cssi/SciSciGPT-SciSciNet huggingface dataset:
Who is at risk for diabetic foot ulceration

Diabetic foot ulceration is the most common cause of nontraumatic, lower-extremity amputation throughout the developed world. This article reviews recent data that report on various risk factors for ulceration. Subsequently, it discusses appropriate risk stratification for both the neuropathic ulcer specifically and the diabetic foot in general, using The University of Texas Diabetic Foot and Diabetic Wound Classification Systems. We believe that knowledge and communication of the most common risk factors precipitating ulceration and subsequent amputation lead to more consistent treatment of the diabetic foot, and, ultimately, to a reduction of its prevalence.
/spl Tscr/-liveness enforcement in Petri nets based on structural net properties

We introduce a semi-decidable procedure which, given a Petri net structure and a set /spl Tscr/ of transitions, synthesizes a supervisor enforcing the transitions in /spl Tscr/ to be live. We call this liveness property /spl Tscr/-liveness. When /spl Tscr/ equals the total set of Petri net transitions, /spl Tscr/-liveness corresponds to liveness. Enforcing only a subset of transitions to be live is useful when some Petri net transitions model undesired events such as failures, and/or when the Petri net structure does not allow enforcing all transitions to be live. The supervisors generated by our procedure are often least restrictive, and their synthesis is independent of the initial marking. No assumptions are made on the Petri net structure: the Petri nets may be unbounded and have integer weights. We have extended the procedure to Petri nets having uncontrollable and unobservable transitions, however, in this paper we restrict our attention to fully controllable and observable Petri nets.
Pseudospark based pulse forming circuit for plasma ignition system

The design and operation of a pulse forming circuit using an advanced pseudospark switch are presented in this paper. The pulse forming circuit has been applied for corona or transient plasma assisted flame ignition in pulsed detonation engines (PDE). A pseudospark based pulse generator together with the ignition circuit is discussed. This application requires the operation of the pseudospark switch at a charging voltage of 30 kV and a repetition rate up to 1 kHz. A single stage lumped element blumlein and a 1:3 matglas-polyethylene-foil core transformer were employed to create high-voltage (more than 80 kV) short-duration (50 ns) pulses.
A vinculin-containing cortical lattice in skeletal muscle : transverse lattice elements ("costameres") mark sites of attachment between myofibrils and sarcolemma

We have found that vinculin is localized at the sarcolemma of skeletal muscle cells in a two-dimensional orthogonal lattice. Perpendicular to the longitudinal axis of the cell, bands of vinculin encircle the muscle cell and repeat along its length with a periodicity corresponding to the subjacent sarcomeres. Because of their appearance and probable function, we call the transverse elements of the lattice "costameres" (Latin costa, rib; Greek meros, part). Costameres have a substructure consisting of densely clustered patches of vinculin; the patches are segregated into two rows which flank the Z line and overlie the I band of the underlying sarcomere. It is likely that the costameres are physically coupled to the underlying myofibrils because: (i) the costameres broaden and narrow in concert with the underlying I band in stretched and contracted muscle, and (ii) adjacent but misaligned myofibrils are mirrored by corresponding discontinuities in the overlying costameres. We hypothesize that the sarcolemmal lattice, detected because vinculin is one of its molecular components, integrates the contractile apparatus with the sarcolemma during lengthening and shortening of the muscle cells.
Nonsurgical Cure of Pulmonary Mucormycosis

Pulmonary mucormycosis is an unusual infection which appears to occur with increased frequency in diabetics. We report the development of pulmonary mucormycosis in an adult onset diabetic which resolved with medical therapy alone. Computerized tomography proved useful in assessing his response to therapy.
Thermodynamics of the formation of atmospheric organic particulate matter by accretion reactions—Part 3: Carboxylic and dicarboxylic acids

Abstract The term “accretion reactions” has been used to describe the collection of reactions by which organic compounds can react with one another and/or other atmospheric constituents, forming products of higher-molecular weight (MW) and lower volatility, and thus increasing their tendency to condense [Barsanti, K.B., Pankow, J.F., 2004. Thermodynamics of the formation of atmospheric organic particulate matter by accretion reactions—Part 1: Aldehydes and ketones. Atmospheric Environment 38, 4371–4382; Barsanti, K.B., Pankow, J.F., 2005. Thermodynamics of the formation of atmospheric organic particulate matter by accretion reactions—Part 2: Dialdehydes, methylglyoxal, and diketones. Atmospheric Environment 39, 6597–6607]. Studies have shown that a significant fraction of atmospheric organic particulate matter (OPM) may be comprised of high-MW/low-volatility compounds [e.g., Havers, N., Burpa, P., Lambert, J., Klockow, D., 1998. Spectroscopic characterization of humic-like substances in airborne particulate matter. Journal of Atmospheric Chemistry 29, 45–54], which would be consistent with the occurrence of such accretion reactions in the atmosphere, [e.g., Jang, M., Czoschke, N. M., Lee, S., Kamens, R. M., 2002. Heterogeneous atmospheric organic aerosol production by acid-catalyzed particle-phase reactions. Science 298, 814–817]. However, many uncertainties exist regarding accretion reactions as they may occur in the atmosphere, including identification of those reactions most likely to contribute to OPM. Barsanti and Pankow (2004, 2005) have developed and applied a general theoretical approach to evaluate the thermodynamic favorabilities of accretion reactions, including the extents to which they may be relevant for OPM formation in the atmosphere. That approach is applied here in the consideration of OPM formation by reactions of four mono- and dicarboxylic acids (acetic, malic, maleic, and pinic) to form esters and amides. It was concluded that for all of the acids considered, ester and amide formation are thermodynamically favored under the assumed conditions. For malic, maleic, and pinic acids, and likely for similar mono- and dicarboxylic acids, significant OPM formation may occur via ester and amide formation in the atmosphere when kinetically favorable.
Increased Risk of Second Primary Malignancy in Pediatric and Young Adult Patients Treated with Radioactive Iodine for Differentiated Thyroid Cancer

