cssi/SciSciGPT-SciSciNet huggingface dataset:
Obscure Cold War nerve agents set to be banned

A class of nerve agents developed during the Cold War by the Soviet Union may soon be banned. During a meeting next month, parties to the Chemical Weapons Convention are expected to bring them under the convention9s verification regime, along with two groups of carbamates that are also highly toxic. Novichoks have long been shrouded in mystery. The first public clues came in 1992 from a Soviet military chemist who later revealed structural details. The U.S. government for years classified the agents as top secret. But last year9s assassination attempt against former Russian spy Sergei Skripal in Salisbury, U.K., thrust the Novichoks into the spotlight. The new openness should spur research on their mechanism of action and on countermeasures and treatments.
Normal Solvability And Existence Theorems For Nonlinear Mappings In Banach Spaces

Introduction: Let X be a topological space, Y a Banach space, f a mapping of X into Y. The mapping f is said to be normally solvable if f(x) is closed in Y . In the preceding paper (Browder [6]), we have described how the theory of normal solvability combines this hypothesis with infinitesimal assumptions upon the mapping f to obtain sufficient conditions for a given element y of Y to lie in f(X).
Non-random distribution of vacuoles in Schizosaccharomyces pombe

A central question in eukaryotic cell biology asks, during cell division, how is the growth and distribution of organelles regulated to ensure each daughter cell receives an appropriate amount. For vacuoles in budding yeast, there are well described organelle-to-cell size scaling trends as well as inheritance mechanisms involving highly coordinated movements. It is unclear whether such regulation is necessary in the symmetrically dividing fission yeast, Schizosaccharomyces pombe, in which random partitioning may be utilized to distribute vacuoles to daughter cells. To test this idea, we utilized machine learning to develop automated methods for segmenting fission yeast cells and locating vacuoles in live fission yeast cells from brightfield and fluorescence micrographs. We have found that the scaling trends of vacuole number, volume and surface area-to-cell size is consistent across a variety of strains, and that vacuole proliferation is a key mechanism for vacuole growth. We also show that vacuoles are not distributed evenly throughout the cell with respect to available cytoplasm. Rather, vacuoles show distinct peaks in distribution close to the nucleus, and this clustering was confirmed in mutants in which nucleus position is perturbed. Future work will establish the molecular mechanism for this clustering.
NOD1 and NOD2 in inflammatory and infectious diseases

It has been long recognized that NOD1 and NOD2 are critical players in the host immune response, primarily by their sensing bacterial peptidoglycan-conserved motifs. Significant advances have been made from efforts that characterize their upstream activators, assembly of signaling complexes, and activation of downstream signaling pathways. Disruption in NOD1 and NOD2 signaling has also been associated with impaired host defense and resistance to the development of inflammatory diseases. In this review, we will describe how NOD1 and NOD2 sense microbes and cellular stress to regulate host responses that can affect disease pathogenesis and outcomes.
Machine learning to accelerate screening for Marcus reorganization energies

Understanding and predicting the charge transport properties of π-conjugated materials is an important challenge for designing new organic electronic devices, such as solar cells, plastic transistors, light-emitting devices, and chemical sensors. A key component of the hopping mechanism of charge transfer in these materials is the Marcus reorganization energy which serves as an activation barrier to hole or electron transfer. While modern density functional methods have proven to accurately predict trends in intramolecular reorganization energy, such calculations are computationally expensive. In this work, we outline active machine learning methods to predict computed intramolecular reorganization energies of a wide range of polythiophenes and their use toward screening new compounds with low internal reorganization energies. Our models have an overall root mean square error (RMSE) of ±0.113 eV, but a much smaller RMSE of only ±0.036 eV on the new screening set. Since the larger error derives from high-reorganization energy compounds, the new method is highly effective to screen for compounds with potentially efficient charge transport parameters.
Gadolinium is not necessary for surveillance MR imaging in children with chiasmatic-hypothalamic low-grade glioma.

BACKGROUND Patients with chiasmatic-hypothalamic low-grade glioma (CHLGG) have frequent MRIs with gadolinium-based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in the brains of children is a potential concern. The purpose of this study is to evaluate whether MRI with GBCA is necessary for determining radiographic tumor progression in children with CHLGG. METHODS Children who were treated for progressive CHLGG from 2005 to 2019 at Texas Children's Cancer Center were identified. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three dimensional measurements and tumor characteristics were evaluated. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared with baseline or best response after initiation of therapy. RESULTS A total of 28 patients with progressive CHLGG were identified with a total of 683 MRIs with GBCA reviewed (mean 24 MRIs/patient; range, 11-43 MRIs). Radiographic progression was observed 92 times, 91 (99%) on noncontrast and 90 (98%) on contrast imaging. Sixty-seven progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (99%) contrast sequences. Tumor growth > 2 mm in any dimension was identified in 184/187 (98%) noncontrast and 181/187 (97%) with contrast imaging. Metastatic tumors were better visualized on contrast imaging in 4/7 (57%). CONCLUSION MRI without GBCA effectively identifies patients with progressive disease. When imaging children with CHLGG, eliminating GBCA should be considered unless monitoring patients with metastatic disease.
Throttle and Brake Combined Control for Intelligent Vehicle Highway Systems

