bluuebunny/crossref_metadata_2025 huggingface dataset:
Carrier transport and improved emission properties of bilayer polymer light-emitting transistors based on crystalized poly(alkylfluorene) films
Authors: Kajii Hirotake , Hashimoto Kazuya , Hara Mikio , Ohtomo Takahiro , Ohmori Yutaka
Published: January 2016

In order to clarify the carrier transport and improve the emission characteristics of polymer light-emitting transistors, the fabrication and properties of top-gated bilayer polymer light-emitting transistors with oriented poly(9,9-dioctylfluorene) (F8) films and a phosphorescent dye doped in F8 are investigated. For bilayer devices with different oriented F8 films, both the hole and electron mobilities of bilayer devices are dependent on those of F8 upper layer. The bilayer devices using an oriented F8 upper layer with the channel direction parallel to the polymer orientation exhibit higher hole and electron mobilities, and improved EL intensity than those with the channel direction perpendicular to the polymer chains orientation. Devices with a phosphorescent dye-doped layer also exhibit the ambipolar and light-emitting properties. Both fluorescence and phosphorescence emissions can be achieved for bilayer devices. We demonstrate the possibility of improved emission for bilayer devices using a conjugated polymer doped with a phosphorescent material as the upper layer.
Barrier properties of ultrathin VN films of low resistivity and high density for Cu interconnects
Authors: Takeyama Mayumi B. , Sato Masaru , Itoi Takaomi , Aoyagi Eiji , Noya Atsushi
Published: January 2016

We have examined vanadium nitride (VN) films as a candidate material for the low-resistivity diffusion barrier of Cu interconnects in Si-LSI technology, aimed at reducing the interconnect resistance. We successfully prepared a continuous and uniform VN film as thin as 5 nm with a nanocrystalline texture with grains 2–5 nm in size. The VN barrier applied to the model system of Cu/VN/SiO2/Si and Cu/VN/SiOC/Si shows excellent barrier properties; the ultrathin barrier shows a negligible structural change and the absence of Cu penetration and/or interfacial reaction in the systems after annealing at 500 °C. The properties of an ultrathin VN barrier, such as low resistivity (50 µΩ cm) and high density (5.8 g/cm3), are attributed to the formation of a stable δ-VN phase in a nanocrystalline texture with grains of size smaller than or equal to the barrier thickness that stands high in a structurally stable and chemically inert barrier.
A simple and rapid method for measuringα-D-phosphohexomutases activity by using anion-exchange chromatography coupled with an electrochemical detector
Authors: Jia Xiaochen , Kang Jian , Yin Heng
Published: January 2016

The interconversion of hexose-6-phosphate and hexose-1-phosphate can be directly analyzed by high-performance anion-exchange chromatography coupled with an electrochemical detector (HPAEC-PAD). Thus, this method can be used to measure the activities of N-acetylglucosamine-phosphate mutase (AGM), glucosamine-phosphate mutase (GlmM) and phosphoglucomutase (PGM), which are the members ofα-D-phosphohexomutases superfamily. The detection limits were extremely low as 2.747 pmol, 1.365 pmol, 0.512 pmol, 0.415 pmol, 1.486 pmol and 0.868 pmol for N-acetylglucosamine-1-phosphate (GlcNAc-1-P), N-acetylglucosamine-6-phosphate (GlcNAc-6-P), glucosamine-1-phosphate (GlcN-1-P), glucosamine-6-phosphate (GlcN-6-P), glucose-1-phosphate (Glc-1-P) and glucose-6-phosphate (Glc-6-P), respectively. By employing HPAEC-PAD, activities ofAtAGM (AGM fromArabidopsis thaliana) on these six phosphohexoses can be detected. TheKmofAtAGM on Glc-1-P determined by HPAEC-PAD was 679.18 ± 156.40 µM, which is comparable with theKmof 707.09 ± 170.36 µM detected by traditional coupled assay. Moreover, the activity ofMtGlmM (GlmM fromMycobacterium tuberculosis) on GlcN-6-P tested by HPAEC-PAD was 7493.40 ± 309.12 nmol∕min ⋅ mg, which is much higher than 288.97 ± 35.28 nmol∕min ⋅ mg obtained by the traditional coupled assay. Accordingly, HPAEC-PAD is a more rapid and simple method than the traditional coupled assays given its high specificity and sensitivity, and will certainly bring convenience to further research ofα-D-phosphohexomutases.
The role of coral colony health state in the recovery of lesions
Authors: Ruiz-Diaz Claudia P. , Toledo-Hernandez Carlos , Mercado-Molina Alex E. , Pérez María-Eglée , Sabat Alberto M.
Published: January 2016