Introduction: The long-term sequelae of radioactive iodine (RAI) for differentiated thyroid cancer (DTC) in pediatric and young adult patients are not well-defined. Epidemiologic analyses of second primary malignancy (SPM) risk have only been performed in the adult population. Existing data are limited to case series with limited follow-up. The objective of this study was to analyze the elevated risk of SPM attributable to RAI in young patients treated for DTC. Methods: Population-based analysis of 3850 pediatric and young adult patients (<25 years old) undergoing treatment with surgery with/without RAI for DTC, followed in the Surveillance, Epidemiology, and End Results cancer registry (1973–2008), equating to 54,727 person-years at risk (PYR). The excess risk of SPM was calculated relative to a reference population and expressed as standardized incidence ratio (SIR) and excess absolute risk (EAR) per 10,000 PYR. Excess risk was compared in RAI-treated and non-RAI-treated patients. Results: A total of 15...
Legalism and Medical Ethics

This essay is concerned with some general questions about methodology in medical ethics. As such it belongs under what is generally called “metaethics” or the “logic of ethics,” that is, the second-level inquiry into moral concepts, rules, and principles and their logical interrelations. I believe that it is important to develop an understanding of some of these methodological questions as a propaedeutic to an inquiry into more substantive moral issues. My position, which I have defended elsewhere, is that metaethics cannot, in the final analysis, be separated from normative ethics: for metaethics itself is a normative enterprise and any metaethical theory necessarily has implications for normative ethics, albeit of a very general nature1 On the other hand, it is impossible to think clearly and coherently about issues in normative ethics, medical ethics, for example, unless one is cognizant of the logical relationships and implications of the concepts and principles that one is using in analyzing these issues. Much of the purport of this essay will be critical, for I believe that discussions of issues in medical ethics have frequently been on the wrong track; in particular, they have been too legalistic. I shall suggest a new approach, as an alternative to legalism, although what I have to say will necessarily be largely programmatic.
Recent advances in diaper dermatitis: etiology and treatment

Diaper dermatitis is a highly prevalent condition that causes discomfort and stress for patients and frustration for healthcare staff. Diaper technology has evolved to substantially lessen the severity of diaper dermatitis, but additional improvements are needed. Premature infants and incontinent adults are particularly at risk for developing diaper dermatitis and its potential consequences. Contributing factors include overhydration, irritants, friction, increased skin pH, diet, gestational age, antibiotic use, diarrhea and medical condition. Treatments aim to reduce hydration, provide a semipermeable ‘layer’ to facilitate skin barrier repair, shield the skin from irritants, deactivate specific fecal components and maintain skin surface contact. The published research on the effects of diaper dermatitis treatments is especially sparse. Controlled clinical trials are needed to provide definitive evidence for selection of effective treatments. This article discusses the incidence and etiology of diaper der...
Rate Enhancement of an Interfacial Biochemical Reaction through Localization of Substrate and Enzyme by an Adaptor Domain

This paper describes a model system to characterize the rate enhancement that stems from localization of an enzyme with its substrate. The approach is based on a self-assembled monolayer that presents a substrate for the serine esterase cutinase along with a peptide ligand for an SH2 adaptor domain. The monolayer is treated with a fusion protein of cutinase and the SH2 domain, and the rate for the interfacial reaction is monitored using cyclic voltammetry. The rate is approximately 30-fold greater for monolayers that present the ligand for the SH2 domain than for those that omit the ligand. The rate enhancement is due to the interaction of the adaptor domain with the immobilized ligand. Further, the rate enhancement increases with the densities of both the ligand and the substrate. This example provides a well-defined model system for quantitatively assessing the magnitude of rate enhancement that is possible with colocalization of an enzyme with its substrate and may be particularly significant for understanding the signaling events that rely on enzyme localization at the cell membrane.
Photoaffinity Labeling of Cytochrome P4501A1 with Azidocumene: Identification of Cumene Hydroperoxide Binding Region