This paper summarizes the design of a throttle and brake combined controller and experimental work done for the longitudinal control of autonomous vehicles. It presents a sliding mode based longitudinal control law, brake system sub-model, brake control law and a throttle/ brake switching algorithm. The developed control strategies were implemented on a test vehicle and the longitudinal combined controls tested with a single vehicle using a predetermined trajectory of desired speed as a function of time. Initial test results shows good tracking, good ride quality, and smooth switching between throttle and brake.
THE NATURE OF SOME SUBTYPES OF A.

The subtype A x B has been encountered and described, along with two new examples of the subtype A x . Anti-A and anti-A,B that has been absorbed by and eluted from erythrocytes of subtype A x are sensitive to at least partial inhibition by the salivary secretions of the A x person, thereby implying that A determinants are expressed in the salivary secretions as well as on the erythrocytes. Saliva of the A x B person did not possess such inhibitory activity. However, family study disclosed that this person was likely to possess an unusual A 2 B genotype in which the B gene suppresses, at the phenotypic level, the expression of paired A . Furthermore, an underlying disease, myeloid metaplasia, may have further suppressed the expression of A determinants on both erythrocytes and in salivary secretions. Three other pedigrees revealed suppression of A by paired B , and in one instance, the genotype A 1 B was found to give rise to the phenotype A 2 B. Some population studies fail to demonstrate satisfactory Hardy-Weinberg equilibrium when tested in accordance with the usual four allele theory of inheritance for the A 1 A 2 BO phenotypes. An additional allele, suppressor B (B [unknown] ) was assumed for five such studies, and a more satisfactory fit between expected and observed values was obtained.
Small webcomputing applied to distributed monte carlo calculations

The software package, Small WebComputing (SWC), has been applied to a Monte Carlo simulation of a system of hard hyperspheres in a variety of dimensions. The SWC environment was chosen because once the framework is embedded in the application code, the user has the choice of running the distributed computations as a set of applets, as parallel threads on a symmetric multiprocessor or as independent processes distributed over a network. A description of the software and a discussion of its ongoing evolution is presented.
Stress-Strain Properties of Compacted Clays

It is pointed out that if the 70 percent and 95 percent points are used in fitting, the laboratory curve and the hyperbolic curve will compare vary well in this region but may differ seriously at low stress levels. The best overall fit between laboratory curves and hypergolas is obtained using the 50 percent and 95 percent points but the user should use points appropriate to the stress levels of major interest. Comment is made on the values of R sub f, and compaction conditions, and a linear failure equation. The use is unidacted of the log-log relationship to obtain a single analytic relationship through the stress range from 10 psi-1,000 psi. Both the tangent Poisson ration model and the hyperbolic model work well for samples compocted wet of optimum because they involve essentially constant values of Poissons ratio and thus degenerated into linear models in both cases. It is pointed out that the use of average axial strain and averate radial strain (derived from average values of volumetric and axial strains) is more likely to yield accurate results than the use of an average axial strain with the radial strain measured at a single point.
Improved coupled integral equations for the regge parameters

A method is given for improving the integral equations for the Regge parameters, given by Cheng and Sharp, and Frautschi, Kaus and Zachariasen. The multichannel, two-body unitarity relation is expanded in a Laurent-type expansiona−1(l −α)−1 +a0 +a1(l −α) +a2(l −α)2+ …; satisfaction to any order in (l −α) may be achieved, which results in additional relations between the residue and trajectories and, therefore, a more complete set of integral equations. In this way exact satisfaction of unitarity may be obtained in principle.
Galaxy as Dynamical System with Accreting Halo

The dynamical evolution of the Galaxy system was analysed under the assumption that its Halo containes beside nonbaryonic matter some fraction of baryons in the form of “invisible” small hydrogen molecular clouds as was proposed by Pfenniger, Combes & Martinet (1994). The behaviour of the Galactic gaseous Disk surface density as a function of time and galactocentric distance strongly depends on baryonic Halo parameters. It was found that only model with additional baryonic Halo having initial mass 2 · 1011 M ⊙ and flat rotation curve, which mimics the Disk rotation curve, fits well modern observational data concerning the Galaxy evolution in the Solar vicinity.
Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated ax...
Evidence that proteosome inhibitors and chemical chaperones can rescue the activity of retinol dehydrogenase 12 mutant T49M.

