cssi/SciSciGPT-SciSciNet huggingface dataset:
Imipenem for Treatment of Tuberculosis in Mice and Humans

Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is problematic because of choices limited to relatively inefficacious and toxic drugs. Some beta-lactam antibiotics are active against Mycobacterium tuberculosis in vitro. We investigated the efficacy of imipenem in a mouse model of tuberculosis and in humans with MDR tuberculosis. Mice infected with M. tuberculosis strain H37Rv were treated with isoniazid or imipenem. Residual organisms in lung and spleen and survival of imipenem-treated mice were compared to those of untreated or isoniazid-treated mice. Ten patients with MDR tuberculosis also were treated with imipenem in combination with other first- or second-line agents; elimination of M. tuberculosis from sputum samples was measured by quantitative culture. Although it was less effective than isoniazid, imipenem significantly reduced the numbers of M. tuberculosis organisms in lungs and spleens and improved survival of mice. Eight of 10 patients with numerous risk factors for poor outcomes responded to imipenem combination therapy with conversion of cultures to negative. Seven remained culture-negative off of therapy. There were two deaths, one of which was due to active tuberculosis. Organisms were eliminated from the sputa of responders at a rate of 0.35 log10 CFU/ml/week. Relapse upon withdrawal of imipenem and development of resistance to imipenem in a nonresponder suggest that imipenem exerts antimycobacterial activity in humans infected with M. tuberculosis. Imipenem had antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis.
Synthesis, characterization and photovoltaic applications of a low band gap polymer based on s-tetrazine and dithienosilole.

A new copolymer of dithienosilole (DTS) and dithienyl-s-tetrazine (TTz), PDTSTTz, has been designed and synthesized. This solution processable polymer shows a low band gap, strong absorption and good thermal stability. Solar cells from the blend of this polymer with PC71BM showed power conversion efficiency (PCE) up to 4.2%.
Adenoviral Gene Vector Tethering to Nanoparticle Surfaces Results in Receptor-Independent Cell Entry and Increased Transgene Expression

The present studies investigated the hypothesis that affinity immobilization of replication-defective adenoviruses (Ad) on the surfaces of biodegradable nanoparticles (NP) can improve transduction through uncoupling cellular uptake from the coxsackie–adenovirus receptor (CAR). Ad was tethered to the surfaces of polylactide-based NP that were surface-activated using a photoreactive polyallylamine–benzophenone–pyridyldithiocarboxylate polymer, which enabled (via thiol chemistry) the covalent attachment of Ad-binding proteins, either the recombinant D1 domain of CAR or an adenoviral knob-specific monoclonal antibody. Gene transfer by NP–Ad complexes was studied in relation to cellular uptake as a function of cell type and the character of NP–Ad binding. NP–Ad complexes, but not Ad applied with or without control nonimmune IgG-modified NP, significantly increased green fluorescent protein reporter expression in endothelioma and endothelial and arterial smooth muscle cells (SMC) in direct correlation to the extent of NP–Ad internalization. CAR-independent uptake of NP–Ad was confirmed by demonstrating inhibition of free Ad- but not NP–Ad complex-mediated transduction by knob protein. Complexes formulated with an Ad encoding inducible nitric oxide synthase inhibited growth of cultured SMC to a significantly greater extent than those with GFPAd or NULLAd or free vector. It is concluded that Ad-specific affinity tethering to biodegradable NP can significantly increase the level of gene expression via a CAR-independent uptake mechanism.
Effect of MLC leaf width on treatment adaptation and accuracy for concurrent irradiation of prostate and pelvic lymph nodes

Purpose: The aim of the study was to evaluate the impact of multileaf collimator (MLC) leaf width on treatment adaptation and delivery accuracy for concurrent treatment of the prostate and pelvic lymph nodes with intensity modulated radiation therapy (IMRT). Methods: Seventy-five kilovoltage cone beam CTs (KV-CBCT) from six patients were included for this retrospective study. For each patient, three different IMRT plans were created based on a planning CT using three different MLC leaf widths of 2.5, 5, and 10 mm, respectively. For each CBCT, the prostate displacement was determined by a dual image registration. Adaptive plans were created by shifting selected MLC leaf pairs to compensate for daily prostate movements. To evaluate the impact of MLC leaf width on the adaptive plan for each daily CBCT, three MLC shifted plans were created using three different leaf widths of MLCs (a total of 225 adaptive treatment plans). Selective dosimetric endpoints for the tumor volumes and organs at risk (OARs) were evaluated for these adaptive plans. Using the planning CT from a selected patient, MLC shifted plans for three hypothetical longitudinal shifts of 2, 4, and 8 mm were delivered on the three linear accelerators to test the deliverability of the shifted plans and to compare the dose accuracy of the shifted plans with the original IMRT plans. Results: Adaptive plans from 2.5 and 5 mm MLCs had inadequate dose coverage to the prostate (D99 < 97%, orD mean < 99% of the planned dose) in 6%–8% of the fractions, while adaptive plans from 10 mm MLC led to inadequate dose coverage to the prostate in 25.3% of the fractions. The average V 56Gy of the prostate over the six patients was improved by 6.4% (1.6%–32.7%) and 5.8% (1.5%–35.7%) with adaptive plans from 2.5 and 5 mm MLCs, respectively, when compared with adaptive plans from 10 mm MLC. Pelvic lymph nodes were well covered for all MLC adaptive plans, as small differences were observed for D99, D mean, and V 50.4Gy. Similar OAR sparing could be achieved for the bladder and rectum with all three MLCs for treatment adaptation. The MLC shifted plans can be accurately delivered on all three linear accelerators with accuracy similar to their original IMRT plans, where gamma (3%/3 mm) passing rates were 99.6%, 93.0%, and 92.1% for 2.5, 5, and 10 mm MLCs, respectively. The percentages of pixels with dose differences between the measurement and calculation being less than 3% of the maximum dose were 85.9%, 82.5%, and 70.5% for the original IMRT plans from the three MLCs, respectively. Conclusions: Dosimetric advantages associated with smaller MLC leaves were observed in terms of the coverage to the prostate, when the treatment was adapted to account for daily prostate movement for concurrent irradiation of the prostate and pelvic lymph nodes. The benefit of switching the MLC from 10 to 5 mm was significant (p ≪ 0.01); however, switching the MLC from 5 to 2.5 mm would not gain significant (p = 0.15) improvement. IMRT plans with smaller MLC leaf widths achieved more accurate dose delivery.
Low Density Lipoprotein Receptor-related Protein-1 (LRP1) Regulates Thrombospondin-2 (TSP2) Enhancement of Notch3 Signaling *