Abstract Cumene hydroperoxide can support cytochrome P450-catalyzed reactions in the absence of molecular oxygen, NADPH, and cytochrome P450-NADPH oxidoreductase. Its binding at the cytochrome P450 active site is governed by the structure of the cumene hydroperoxide binding region. In order to define the region of cytochrome P4501A1 at which cumene hydroperoxide binds, we prepared an analog of cumene hydroperoxide for use as a photoaffinity label. p -Azido-isopropylbenzene (azidocumene) and its tritiated derivative were photolyzed in water solution by uv light with a half-life of 29 s. The 7-ethoxycoumarin deethylatation catalyzed by P450 using the cumene hydroperoxide-supported system was strongly inhibited by the presence of the label. Covalent binding to the protein after photoactivation was blocked by 50% in the presence of cumene hydroperoxide. HPLC analysis after trypsin digestion of the labeled protein showed that [ 3 H]azidocumene was attached covalently to the peptide VDMTPAYGLTLK corresponding to residues 492–503 in the 1A1 sequence. The radioactivity level of this fraction was reduced by 50% when the labeling was carried out in the presence of cumene hydroperoxide. To confirm the identified region the labeled protein was cleaved by cyanogen bromide. HPLC separation of the CNBr digest showed two peaks with a high level of radioactivity. The SDS/Tricine PAGE analysis of the radioactive fraction with an elution time of 43 min revealed a 2.4-kDa peptide carrying a high level of covalently bound radioactivity. The N-terminal sequence identified the labeled peptide to be a fragment generated by CNBr corresponding to residues 494–512. The N-terminal sequence of the labeled peptide with elution time of 27 min, TLKH, matches amino acid residues 501–504 in the P4501A1 sequence. We can conclude that in the overlapping region of all three identified peptides, T501–L502–K503, is the site where azidocumene covalently binds to P4501A1. The sequence alignment of cytochrome P4501A1 with cytochrome P450102 predicts that this region might correspond to β-sheet structure localized on the distal side of the heme ring near the I helix and the oxygen binding pocket. To our knowledge, this is the first report to localize the cumene hydroperoxide binding region in the cytochrome P450 active site.
Stereochemical studies of epoxides relevant to the ansa chain of the streptovaricins

Abstract The asymmetric synthesis of the C(5)-C(15) fragment of the highly oxygenated ansa chain of streptovaricin A is reported.
Distinct cervical microRNA profiles are present in women destined to have a preterm birth.

Objective Although premature cervical remodeling is involved in preterm birth (PTB), the molecular pathways that are involved have not been elucidated fully. MicroRNAs (miRNAs) that are highly conserved single-stranded noncoding RNAs that play a crucial role in gene regulation have now been identified as important players in disease states. The objective of this study was to determine whether miRNA profiles in cervical cells are different in women who are destined to have a PTB compared with a term birth. Study Design A nested case-control study was performed. With the use of a noninvasive method, cervical cells were obtained at 2 time points in pregnancy. The cervical cell miRNA expression profiles were compared between women who ultimately had a PTB (n = 10) compared with a term birth (n = 10). MiRNA expression profiles were created with the Affymetrix GeneChip miRNA Array. The data were analyzed with the Significance of Analysis of Microarrays and Principle Components Analyses. A false-discovery rate of 20% was used to determine the most differentially expressed miRNAs. Validation was performed with quantitative polymerase chain reaction. In vitro studies were performed to confirm expression and regulation of select miRNAs. Results With a false-discovery rate of 20% of the 5640 miRNAs that were analyzed on the array, 99 miRNAs differed between those with a PTB vs a term birth. Qualitative polymerase chain reaction validated the array findings. In vitro studies confirmed expression of select miRNAs in cervical cells. Conclusion MiRNA profiles in cervical cells may distinguish women who are at risk for PTB months before the outcome. With the large downstream effects of miRNAs on gene expression, these studies provide a new understanding of the processes that are involved in premature cervical remodeling and allow for the discovery of new therapeutic targets.
Experimental petrology of the Mars Pathfinder rock composition: Constraints on the interpretation of Martian reflectance spectra

[1] Experiments to determine the crystallization sequence of the Mars Pathfinder (MPF) rock composition have been carried out to explore the range of possible mineral assemblages in this SiO2-rich (57.4 wt %) Martian igneous rock. Recent Mars Global Surveyor thermal emission spectrometer observations have suggested the presence of large volumes of andesitic lava covering the northern hemisphere of Mars, but this interpretation has been called into question. Experimentally produced mineral assemblages can be used to infer spectral characteristics that would exist in andesitic lavas similar in composition to the MPF rock. The inferred spectra could then be used with remotely sensed data to further constrain the identity of surface rock types on Mars. We performed a series of experiments at 0.1 MPa at the quartz-fayalite-magnetite and iron-quartz-fayalite oxygen buffers and 100 MPa at the Ni-NiO oxygen buffer using the calculated soil free MPF composition. Potential mineralogies for a lava with the MPF composition would be SiO2 (57 wt %), FeO (18 wt %) rich glass, plagioclase, quartz, augite, and Fe-Ti oxides. A contoured pyroxene quadrilateral (with band I and II minima) was used to predict pyroxene composition on the basis of reflectance spectra. Using the quadrilateral in reverse, the augite produced in the experimental series should have band I and II minima at 0.97 μm and 2.15 μm, respectively. The absence of the 1-μm minima in the Imager for Mars Pathfinder (IMP) spectra could be due to masking phases, possibly the Fe-Ti oxides produced in our experiments at 1000°C.
Infinite families of perfect binary arrays

The author constructs four infinite families of perfect binary arrays. Jedwab and Mitchell have constructed some small perfect binary arrays using quasiperfect binary arrays and doubly quasiperfect binary arrays. The author shows that a doubly quasi-perfect binary array is equivalent to a quasiperfect binary array. This means Jedwab and Mitchell's construction can be iterated to obtain larger perfect binary arrays. >
The renal metabolism of 25-hydroxyvitamin D3 in the rat: regulation by 1,25-dihydroxyvitamin D3.