Abstract Retinol dehydrogenase 12 (RDH12) is a microsomal enzyme that catalyzes the reduction of all-trans-retinaldehyde to all-trans-retinol when expressed in cells. Mutations in RDH12 cause severe retinal degeneration; however, some of the disease-associated RDH12 mutants retain significant catalytic activity. Our previous study (Lee et al., 2010 [9] ) demonstrated that the catalytically active T49M and I51N variants of RDH12 undergo accelerated degradation through the ubiquitin–proteosome system, which results in reduced levels of these proteins in the cells. Here, we investigated whether the stabilization of T49M or I51N RDH12 protein levels through the inhibition of proteosome activity or improved folding could rescue their retinaldehyde reductase activity. For the T49M variant, the inhibition of proteosome activity resulted in an increased level of T49M protein in the microsomal fraction. The higher level of the T49M variant in microsomes correlated with the higher microsomal retinaldehyde reductase activity. T49M-expressing living cells treated with the inhibitors of proteosome activity or with dimethyl sulfoxide exhibited an increase in the conversion of retinaldehyde to retinol, consistent with the recovery of functional RDH12 protein. On the other hand, accumulation of the I51N variant in the microsomes did not result in higher retinaldehyde reductase activity of the microsomes or cells. These results provide a proof of concept that, at least in the case of the T49M variant, the prevention of accelerated degradation could lead to restoration of its function in the cells. This finding justifies further search for more efficient and clinically relevant compounds for stabilizing the T49M variant activity.
Promotion by phosphorus compounds of ruthenium-catalyzed methyl formate homologation

Abstract Trivalent phosphorus compounds are promoters for methyl formate homologation to ethanol and ethyl formate catalyzed by ruthenium compounds in the presence of iodide at 220°C and 27 MPa of synthesis gas. Under these conditions the phosphines are quaternized, but decomposition of phosphonium salts occurs during the reaction. Promotion is also observed for methyltriphenyl-phosphonium bromide and triphenylphosphine sulfide, but benzyltrimethyl-ammonium bromide, triphenylarsine, and triphenylantimony are not effective. The major ruthenium species present is Ru(CO) 3 I 3 - but with triphenylantimony a trimethylantimony complex, Ru(CO) 2 (Sb(CH 3 ) 3 ) 2 I 2 , can be isolated in high yield.
Diphenylhydantoin: Placental transport, fetallocalization, neonatal metabolism, and possible teratogenic effects

The passage of diphenylhydantoin across the human placenta has been demonstrated in7 subjects receiving the drug orally and in 3 patients receiving intravenous injections. Maternal plasma levels of diphenylhydantoin ranged from 1.0 to 6.3 μg per milliliter (mean 3.6±0.7), despite a relatively uniform dosage schedule in all patients on chronic anticonvulsant therapy. Neonatal elimination of placentally transferred diphenylhydantoin was very slow on postpartum days 1 and 2, increased markedly on postpartum day 3, and was completed by postpartum day 5. The plasma half-life for diphenylhydantoin ranged from 55 to 69 hours in the 7 neonates studied. Breast milk obtained from epileptic mothers receiving diphenylhydatoin contained very low concentrations of the drug and did not appear to constitute a clinical hazard for the infants of nursing mothers. The distribution of diphenylhydantoin in fetal tissues was widespread; the highest concentrations were noted in the liver, adrenal gland, heart, and kidney. No pharmacologic effects directly attributable to diphenylhydantoin were discernible in any of the neonates. The congenital anomalies (cleft lip in 2 and microcephaly in 1) noted in 3 of the 7 infants delivered to mothers treated with diphenylhydantoin suggests that a larger prospective study to evaluate the potential teratogenic influences of this compound may be desirable.
Exploiting Signal Transduction Pathways in Acute Myelogenous Leukemia

Traditional cytotoxic chemotherapy is effective at temporizing AML in the majority of patients but cures a small minority. Thus, enrollment in clinical trials remains a recommended approach for nearly all patients. While signal transduction inhibition is a promising area to advance AML therapy, no agent as monotherapy has demonstrated obvious clinical benefit over traditional cytotoxic chemotherapy. Tipifarnib is perhaps an exception as it is the only signal transduction inhibitor in AML that reproducibly shows clinical benefit using traditional chemotherapy response criteria. Due to toxicity and low response rates, however, the potential advantages of tipifarnib over either traditional cytotoxic chemotherapy or best supportive care alone await confirmation from phase III studies. Available data suggest that combining signal transduction inhibitors with chemotherapy will improve response rates. Clinical trials to test this hypothesis are ongoing using various agents directed against targets such as FLT3, ras/raf/MAPK, mTOR, KIT, and VEGF, but the optimal approach is yet to be defined. Similarly unclear is the benefit of a potent specific kinase inhibitor versus a broad inhibitor of multiple kinases that could prove relevant to leukemia biology. In general, the incomplete understanding of many signal transduction inhibitors' true mechanism of action limits our ability to identify pretreatment predictors of response. To this end, the extensive measures applied to correlate the biologic activity of FLT3 inhibitors with clinical responses are noteworthy and provide useful lessons for clinical trial design and drug development both in leukemia and other cancers.
Re-innervation patterns of chick auditory sensory epithelium after acoustic overstimulation