Intracellular trafficking of Notch and Notch ligands modulates signaling, suggesting that choreography of ligand and receptor translocation is essential for optimal Notch activity. Indeed, a major model for Notch signaling posits that Notch trans-endocytosis into the ligand-expressing (signal sending) cell is a key driving force for Notch signal transduction. The extracellular protein thrombospondin-2 (TSP2) enhances Notch signaling and binds to both Jagged1 and Notch3 ectodomains, potentially bridging two essential extracellular components of Notch signaling. We investigated the role of low density lipoprotein receptor-related protein-1 (LRP1), a TSP2 receptor, in the regulation of Notch3 signaling. TSP2 potentiation of Notch is blocked by the receptor-associated protein (an inhibitor of low density lipoprotein receptor-related protein function) and requires LRP1 expression in the signal-sending cell. TSP2 stimulates Notch3 endocytosis into wild type fibroblasts but not LRP1-deficient fibroblasts. Finally, recombinant Notch3 and Jagged1 interact with the LRP1 85-kDa B-chain, a subunit that lacks known ligand binding function. Our data suggest that LRP1 and TSP2 stimulate Notch activity by driving trans-endocytosis of the Notch ectodomain into the signal-sending cell and demonstrate a novel, non-cell autonomous function of LRP1 in cell-cell signaling.
Effects of mesenchymal stem cell and fibroblast coating on immunogenic potential of prosthetic meshes in vitro

The aim of this study was to reveal the effect of fibroblast or mesenchymal stem cell (MSC) coating on the mesh-induced production of IL-1β, IL-6, and VEGF by macrophages. Four commonly used surgical meshes were tested in this study, including Parietex, SoftMesh, TIGR, and Strattice. One-square-centimeter pieces of each mesh were placed on top of a monolayer of human fibroblasts or rat MSCs. The coating status was monitored with a light microscope. The human promonocytic cell line U937 was induced to differentiate into macrophages (MΦ). Three weeks later, meshes were transferred to new 24-well plates and cocultured with the MΦs for 72 h. Culture medium was collected and analyzed for IL-1β, IL-6, and VEGF production using standard ELISA essays. Parallel mesh samples were fixed with paraformaldehyde or glutaraldehyde for histology or transmission electronic microscopy (TEM) analyses, respectively. Uncoated meshes induced increased production of all three cytokines compared with macrophages cultured alone. HF coating further increased the production of both IL-6 and VEGF but reduced IL-1β production. Except for the SoftMesh group, MSC coating significantly blunted release of all cytokines to levels even lower than with MΦs cultured alone. MΦs tended to deteriorate in the presence of MSCs. Both histology and TEM revealed intimate interactions between cell-coated meshes and MΦs. Cytokine response to fibroblast coating varied, while MSC coating blunted the immunogenic effect of both synthetic and biologic meshes in vitro. Cell coating appears to affect mesh biocompatibility and may become a key process in mesh evolution.
A Global Analysis of Constrained Behavior: The LeChatelier Principle "In the Large"

New global results are obtained on the LeChatelier-Samuelson principle reflecting the properties of constrained behavior. Relying on the saddle point characterization of the Lagrangean, simple yet powerful LeChatelier results are derived and investigated under general conditions. The results do not require differentiability assumptions or unique solution, and they hold for discrete changes. The usefulness of the approach is illustrated in several applications, showing how the analysis generates insights into global economic adjustments.
The role of the kynurenine pathway in suicidality in adolescent major depressive disorder

The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents—composed of past attempters and those who expressed active suicidal intent—30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid (3-HAA), and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide.
Some methods of assessing postnatal craniofaciodental growth: a retrospective of personal research.