To determine the effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the renal metabolism of 25-hydroxyvitamin D3 [25(OH)D3], the influence of 1,25(OH)2D3 and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] was compared in vitamin D-deficient rats. Serum calcium (Ca), serum immunoreactive parathyroid hormone (iPTH) and the specific activities (SA) of renal 25(OH)D3: 24-hydroxylase (24-hydroxylase) and 25(OH)D3: 1α-hydroxylase (1-hydroxylase) were measured. In vitamin D-deficient rats, mean serum Ca was low, serum iPTH was increased, renal 1-hydroxylase was increased, and renal 24-hydroxylase was below the limit of detection. Treatment with either 1,25(OH)2D3 or 24,25(OH)2D3, 50 ng/d for 2 days, significantly increased mean serum Ca but did not change serum iPTH, renal 1-hydroxylase SA, or renal 24-hydroxylase SA. 1,25(OH)2D3, 50 ng/d for 7 days, returned serum Ca and iPTH to normal, lowered renal 1-hydroxylase SA, and induced renal 24-hydroxylase activity. In contrast, 24,25(OH)2D3, 50 ng/d for 7 days, similarly lowered renal 1-hydroxylase SA but did not induce renal 24-hydroxylase activity. Thyroparathyroidectomy of vitamin D-deficient rats resulted in a rapid decline in 1-hydroxylase SA. The results indicate that in vitamin D-deficient rats a) 1,25(OH)2D3 reduces renal 1-hydroxylase SA and increases renal 24-hydroxylase SA and b) 24,25(OH)2D3 reduces renal 1-hydroxylase SA and does not alter renal 24-hydroxylase SA. Inhibition of renal 1-hydroxylase by the two metabolites is apparently mediated through changes in serum Ca and circulating iPTH, whereas stimulation by 1,25(OH)2D3 of renal 24-hydroxylase activity is direct.
Translational Joints in Flexible Multi body Dynamics

ABSTRACT Formulations of translational kinematic constraints between flexible bodies are developed to model deformation of flexible surfaces that move relative to one another. Three types of flexible translational articulated joints are presented and illustrated in analysis of prototype systems. Global deformation modes and substructure local deformation modes are used in dynamic analysis and compared via numerical examples.
Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutations

Glutamate dehydrogenase (GDH) catalyses the reversible oxidative deamination of l-glutamate to 2-oxoglutarate in the mitochondrial matrix. In mammals, this enzyme is highly regulated by allosteric effectors. The major allosteric activator and inhibitor are ADP and GTP, respectively; allosteric activation by leucine may play an important role in amino acid-stimulated insulin secretion. The physiological significance of this regulation has been highlighted by the identification of children with an unusual hyperinsulinism/hyperammonaemia syndrome associated with dominant mutations in GDH that cause a loss in GTP inhibition. In order to determine the effects of these mutations on the function of the human GDH homohexamer, we studied the expression, purification and characterization of two of these regulatory mutations (H454Y, which affects the putative GTP-binding site, and S448P, which affects the antenna region) and a mutation designed to alter the putative binding site for ADP (R463A). The sensitivity to GTP inhibition was impaired markedly in the purified H454Y (ED(50), 210 microM) and S448P (ED(50), 3.1 microM) human GDH mutants compared with the wild-type human GDH (ED(50), 42 nM) or GDH isolated from heterozygous patient cells (ED(50), 290 and 280 nM, respectively). Sensitivity to ADP or leucine stimulation was unaffected by these mutations, confirming that they interfere specifically with the inhibitory GTP-binding site. Conversely, the R463A mutation completely eliminated ADP activation of human GDH, but had little effect on either GTP inhibition or leucine activation. The effects of these three mutations on ATP regulation indicated that this nucleotide inhibits human GDH through binding of its triphosphate tail to the GTP site and, at higher concentrations, activates the enzyme through binding of the nucleotide to the ADP site. These data confirm the assignment of the GTP and ADP allosteric regulatory sites on GDH based on X-ray crystallography and provide insight into the structural mechanisms involved in positive and negative allosteric control and in inter-subunit co-operativity of human GDH.
Multiplexed memories: a view from human cortex

A study recording directly from the human brain shows that connectivity between the prefrontal cortex, parietal cortex and the medial temporal lobe across different frequency bands underlies successful memory retrieval.
Post-Colonial Domesticity amid Diaspora: Home and Family in the Lives of Two English Sisters from India