There is evidence from several studies showing that sensory cells which are destroyed by trauma in the chick auditory epithelium are replaced by new cells. The fate of neurons that innervate the injured and degenerating sensory cells in the lesion, and the temporal sequence of re-innervation of regenerated hair cells are not well understood. This study examined efferent terminals in the chick auditory sensory epithelium following acoustic overstimulation using synapsin-specific immunocytochemistry. Chicks were exposed to an octave band noise (1.5 kHz center frequency, 116 dB SPL, 16 h) and killed on each day from 0 to 9 days postexposure. In the proximal half of control whole mounts of the basilar papillae, synapsin-specific immunoreactivity stained efferent terminals throughout the abneural portion of the sensory epithelium (the short hair cell region). In this area, the labeling appeared as 2-3 bouton-shaped clusters along the abneural edge of each hair cell. After acoustic overstimulation, a lesion was observed at the abneural edge of the papilla where many short hair cells were lost. The center of the lesion was located at 40% distance from the proximal end of each traumatized papilla. Synapsin-specific labeling was not found in sites where expanded supporting cells had replaced missing hair cells. Hair cells which survived the trauma exhibited a shrunken apical area, and synapsin-labeled boutons were observed near their basal domains. New hair cells, which first appeared in the papilla 4 days after trauma, were not initially associated with synapsin-labeled boutons. Regenerated hair cells first displayed contacts with synapsin-labeled boutons 7 days after trauma. Nine days after acoustic overstimulation, most new hair cells appeared to be associated with synapsin-labeled boutons which resembled the normal horseshoe configuration of efferent terminals. The data suggest that direct contact with functional efferent synapses is not necessary for the generation and differentiation of new hair cells.
RESECTION OF A SOLITARY PULMONARY ARTERIOVENOUS MALFORMATION BY VIDEO-ASSISTED THORACIC SURGERY

Pulmonary arteriovenous malformation (PAVM) is an unusual tumor of the lung. It produces direct connections between pulmonary arterial and venous vessels, resulting in right-to-left shunts. Surgical resection offers definitive cure, but transcatheter ablation is used more often because of lower morbidity and mortality rates. The advent of minimally invasive surgical techniques offers the advantage of both treatments: definitive therapy with minimal morbidity and mortality rates. We report a case of this unusual tumor successfully treated with video-assisted thoracoscopic resection (VATS). Clinical summary. A 37-year-old man had visual disturbances and dizziness. He also complained of cough, shortness of breath, and decreased exercise tolerance. A magnetic resonance image of the brain showed an occipital infarct. A chest radiograph showed a right lower lobe density. A computed tomographic (CT) scan of the thorax revealed a 4-cm welldefined mass in the right lower lobe of the lung supplied by large vessels (Fig 1). A tagged red cell perfusion-imaging scan documented a 14% right-to-left shunt (normal, <5%). Echocardiographic bubble study confirmed the shunt (Fig 2). The patient underwent uneventful VATS and wedge resection of the PAVM. Pathologic examination showed a benign PAVM. Pulmonary angiography, tagged red cell scan, and echocardiography were normal after operation (Fig 3). He continues to do well 4 months later. Discussion. PAVMs are unusual tumors of the lung, which occur spontaneously or in diseases such as hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) or hepatic cirrhosis. 1 On CT scan they are diagnosed by their large feeding vessels. 2 They result in right-to-left shunting with dyspnea, fatigue, hypoxemia, and cyanosis. 3 Stroke or cerebral abscess may result from paradoxic embolization. The treatment goals are obliteration of the PAVM to resolve symptoms and prevent complications. Options for treatment include transcatheter embolization or surgical resection. Transcatheter embolization with balloons or stainless steel
Characterizing Vulnerability of Network Interfaces in Embedded Chip Multiprocessors

In Networks-on-Chip (NoC), with ever-increasing design complexity and technology scaling, soft errors have become a key design challenge. In this work, we extend the concept of architectural vulnerability factor (AVF) from the microprocessor domain and propose a network vulnerability factor (NVF) to characterize the susceptibility of Network Interfaces (NIs) to soft errors. For the first time, a detailed characterization of vulnerability is performed on a state-of-the-art AXI-based NI architecture using full system simulation. Our studies reveal that different NI buffers behave quite differently in the presence of transient faults and each buffer can have different inherent tolerance to faults. Our analysis also considers the impact of thermal hotspot mitigation techniques on the NVF estimation.
Effect of sodium doping on the oxygen distribution of Hg-1223 superconductors

Abstract Low-temperature oxygen annealing was performed on Na-doped and undoped Hg-1223 phases. It is argued that Na could perturb the electronic band structure of the material by changing the distribution of oxygen in the Hg–O layer, which then could affect the superconductivity of the material during the annealing process. It has been found that T c can be increased by more than 20 K using an annealing temperature of 300°C for 10 h, while annealing above 350°C leads to loss of superconductivity due to Hg loss. Normal state- ρ tends to decrease with increasing annealing temperatures up to 400°C. In addition, flattening in the normal state- ρ curves of doped samples indicated an increasingly insulating behavior.
Intestinal Ischemic Preconditioning After Ischemia/Reperfusion Injury in Rat Intestine: Profiling Global Gene Expression Patterns