Abstract Objective: The purposes of this review and summary are to evaluate several selected significant clinical and basic science methods utilized to assess growth of bone(s), and in particular craniofaciodental growth: appositional and resorptive (bone), endochondral (bones), and sutural (bones).This personal retrospective report includes in part anthropometry, impressions and casts, vital markers, histology, radiopaque implant markers with and without serial cephalometric radiographs, and autoradiography. Knowledge obtained from the use of these various methods on rats, ground squirrels, rabbits, pigs, dogs, monkeys, and humans has contributed to a deeper and more fundamental understanding of both the processes and roles that craniofaciodental biology plays in the advancement not only of basic biology but also of craniofacial surgery. Growth and development of the skeletal system has an important role in determining body form. The dynamics of growth of bones is a complicated process. A number of diffe...
Interhead fluorescence energy transfer between probes attached to translationally equivalent sites on the regulatory light chains of scallop myosin.

Interhead fluorescence energy transfer studies between probes located at translationally equivalent sites on the two heads of scallop myosin indicates that the distance between such sites is no less than 50 A. Regulatory light chains, possessing either one (Mercenaria, chicken gizzard) or two (Loligo, rabbit skeletal) sulfhydryl groups, were modified either with 1,5-IAEDANS (N′-iodoacetyl-N′-(1-sulfo-5-n-naphthyl)ethylenediamine), as energy transfer donor, or with IAF (5-(iodoacetamido)fluorescein) or DABMI (4-dimethylamino-phenylazophenyl-4′-maleimide), as energy transfer acceptor. The sulfhydryl groups on these light chains are located at different positions within the regulatory light-chain primary sequence; this enables one to probe a variety of locations, with respect to regulatory light-chain topology, on each myosin head. These independently modified regulatory light chains were added back to desensitized scallop myosin under a variety of conditions, including biphasic re-addition, the aim being to maximize the number of interhead energy transfer couples present. The efficiency of energy transfer was determined on the same samples by both steady-state and time-decay techniques. Results obtained by these two techniques were in good agreement with each other and indicated that the efficiency of energy transfer did not exceed 20% in any of the hybrids studied. Transfer efficiencies were invariant, irrespective of the presence or absence of MgATP, calcium or actin, either separately or in combination. Results using heavy meromyosin at low ionic strength were identical. It is shown that these results, in conjunction with the results of recent crosslinking studies performed on comparable myosin hybrids, may place certain restrictions on the configurations of the two heads of myosin.
The Control of Dicumarol Therapy in Myocardial Infarction by a Simple Blood Prothrombin Test

Effective anticoagulant therapy is dependent upon adequate and reliable blood prothrombin determinations. The initiation of such therapy usually requires hospitalization. The currently available blood prothrombin tests require special laboratory facilities and trained personnel. The authors of this report present the results of Dicumarol in myocardial infarction and a simple blood prothrombin test for the control of such anticoagulant therapy. The test has been employed for more than eight years. The method has proved to be simple, accurate, and practical, and has made anticoagulants possible for patients at home as well as in the hospital.
Evolutionary biology of the devonian brachiopoda of new york state no correlation with rate of change of sea level

McGhee, G. R., Jr. 1992 04 15: Evolutionary biology of the Devonian Brachiopoda of New York State: no correlation with rate of change of sea-level?Lethaia, Vol. 25, pp. 165–172. Oslo. ISSN 0024–1164. Previous study has revealed the surprising lack of a relationship between relative sea-level position and the evolutionary biology of the Brachiopoda during the Devonian. To further explore this seeming anomaly, the potential relationship between the rate of change of sea-level and the evolutionary biology of these sessile benthic organisms is analyzed here. Successive linear modeling reveals a lack of correlation between the rate of change of sea-level and either extinction rate, origination rate, or diversity of the Devonian brachiopods. *Sea-level, rate of sea-level change, extinction, origination, diversity, Brachiopoda.
Uniform and universal Glivenko-Cantelli classes

A class\(\widetilde{F}\) of measurable functions on a probability space is called a Glivenko-Cantelli class if the empirical measuresPn converge to the trueP uniformly over\(\widetilde{F}\) almost surely.\(\widetilde{F}\) is a universal Glivenko-Cantelli class if it is a Glivenko-Cantelli Cantelli class for all lawsP on a measurable space, and a uniform Glivenko-Cantelli class if the convergence is also uniform inP. We give general sufficient conditions for the Glivenko-Cantelli and universal Glivenko-Cantelli properties and examples to show that some stronger conditions are not necessary. The uniform Glivenko-Cantelli property is characterized, under measurability assumptions, by an entropy condition.
Two-point transonic airfoil design using optimization for improved off-design performance

A two-point, aerodynamic design method is presented that improves the aerodynamic performance of transonic airfoils over a range of the flight envelope. It couples an Euler flow solver and a numerical optimization tool. The major limitation of single-point design is the poor off-design performance. Two-point design is used to extend the optimized performance range over more of the desired flight envelope. The method is applied to several transonic flow design points, and the results are compared to single-point design results. The secondary design points are chosen by varying the Mach number and the angle of attack. The two-point designs perform better than the single-point design over the design-point range.
Automated sequence reading and analysis

We report on a system developed by Bio-Rad Laboratories, Inc. which combines automated reading of DNA sequencing autoradiograms with comprehensive software for shotgun overlapping of the readings, analysis of the sequences derived and searching of databases. Reading is accomplished using a high speed optical scanner and pattern recognition software operating on a personal computer. Overlapping, analysis and database searching software each incorporate significant advances over prior systems.
The role of phenylalanine in differentiating amphibian melanocytes.