Through oral history, this essay explores the relationship among home, family and place in the memories and life experiences of two women who are part of the post-colonial British diaspora. Children at the time of Pakistani independence in 1947, Josephine and Judy Beck grew up in an English family in Baluchistan and the North West Frontier Province, where their father worked as a police official. While still children, decolonization transformed the sisters into "remnants of something." Middle-class femininity and domesticity emerged as their primary identity, inflecting other forms of belonging, including nationality. Each woman adapted familiar aspects of her colonial childhood to an adult life in which personal relationships and geographical mobility have remained central. Josephine settled in a region of the American west that visually resembles Pakistan while Judy has spent much of her life abroad in expatriate western communities that socially resembled those of her youth.
Specific agglutination of polyacrylamide derivatives of protein antigens.

Abstract Proteins such as β-lactoglobulin, bovine serum albumin, α-lactalbumin, and bovine γ-globulin were coupled by covalent bonds to crosslinked copolymers of acrylamide and methyl acrylate through reaction with azide derivatives of the methyl acrylate residues. Substantial amounts of proteins (1–5 mg/100 mg polymer) were bound to the surface of the copolymer particles. The use of these derivatives to assay for the specific antibodies in rabbit antisera was tested. Specific agglutination of the protein derivatives was obseved with antisera containing as little as 0·05 μg antibody per ml. Antibody titers against the protein derivatives as high as 1:10,000 were retained on storage of the polymer-protein derivatives at 4°C in saline solutions for 3 months. The protein derivatives removed specific antibodies from immune sera.
Seseo vs. Θ in the Classroom

Author's summary.— It seems logical that the American student of Spanish should now be taught the seseo, since his oral and aural contact with the language will probably be with the Spanish-American pronunciation, and since even in the study of the literature of Spain the seseo will not be a serious hindrance.
Problems with The Concept of Thermal Budget: Experimental Demonstrations

Up to now, kinetic effects in rapid thermal processing (RTP) have been assessed using the concept of thermal budget, with the idea that thermal budget minimization should minimize dopant diffusion and interface degradation. This work highlights shortcomings with that principle. Experiments comparing directly the rate of Si chemical vapor deposition with that of dopant diffusion show how thermal budget minimization can actually worsen diffusion problems rather than mitigate them. We present a straightforward framework for improving the results through comparison of activation energies of the desired and undesired phenomena. This framework explains the experimental results and provides strong kinetic arguments for continued development of rapid isothermal processing and small batch fast ramp methods.
Laboratory measurements of D/H ratios in interplanetary dust

Measurements of noble gas elemental and isotopic abundance patterns have provided evidence that a subset of the particles collected in the upper atmosphere by NASA aircraft are micrometeorites. It is found that the deuterium in two such particles is enriched relative to hydrogen by 500-1100 per thousand when compared with the terrestrial SMOW standard. This result confirms the extraterrestrial origin of the dust particles and demonstrates that the material preserves a potentially unique isotopic record which may reflect a memory of processes occurring during or before the formation of the solar system. In addition, the deuterium enrichment seen in the particles is analogous to that observed in bulk samples of one carbonaceous meteorite and two unequilibrated ordinary chondrites as well as in chemical separates of a number of other meteorites.
Anti‐tetanus toxoid antibody synthesis after booster immunization in systemic lupus erythematosus

The in vivo and in vitro synthesis of anti-tetanus toxoid antibody (anti-tet) was measured after booster immunization with tetanus toxoid in 9 patients with systemic lupus erythematosus (SLE) and 9 controls. In vitro culture of peripheral blood lymphocytes (PBL) from both patients and controls showed maximal antitet synthesis 7 days after booster immunization, and maximal serum titers occurred by day 14. The initial in vitro burst of anti-tet synthesis was not dependent upon pokeweed mitogen (PWM) stimulation, whereas later synthesis was PWM dependent. Two differences between patients and controls were observed:1) patients with SLE had a lower mean pre-boost serum titer of anti-tet, and 2) one-third of the patients showed a blunted serum anti-tet response. To study whether these abnormalities were a result of altered immune regulation, anti-tet synthesis was measured by the coculture of separated SLE-B or control-B cells and separated SLE-T or control-T or control-T cell populations (± irradiation to remove suppressor T cell activity). These coculture studies showed that both abnormalities were due to a lack of SLE-B cell response, not to abnormalities of SLE-helper T or SLE- suppressor T cell function.
Dopaminergic neurons in the rat ventral tegmental area. III. Effects of d-and l-amphetamine

