cssi/SciSciGPT-SciSciNet huggingface dataset:
Cytolytic antibodies to murine lymphomas elicited by immunization with allogenic and syngenic tumors

Abstract C57BL/6 mice immunized with allogenic L#2 tumor cells or syngenic EL-4 tumor cells produced lytic antibodies directed against cell-surface antigens present on EL-4 tumor cells but absent from normal C57BL/6 tissues. Such immunized C57BL mice also exhibited prolonged survival after challenge with syngenic EL-4 tumor cells.
P01-243 Correlation between depression and interferon-beta therapy in patients with multiple sclerosis: A systematic review

Introduction Depression is the most frequent psychiatric disorder encountered in patients with Multiple Sclerosis (MS), with a life-time prevalence of approximately 50%. INF-beta (INF-β) shows beneficial effect on the course of MS. Although it has been suggested that interferons may be associated to depression, the validity and the nature of this relationship remain unclear regarding INF-β. The objective of this study is to review the scientific literature in order to elucidate the relationship between depression and INF-β therapy. Methods This systematic review was based on Medline, Embase and, PsycLIT literature searches (through January 2005), supplemented by bibliographical citations in identified papers. Results The majority of studies ruled out a correlation between INF-β1a/1b and depression in MS patients. However, patients with a recent history of depression may be at higher risk for depression particularly in the early phase of treatment (first 6 months), even if they are not depressed at the initiation of medication. There is an association between depressive symptoms and discontinuation of INF therapy but INF-β does not seem to be associated with suicide attempts. Treating patient-reported depression increases adherence to treatment. Conclusions Clinicians should not refrain from including patients with MS in INF-β treatment programs, even those with depression in the past or at the present time. Screening, monitoring, and early antidepressant treatment is necessary to optimize IFN therapy for the majority of patients with MS.
CO2-Protected Amine Formation from Nitrile and Imine Hydrogenation in Gas-Expanded Liquids

Gas-expanded liquids are tunable media for reaction and separation. We report that gas-expanded liquids under CO2 pressure are unique media for amine formation and separation. In the heterogeneous hydrogenation of benzonitrile and phenylacetonitrile with NiCl2/NaBH4 in CO2-expanded ethanol, the primary amines are protected by CO2 so that the yield of the primary amines is greatly increased and the production of the secondary amines is effectively suppressed. In the homogeneous hydrogenation of benzonitrile and phenylacetonitrile with RhH(P-i-Pr3)3 and benzophenone imine with Rh(1,5-C8H12){P(C6H5)3}2]PF6 in CO2-expanded tetrahydrofuran, the primary amines are separated in situ in the form of solid carbamic acids and/or ammonium carbamates with increased yield while the catalyst remains in the solution. These results demonstrate the potential for using modest pressures of CO2 to facilitate reactions as well as to separate products.
The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender.

Abstract Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7±0.7; M 2.8±0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F 0.3±0.1; M 0.2±0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2±0.02; M 0.2±0.02; Ccr: F 1.2±0.1; M 1.6±0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p
Pharmacological studies of a novel prolyl endopeptidase inhibitor, JTP-4819, in rats with middle cerebral artery occlusion

We studied behavioral and pharmacological effects of a novel prolyl endopeptidase inhibitor, (S)-2-[[(S-2-(hydroxyacetyl)-1-pyrrolidiny]carbonyl]-N-(phenylmethyl)-1-pyrrolidine-carboxamide (JTP-4819), in rats with middle cerebral artery occlusion. Administration of JTP-4819 (0.1 and 1 mg/kg p.o. for 7 days) significantly prolonged passive avoidance latency, while the latency of rats with middle cerebral artery occlusion receiving the vehicle was significantly shorter than that of sham-operated rats. The prolonged escape latency in the Morris water maze task in rats with middle cerebral artery occlusion was also significantly reduced by administration of JTP-4819 (0.3 and 1 mg/kg p.o.). Interestingly, administration of JTP-4819 (0.3–3 mg/kg p.o. for 15 days) restored the decreased cortical thyrotropin-releasing hormone (TRH)-like immunoreactivity content of rats with middle cerebral artery occlusion but did not affect the cortical and hippocampal substance P- or arginine vasopressin-like immunoreactivity content. These results suggest that JTP-4819 ameliorates memory impairment due to middle cerebral artery occlusion by restoring the cortical TRH content.
Identification of mycobacteria based on spectroscopic analyses of mycolic acid profiles.