Coral disease literature has focused, for the most part, on the etiology of the more than 35 coral afflictions currently described. Much less understood are the factors that underpin the capacity of corals to regenerate lesions, including the role of colony health. This lack of knowledge with respect to the factors that influence tissue regeneration significantly limits our understanding of the impact of diseases at the colony, population, and community level. In this study, we experimentally compared tissue regeneration capacity of diseased versus healthy fragments ofGorgonia ventalinacolonies at 5 m and 12 m of depth. We found that the initial health state of colonies (i.e., diseased or healthy) had a significant effect on tissue regeneration (healing). All healthy fragments exhibited full recovery regardless of depth treatment, while diseased fragments did not. Our results suggest that being diseased or healthy has a significant effect on the capacity of a sea fan colony to repair tissue, but that environmental factors associated with changes in depth, such as temperature and light, do not. We conclude that disease doesn’t just compromise vital functions such as growth and reproduction in corals but also compromises their capacity to regenerate tissue and heal lesions.
Regional heterogeneity in the water content of the Cenozoic lithospheric mantle of Eastern China
Authors: Hao Yan‐Tao , Xia Qun‐Ke , Jia Zu‐Bing , Zhao Qi‐Chao , Li Pei , Feng Min , Liu Shao‐Chen
Published: January 2016

The major and trace elements and H2O contents of minerals in peridotite xenoliths hosted by the Cenozoic basalts in Northeast China (NEC) were evaluated using electron microprobe, laser‐ablation inductively coupled plasma–mass spectrometry and Fourier transform infrared spectroscopy, respectively. Although a potential loss of H during the xenoliths' ascent cannot be excluded for olivine, orthopyroxene (opx) and clinopyroxene (cpx) largely preserved the H2O contents of their mantle source in all of the samples, as inferred from (1) the homogenous H2O contents within single pyroxene grains and (2) the equilibrium H2O partitioning between cpx and opx. No OH was detected for pyroxenes of peridotite xenoliths from the north part of NEC (NNEC). Combined with previously published data from the North China Craton (NCC) and the South China Block (SCB), the regional heterogeneity in the water contents in the Cenozoic lithospheric mantle beneath the whole Eastern China has been revealed. The lithospheric mantle beneath the NNEC is completely dry. The “bulk” water contents of the lithospheric mantle of the south part of NEC and the NCC have similar ranges and average values, whereas those of the SCB are much higher (12–195 ppm, average 90 ± 45 ppm for whole rock). The regional variations in the H2O content of the Cenozoic lithospheric mantle of Eastern China cannot be caused by partial melting, mantle metasomatism, or variations in redox state. We propose that the lithospheric mantle beneath the different regions of Eastern China may have distinct origins and may have undergone distinct geodynamic processes.
Sound velocities of δ‐AlOOH up to core‐mantle boundary pressures with implications for the seismic anomalies in the deep mantle
Authors: Mashino Izumi , Murakami Motohiko , Ohtani Eiji
Published: January 2016

Recent studies show that δ‐AlOOH is stable up to the base of the mantle. This phase is, therefore, a possible carrier and host of water in the deep mantle. To uncover the physical properties of δ‐AlOOH under deep mantle pressure conditions, we have conducted high‐pressure acoustic wave velocity measurements of δ‐AlOOH by using Brillouin spectroscopy combined with high‐pressure Raman spectroscopic measurements in a diamond anvil cell up to pressures of 134 GPa. There is a precipitous increase by ~14% in the acoustic velocities of δ‐AlOOH from 6 to 15 GPa, which suggests that pressure‐induced O‐H bond symmetrization occurs in this pressure range. The best fit values for the high‐pressure form of δ‐AlOOH of K0 = 190 (2) (GPa), G0 = 160.0 (9) (GPa), (∂K/∂P)0 = K0′ = 3.7 (1), and (∂G/∂P)0 = G0′ = 1.32 (1) indicate that δ‐AlOOH has a 20–30% higher VS value compared to those of the major constituent minerals in the mantle transition zone, such as wadsleyite, ringwoodite, and majorite. On the other hand, the VS of δ‐AlOOH is ~7% lower than that of Mg‐bridgmanite under lowermost mantle pressure conditions because of the significantly lower value of the pressure derivative of the shear modulus. By comparing our results with seismic observations, we can infer that δ‐AlOOH could be one of the potential causes of a positive VS anomaly observed at ~600 km depth beneath the Korean peninsula and a negative VS jump near 2800 km depth near the northern margin of the large low‐shear‐velocity province beneath the Pacific.
Built Conservation and the Unfinished Fabrics of Time
Authors: Goffi Federica
Published: January 2016

Differentiating between the static impulse to preserve and the more open‐ended and imaginative process of conservation, Federica Goffi presents a building as ‘a fabric that, even when complete, is unfinished and open to change’. Associate Professor and Associate Director of Graduate Programs at the Azrieli School of Architecture and Urbanism at Carleton University in Ottawa, Goffi has written widely on the topic of time, particularly taking St Peter's in the Vatican by way of example.
Juxtaposing the New and the Old
Authors: Parry Eric
Published: January 2016

The reputation of the renowned London‐based architect Eric Parry rests on his contemporary, but highly contextual approach to the designing of buildings in historic and highly visible city‐centre sites. The author of Context: Architecture and the Genius of Place (Wiley, 2015), Parry acknowledges here the debt that he owes to the thinking of Dalibor Vesely, while describing how it plays out in his renewal project for St Martin‐in‐the‐Fields in London and the extension of the Holburne Museum in Bath.
Time as a Medium: Early Work of Miralles
Authors: Speranza Philip
Published: January 2016