Abstract The effect of d - and l -isomers of amphetamine on the activity of mesolimbic and mesocortical dopamine (DA) neurons in the ventral tegmental area (VTA or A10) was studied in chloral hydrate anesthetized rats. Mesolimbic and mesocortical DA neurons were identified by their antidromic responses to stimulation of the nucleus accumbens (NAc) and the frontal-cingulate cortices, respectively. Similar to their effects on A9 DA cells, d -A was found to be 9.2-fold more potent than l -A in producing 50% inhibition of discharge rate of A10 DA neurons. In addition, pre-treatment with αMT caused approximately a 5-fold increase in the ID 50 of d -A. The depressant effect of d -A could be completely prevented by pre-treatment with both reserpine and αMT; the blockade of d -A effect by reserpine and αMT could be reversed by injections of low doses of l -DOPA. However, unlike its effect on A9 DA cells, the depressant action of d -A on A10 DA neurons was not mediated by forebrain feedback pathways; in rats with either destruction of neuronal perikarya in the NAc by ibotenic acid or acute dience-phalic transection, the IDso of d -A on A10 DA cells remained unchanged. It is concluded that 1. (1) d -A is much more potent than l -A in depressing firing activity of identified A10 DA neurons, and 2. (2) the depressant effect of amphetamine on A10 DA cells is not mediated via a forebrain feedback loop; it may be mediated by a DA dendro-dendritic and/or axon collateral autoregulatory system.
Evaluation of 2,6-diamino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)- hexanamide (NPC 15437), a protein kinase C inhibitor, as a modulator of P-glycoprotein-mediated resistance in vitro.

We assessed the effect of the protein kinase C inhibitor 2,6-diamino-N-([1-(1-oxotridecyl)-2-piperidinyl] methyl)hexanamide (NPC 15437) on the action of anthracyclines, epipodophyllotoxins and vinca alkaloids in P-glycoprotein (Pgp)-expressing CHRC5 hamster ovary and MCF-7/AdriaR human breast cancer cells. Flow microfluorimetry revealed that treatment of CHRC5 cells with 75 μM NPC 15437 for 1 h resulted in a 6- to 10-fold increase in the nuclear accumulation of daunorubicin. Colony forming assays revealed that treatment with 75 μM NPC 15437 was associated with a 4-fold decrease in the LD90 for etoposide and a 2.5-fold decrease in the LD50 for vincristine. At higher concentrations of NPC 15437, greater modulation of anthracycline accumulation was observed; but NPC 15437 itself inhibited subsequent colony formation. Similar effects on drug accumulation and cytotoxicity were observed in MCF-7/AdriaR cells. Experiments designed to investigate the mechanism by which NPC 15437 exerts these effects revealed that treatment with the protein kinase C activator phorbol-12-myristate 12-acetate partially reversed the effect of NPC 15437, suggesting that NPC 15437 was exerting an effect through protein kinase C. Photoaffinity labeling experiments revealed that NPC 15437 also inhibited the binding of [3H]-azidopine to Pgp in isolated membrane vesicles. These results identify NPC 15437 as the prototype of a new class of potential Pgp modulators but indicate that the effects of this agent as a modulator are potentially limited by its cytotoxicity.
SnapShot: Kinase Inhibitors I

Selective small-molecule inhibitors of protein kinases can serve as powerful tools to elucidate biological function. Efforts to develop potential drug candidates have yielded a wealth of kinase inhibitors. However, selecting the optimal kinase inhibitor for a particular application can be challenging. While the optimal inhibitor will be application specific, we have attempted to summarize some of the best reported inhibitors for various kinases.
EMG variability during maximum voluntary isometric and anisometric contractions is reduced using spatial averaging

Electromyography (EMG) is a commonly used tool that can be plagued with poor signal-to-noise ratios. One result of poor signal-to-noise ratios is increased within- and between-subject variability of quantified EMG variables, for example, the integrated EMG. Methods that reduce within- and between-subject variability of quantified EMG variables can increase the statistical power of an experimental design and aid in the functional interpretation of experimental results. The purpose of this investigation was to determine the effectiveness of spatially averaging the surface EMG signal to reduce the variability of the quantified EMG obtained during maximum voluntary contractions (MVC). The present study extends the work of earlier investigators describing the enhanced signal characteristics obtained by spatially averaging the surface EMG measured during submaximum voluntary isometric contractions and stretch reflexes. Ten subjects performed maximum voluntary isometric and anisometric (concentric and eccentric) contractions of the elbow flexors. Four electrodes, forming two pairs of bipolar electrodes were placed over both the biceps brachii and brachioradialis muscles. Four rectified and integrated EMG signals from the electrode array were compared. Data from each subject's contraction condition and from each muscle were used to compute a coefficient of variation that was considered representative of the within-subject variability. These data were analysed with a multifactorial repeated measures analysis of variance (ANOVA). The results revealed a muscle-specific, statistically significant superiority of one of the methods in reducing the variability of the rectified and integrated EMG signal. Summing the rectified and integrate signals from each bipolar pair of electrodes in the array was shown to reduce significantly the within-subject variability.
Carcinosarcoma de novo of the parotid gland: case report.

Background Salivary gland carcinosarcoma is a rare and aggressive malignant mixed tumor in which carcinomatous and sarcomatous elements coexist and metastasize together. The tumor may occur in the background of a preexisting pleomorphic adenoma or may arise de novo. We report a case of a woman presenting with a carcinosarcoma de novo of the parotid gland. Methods and Results Our patient underwent surgical resection and adjuvant radiotherapy and demonstrates no evidence of recurrence at 14 months posttreatment. Conclusions Review of the literature supports combined modality, surgery with postoperative radiation, as the standard of care for this malignancy, although the long-term prognosis for these patients is unclear. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Tissue engineering for plastic surgeons: a primer.