This report examines lipophilic extracts containing mycolic acids isolated from tuberculosis (MTB) and non-tuberculosis (NTM) mycobacterial strains using chromatography, mass spectrometry (MS), nuclear magnetic resonance (NMR), and Raman spectroscopy. Gas chromatography-MS was used to identify major fatty acid mycolate components, while proton NMR confirmed the presence of characteristic cis- and trans-cyclopropane rings within different mycolic acid sub-types. Surface-enhanced Raman (SERS) spectra were obtained from the mycolic acids extracted from the bacterial cell envelopes of the MTB or NTM mycobacterial species. The Raman spectral profiles were used to develop a classification method based on chemometrics for identification of the mycobacterial species. Multivariate statistical analysis methods, including principal component analysis (PCA), hierarchical cluster analysis (HCA), and partial least squares discriminant analysis (PLS-DA) of the SERS spectra enabled differentiation of NTM mycobacteria from one another with 100% accuracy. These methods are also sensitive enough to differentiate clinically-isolated MTB strains that differed only by the presence or absence of a single extracytoplasmic sigma factor with 83–100% sensitivity and 80–100% specificity. The current work is the first report on discrimination of mycobacteria strains based on the SERS spectra of the constituent mycolic acids in lipophilic extracts. These results suggest that SERS can be used as an accurate and sensitive method for species and strain discrimination in mycobacteria.
B Cell Precursors in Senescent Mice Exhibit Decreased Mitotic Recruitment, Increased Apoptosis, and Altered Expression of Bcl-2 Family Members

INTRODUCTION. Senescence in inbred strains of mice affects lymphopoiesis within the bone marrow (1,2). In the development of B lineage cells, old age is associated with a significant decline in pre-B cells. This could result from increased cell death (apoptosis) and/or decreased mitotic activity. We have determined the mitotic activity of B cell precursors from aged mice ex vivo and the kinetics of aged pro-B cell proliferation in vitro at the single-cell level in response to IL-7. Furthermore, we have assessed susceptibility of ex vivo aged B cell precursors to apoptosis and expression of the survival molecules Bcl-xL and Bcl-2 and the proapoptotic molecule Baxa in vitro.
Surface energy anisotropy of tungsten

Abstract Field-ion microscopy was used to study the faceting behavior and/or surface energy anisotropy of tungsten in vacuum and in hydrogen. In vacuum below 1700 K the activation energy for {110} facet growth agreed with values previously reported for surface diffusion on tungsten. The observed anisotropy values at 0.5 Tm, where Tm is the absolute melting temperature of tungsten (∼3680 K), were different from those previously reported at higher temperatures and more nearly agreed with broken bond calculations based on Mie potential using m = 5, n = 8, and a 1.5% lattice expansion. Hydrogen appeared to have a negligible effect on surface energy anisotropy, but did preferentially increase surface diffusion rates on {310} regions.
Molecular characterisation of the tyrosine tRNA genes of yeast