Regarding permanence ‘as contrary to existence’, Enric Miralles employed architecture as a means of providing people with experiences of the passage of time. Here Philip Speranza, Assistant Professor in the School of Architecture and Allied Arts at the University of Oregon and Director of its Barcelona Urban Design Program, describes three early works that Miralles and his partner Carme Pinós undertook in the early 1990s with this preoccupation in mind: the Boarding School in Morella, Castellon, Spain; the pergola walkway for the Paseo Icaria, in Barcelona's Olympic Village; and the Igualada Cemetery in Barcelona.
The Presence of the Weather
Authors: Nute Kevin
Published: January 2016

Modern architecture has dedicated much of its discourse to crystal‐ball gazing – dwelling on the visionary and the speculative. Conversely, Kevin Nute, Professor of Architecture at the University of Oregon, puts the case for the present over the future and the past. To enhance experiences of the present, he describes how architects can harness the effects of changing temporal and weather conditions – sun and shadow, wind and rain. Design can heighten the sensory stimuli these conditions generate, keeping us ‘in the moment’ while still enjoying the comfort of being indoors.
Drawing in Time: Processes of Design and Fabrication
Authors: Bryan Babak , Grosman Henry
Published: January 2016

Drawing embeds time within itself, notating changes in space and duration. For Babak Bryan and Henry Grosman, founding partners of BanG studio in Long Island City, New York: ‘The drawing is a result of process, but it also describes process.’ It is only through this temporal practice that an essential connection is developed between drawing and building. With the widespread adoption of building information modelling (BIM), linear graphic representation finds itself in crisis, challenged by the static inertia of the model. As Bryan and Grosman describe, the well‐crafted drawing remains essential to their studio's approach informing the method of ‘making and remaking’.
Architecture Takes Time
Authors: Armborst Tobias , D'Oca Daniel , Theodore Georgeen
Published: January 2016

Though condensed between the stages of design and completion, the conventional process of designing a building is time consuming, involving various stakeholders, planning processes and a wide team of consultants and contractors. What happens, though, if the time period of an architect's involvement is expanded? How might a more process‐orientated approach shift the role of the architect? Tobias Armborst, Daniel D'Oca and Georgeen Theodore, principals of Interboro Partners in New York, describe how they have developed projects that have sought opportunities in expanding the timescale and remit of traditional practice.
Finding Time
Authors: Makower Tim
Published: January 2016

What has our sense of the acceleration of time got to bear on our experience of cities? How might it be consciously countered by architects ‘finding time’ through ‘thoughtful design and measured observation’. ‘A self‐declared ‘cultural polymath’, Tim Makower is the founder of Makower Architects. A partner at Allies and Morrison for many years, he has significant experience in leading large‐scale projects, ranging from the King's Cross Masterplan in London to the Old Doha Regeneration Framework, which he draws on here and in his book Touching the City: Thoughts on Urban Scale (Wiley, 2014).
Metal‐Free Oxidative Cross Esterification of Alcohols via Acyl Chloride Formation
Authors: Gaspa Silvia , Porcheddu Andrea , De Luca Lidia
Published: January 2016

A novel metal‐free oxidative cross esterification of alcohols has been achieved using trichloroisocyanuric acid as an oxidant. The alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with primary and secondary aliphatic, benzylic and allylic alcohols and phenols. A wide variety of esters was obtained in satisfactory yields.

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Model‐predictive safety system for proactive detection of operation hazards
Authors: Ahooyi Taha Mohseni , Soroush Masoud , Arbogast Jeffrey E. , Seider Warren D. , Oktem Ulku G.
Published: January 2016

A method of designing model‐predictive safety systems that can detect operation hazards proactively is presented. Such a proactive safety system has two major components: a set of operability constraints and a robust state estimator. The safety system triggers alarm(s) in real time when the process is unable to satisfy an operability constraint over a receding time‐horizon into the future. In other words, the system uses a process model to project the process operability status and to generate alarm signals indicating the presence of a present or future operation hazard. Unlike typical existing safety systems, it systematically accounts for nonlinearities and interactions among process variables to generate alarm signals; it provides alarm signals tied to unmeasurable, but detectable, state variables; and it generates alarm signals before an actual operation hazard occurs. The application and performance of the method are shown using a polymerization reactor example. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2024–2042, 2016
Biosynthesis of palladium nanoparticles using Rosa canina fruit extract and their use as a heterogeneous and recyclable catalyst for Suzuki–Miyaura coupling reactions in water
Authors: Veisi Hojat , Rashtiani Asra , Barjasteh Venous
Published: January 2016