Objective Intestinal ischemia/reperfusion (IR) injury involves activation of inflammatory mediators, mucosal necrosis, ileus, and alteration in a variety of gene products. Ischemic preconditioning (IPC) reduced all the effects of intestinal injury seen in IR. In an effort to investigate the molecular mechanisms responsible for the protective effects afforded by IPC, we sought to characterize the global gene expression pattern in rats subjected to IPC in the setting of IR injury.
SU-E-T-352: Commissioning and Quality Assurance of the First Commercial Hybrid MRI-IMRT System

Purpose: To describe the commissioning process for the first installed commercial MRI‐guided IMRT system (ViewRay, Village of Oakwood, OH) and outline quality assurance methods for this novel treatment modality. Methods: The ViewRay™ System (510(k) pending) consists of a 0.35‐T double‐doughnut MRI coupled with a gantry that houses three Co‐60 sources,each with an activity up to 15,000 Ci (120° apart). IMRT delivery is enabled by doubly‐focused MLCs that serve as the only beam‐shaping collimators for each head, allowing a maximum field size of 27.3 cm2 at the 105‐cm isocenter. MRIimaging is used prior to and during delivery for setup evaluation, adaptive radiotherapy, and gating. The challenges in commissioning as well as periodic and patient‐specific QA arise due to the presence of the magnetic field, unique geometry of this device which is not compatible with many of conventional RT QA devices and techniques, and the penumbra of a 2‐cm wide Co‐60 source. The following devices were used for commissioning and quality assurance tests: radiochromic and radiographic film, ionization chambers (Exradin A12 & A16), Sun Nuclear's IC Profiler (Melbourne, FL), and a water tank. Tests were conducted to evaluate the beam profiles, penumbra, and PDDs. Also, tests to check MLC accuracy and reproducibility were evaluated. Results: Tests were developed to validate geometric performance of the device including a comprehensive set of MLC tests. Due to the low strength of the magnetic field, the mean free path of electrons in the ionization chamber volume is too long to have a noticeable curvature; therefore the magnetic field is not expected to have a noticeable effect on dose measurement. Conclusions: While the presence of the magnetic field limited the choice of QA devices, it was found that satisfactory methods for MRI‐IMRT machine QA exist and can be successfully employed. Drs. Green, Goddu, and Mutic served as scientific consultants for ViewRay, Inc. Dr. Mutic is on the clinical focus group for ViewRay, Inc., and his spouse holds shares in ViewRay, Inc.
White thromboembolism in the hamster cheek pouch after trauma, infection and neoplasia.

White thrombosis and embolism were investigated by cinephotomicroscopy in the transillumined cheek pouch of the hamster in an experimental study of factors which may be involved in the febrile hemolytic syndrome in man, characterized by a finding of generalized platelet thrombosis of arterioles, capillaries and veins at autopsy. Endothelial trauma resulting from vascular occlusion produced platelet thrombosis and embolism. Dicumarol prevented the formation of platelet thrombosis and embolism after trauma. Heparin produced spontaneous platelet emboli and both heparin and dicumarol resulted in a leukocytic thrombosis. Platelet and leukocytic coatings and embolization were photographed during staphylococcus infection and malignant neoplasia. Sludged blood was not found in trauma, infection or malignant neoplasia.
Process reliability analysis

This paper presents a unified approach for obtaining system reliability and availability parameters from block diagram representations of process systems. It starts with computer algorithms for obtaining the minimal paths in a system, then shows how this information can be combined with unit reliability data to obtain the overall system reliability, and the response of system reliability to changes in unit reliability (sensitivities). It then demonstrates how these sensitivities can be used to optimize the system reliability and availability by equipment redundancy. Extension of the methodology to the automated production of system fault trees as well as the mathematical relationship between fault trees and block diagrams are noted.
An ophthalmologist's guide to understanding antibiotic susceptibility and minimum inhibitory concentration data.