MANY of the tRNA genes of yeast are observable genetically as nonsense suppressors1. In particular, the set of unlinked suppressor loci SUP2 to SUP8 and SUP11 have been shown to insert tyrosine at nonsense codons in yeast iso-1-cytochrome c2,3. Direct biochemical evidence for the presence of suppressor tRNA in yeast strains bearing these suppressor genes has been obtained using in vitro translation systems4,5 and by the demonstration that a new minor tyrosine tRNA species with a suppressor anti-codon appears in a SUP5 strain6. Although these findings suggest that there are eight different loci in yeast which code for tRNAtyr, only a single nucleotide sequence has been observed for tyrosine tRNA in wild-type yeast strains7. Thus it seems that all eight genes may share a common base sequence, at least in their structural regions. Because the yeast tRNAtyr SUP genes occupy known positions on the genetic map8 and are complementary to a well characterised RNA molecule they are attractive candidates for molecular analysis. As a first step, we have labelled yeast tRNAtyr with 125I and have hybridised this probe to electrophoretically fractionated Eco RI fragments of yeast DNA; eight Eco RI fragments of different sizes hybridise to tRNAt yr.
Community characteristics and policy implications: Some exploratory findings about two categories of municipal police chiefs

Abstract There is a great deal of evidence that would indicate that the characteristics of a community are related to public policy decisions. This investigation examines and compares the community and departmental characteristics of cities that employ college- educated chiefs of police by means of lateral entry with a group of matched communities that do not. It is hypothesized that the particular characteristics of cities in terms of general socio- economic status (SES) characteristics will play an important role in the style of law enforcement that prevails. By uncovering these characteristics, some generalized assumptions can be made about what citizen expectations of police managers and police department policies might be.
Isolation and Characterization of a Neutral Imino-semiquinone Radical

The neutral imino-semiquinone, 4,6-di-tert-butyl-2-tert-butylimino-semiquinone (isqH•), can be prepared by a conproportionation of the parent aminophenol and iminoquinone compounds. The neutral radical species has been characterized in the solid state by X-ray diffraction and in solution by EPR and UV−vis absorption spectroscopy. The stability of the open-shell radical is derived from the basicity of the tert-butylimino group and the intramolecular hydrogen bond.
The effect of typical and atypical antipsychotic drugs on the stimulation of phosphoinositide hydrolysis produced by the 5-HT3 receptor agonist 2-methyl-serotonin.

Abstract The atypical antipsychotic drug clozapine (CLOZ) and a structurally related compound RMI 81,582 (RMI) dose-dependently inhibited the stimulation of phosphoinositide hydrolysis induced by the 5-HT 3 receptor agonist 2-methyl-serotonin in the rat fronto-cingulate and entorhinal cortices. The antagonism of 2-methyl-serotonin's stimulation of phosphoinositide hydrolysis by CLOZ and RMI was comparable to that observed with 5-HT 3 antagonists such as granisetron, ondansetron, ICS 205–930 and zacopride. By contrast, the typical antipsychotic drugs haloperidol (HAL) and chlorpromazine (CPZ) did not antagonize the stimulation of phosphoinositide hydrolysis induced by 2-methyl-serotonin. The 5-HT 3 receptor antagonizing effect of CLOZ and RMI may contribute to the ‘atypical’ pharmacological profile of these antipsychotic drugs.
Endothelium as a transducing surface.

Abstract Endothelial cells responses to a variety of agonists include release of endothelium dependent vasodilators, such as endothelium dependent relaxing factor (EDRF) and prostacyclin (PGI 2 ). These substances act on vascular smooth muscle to cause relaxation and also have potent anti-aggregatory effects on platelets. A study of the mechanisms of signal transduction involved in these processes was undertaken. An investigation of intracellular calcium using FURA-2 and INDO-1 loaded endothelial cells shows transient elevation in response to vasodilator agonists. The calcium content of endothelial cells calculated using 45 Ca flux techniques is increased in response to bradykinin and thrombin. Receptor activation leads to increased phosphoinositide turnover in endothelial cells and activates protein kinase C, the latter may be involved in feedback regulation. Patch clamp studies have demonstrated receptor-operated ionic channels in the endothelial cell membrane. Thus, intracellular calcium concentration is elevated in response to receptor activation, both as a result of liberation of calcium from intracellular stores and calcium entry from extracellular sources. Endothelial cells also respond to particulate stimuli. They can selectively bind and phagocytize bacteria. Phagocytosis leads to generation of superoxide aionin, a process which also seems to be controlled by elevation of intracellular calcium and activation of protein kinase C. In addition phagocytosis activates endothelial cells resulting in increased migration, division and further phagocytosis. All in all, the plethora of different endothelial responses to a variety of stimuli suggests a complex and multipotent cell type. However, the conservatism of the mechanisms of signal transduction may indicate that endothelial cells do not respond to one signal with one response but that “activation” may occur in response to a variety of stimuli.
Spry1 as a novel regulator of erythropoiesis, EPO/EPOR target, and suppressor of JAK2