A facile and green route for the synthesis of palladium nanoparticles was developed utilizing non‐toxic and renewable natural Rosa canina fruit extract as the reducing, stabilizing and capping agent, and they were applied as a heterogeneous catalyst for Suzuki coupling reactions between phenylboronic acid and a range of aryl halides containing iodo, bromo and chloro moieties in water under moderate reaction conditions. The structural investigation of the generated nanoparticles was performed with UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and energy‐dispersive X‐ray analysis. The method has some advantages such as high yields, efficiency, elimination of surfactant, chemical reductants, ligand and organic solvent, economic, cleaner reaction profiles, heterogeneous catalysis, simple methodology and easy workup. The catalyst can be recovered and reused seven times without any significant decrease in catalytic activity. Copyright © 2016 John Wiley & Sons, Ltd.
New records of the distribution and conservation status of the endangered limpet Patella ferruginea in Sardinia (Italy, W Mediterranean)
Authors: Marra Stefano , de Lucia G. Andrea , Camedda Andrea , Espinosa Free , Coppa Stefania
Published: January 2016

Patella ferruginea is an endemic and endangered limpet of the Mediterranean Sea. Its distributional range has been greatly reduced over the past century, mainly as a consequence of human pressure on coastal habitats, and its presence is now confined to a few sites in the western Mediterranean basin.

It was assumed that the island of Mal di Ventre was the only location hosting P. ferruginea in the central‐western area of Sardinia (Italy), but reports from local people and the discovery of empty shells in surrounding areas suggested its distribution range may be greater than previously thought.

Several systematic surveys for the presence of P. ferruginea were conducted during the summers of 2013 and 2014 at different locations of central‐western Sardinia to improve knowledge about its conservation status and to verify various reported occurrences.

Findings from this study confirm the critical status of conservation of the species in central‐western Sardinia. The island of Mal di Ventre was confirmed as the main location hosting P. ferruginea and only one new small nucleus of limpets was found in a hardly accessible site on the coastline of the Sinis Peninsula (Cape San Marco). This nucleus represents the new southern distribution limit of the species in Sardinia.

This work highlights the importance of awareness‐raising activities and local environmental knowledge (‘citizen science’) as a source of information that can result in a better understanding of the distribution of this endangered species. Hardly accessible sites represent ideal locations to put in place conservation measures for the local P. ferruginea population but further studies, specifically aimed at determining the larval dispersal and connectivity among different limpet nuclei, are required.

Copyright © 2016 John Wiley & Sons, Ltd.
Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity?
Authors: Izsvák Zsuzsanna , Wang Jichang , Singh Manvendra , Mager Dixie L. , Hurst Laurence D.
Published: January 2016

Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic “junk yard”, functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone.
Quenching of fluorescence of phenolic compounds and modified humic acids by cadmium ions
Authors: Tchaikovskaya O. N. , Nechaev L. V. , Yudina N. V. , Mal'tseva E. V.
Published: January 2016

The interaction of a number of phenolic compounds, being ‘model fragments’ of humic acids, with cadmium ions was investigated. The fluorescence quenching method was used to determine the complexation constants of these compounds with cadmium ions. It was established that bonding of phenolic compounds by cadmium ions at рН 7 is weak and reaches a maximum value of 15% for interaction with resorcinol. It was demonstrated that modification of humic acids by the mechanoactivation method increases by three times bonding of cadmium ions, which is caused by strengthening the acid properties of carboxyl and hydroxyl groups at the aromatic ring. Copyright © 2016 John Wiley & Sons, Ltd.
Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells
Authors: Lin Zuo‐Lin , Wu Hsin‐Jou , Chen Jin‐An , Lin Kuo‐Chih , Hsu Jung‐Hsin
Published: January 2016

Cyclophilin A (Cyp A), a member of the peptidyl‐prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3‐kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin‐6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus‐activated kinase 2/STAT3 signalling pathway. Copyright © 2015 John Wiley & Sons, Ltd.
Enhanced Hydrogen Evolution Catalysis Based on Cu Nanoparticles Deposited on Carbon Nanotubes at the Liquid/Liquid Interface
Authors: Aslan Emre , Akin Ilker , Patir Imren Hatay
Published: January 2016

Copper nanoparticles were electrodeposited in situ on a conductive multi‐walled carbon nanotubes (MWCNT) support at a free‐standing water/1,2‐dichloroethane interface. The Cu/MWCNT nanocomposites act as highly active hydrogen evolution catalysts at the interface in the presence of lipophilic decamethylferrocene as the reducing agent.
The clinical use of an epoxide alkylating agent, epoxypropidine, in neoplastic disease
Authors: Miller Daniel G. , Diamond Henry D. , Craver Lloyd F.
Published: January 2016