Abstract To see whether phenylalanine serves as a substrate in melanogenesis, hanging drop explants of neural crest from amphibian (Ambystoma maculatum and A. mexicanum) embryos were subjected on the seventh day in vitro to treatment with phenylalanine-3H and studied by means of light microscopic radioautography. All melanin-containing cells showed label. On the other hand, when puromycin, an inhibitor of protein synthesis, together with the labeled amino acid was administered to the cultures, no radioactivity was incorporated by pigmented cells. Comparable results were obtained when leucine was substituted for phenylalanine. In control experiments, puromycin and labeled tyrosine or 3,4-dihydroxyphenylalanine (DOPA), both known precursors for melanin synthesis, were administered to the neural crest cultures. In these experiments, puromycin had no effect on the incorporation of label by pigmented cells. Our data strongly indicate that in differentiating amphibian melanocytes with functional pigment-forming systems, phenylalanine is used in protein synthesis, but does not serve as a substrate for the tyrosine-tyrosinase system. In another series of experiments, explants of neuroepithelium (neural crest anlage) were grown from the time of explantation to the seventh day in vitro in the presence of phenyllactic acid, an analog of phenylalanine. Pigment cells developed normally. These results suggest that phenylalanine plays little or no role in pigment cell differentiation.
Spatial principle components analysis: application to flightline C1

An application of including spatial information into a principle components analysis (PCA) image classification through an eigenvector spatial filter is given. The spatial filter is created as a linear combination of the chosen eigenvectors based on the spatial information in the image. These eigenvectors are extracted from the defined connectivity of the image pixels and are different from those eigenvectors used in conventional PCA. The surface connectivity of the image is based on the binary matrix of image pixel neighbors (i.e. if i and j are neighbor pixels in an image and i does not equal j than matrix entry c ij = 1 other c ij = 0). The proposed methodology is applied to an image example (i.e. Flightline C1) with 12 spectral bands from an airborne sensor as a selected case study dataset. An explanation of how a spatial filter should be incorporated into PCA classification is given and two possibilities for gaining efficiency in the algorithm, through distributed computing and sampling is described. The advantages and drawbacks of both approaches, in terms of computing time, and amount of variance accounted for in the image is discussed.
Safety and efficacy of an accelerated dobutamine stress echocardiography protocol in the evaluation of coronary artery disease.

Although dobutamine requires up to 10 minutes to achieve steady state, dobutamine stress echocardiography is routinely performed using stepwise increments at 3-minute intervals. Consequently, the full effect of any infusion rate is not attained before the dobutamine dose is advanced to the next level. This study sought to test the safety and efficiency of high-dose continuous dobutamine infusion. One hundred consecutive patients underwent an accelerated protocol using a constant infusion of 50 μg/kg/min. In the absence of a stress echocardiographic end point (≥85% of maximal predicted heart rate, new wall motion abnormalities, hypotension, arrhythmia, or intolerable symptoms), dobutamine infusion was discontinued at 10 minutes. Hemodynamic responses and adverse effect profile were compared with 100 patients who underwent a standard stepwise dobutamine stress protocol. Peak heart rate (140 ± 16 vs 140 ± 19 beats/min, p = 0.95) and systolic blood pressure (169 ± 32 vs 162 ± 31 mm Hg, p = 0.08) were similar in both protocols. Accelerated dobutamine administration produced a rapid increase in heart rate (12.5 ± 6.2 vs 5.7 ± 2.6 beats/min, p <0.001), and a substantial reduction in test duration (6.4 ± 2.4 vs 12.9 ± 3.0 minutes, p <0.001). The mean weight-adjusted cumulative dobutamine dose was lower in the accelerated protocol group (320 ± 111 vs 353 ± 133 μg/kg, p = 0.016). No significant differences were noted between the 2 groups with respect to various side effects. These data demonstrate that a high-dose, single-stage dobutamine echocardiographic stress protocol is a feasible, well-tolerated alternative to standard dobutamine stress echocardiography, and results in a substantial reduction in test time while maintaining a low complication rate.
Medical intensive care for lung cancer patients: better than we thought?