Sprouty proteins are established modifiers of receptor tyrosine kinase (RTK) signaling and play important roles in vasculogenesis, bone morphogenesis, and renal uteric branching. Little is understood, however, concerning possible roles for these molecular adaptors during hematopoiesis. Within erythroid lineage, Spry1 was observed to be selectively and highly expressed at CFU-e to erythroblast stages. In analyses of possible functional roles, an Mx1-Cre approach was applied to conditionally delete Spry1. At steady state, Spry1 deletion selectively perturbed erythroid development and led to reticulocytosis plus heightened splenic erythropoiesis. When challenged by hemolysis, Spry1-null mice exhibited worsened anemia and delayed recovery. During short-term marrow transplantation, Spry1-null donor marrow also failed to efficiently rescue the erythron. In each anemia model, however, hyperexpansion of erythroid progenitors was observed. Spry function depends on phosphorylation of a conserved N-terminal PY motif. Through an LC-MS/MS approach, Spry1 was discovered to be regulated via the erythropoietin receptor (EPOR), with marked EPO-induced Spry1-PY53 phosphorylation observed. When EPOR signaling pathways were analyzed within Spry1-deficient erythroid progenitors, hyperactivation of not only Erk1,2 but also Jak2 was observed. Studies implicate Spry1 as a novel regulator of erythropoiesis during anemia, transducer of EPOR signals, and candidate suppressor of Jak2 activity.
Etching of Polymeric Surfaces: A Review

Abstract The selective etching of polymeric surfaces has been of considerable interest to many polymer scientists and engineers. Some prime concerns of selective etching have been to increase the roughness of polymeric surfaces, change the surface chemical constitution, degrade or dissolve low molecular weights which migrate to the surface, and relieve residual surface stresses. Every polymeric surface, thermoplastic or thermoset, amorphous or crystalline, has, to some extent, different morphology from the bulk. Etching can considerably change the morphology and chemical properties of polymeric surfaces. An important commercial example is the etching of polymers prior to the subsequent metal plating [35, 74]. The adhesion and durability of the metal plate are greatly influenced by the condition of the polymeric surface. The increased surface area gives rise to a larger density of sites for the subsequent metal deposition. In many cases the chemical reactivity of etched surfaces is also increased upon etch...
Kalai's Squeezed Spheres Are Shellable

Kalai constructs a large collection of simplicial spheres to show that there is a substantial gap between the numbers of simplicial polytopes and of simplicial spheres. We prove here that Kalai's spheres are shellable.
Defensive behavior of the rat in a shock-prod situation: Effects of the subject’s location preference

Experiment 1 investigated the proposition that rats cover the source of aversive stimulation with the bedding material available to them and sought to determine whether familiarization with this material would affect burying. The results indicated that rats are no more likely to cover an aversive object than they are not to cover it, although they collect a considerable amount of bedding material in the area surrounding the aversive object. Experiment 2 demonstrated that the rat’s defensive “burying” toward an aversive object is affected by the subject’s predisposition to displace material toward the front side of the apparatus. Some theoretical complexities involved in considering the act of “burying” toward an aversive object as a defensive behavior are discussed.
Abnormalities in Cortical Bone, Trabecular Plates, and Stiffness in Postmenopausal Women Treated With Glucocorticoids

Context: The mechanisms by which glucocorticoids (GCs) increase skeletal fragility are not well understood. Objective: The objective of the study was to evaluate the microarchitecture, trabecular morphology, and biomechanical properties of bone in postmenopausal women treated with GCs. Design: This was a case-control study. Setting: The study was conducted at a university hospital outpatient facility. Patients: Postmenopausal women treated with oral GCs for longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated in the study. Main Outcome Measures: Areal bone mineral density aBMD (BMD) by dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia were also measured. Whole-bone stiffness was estimated by finite element analysis. A novel technique, individual trabecula segmentation, was used to evaluate trabecular type (as plate or rod), ori...
Advantages of a targeted approach in minimally invasive radioguided parathyroidectomy surgery for primary hyperparathyroidism.

