum cost LUBT for a given topology under a linear delay model. Unlike recent works which control only the difference between the maximum and the minimum source-sink delay, we construct routing trees which satisfy distinct lower and upper bound constraints on the source-sink delays. This formulation exploits all the flexibility that is present in low power and high performance clock routing tree design.
Measurement of small capacitances using phase measurement

A method for measuring small capacitance values without expensive test setups is presented. This method utilizes phase measurement with standard laboratory equipment. In the process of measuring the capacitance, the loss factor of the capacitance is also determined. This method lends itself to measuring a wide range of capacitances over a wide frequency range. >