Ayman O Soubani† & Abdulgadir K Adam †Author for correspondence Karmanos Cancer Center and Wayne State University School of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, 3990 John R3 Hudson, Detroit, MI 48201, USA Tel.: +1 313 745 8471; Fax: +1 313 993 0562; asoubani@med.wayne.edu ‘The intensive care unit outcome of lung cancer patients has been progressively improving, and is approximating that of the general critically ill population.’
Discovery of an L-Fucono-1,5-Lactonase from cog3618 of the Amidohydrolase Superfamily

A member of the amidohydrolase superfamily, BmulJ_04915 from Burkholderia multivorans, of unknown function was determined to hydrolyze a series of sugar lactones: l-fucono-1,4-lactone, d-arabino-1,4-lactone, l-xylono-1,4-lactone, d-lyxono-1,4-lactone, and l-galactono-1,4-lactone. The highest activity was shown for l-fucono-1,4-lactone with a kcat value of 140 s–1 and a kcat/Km value of 1.0 × 105 M–1 s–1 at pH 8.3. The enzymatic product of an adjacent l-fucose dehydrogenase, BmulJ_04919, was shown to be l-fucono-1,5-lactone via nuclear magnetic resonance spectroscopy. l-Fucono-1,5-lactone is unstable and rapidly converts nonenzymatically to l-fucono-1,4-lactone. Because of the chemical instability of l-fucono-1,5-lactone, 4-deoxy-l-fucono-1,5-lactone was enzymatically synthesized from 4-deoxy-l-fucose using l-fucose dehydrogenase. BmulJ_04915 hydrolyzed 4-deoxy-l-fucono-1,5-lactone with a kcat value of 990 s–1 and a kcat/Km value of 8.0 × 106 M–1 s–1 at pH 7.1. The protein does not require divalent cations...
Biosynthesis of oleic acid and docosahexaenoic acid by a heterotrophic marine dinoflagellate Crypthecodinium cohnii

Abstract The major unsaturated fatty acids of Crypthecodinium cohnii , a hetero-trophic marine dinoflagellate, were 18:1( n −9) and all- cis 22:6( n −3). When C. cohnii was grown with [1- 14 C] acetate or with [1- 14 C] octanoate, all of its fatty acids were labeled. After growth with [1- 14 C]octanoate, the distribution of 14 C in 18:1( n −9) and 22:6( n −3) indicated that octanoate was used as a source of C 2 units and was not chain-elongated. When C. cohnii was grown with 14 C-labeled C 10 –C 18 fatty acids that were anticipated as precursors of 18:1( n −9) and 22:6( n −3), 18:1( n −9) was labeled but 22:6( n −3) was not. Extensive randomization of 14 C did not occur, and all of the labeled fatty acids introduced 14 C into the neutral and polar lipids. The precursor-product relationships, inferred from the patterns of distribution of radioactivity, suggested that the biosynthesis of 18:1( n −9) was compartmentalized from that of 22:6( n −3), and that known pathways to the (n−3) poly unsaturated fatty acids were either inaccessible to exogenous intermediates or did not operate in C. cohnii .
Stacked dual-oxide MOS energy band diagram visual representation program (IRW student paper)

Energy band diagrams for MOS devices are essential for understanding device performance and reliability. Introduction of high-k gate stacks with a silicon dioxide (SiO2) interfacial layer requires an even greater understanding of the energy band behavior. A program that quickly determines the band diagrams based on a simple analytical model was created. It is used to explore the behavior of various oxide stacks with the ability to easily vary important parameters like oxide material, electron affinity, bandgap, dielectric constant, and thickness. The usefulness of this program to predict potential reliability issues is also demonstrated
Virologic Failure in First-Line Human Immunodeficiency Virus Therapy with a CCR5 Entry Inhibitor, Aplaviroc, plus a Fixed-Dose Combination of Lamivudine-Zidovudine: Nucleoside Reverse Transcriptase Inhibitor Resistance Regardless of Envelope Tropism

The CCR102881 (ASCENT) study evaluated the antiviral activity of the novel CCR5 entry inhibitor aplaviroc plus a fixed-dose combination of lamivudine-zidovudine (Combivir) in drug-naive human immunodeficiency virus type 1-infected subjects with only CCR5-tropic virus detected in plasma. Although the trial was stopped prematurely due to idiosyncratic hepatotoxicity, eight subjects met protocol-defined virologic failure criteria. Clonal analyses of the viral envelope tropism, aplaviroc susceptibility, and env sequencing were performed on plasma at baseline and at the time of virologic failure. Molecular evolutionary analyses were also performed. The majority of the subjects with virologic failure (six of eight) acquired the lamivudine resistance-associated mutation M184V, and none had evidence of reduced susceptibility to aplaviroc at the time of virologic failure, even at the clonal level. Six subjects with virologic failure maintained CCR5 tropism, while two exhibited a change in population tropism readout to dual/mixed-tropic with R5X4-tropic clones detected prior to therapy. Two evolutionary patterns were observed: five subjects had no evidence of population turnover, while three subjects had multiple lines of evidence for env population turnover. The acquisition of the M184V mutation is the primary characteristic of virologic failure in first-line therapy with aplaviroc plus lamivudine-zidovudine, regardless of the envelope tropism.
Pharmacotherapy of addictions

Addiction to drugs, such as heroin, cocaine and alcohol, exacts great human and financial costs on society, but the development of pharmacotherapies for addiction has been largely neglected by the pharmaceutical industry. With advances in our understanding of the underlying biology of addictions now opening the door for the development of novel pharmacotherapies, it could be time for a reassessment of involvement in this increasingly important therapeutic area. Here, we summarize the current approved and implemented pharmacotherapeutic approaches to the treatment of addiction, and then highlight the most promising areas for future drug development from the perspective of our laboratory and our National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) Research Center.
Carcinoma of the uterine cervix metastatic to behind the zygomatic arch: A case report