Objective: In a large series of patients, we associated the need for preoperative parathyroid hormone (PTH) and calcium levels as a vital component in our approach to the radioguided minimally invasive parathyroidectomy (MIRP) procedure. Our objective was to determine whether these preoperative levels indeed complemented the procedure. Our study also included a postoperative assessment of excised gland volume and length of operation. Study Design: This was a prospective cohort study. Methods: One hundred seventy-three patients with primary hyperparathyroidism enrolled in our radioguided MIRP protocol. Patients were divided into groups based on the results of sestamibi scans. Comparisons were made between these results and the assessed preoperative PTH and calcium levels and the postoperative excised gland volume and length of operation. Results: PTH and calcium levels did not statistically relate with the likelihood of having a “positive,” “equivocal,” or “negative” sestamibi scan, but the volume of excised gland was significantly different among the three groups (P < .01). There was no significant difference between positive and equivocal scans (P = .40). Operative time was significantly different between positive and equivocal scans (P < .01), positive and negative scans (P < .01), and equivocal and negative scans (P < .01). Conclusions: Routine preoperative PTH and calcium levels are necessary for the biologic diagnosis of hyperparathyroidism, but they do not appear to relate to the outcome of a sestamibi scan and therefore do not complement the radioguided MIRP procedure. Because the size of the affected gland, however, did correlate with a positive sestamibi scan, we conclude that as the volume of the gland increases, so does the likelihood of a successfully chosen minimally invasive surgical approach.
Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats

Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABA(A) antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 microM) into the posterior VTA increased extracellular dopamine levels locally (80% above baseline) and in the ACB shell and core (70% above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30% above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 microM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABA(A) receptor-mediated tonic inhibition.
A statistical mechanical model of aqueous two-phase systems

Abstract A predictive model for the phase diagrams of two-polymer aqueous two-phase systems has been developed from the solution theory of Hill (1957, 1959). This theory gives chemical potentials in terms of isobaric isothermal osmotic virial coefficients representing polymer pair interactions. We have developed predictive expressions for the dependence of these coefficients on molecular weight and polydispersity from Renormalization Group theory. For a two-polymer system our model contains three monomer interaction coefficients (b ij ), one for each polymer pair, and two scaling exponents (ν i ), one for each polymer. Phase diagrams for four different systems have been calculated from our model at ambient conditions and shown to agree with experiment within 1–2% in polymer weight fraction. Two of the systems contain polyethylene glycol and dextran with molecular weights from 4000 to 280,000. The other two systems contain methylcellulose and dextran with molecular weights from 30,000 to 280,000.
Ice Age Winds: An Aquaplanet Model

Abstract Factors controlling the position and strength of the surface winds during the Last Glacial Maximum (LGM) are examined using a global, multilevel, moist, atmospheric model. The idealized aquaplanet model is bounded below by a prescribed axisymmetric temperature distribution that corresponds to an ocean-covered surface. Various forms of this distribution are used to examine the influence of changes in the surface cooling and baroclinicity rates. The model omits seasonal variations. Increasing the cooling lowers the tropopause and greatly reduces the moist convection in the Tropics, thereby causing a weakening and equatorward contraction of the Hadley cell. Such a cooling also weakens the surface westerlies and shifts the peak westerly stress equatorward. An extra surface baroclinicity in midlatitudes—implicitly associated with an increase in the polar sea ice—also shifts the peak westerly stress equatorward, but strengthens the surface westerlies. Thus, calculations with combined surface cooling an...
POLYMYXIN B AND HEART MUSCLE