A central tenet of reconstructive surgery is the principle of “replacing like with like.” However, due to limitations in the availability of autologous tissue or because of the complications that may ensue from harvesting it, autologous reconstruction may be impractical to perform or too costly in terms of patient donor-site morbidity. The field of tissue engineering has long held promise to alleviate these shortcomings. Scaffolds are the structural building blocks of tissue-engineered constructs, akin to the extracellular matrix within native tissues. Commonly used scaffolds include allogenic or xenogenic decellularized tissue, synthetic or naturally derived hydrogels, and synthetic biodegradable nonhydrogel polymeric scaffolds. Embryonic, induced pluripotent, and mesenchymal stem cells also hold immense potential for regenerative purposes. Chemical signals including growth factors and cytokines may be harnessed to augment wound healing and tissue regeneration. Tissue engineering is already clinically prevalent in the fields of breast augmentation and reconstruction, skin substitutes, wound healing, auricular reconstruction, and bone, cartilage, and nerve grafting. Future directions for tissue engineering in plastic surgery include the development of prevascularized constructs and rationally designed scaffolds, the use of stem cells to regenerate organs and tissues, and gene therapy.
Prospecting for valuable evidence: why scholarly research can be a goldmine for managers

States the top reason why managers should take notice of scholarly research is because actions based on sound evidence beat those based on suspect intuition every time. Posits that even academic research at its best is perhaps not that much of a better alternative to guru’s fads and fantasies.
Hepatic Resection in the Treatment of Hilar Cholangiocarcinoma

Every year, nearly 7500 patients in the United States are diagnosed with biliary tract cancer [1]. Although most of these cancers arise from the gallbladder, one third arise from the bile ducts. Biliary tract cancers have been divided traditionally into four categories based on the site of origin and the anatomic implications for management: intrahepatic, gallbladder, extrahepatic periampullary, and extrahepatic nonperiampullary. Biliary tract cancers that arise from the latter site of origin have been referred to as hilar or perihilar cholangiocarcinomas. Altmeier et al [2] and Klatskin [3] independently highlighted the clinical presentation and problems posed by perihilar cholangiocarcinoma (PCC). This article focuses on the surgical management of PCC and addresses the relevance of hepatic resection in the treatment of these tumors. The clinicopathology and patterns of spread of PCC are reviewed. The options for preoperative imaging, perioperative preparation, and outcomes related to the role of hepatic resection are assessed. It is hoped that this article provides clinical evidence that supports hepatic resection as an essential and efficacious component of the surgical management of PCC in selected patients.
Surgical management of acute necrotizing enterocolitis in infancy

Abstract Necrotizing enterocolitis (N.E.C.) occurring in the neonatal period was first described in the late 1800's. 1 Increasing attention has recently been directed to this disease because of the poor survival rate and an apparently increased incidence. 2–4 The poor survival rate has been attributed to intestinal necrosis and perforation which could be corrected by appropriate surgical intervention; however, the timing and indications for surgery have not been clearly defined. We have reviewed the records of 65 patients with acute necrotizing enterocolitis seen in the neonatal unit of the Los Angeles County-University of Southern California Medical Center from July, 1970 through December, 1972. Particular attention has been directed to those patients who underwent a surgical procedure.
Anaerobiosis Produced by Glucose Oxidase to Control Growth of Test Bacteria in Antibiotic Assays

Summary Methylene blue studies revealed traces of oxygen in solidified agar which was subjected to the method outlined by Kosikowski; however, Clostridium sporogenes grew slowly under these conditions. This residual oxygen was rapidly removed by reactions catalyzed by glucose oxidase and catalase. Substituting sodium thioglycollate for glucose oxidase was without effect. Inclusion of catalase and proper buffering capacity prevented any antibacterial action of glucose oxidase. Clostridium sporogenes grew rapidly under this technique, which provided anaerobiosis for individual petri dishes.
Post-column complexion technique for the spectrophotometric detection of poly(oxy-1,2-ethanediyl) oligomers in steric exclusion chromatography

Abstract A solid-phase complexation column (SPCC), which consists of ammonium cabaltothiocyanate (ACTC) adsorbed on a solid support, has been developed as part of a selective detection technique for molecules bearing one or more poly(oxy1,2-ethanediyl) oligomers (POEs). Due to the ion-dipole attraction between the ammonium ion and the negative dipoles of the polyether oxygen atoms, a quantity of ACTC is solubilized in the mobile phase as the POE-ACTC complex. The complexed ACTC is readily quantitated at 320 or 620 nm because of the strongly absorbing cobaltothiocyanate anion. The detection technique is approximately 100 times more sensitive than the differential refractive index detector for this class of compounds. This detector is used with steric exclusion chromatography on Sephadex LH-20 and μStyragel columns.
Synthesis and Performance of Polymerizable Room-Temperature Ionic Liquids as Gas Separation Membranes