Abstract Purpose: We propose to present a novel case of a genital malignancy metastatic to the head and neck. Carcinoma of the uterine cervix is the third most frequent malignancy of the female genital tract. Early detection and improved radiation and surgical techniques have resulted in better control of the pelvic tumor and a greater incidence of distant metastasis. Metastases to the soft tissue of the head and neck region have not been reported. Methods: We present the first known case of a 35-year-old woman with cancer of the uterine cervix who presented with metastasis to the soft tissue behind the zygomatic arch. Results: The patient received radiation therapy to the zygomatic region and cisplatin therapy with a near-complete remission. Conclusion: This case shows that not all squamous cell cancers detected above the clavicles are from a thoracic or a head and neck primary tumor. The atypical location should alert the physician to suspect distant metastasis, rather than locoregional disease.
A calibration technique for polarimetric coherent-on-receive radar systems

A new technique for calibrating a coherent-on-receive polarimetric radar system is proposed. A coherent-on-receive polarimetric radar is capable of measuring the Mueller matrix of point or distributed targets directly by transmitting at least four independent polarizations and measuring the vertical and horizontal components of the backscatter signal simultaneously. The technique requires the use of two calibration targets, a target with known scattering matrix (such as a metallic sphere or a trihedral corner reflector) and any depolarizing target (for which knowledge of its scattering matrix is not required) to determine the system distortion parameters. The system distortion parameters, which include the channel imbalances, the cross-talk factors of both the transmit and the receive antennas, and the phase shifts and amplitude variations of the transmitter polarizers, are determined by measuring the calibration targets for four different transmit polarizations. The validity of the new calibration technique is examined by measuring the scattering matrices of spheres and cylinders as test targets using a coherent-on-receive radar operating at 34.5 GHz. Excellent agreement between the theoretical and the measured scattering matrices for the test targets are obtained. >
The use of affinity‐seeking in producing liking and learning in the classroom

Abstract The affinity‐seeking typology (Bell & Daly, 1984) was developed and validated for interpersonal contexts, but has been used quite extensively in recent years in the instructional setting. Teacher use of affinity‐seeking has been associated with learning, motivation, and teacher credibility. The present research had two primary objectives. The first objective was to validate the use of the affinity‐seeking typology in the instructional context. The second objective was to test two causal models of the affinity‐seeking and learning relationship. The motivation model proposed that motivation played a mediating role between liking produced by affinity‐seeking and student learning. The direct‐effects model proposed that liking had a direct effect on student learning. Using panel data collected over the period of a semester, some affinity‐seeking strategies were found to be more useful in the instructional context than others, and greater support was found for the motivation model.
Thromboelastographic changes after gonadectomy in retired racing greyhounds

Twenty-one healthy greyhounds with no history or clinical signs of bleeding disorders, and no abnormalities on physical examination, complete blood count, serum biochemistry profiles (in dogs more than five years of age), and SNAP-4DX test for vector borne diseases underwent routine gonadectomies at the Ohio State University Veterinary Teaching Hospital. Blood samples were collected 24 hours before and after surgery by jugular venepuncture for thromboelastography and haemostasis assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration). The magnitude of the bleeding in each patient was estimated using a bleeding scoring system recently validated in greyhounds. Eight dogs were classified as bleeders and 13 as non-bleeders. Thromboelastograph (TEG) tracings in bleeders were different to that of non-bleeders. Neither sex (odds ratio [OR]: 0.148, P=0.05), haematocrit (OR: 0.907, P=0.39), platelet count (OR: 0.996, P=0.65) or age (OR: 0.949, P=0.83) were predictors of the outcome. None of the variables that evaluated clot kinetics, and fibrinolysis (that is, aPTT OR: 0.781, P=0.51; PT OR: 1.337, P=0.63; TEGR OR: 1.269, P=0.06; TEGK OR: 1.696, P=0.05; TEGLY60 OR: 1.028, P=0.81) were able to predict the bleeding episodes. Only the TEG variables that represent the fibrin cross-linking of the clot (TEGangle OR: 0.903, P=0.03); and the strength of the clot (TEGMA OR: 0.833, P=0.03) were considered predictors of the outcome.
Helpful introduction to signal transduction

![Figure][1] Structure and Function in Cell Signalling By John Nelson Wiley (2008) 410 pages, ISBN 978-0-470-02551-2, £34.95 (paperback) When studying cell signaling, it is easy to get overwhelmed with the complexity of each pathway and with the crosstalk between them. Teaching the
The determinants of board composition: An agency theory perspective

This study examines the interrelation between board composition and variables that capture various agency and financial dimensions of the firm. The agency literature suggests that outside directors on the board provide important monitoring functions in an attempt to resolve, or at least mitigate, agency conflicts between management and shareholders. The agency literature indicates that other mechanisms such as managerial equity ownership, dividend payments, and debt leverage also serve as important devices in reducing agency conflicts in firms. This study argues and documents that an inverse relationship exists between the proportion of external members on the board and managerial stock ownership, dividend payout, and debt leverage. This is consistent with the hypothesis that individual firms choose an optimal board composition depending upon alternative mechanisms employed by the firm to control agency conflicts. Board composition is also found to be systematically related to a number of other variables including institutional holdings, growth, volatility, and CEO tenure.
BEAMLAB AND REPRODUCIBLE RESEARCH