Purpose To address the need to establish appropriate evaluation criteria for analyzing in vitro antibiotic susceptibility based on original data. Design In vitro laboratory investigation. Participants Bacterial isolates from patients with conjunctivitis. Main Outcome Measures Minimum inhibitory concentrations (MICs), descriptive statistics, antibiotic susceptibility, potency, and statistical analysis. Methods Minimum inhibitory concentrations were determined for 80 bacterial conjunctivitis isolates to moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin. Using the MIC values, descriptive statistics (median, MIC 50 , MIC 90 , mode, range), antibiotic susceptibility, and potency of each antibiotic were calculated for each bacterial group. The data were analyzed statistically using appropriate randomization and nonparametric tests. Results The descriptive statistics of gram-positive bacteria ( Staphylococcus aureus, Streptococcus pneumoniae ) followed a consistent trend where the median, MIC 50, MIC 90 , and mode demonstrated the lowest values, in all instances, for moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin. The descriptive statistics for Haemophilus species (the predominant gram-negative bacteria implicated in conjunctivitis) did not describe any consistent trend. In contrast, antibiotic susceptibility testing did not demonstrate any advantage among the 5 fluorquinolones tested, except for moxifloxacin in the S. aureus fluoroquinolone-resistant group. Potency studies indicated that moxifloxacin and gatifloxacin were the most potent for gram-positive bacteria, whereas gatifloxacin and ciprofloxacin were the most potent for Haemophilus species. Conclusion In the absence of human clinical trial data to guide care, in vitro susceptibility data should be analyzed with a set of descriptive statistics along with a nonparametric statistical analysis. No single parameter or test should be relied upon in all instances to demonstrate the in vitro superiority of one antibiotic over another. In this study, fourth-generation fluoroquinolones did have some potency advantages over second-generation fluoroquinolones against gram-positive conjunctival bacterial isolates, but not for Haemophilus isolates.
Metabotropic Glutamate Receptors Drive Global Persistent Inhibition in the Visual Thalamus

Within the dorsal lateral geniculate nucleus (dLGN) of the thalamus, retinal ganglion cell (RGC) projections excite thalamocortical (TC) cells that in turn relay visual information to the cortex. Local interneurons in the dLGN regulate the output of TC cells by releasing GABA from their axonal boutons and specialized dendritic spines. Here we examine the functional role of these highly specialized interneurons and how they inhibit TC cells in mouse brain slices. It was widely thought that activation of metabotropic glutamate receptor type 5 (mGluR5) on interneuron spines leads to local GABA release restricted to sites receiving active RGC inputs. We reexamined experiments that supported this view, and found that in the presence of TTX, mGluR5 agonists evoked GABA release that could instead be explained by interneuron depolarization and widespread intracellular calcium increases. We also examined GABA release evoked by RGC activation and found that high-frequency stimulation induces a long-lasting subthreshold afterdepolarization, persistent firing, or prolonged plateau potentials in interneurons and evokes sustained GABA release. mGluR5 antagonists virtually eliminated sustained spiking and the resulting widespread calcium-signals, and reduced inhibition by >50%. The remaining inhibition appeared to be mediated by a fraction of interneurons in which plateau potentials produced large and widespread calcium increases. Local calcium signals required for local GABA release were not observed. These findings indicate that, contrary to the previous view, RGC activation does not simply evoke localized GABA release by activating mGluR5, rather, synaptic activation of mGluR5 acts primarily by depolarizing interneurons and evoking widespread dendritic GABA release.
Evaluation and treatment of osetoporotic distal radius fracture in the elderly patient

Distal radius fractures are an increasingly prevalent upper extremity injury, especially among elderly patients. While treatment guidelines for the acute bony injury have been well documented, treatment of the underlying metabolic bone disease has been less commonly discussed in the orthopedic literature. Distal radius fractures in the elderly patient should be considered a sentinel event for injuries associated with greater morbidity and mortality, such as hip fracture. Management of fracture-related factors, such as osteoporosis and increased fall risk following a distal radius fracture, may prevent the mortality and morbidity of future injuries. This review highlights both the fracture-specific and medical goals of treatment in the elderly patient with a distal radius fracture.
The history of the germ cells in the domestic fowl

Material of the domestic fowl of appropriate ages, ranging from twelve hours' incubation to the adult bird, was prepared for the purpose of studying the production and development of the germ cells. The primordial germ cells arise in the extra-embryonic region anterior to the head fold in the region of the zone of junction during the primitive-streak stage. These germ cells migrate, through the blood stream, to the region of the future gonad, where they develop into the definitive germ plasm. There is no widespread degeneration of the primordial germ cells after their arrival in the gonadal region, nor is there any widespread transformation of somatic cells into definitive germ cells.
Predictive Performance of a Summer Microhabitat Model for the Threatened Niangua Darter, Etheostoma nianguae

ABSTRACT The Niangua darter (Etheostoma nianguae) is a threatened stream fish endemic to the Osage River basin in southcentral Missouri, USA. Knowledge of Niangua darter habitat relationships has been identified as an important component of recovery. We assessed the predictive performance of a previously developed summer microhabitat model for this species. The original model was developed with multiple logistic regression using Little Niangua River data, with water depth and substrate particle size serving as predictors of darter presence or absence. New data were collected in Little Niangua River and Maries River at microhabitats occupied (n = 16) and unoccupied (n = 72) by the darter. About one in four microhabitats was misclassified by the model and values of Cohen's kappa generally did not exceed 0.40, indicating that the model's performance could only be rated as fair. Performance was slightly better in Little Niangua River than in Maries River, with a substantial number of false positives in the la...
Dabigatran in the setting of catheter ablation of atrial fibrillation: the road ahead

To the Editor We read with interest the study by Providencia et al 1 which demonstrated that dabigatran had a similar efficacy and safety profile as warfarin in the setting of catheter ablation (CA) of atrial fibrillation (AF). These findings concur with two other meta-analyses on the same topic (including one from our group), which have been …
Comments on median split procedures for scoring androgyny measures

With Bem's shift from advocacy of t-difference to median split procedures for scoring the Bem Sex Role Inventory (BSRI), all the major androgyny measures are now scored according to median splits. These comments are directed to ward differences in interpretation of the scale as a result of varying scoring methods, and the psychometric problems introduced by median split procedures.
Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats.