In a study of a series of synthetic bis‐epoxide alkylating agents, a correlation was found between base strength and antileukemic effectiveness. Epoxypropidine (1,1'‐bis (2,3 epoxypropyl)‐4,4'‐dipiperidyl) was the most active analog in this regard and, in addition, possessed physical characteristics desirable for a pharmacologic agent. Preclinical trials revealed greater antitumor activity on a weight‐for‐weight basis than that of an analog of the same series which had been demonstrated to be of clinical usefulness. Epoxypropidine was used clinically in the treatment of 21 patients with neoplastic diseases. Objective response and significant clinical improvement were nated in patients with Hodgkin's disease, lymphosarcoma, reticulum cell sarcoma, and chronic myelogenous leukemia. Clinical experience with this agent in a dose causing comparable leukopenia was similar to that with another alkylating agent of the epoxide class, diepoxypropylpiperazine, and with nitrogen mustard. Epoxypropidine caused none of the visual aberrations seen with diepoxypropylpiperazine and, in divided doses, less nausea and vomiting than are seen with comparable doses of nitrogen mustard. Despite the greater activity by weight of this compound compared to the piperazine analog, the therapeutic index was not improved. Although compounds of greater clinical convenience have been devised, the general experience with alkylating agents to date argues against the probability of increasing anticancer activity by altering prosthetic groups.
Renal effects of hydrochlorothiazide in normal and toxemic pregnancy
Authors: Assali N. S.
Published: January 2016

The effect of hydrochlorothiazide was studied in 10 hospitalized patients (7 with pre‐eclampsia and 3 with normal pregnancy) and 48 ambulatory sub;ects (30 with normal pregnancy and 18 with toxemia of pregnancy). Hydrochlorothiazide increased the excretion of Na+, Cl−, K+, and water without any significant change in renal plasma flow or glomerular filtration rate. The increase in electrolyte excretion was more marked in the patients with toxemia of pregnancy than in those with normal pregnancy. On the basis of electrolyte excretion hydrochlorothiazide is approximately 10 times as potent as chlorothiazide in pregnant women. As in the case of chlorothiazide, the drug is more effective when edema is present.
Newer drugs in amebiasis
Authors: Anderson Hamilton H.
Published: January 2016

Amebiasis, a systemic disease due to Endamoeba histolytica, is not confined to the tropics. Its incidence reflects the sanitary level of the environment.

In the colon, associated bacteria are believed to play a role in its pathogenesis, but not in the liver and other extraintestinal tissues. Realistically, the therapeutic regime depends upon the site of amebic invasion, and whether or not associated organisms are believed to be contributory to the disease complex. “Specific” amebicides are available, capable of clearing the majority of cases, i.e., of chronic amebiasis as seen in the United States. In a minority, however, recurrence of infection, due to amebae with or without associated bacteria, is persistent. To combat recurrence, especially in environments of high endemicity, personal and community hygiene is mandatory.

Newer drug types currently under trial are: glycobiarsol, N.F.; representative dichloracetamides, of which Mebinol is an example; certain phenanthrolines, such as Entobex; diamino derivatives, such as MA‐307; and paromomycin (Humatin), an antibiotic. Suppressive therapy and adequate hygienic precautions provide a more enlightened approach to the control of amebiasis. No one therapeutic agent, or combination, is indicated universally in combating this disease.
Clinical pharmacology of analgesics: 1. A method of assaying analgesic effect
Authors: Houde R. W. , Wallenstein S. L , Rogers Ada
Published: January 2016

Animal screening tests and methods employing induced pain in human volunteers have failed to predict with any consistency the clinical performance of analgesic drugs. These drugs must be assayed in a clinical setting in which they might be used therapeutically. The lack of adequate objective standards for the measurement of pain or pain relief, the variability in responses among patients, and the influence of environmental factors on these responses, all make it essential that the study be adequately controlled and so designed as to provide some measure of the sensitivity of the method and of the statistical significance of the results.

Such a method for evaluating analgesics in patients with chronic pain due to cancer has been employed at the Memorial Cancer Center for the past 8 years. Measurements of analgesia are derived from the patients' own estimates of pain intensity both before and at hourly intervals after a test medication Yielding data which allow comparison of drugs in terms of peak and total effects. Using these criteria, studies of the effects of morphine and a placebo were carried out and provide the basis for a method of assaying other analgesic drugs. A prototype of the latter is presented in the form of a study of aspirin, morphine, and a combination of these drugs.
Orally active hypoglycemic substances and the rationale of their use
Authors: Levine Rachmiel , Berger Sheldon
Published: January 2016

The introduction of the orally active hypoglycemic agents has already had a profound effect on the therapy of diabetes. Unfortunately, despite a great deal of discussion in the literature, there is still much about these drugs which is uncertain and unsettled and, in general, information about their limitations is not so widely spread as claims for their utility. Although the modern era of interest in oral hypoglycemic agents began about 40 years ago with the association of this effect with the guanidines, it was first observed and confirmed more than 80 years ago as the result of salicylate therapy. Hypoglycemic effects have been noted after the oral administration of such unrelated materials as (1) sulfonamides and sulfonylureas (e.g., tolbutamide), (2) guanidines (e.g., synathalin A), (3) extracts of the akee plant (hypoglycin A and B), and (4) salicylates. It is also reasonable to suppose that more are on their way. The state of our knowledge of the modes of action of the several groups of orally active hypoglycemic agents based on clinical and experimental observations as well as their clinical uses, limitations, and dangers are discussed.
Effect of certain drugs on the incidence of seasickness
Authors: Trumbull Richard , Chinn Herman I. , Maag Clinton H. , Milch Lawrence J. , Handford S. Wing , Seibert Richard , Sperling Philip , Smith Paul K.
Published: January 2016

Several drugs were tested, some of them for the first time, against seasickness in military personnel on transport ships on the North Atlantic ocean. All of the drugs were given three fimes a day. Of the new ones tested phenglutarmide, 2.5 mg., and cinnarazine, 7.5 mg., were significantly effective on a single trip. Somewhat less effective were atropine and orphenadrine.