The effects of the polypeptide antibiotic, polymyxin B, on myocardial contractility were studied in the isolated rat heart muscle. Five different doses of polymyxin B were tested. There were no changes in contractility with doses ranging from the clinical therapeutic value to three times greater. There was an initial increase and then depression with a dose six times greater than the therapeutic dose. There was no direct competitive interaction between polymyxin B and halothane or Ca2+. This suggests that polymyxin B does not depress the myocardium in clinical doses and does not interfere with Ca2+ influx at the myocardial cell membrane.
Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma.

BACKGROUND: The outcome of patients with systemic diffuse large B-cell lymphoma (DLBCL) had improved over the past decade with the addition of monoclonal antibody therapy. Unfortunately, approximately 5% of these patients still developed a secondary central nervous system (CNS) recurrence followed invariably by rapid death. This rate is substantially increased in patients with certain high-risk features. Although prophylaxis against CNS recurrence with either intrathecal or intravenous methotrexate is commonly used for such patients, to the authors' knowledge, there is no standard of care. Retrospectively evaluated was the role of high-dose systemic methotrexate combined with standard cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) chemotherapy to decrease CNS recurrence in high-risk patients. METHODS: A total of 65 patients with DLBCL and CNS risk factors were identified at the study institution between 2000 and 2008 who received intravenous methotrexate as CNS prophylaxis concurrent with standard systemic therapy with curative intent. CNS recurrence rate, progression-free survival, and overall survival were calculated. RESULTS: Patients received a median of 3 cycles of methotrexate at a dose of 3.5 gm/m2 with leucovorin rescue. The complete response rate was 86%, with 6% partial responses. At a median follow-up of 33 months, there were only 2 CNS recurrences (3%) in this high-risk population. The 3-year progression-free and overall survival rates were 76% and 78%, respectively. Complications associated with methotrexate therapy included transient renal dysfunction in 7 patients and a delay in systemic chemotherapy in 8 patients. CONCLUSIONS: Intravenous methotrexate can be safely administered concurrently with R-CHOP and is associated with a low risk of CNS recurrence in high-risk patients. Cancer 2010. © 2010 American Cancer Society.
Particle modelling of the cavity problem for liquids

Abstract The engineering lumped mass technique is applied in the large to simulate the two-dimensional cavity problem for liquids. We exhibit primary vortex and turbulent flows. The modelling is an extension of molecular mechanics modelling.
A Novel 3-Year Longitudinal Pilot Study of Medical Students’ Acquisition and Retention of Screening Eye Examination Skills

Objective To assess the acquisition and retention of screening ophthalmic clinical skills over 3 years of medical school. Design Observational, longitudinal, multiple skills measures. Participants All 96 students enrolled in a single graduating class at a public medical school in California. Methods Immediately after the second-year ophthalmic clinical skills course, all students were evaluated by their preceptors and self-rated for competence in defined skills. Follow-up assessments were done during 2 required third-year clerkships without additional formal ophthalmic clinical exposure. Three complete history and physical examination chart notes routinely submitted for course grading in third-year clerkships were selected randomly for each student by clerkship directors in family medicine and internal medicine, masked for identity, and then scored for appropriateness. Funduscopic skills were assessed objectively with a simulator in the third-year Clinical Performance Examination. During a fourth-year 4-day ophthalmology clerkship, students were trained and reassessed with the same simulator. Just before graduation, a self-assessment questionnaire was administered to the entire class. Main Outcomes Measures Twelve skills were assessed: ability to evaluate visual acuity (VA); pupils; extraocular muscles; confrontation fields; lids; cornea; conjunctiva/sclera; anterior chamber depth; and, funduscopically, the disc, macula, vessels, and retina. Results Faculty rated 88% to 90% of students as able to assess acuity, pupils, ductions, and fields, and 72% to 82% as able to visualize various parts of the fundus. Seventy-six percent of students felt comfortable after funduscopic training. In 364 analyzed chart notes, one VA was measured, and pupils were examined in 66% of notes, ductions in 54%, and fields in 3%. Only 11% of notes documented attempted funduscopy; Conclusions There is worrisome erosion of students' acquired screening skills across the third-year clerkships. Skill reinforcement in the fourth year yielded improved performance. Attention must be directed to reinforcing basic ophthalmology skills training within medical school curricula to assure competence of graduates.
Upper airway and its surrounding structures in obese and nonobese patients with sleep-disordered breathing