An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to determine the effect of increased aortic stiffness on PP and endothelial dysfunction as prec...
U.S. Department of Energy Wind Energy Research Program for low wind speed technology of the future

The United States is facing many challenges as it prepares to meet its energy needs during the twenty-first century. Electricity supply crises in California, fluctuating natural gas and gasoline prices, heightened concerns about the security of the domestic energy infrastructure and of foreign sources of supply, and uncertainties about the benefits of restructuring are all elements of the energy policy challenge. In May 2001, the President’s National Energy Policy Development Group released a set of recommendations that have become the cornerstone of U.S. Energy Policy under the George W. Bush Administration @1#. Pursuant to the release of the National Energy Policy recommendations, Secretary of Energy, Spencer Abraham, described the three priorities of the Department of Energy as:
Analysis of circulation of neuronal activity in the waking cortex.

Abstract It is well known that the rhythmic activity of the cerebral cortex is closely associated with a highly organized circulation of neuronal impulses through the networks in which the activity develops. The present study has attempted to determine by quantitative methods, the consistency of this circulation and of its association with the cortical waves, over relatively long periods. Cortical gross waves and neuronal activity have been recorded by means of arrays of extracellular microelectrodes, in freely moving cats as well as in cats immobilized with flaxedil. Autocorrelations have been performed on trains of rhythmic waves and on associated clusters of action potentials; cross-correlations and multiple correlations have been performed between waves and action potentials and between action potentials generated by different groups of neurons. It has been found that the rhythmicity of the waves, the rhythmicity of the associated clusters of action potentials, the time and phase relations between them, and the circulation of neuronal activity through the networks, remain highly consistent over periods as long as two hours.
Hybrid Capture 2 is as Effective as PCR Testing for High Risk Human Papillomavirus in Head and Neck Cancers

High-risk human papillomavirus (HPV) infection is a common cause of oropharyngeal squamous cell carcinoma, especially in young male nonsmokers. Accurately diagnosing HPV-associated oral cancers is important, because they have a better prognosis and may be treated differently than smoking-related oral carcinomas. Various methods have been validated to test for high-risk HPV in cervical tissue samples, and they are in routine clinical use to detect dysplasia before it progresses to invasive disease. Similarly, future screening for HPV-mediated oropharyngeal dysplasia may identify patients before it progresses. Our objective was to compare 4 of these methods in a retrospective series of 87 oral and oropharyngeal squamous cell carcinomas that had archived fresh-frozen and paraffin-embedded tissue for evaluation. Patient age, sex, smoking history, and tumor location were also recorded. DNA prepared from fresh-frozen tissue was tested for HPV genotypes by multiplex polymerase chain reaction analysis, and high-risk HPV screening was carried out using Hybrid Capture 2 and Cervista. Histologic sections were immunostained for p16. HPV-positive outcome was defined as agreement between at least 2 of the 3 genetic tests and used for χ analysis and calculations of diagnostic predictive value. As expected, high-risk HPV-positive oral cancers were most common in the tonsil and base of the tongue (oropharynx) of younger male (55 vs. 65 y) (P=0.0002) nonsmokers (P=0.01). Most positive cases were HPV16 (33/36, 92%). Hybrid Capture 2 and Cervista were as sensitive as polymerase chain reaction and had fewer false positives than p16 immunohistochemical staining.
Molecular cloning of a rac family protein kinase and identification of a serine/threonine protein kinase gene family of Entamoeba histolytica.

Abstract Eleven Entamoeba histolytica protein-serine/threonine-kinase gene segments were identified using the polymerase chain reaction (PCR) and degenerate oligonucleotide primers to conserved amino acids in subdomains VI and VIII of the catalytic domain of protein-serine/threonine kinases. These ameba gene segments were homologous to myosin light chain kinases, protein kinase C, phosphorylase b kinase, and kinases that regulate glucose repression in yeast and cell growth in mammalian cells. One of these PCR products, which was homologous to the Dictyostelium discoideum protein kinase 2, was used to identify a full-length protein-serine/threonine-kinase gene ( Eh racl ) from an E. histolytica genomic library. The open reading frame of Eh racl was 409 amino acids long (encoding a 47-kDa protein) and included an amino terminal segment containing 87 mostly charged and polar amino acids and a 322-amino acid carboxyl terminal segment containing the catalytic domain. The catalytic domain of Eh racl was homologous to the rac family of protein-serine/threonine-kinases, which are related to cAMP-dependent protein kinases and protein kinase Cs. Southern blots of ameba DNA showed that the Eh racl gene was present as a single copy in all strains tested, however pathogenic amebae expressed four times more Eh racl mRNAs than did nonpathogenic amebae. These studies suggest that E. histolytica , a primitive unicellular eukaryote, has a complex protein kinase family.
Effect of circulatory mechanics on hydrostatic forces producing pulmonary edema