Ineffective new drugs were procyclidine, diethazine, cycrimine, caramiphen, pheniprazine, nialamide, phenelzine, benactyzine, and promazine.

Cyclizine and meclizine, in doses of 50 mg. three times a day, were again found to be effective.
The stimulant effect of 2‐dimethylaminoethanol (deanol) in human volunteer subiects
Authors: Murphree Henry B. , Pfeiffer Carl C. , Backerman Ivan A.
Published: January 2016

A double blind comparison of deanol, 10 to 30 mg. base, as the tartrate salt was made with an identical placebo in 35 volunteer subjects. No significant changes from the controls were observed in blood pressures, pulse rate, muscle strength, hand tremor, vital capacity, or body weight. Blood cholesterol levels were not changed. Blood protein bound iodine showed a slight tendency to decrease at the start of therapy, but this was not statistically significant. Gastric acid secretion was not changed, although volume of secretion was. Of the psychological and subjective responses, the significant findings were an increase in muscle tone, better mental concentration, and changes in sleep habits which were (1) less sleep needed, (2) sounder sleep, and (3) absence of the customary period of inetficiency in the morning in the deanol‐treated group.
The pharmacologic basis of the treatment of myasthenia gravis
Authors: Schwab Robert S.
Published: January 2016

The origins of the modern treatment of myasthenia gravis go back to the fundamental work of Loewi and Dale, identifying a chemical transmission at the myoneural junction related to the enzyme cycles built around acetylcholine. The normal cycle is described involving cholinesterase and choline acetylase to restore the enzyme to its normal state. Abnormal cycles including competitive block due to curare‐like substances as well as equally serious depolarizing block from too much anticholinesterase compound present, and similarities and differences between curare poisoning and myasthenia are discussed. The difficulties in controlling the symptoms of myasthenia are described in detail. It is shown that many patients can be restored to only 50 or 60 per cent of normal and that the most effectual and carefully selected medication achieves 80 to 95 per cent normality in only about one fourth of the patients; in another fourth well over 50 per cent normalcy is reached. There is, however, a third group who attain only 40 to 60 per cent normalcy, and a final group of patients who eannot reach even 40 per cent of normal function on the most effective currently available medication.
The drug explosion
Authors: Modell Walter
Published: January 2016

If the pharmaceutical chemists took the time to look back at the net result of their prolificacy, would they be shocked to discover that the point of no return may have been passed? Do they suspect that now, instead of helping mankind with new drugs, they may be making matters worse? Will they realize that there is such a thing as too many drugs, that as matters stand there are too many drugs for the patient, for the physician, and, surprisingly enough, for the pharmaceutical industry? Although no one would suggest that they cease or even slow the pace of their search for useful drugs, if they are at all interested, I suggest that they do take the time to follow the effect of their creativity to its ultimate conclusion.
Prolonged coma caused by glutethimide
Authors: Winters William , Grace William J.
Published: January 2016

The clinical course of a patient who ingested a large amount of glutethimide is described. The patient remained in a coma for 6 days but ultimately made a complete recovery. In the management of the patient, meticulous attention to the airway, pulmonary ventilation, and maintenance of blood pressure is emphasized. The usefulness of the Morsch respirator is described. Reports of similar patients in the literature are reviewed.
II. The limiting factor in the utilization of intravenous anesthetics during surgical operations
Authors: Keeri‐Szanto Michael
Published: January 2016

The construction of mean time/dose curves of intravenous anesthetic drugs during surgical operations under standardized conditions is a simple and sensitive way to determine the equipotent doses of anesthetic agents. Such curves were determined for meperidine and oxymorphone, and the results were compared with the corresponding data previously established for thiopental.

In spite of differences in the anesthetic potency of these agents by a factor approaching 500, the mathematical characteristics of the time/dose curves correspond so closely as to suggest that under the conditions of this study, a common factor limits the drug requirements. Arguments are presented in favor of the hypothesis that the common factor might be the effective blood flow through the liver or the permeability of the hepatic cell membrane.
The measurement of uncertainty
Authors: Werner Gerhard
Published: January 2016

To express results of experimentation in statistical notation has become a common practice and standard requirement. Indeed, statistics has been adopted as routine aspect of the conduct of experiments to an extent which makes statistical terminology seemingly self‐evident. This clearly indicates how deeply the vocabulary of probabilistic thinking has molded our scientific and “common sense” habits of thought. Yet, usage of statistical terms is not commonly paralleled by an adequate appreciation of magnitude and scope of the intellectual revolution from which statistical methodology arose.
The effect of psychopharmacologic agents on behavior, measured by the interaction chronograph
Authors: Tuason Vicente B. , Guze Samuel B.
Published: January 2016