In the first 'Wavelets and Statistics' conference proceedings 1, our group published 'Wavelab and Reproducible Research', in which we advocated using the internet for publication of software and data so that research results could be duplicated by others. Much has happened in the last decade that bears on the notion of reproducibility, and we will review our experience. We will also describe a new software package BEAMLAB containing routines for multiscale geometric analysis, and describe some of its capabilities. BEAMLAB makes available, in one package, all the code to reproduce all the figures in our recently published articles on beamlets, curvelets and ridgelets. The interested reader can inspect the source code to see what algorithms were used, and how parameters were set to produce the figures, and will then be able to modify the source codes to produce variations of our results. Some new examples of numerical studies based on BEAMLAB are provided here.
Fatigue in Cardiopulmonary Disease

Fatigue is often the major presenting complaint in patients with cardiac or pulmonary disease. This review explores a number of the multiple possible causes of fatigue in this population of patients. The identification of fatigue and possible approaches to the treatment of fatigue in cardiopulmonary patients are presented. Finally, the role of exercise and appropriate exercise prescription for treatment of fatigue for cardiac and pulmonary patients is discussed.
A two-person technique for fiberscope-aided tracheal extubation/ reintubation in intensive care unit (ICU) patients

The technique of fiberoptic-aided intubation for management of a difficult airway is often limited in the presence of blood or secretions and conditions in which the passage of a fiberoptic bronchoscope ("fiberscope") beneath the epiglottis and into the glottic opening may prove difficult. Direct laryngoscopy can be utilized in combination with the fiberscope as a two-person technique to overcome these challenges. We report the usefulness of a two-person technique using the flexible fiberscope in combination with direct laryngoscopy for extubation/reintubation in two intensive care unit patients with known difficult airways.
Hepatitis A Transmitted by Food

Hepatitis A is caused by hepatitis A virus (HAV). Transmission occurs by the fecal-oral route, either by direct contact with an HAV-infected person or by ingestion of HAV-contaminated food or water. Foodborne or waterborne hepatitis A outbreaks are relatively uncommon in the United States. However, food handlers with hepatitis A are frequently identified, and evaluation of the need for immunoprophylaxis and implementation of control measures are a considerable burden on public health resources. In addition, HAV-contaminated food may be the source of hepatitis A for an unknown proportion of persons whose source of infection is not identified.
Sexual Harassment Victimization During Emerging Adulthood A Test of Routine Activities Theory and a General Theory of Crime

Sexual harassment of college students may lead to more serious forms of sexual assault. Few studies have investigated sexual harassment predictors framed within competing theoretical perspectives. In this study, the literature is extended by examining (a) three types of sexual harassment on a college campus, (b) the nature of reporting, and (c) whether routine activities and self-control theories effectively explain sexual harassment. Findings indicate that one fourth of the participants in the sample were sexually harassed, assaulted students are extremely unlikely to officially report incidents, and measures of routine activities theory are important predictors of sexual harassment. Prevention and education policies should focus on increased reporting to university authorities and helping students understand the situational contexts in which these behaviors are likely to occur.
Optimizing rice yields while minimizing yield‐scaled global warming potential

To meet growing global food demand with limited land and reduced environmental impact, agricultural greenhouse gas (GHG) emissions are increasingly evaluated with respect to crop productivity, i.e., on a yield-scaled as opposed to area basis. Here, we compiled available field data on CH4 and N2 O emissions from rice production systems to test the hypothesis that in response to fertilizer nitrogen (N) addition, yield-scaled global warming potential (GWP) will be minimized at N rates that maximize yields. Within each study, yield N surplus was calculated to estimate deficit or excess N application rates with respect to the optimal N rate (defined as the N rate at which maximum yield was achieved). Relationships between yield N surplus and GHG emissions were assessed using linear and nonlinear mixed-effects models. Results indicate that yields increased in response to increasing N surplus when moving from deficit to optimal N rates. At N rates contributing to a yield N surplus, N2 O and yield-scaled N2 O emissions increased exponentially. In contrast, CH4 emissions were not impacted by N inputs. Accordingly, yield-scaled CH4 emissions decreased with N addition. Overall, yield-scaled GWP was minimized at optimal N rates, decreasing by 21% compared to treatments without N addition. These results are unique compared to aerobic cropping systems in which N2 O emissions are the primary contributor to GWP, meaning yield-scaled GWP may not necessarily decrease for aerobic crops when yields are optimized by N fertilizer addition. Balancing gains in agricultural productivity with climate change concerns, this work supports the concept that high rice yields can be achieved with minimal yield-scaled GWP through optimal N application rates. Moreover, additional improvements in N use efficiency may further reduce yield-scaled GWP, thereby strengthening the economic and environmental sustainability of rice systems.
Infectious Decay of Human Immunodeficiency Virus Type 1 in Plasma