An appreciation of the mechanical basis of pulmonary edema formation and the role of pleural pressure in modifying cardiac performance is important for managing patients with pulmonary edema. The role of hydrostatic forces in the development of lung edema may have magnified influence in acute lung injury and pulmonary edema formation. Although there is much to be learned, an understanding of the determinants of pulmonary blood volume is important to understand the hydrostatic forces that promote transvascular fluid filtration. Pulmonary blood volume is determined by the interaction of the compliant properties of the pulmonary circulation, downstream resistances, and the interaction of surface pressure, left atrial pressure, and pulmonary blood flow. Both cardiac output and left atrial pressure have important effects on lung, blood volume, and edema formation, Increasing pleural pressure will tend to reduce edema formation through a reduction in both cardiac output and pulmonary venous pressures. Cardiac output reduction will predominate when cardiac contractility is good, and left strial pressure reduction will predominate when contractility is poor. Overinflation of the lung, however, may lead to a net increase in pulmonary blood volume and obviate the beneficial effect of increasing pleural pressure.
Using an open-loop inverse control strategy to regulate CA1 nonlinear dynamics for an in vitro hippocampal prosthesis model

A modeling-control paradigm to regulate output of the hippocampus (CA1) for a hippocampal neuroprosthesis was developed and validated using an in vitro slice preparation. Our previous study has shown that the VLSI implementation of a CA3 nonlinear dynamic model can functionally replace the CA3 subregion of the hippocampal slice. The propagation of temporal patterns of activity from DG→VLSI→CA1 reproduces the activity observed experimentally in the biological DG→CA3→CA1 circuit. In this project, we incorporate an open-loop controller to optimize the output (CA1) response. Specifically, we seek to optimize the stimulation signal to CA1 using a predictive dentate gyrus (DG)-CA1 nonlinear model (i.e., DG-CA1 trajectory model) and a CA1 input-output model (i.e., CA1 plant model), such that the ultimate CA1 response (i.e., desired output) can be first predicted by the DG-CA1 trajectory model and then transformed to the desired stimulation intensity through the CA1 inverse plant model. Laguerre-Volterra kernel model for random - interval, graded - input, contemporaneous – graded -output system is formulated and applied to build the DG-CA1 trajectory model and the CA1 plant model. The inverse model to transform desired output to input is also derived and validated. We validated the paradigm in hippocampal slices, and results showed the CA1 response evoked by the controlled stimulation signal reinstated the CA1 response evoked by the trisynaptic pathway.
Neuroscience: Spikes timed through inhibition.

Purkinje cells in the brain region known as the cerebellum act by inhibiting their target neurons. A paper in this issue provides an explanation for how this inhibition might be used to control the timing of action potentials. But experts are not equally convinced about the functional relevance of this finding. See Letter p.502 The sole output of the cerebellar cortex consists of Purkinje cells, which are GABAergic, and hence expected to inhibit their targets, the cerebellar nuclei. However, an inverse relationship in firing rate is not always observed between Purkinje and nuclear cells. Abigail Person and Indira Raman now propose that through a combination of kinetics, intrinsic firing rates and convergence of projections, synchronous activation of a small number of Purkinje cells can transmit information about spike timing. This work suggests a role for synchronous activity previously reported in cerebellar cortex, and demonstrates more generally how synchronous inhibition could be used to generate phase-locked activity.
Oral delivery of G protein-coupled receptor modulators: An explanation for the observed class difference

G protein-coupled receptors (GPCRs) represent important targets for drug intervention. However, analysis of GPCR modulator drugs exhibits an important class difference, with many drugs available against aminergic GPCR targets, but relatively few against non-aminergic targets. The reason for this is that commonly drugs mimic the physicochemistry of the receptor ligand. Aminergic ligands generally exhibit physicochemical properties (molecular weight, lipophilicity and hydrogen bonding potential) that are consistent with extensive oral absorption. In contrast, non-aminergic ligands generally exhibit physicochemical properties that are at odds with oral delivery. Thus, combining required potency versus the receptor, with oral delivery potential is a significant challenge, and drug discovery becomes a question of finding the exceptional compound that lies at the edge of ADME space.
Prediction of ozone concentration from sulphur and nitrogen dioxides in ambient air: part 1 (regression analyses)

Computer modeling and simulation, of ambient air pollutants, for predictive purposes are somewhat incomplete. Based on real time observations of O3, SO2 and NO2 concentrations in ambient air and subsequent linear analyses of these data, regression equations have been obtained that are suitable for predicting concentrations of these ambient air pollutants. Ozone concentration can best be predicted from the combined concentrations of SO2 and NO2.