This study is concerned with the objective measurement of drug‐induced changes in interview behavior by means of the interaction chronograph, a device which allows an observer to record in time units with a high degree of precision the behavioral interaction of two individuals during a standardized interview in which the interviewer follows certain predetermined rules of interviewing. The background and details of the method are described. Sixty new patients, selected by chance from the Washington University Psychiatry Clinic, were given one of three possible drugs in a double blind procedure. They were subjected to a test‐retest interview, using a standardized interview as a research tool and the interaction chronograph as the measure of response. Analysis of the data revealed statistically significant difference in the chlorpromazine group and no significant difference in the phenobarbital and placebo groups. The limitations and possibilities of the method are discussed.
Nomenclature of cancer chemotherapy agents
Authors: Ihndris Ray W.
Published: January 2016

This paper does not attempt to define all of the rules of nomenclature but only points out a few of the basic rules and gives examples of how they are used in naming compounds of interest as cancer agents.
An assessment of the responses to drugs acting on the central nervous system
Authors: Wilson Cedric W. M. , Huby Pamela M.
Published: January 2016

A quantitative assessment of the subjective and objective responses to caffeine, secobarbital (quinalbarbitone), thiopropazate, and a placebo has been carried out in normal subjects. The order of administration of the drugs was randomized, but the actions of the drugs were explained to the subiects. The subiects were asked to describe the effects of the drugs and to assess which drug they had received on each occasion. It was found that there was an association between the actions of the drugs and the subiects' opinions about which drugs they thought they had received. When they guessed correctly, they responded to it vigorously; where they guessed incorrectly, the effects of the drug were partially or completely inhibited. The implications of this observation are discussed. The percentage of placebo reactors was within the normal range, arul it is suggested that their symptoms may be related to the stress induced at the beginning of the experiment.
Method for evaluating antipruritic agents Studies on methdilazine
Authors: Friend Dale G.
Published: January 2016

Pruritus, a common complaint, is a most difficult symptom to evaluate and is altogethe; analogous to pain in this respect. A method for evaluating the antipruritic activity of drugs is described which makes use of the reaction produced by urushiol. A skin lesion is created in healthy volunteers sensitive to poison ivy by application of a diluted solution of urushiol, The fully developed lesion produces severe itching, and the response of the subiect can be studied. by the standard double blind technique for the antipruritic effect of a drug compared with that of placebo. The lesion continues uniform in intensity for a period long enough to permit the subjects to serve as their own controls.

In this technique, methdilazine and trimeprazine were compared to a placebo. Both drugs showed antipruritic efficacy, methdilazine producing a better response than trimeprazine under the conditions of the evaluation.
Clinical pharmacology of the anti‐inflammatory steroids
Authors: Liddie Grant W.
Published: January 2016

The physiologic as well as the supraphysiologic manifestations of hydrocortisone and its congeners are reviewed. The effeets on metabolic, electrolyte, and tissue systems are considered. These are related to structure and potency of the many congeners of cortisol whieh have been synthesized. Finally, clinical application to disease is related to basic pharmacologic data.
Pharmacology and toxicology of trichloroethylene: A critical review of the world literature
Authors: Defalque Ray J.
Published: January 2016

A review of the world literatute on trichloroethylene has revealed a general inadequacy in medical reports and the need for further studies if this compound is to remain in the medical armamentarium. Even studies on toxicology leave much to be desired. It is hoped that the extensive bibliography provided will permit future investigators to approach studies of trichloroethylene with a readily available background of work already accomplished.
Pharmacologic effects of intravenous vanillic acid diethylamide in man
Authors: Miller Murray J. , Hand B. Marvin , Crellin J. Antrim
Published: January 2016

Vanillic acid diethylamide, a respiratory stimulant, was injected intravenously in doses of 0.5 to 2 mg. per kilogram. Effects were noted within 30 seconds; they lasted approximately 10 minutes. There was an average increase in tidal respiratory volume of 48 per cent and in respiratory rate of 24 per cent. Electroencephalograms were made bejore and after administration. The drug led to diminution of alpha activity, scattered high voltage spikes, cerebral dysrhythmias, and in 1 patient a tonic seizure. There were no significant changes in pulse rate or blood pressure.
Effect of steroids on bundle branch block caused by arteriosclerotic heart disease
Authors: Schoenfeld Myron R. , Messeloff Charles R.
Published: January 2016

A 5 day course of triamcinolone, 32 mg. daily, uias given to 12 patients with coronary heart disease and an intraventricular conduction time of 12 seconds or more. In none of the cases toas the duration of the QRS complex shortened by the steroid therapy.
Effects in normal man of α‐methyltryptamine and α‐ethyltryptamine
Authors: Murphree Henry B. , Dippy Roy H. , Jenney Elizabeth H. , Pfeiffer Carl C.
Published: January 2016

DL‐α‐Methyltryptamine methyl sulfate in oral doses of 20 mg. and DL‐α‐ethyltryptamine acetate in oral doses of 150 mg. were compared objectively and subjectively in a group of trained, normal human volunteers. Blood pressure, pulse rate, pupil diameter, oral temperature, and grip strength were recorded hourly. Subjective effects were recorded 3 and 24 hours after administration of the drugs.