AIDS is caused by the human immunodeficiency virus type 1 (HIV-1). Recent methods have been developed to estimate infectious titer in various bodily fluids, including blood. However, lack of information about HIV-1 stability in blood has restricted the use of these techniques to fresh samples in immediately accessible virology laboratories. In studies of infectious virus decay, it was found that at room temperature, complete decay of infectious HIV-1 in plasma can require > 7 days. Furthermore, the stability of HIV-1 was enhanced by storage at 4 degrees C, suggesting that fresh plasma could be sent on ice to core laboratories for viral quantitation. These studies also emphasize the need for thorough decontamination of all potentially infectious material.
Recombinant‐protein production in insect cells utilizing a hollow‐fibre bioreactor

Here, we demonstrate for the first time that the hollow-fibre bioreactor is an excellent tool for the production of Drosophila-expressed recombinant proteins. Using the example of the soluble extracellular portion of the human IL-5 (interleukin 5) receptor alpha expression in S2 (Schneider's Drosophila melanogaster cell line 2) cells, we found that it is possible to produce multi-milligram amounts of functional recombinant protein continuously for several months on a laboratory scale with minimal maintenance requirements. The insect cells grow to high density and express concentrated functional recombinant protein in a small volume, simplifying and economizing downstream purification.
Effects of antibiotics on the survival of Salmonella in the American cockroach.

Abstract The faecal survival of Salmonella typhimurium orally administered to restrained American cockroaches maintained on an antibiotic diet was investigated. Significant reductions in median numbers of total aerobic faecal microorganisms were noted in insects fed antibiotics daily, and when Salmonella was introduced to this modified micro-environment, it persisted for 44 days in all specimens. Multiplication of the pathogen was also observed in these insects, with numbers often exceeding 10(3) times that of the initial input. This differs significantly from our previous results showing that the pathogen is unable to multiply in conventional cockroaches. Attempts to restore the normal flora by feeding a faecal suspension from untreated cockroaches resulted in a decrease in numbers of Salmonella excreted, but did not result in their elimination. Carcasses of infected cockroaches retained viable Salmonella for at least 60 days post mortem, or 104 days after the infective meal.
LRR-containing receptors regulating plant development and defense

Despite the presence of more than 400 genes that encode receptor-like kinases (RLKs) in the Arabidopsis thaliana genome, very little is known about the range of biological processes that they control, or the mechanisms by which they function. This review focuses on the most recent findings from studies of several leucine-rich-repeat (LRR) class RLKs in A. thaliana, and their implications for our understanding of plant receptor function and signaling. We compare the biological functions of plant and animal LRR-containing receptors, and the potential commonalities in the signaling mechanisms employed.
‘Let Us Protect Our Future’ a culturally congruent evidenced-based HIV/STD risk-reduction intervention for young South African adolescents

One of the worst HIV/AIDS epidemics in the world is occurring in South Africa, where heterosexual exposure is the main mode of HIV transmission. Young people 15–24 years of age, particularly women, account for a large share of new infections. Accordingly, there is an urgent need for behavior-change interventions to reduce the incidence of HIV among adolescents in South Africa. However, there are few such interventions with proven efficacy for South African adolescents, especially young adolescents. A recent cluster-randomized controlled trial of the ‘Let Us Protect Our Future!’ HIV/STD risk-reduction intervention for Grade 6 South African adolescents (mean age = 12.4 years) found significant decreases in self-reported sexual risk behaviors compared with a control intervention. This article describes the intervention, the use of the social cognitive theory and the reasoned action approach to develop the intervention, how formative research informed its development and the acceptability of the intervention. Challenges in designing and implementing HIV/STD risk-reduction interventions for young adolescents in sub-Saharan Africa are discussed.
Effects of humidity on aerosols in southern Africa during the biomass burning season

Measurements of the aerosol total light scattering coefficient, asp, and the aerosol hemispheric backscatter ratio, p(1), as functions of relative humidity (RH in %) (so-called humidographs) at three wavelengths (450,550, and 700 nm) were obtained in the dry season in southern Africa (1) in ambient air in South Africa, Botswana, Mozambique and Zambia, (2) at various distances downwind in identifiable smoke plumes from biomass fires, and (3) along the southwest coast of Africa. The ratio of sigma(sub sp) at an RH of 80% to that at 30% provides a measure of the effects of RH on sigma(sub sp), and similarly for Beta(1). For the three broad sampling categories given above, and at a wavelength of 550 nm, these ratios varied from 1.42 +/- 0.05 to 2.07 +/- 0.03 for sigma(sub sp), and from 0.69 +/- 0.05 to 0.99 +/- 0.14 for Beta(1). In general, humidographs for the ambient air samples showed a greater dependence on RH than those for smoke from identifiable biomass fires. During a period when dense, aged smoke was transported to the region from the north, the humidographs for sigma(sub sp) for ambient air samples were similar to those for identifiable smoke plume samples just approximately 10- to 50-min old. This suggests that as far as the effects of RH on sigma(sub sp) are concerned the effects of aging of smoke and its mixing with ambient air are realized within less than about an hour.