Room-temperature ionic liquids (RTILs) with polymerizable groups can be readily converted into solid, dense poly(RTILs) for use as gas separation membranes. A series of RTIL monomers with varying length n-alkyl substituents were synthesized and converted into polymer films. These membranes were tested for their performance in separations involving CO2, N2, and CH4. CO2 permeability was observed to increase in a nonlinear fashion as the n-alkyl substituent was lengthened. CO2/N2 separation performance was relatively unaffected as CO2 permeability increased. Plotting the performance of these membranes on a “Robeson plot” for CO2/N2 shows that first-generation poly(RTILs) “hug” the “upper bound” of the chart, indicating that they perform as well or better than many other polymers for this separation. The CO2/CH4 separation is less impressive when compared to other polymer membranes on a “Robeson plot”, but poly(RTILs) perform as well or better than molten RTILs do in bulk fluid gas absorptions for that gas p...
Current national practice patterns for inpatient management of ventral abdominal wall hernia in the United States

The health-care burden related to ventral hernia management is substantial, with more than 3 billion dollars in expenditures annually in the US. Previous studies have suggested that the utilization of laparoscopic repair remains relatively low although national volume estimates have not been reported. We sought to estimate the inpatient national volume of elective ventral hernia surgery and characterize the proportion of laparoscopic versus open operations. We analyzed data from the Nationwide Inpatient Sample to identify adults with a diagnosis of an umbilical, incisional, or ventral hernia who underwent an elective inpatient repair between 2009 and 2010. Cases that involved other major abdominal or pelvic operations were excluded. Covariates included patient demographics, surgical approach, and use of mesh. National surgical volume estimates were generated and length of stay and total hospital charges were compared for laparoscopic versus open repairs. A total of 112,070 ventral hernia repairs were included in the analysis: 72.1 % (n = 80,793) were incisional hernia repairs, while umbilical hernia repairs comprised only 6.9 % (n = 7,788). Laparoscopy was utilized in 26.6 % (n = 29,870) of cases. Mesh was placed in 85.8 % (n = 96,265) of cases, including 49.3 % (n = 3,841) of umbilical hernia repairs and 90.1 % (n = 72,973) of incisional hernia repairs. Length of stay and total hospital charges were significantly lower for laparoscopic umbilical, incisional, and “other” ventral hernia repairs (p values all <0.001). Total hospital charges during this 2-year period approached 4 billion dollars ($746 million for laparoscopic repair; $3 billion for open repair). Utilization of laparoscopy for elective abdominal wall hernia repair remains relatively low in the US despite its excellent outcomes. Given the substantial financial burden associated with these hernias, future research focused on preventing the development and optimizing the surgical treatment of ventral abdominal wall hernias is warranted.
Role of the urokinase-fibrinolytic system in epithelial-mesenchymal transition during lung injury.

Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β–, or passive cigarette smoke–induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β–, or passive cigarette smoke–induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells.
Direct observation of the recovery of an antiferroelectric phase during polarization reversal of an induced ferroelectric phase

Electric fields are generally known to favor the ferroelectric polar state over the antiferroelectric nonpolar state for their Coulomb interactions with dipoles in the crystal. In this paper, we directly image an electric-field-assisted ferroelectric-to-antiferroelectric phase transition during polarization reversal of the ferroelectric phase in polycrystalline $\mathrm{P}{\mathrm{b}}_{0.99}{\mathrm{N}{\mathrm{b}}_{0.02}{[{(\mathrm{Z}{\mathrm{r}}_{0.57}\mathrm{S}{\mathrm{n}}_{0.43})}_{0.92}\mathrm{T}{\mathrm{i}}_{0.08}]}_{0.98}}{\mathrm{O}}_{3}$. With the electric-field in situ transmission electron microscopy technique, such an unlikely phenomenon is verified to occur by both domain morphology change and electron-diffraction analysis. The slower kinetics of the phase transition, compared with ferroelectric polarization reversal, is suggested to contribute to this unusual behavior.
Effects of user training with electronically-modulated sound transmission hearing protectors and the open ear on horizontal localization ability.

AbstractObjective: To determine if training with electronically-modulated hearing protection (EMHP) and the open ear results in auditory learning on a horizontal localization task. Design: Baseline localization testing was conducted in three listening conditions (open-ear, in-the-ear (ITE) EMHP, and over-the-ear (OTE) EMHP). Participants then wore either an ITE or OTE EMHP for 12, almost daily, one-hour training sessions. After training was complete, participants again underwent localization testing in all three listening conditions. A computer with a custom software and hardware interface presented localization sounds and collected participant responses. Study sample: Twelve participants were recruited from the student population at Virginia Tech. Audiometric requirements were 35 dBHL at 500, 1000, and 2000 Hz bilaterally, and 55 dBHL at 4000 Hz in at least one ear. Results: Pre-training localization performance with an ITE or OTE EMHP was worse than open-ear performance. After training with any given li...
Unintended Consequences: The Accreditation Council for Graduate Medical Education Work-Hour Rules in Practice

It had been a frenetic day for me and my team. We were swamped with patients, and keeping up was exacting, made worse by the pace. But in addition to the volume of admissions, our night felt increa...