A significant decrease in heart rate occurred 2 hours after α‐ethyltryptamine. Significant rises in systolic and diastolic blood pressure occurred 3 hours after α‐methyltryptamine. There also were significant increases in pupil diameter after each drug.

The subjective effects were similar in many respects, but there were important differences. The onset of action was rapid for α‐ethyltryptamine and slow for α‐methyltryptamine; duration of action was longer for the latter than for the former. The most common effect, reported by 8 of the 11 subjects taking α‐ethyltryptamine, was a feeling of being elated or intoxicated. The most common effects reported by those who took α‐methyltryptamine were nervous tension and restlessness not unlike those produced by 50 to 60 γg of lysergic acid diethylamide.
Clinical evaluation of phendimetrazine bitartrate
Authors: Ressler Charles , Schneider Stanley H.
Published: January 2016

Clinical investigation of a phenmetrazine congener, phendimetrazine, was performed by using double blind controls. Of 50 obese patients who participated, 36 completed one adequate course of active drug or placebo and 20 completed both phases of the study. The average total weight lost and the average weight lost weekly by patients who received phendimetrazine were ahout 20 times as much as those of patients who received placebo. Comparison of the two groups showed no significant difference in undesirable effects. The over‐all incidence of subjective complaints or minor toxic reactions was negligible, and examination including pulse, blood pressure, blood count, and urinalysis showed no evidence of major change.
Comment
Authors: Modell Walter
Published: January 2016

It is a policy of this journal that, with their permission, any sufficiently interesting exchange of comments between author and Editor or author and referees may be published along with the paper in the way discussion of papers is presented at symposia. Here, it was Dr. Henry K. Beecher, as author of the editorial, who requested that the correspondence between himself and the Editor be printed. In deference to Dr Beecher, the Editor, to his delight, had to swallow his private modesty for the public benefit since Dr. Beecher was kind enough to say that there were sections of his letter “in which for the first time you gave me a rational way of thinking about the major unsolved problem dealt with here.” Those sections follow.
Circulatory effects of halothane in patients with heart disease
Authors: Kubota Yukio , Vandam Leroy D.
Published: January 2016

Halothane in an inspired concentration of 0.5 per cent in nitrous oxide and oxygen was given to 10 patients with advanced heart disease who were to undergo open cardiac operation. There was either no change or an elevation in systolic, diastolic, and mean arterial pressures. Higher concentrations of halothane, from 1 to 1.5 per cent, reduced the pressure moderately in some cases, more markedly in others. Pronounced change in pulse rate or increased myocardial irritability was not seen with either concentration. With both concentrations, significant diminution in the cardiac output was observed. This depression may have been enhanced by positive pressure control of respiration. The decrease in cardiac output and the tendency toward lowering of blood pressure were accompanied by an elevation in the over‐all peripheral vascular resistance. Changes in circulation time, central venous pressure, and central blood volume were observed but were not, because of lack of more specific information, helpful in the interpretation of the basic circulatory changes.
Clinical pharmacology of the semisynthetic penicillins
Authors: Dineen Peter
Published: January 2016

The semisynthetic penicillins are considered from the microbiologic and clinical standpoint. The various compounds are the product of the addition of various prosthetic groups to a basic building block, 6‐aminopenicillanic acid.

Although penicillinase rapidly inactivates penicillin G, the addition of larger prosthetic groups to 6‐aminopenicillanic acid protects the molecule from penicillinase action.

The group of semisynthetic penicillins which are resistant to the action of penicillinase constitutes a new frontier in the clinician's war against Staphylococcus aureus.

The use of methicillin in patients has been gratifying, particularly in penicillin‐resistant Staph. aureus infections. There has been a 64 per cent rate of cure of bacteremias caused by this organism.

Resistance of Staph. aureus to methicillin at a clinical level has not been apparent as yet.
Clinical pharmacology: A definition
Authors: Modell Walter
Published: January 2016

This may seem like a late date for such a statement, but clinical pharmacology, the latest portfolio in medicine, suffers from the lack of an established and recognized definition; and what is even more distressing to clinical pharmacologists is that, even to those who use the term with some assurance, it often seems to mean different things. The reason for the confusion is not newness alone; the term itself is basically unclear and to a degree even inaccurate. It seems at once to imply such diverse aspects of drugs and their nature and application as applied pharmacology, clinical trials, therapeutics, drug screening, and pharmacology in the clinic (as against the animal laboratory) as well as human pharmacology and, of course, all the methodology involved. As a result in different hands it is used differently. Yet, despite the need to consolidate the subject, there are reasons for perpetuating a title which so early in its history already seems to be a misnomer. It has gained wide acceptance; to shift to a different and more precise but unrecognized term might result in a large step backward at a critical juncture when the need for progress in the discipline is urgent and at a time when the discipline has received its initial invitations to participate on an equal basis in modern medical society.