Objectives/Hypothesis: The objective was to understand the pathophysiological relationship between obesity and sleep-disordered breathing by using cephalometry with the Muller maneuver. Study Design: A prospective study. Methods: One hundred habitually snoring men were evaluated for sleep-disordered breathing at the Sleep Center of Chang Gung Memorial Hospital (Taipei, Taiwan). Each subject received overnight polysomnography and two lateral cephalograms at the end-expiration phase (L1) and the Muller maneuver (L2), respectively, to evaluate the facial skeleton and the upper airway and its surrounding structures (soft palate, tongue, epiglottis, and hyoid bone). After excluding 14 patients from the study because of jaw opening during cephalometry, 86 (39 nonobese and 47 obese) patients with sleep-disordered breathing were enrolled. Results: Patients with varying degrees of obesity significantly differed in terms of the facial skeleton and the structure and function of the upper airway and its surrounding structures. The Muller maneuver caused dynamic changes in the hypopharyngeal airway and position of the tongue, and these dynamic changes were related to the pathogenesis of sleep-disordered breathing for the two groups (nonobese and obese patients). The regression model generated for the nonobese group revealed that the apnea hypopnea index was significantly related to the pharyngeal length (L2) and the soft palate thickness (L1). In contrast, the regression model generated for the obese group revealed that the apnea hypopnea index was significantly related to the soft palate (length [L1] and dynamic position change), the hyoid position (vertical [L1] and horizontal [L2]), the tongue (dynamic position change), and body mass index. Conclusion: Cephalometry with the Muller maneuver may provide further insight into the pathogenesis of sleep-disordered breathing for the two groups of patients (nonobese and obese patients).
Condensed Genome Structure

Large, tailed dsDNA-containing bacteriophage genomes are packaged to a conserved and high density (∼500 mg/ml), generally in ∼2.5-nm, duplex-to-duplex, spaced, organized DNA shells within icosahedral capsids. Phages with these condensate properties, however, differ markedly in their inner capsid structures: (1) those with a naked condensed DNA, (2) those with many dispersed unstructured proteins embedded within the DNA, (3) those with a small number of localized proteins, and (4) those with a reduced or DNA-free internal protein structure of substantial volume. The DNA is translocated and condensed by a high-force ATPase motor into a procapsid already containing the proteins that are to be ejected together with the DNA into the infected host. The condensed genome structure of a single-phage type is unlikely to be precisely determined and can change without loss of function to fit an altered capsid size or internal structure. Although no such single-phage condensed genome structure is known exactly, it is known that a single general structure is unlikely to apply to all such phages.
Normal mode multiplet coupling on an aspherical, anelastic earth

SUMMARY Calculating the singlet eigenfrequencies and eigenfunctions of a non-rotating, aspherical, anelastic earth model is a computationally intensive procedure, particularly when the number of coupled multiplets incorporated in the basis set is large. Several methods of improving the computational efficiency of this task are developed and tested in this paper. By using a complex-to-real basis transformation and making some justifiable approximations, we reduce the original complex symmetric generalized eigenvalue problem for each target multiplet to a real symmetric ordinary eigenvalue problem. In addition, we improve the accuracy of the subspace projection method by extending the analysis to second order in the eigenfunctions and third order in the eigenfrequencies.
A global criticality/local phase driven algorithm for the constrained hardware/software partitioning problem

An algorithm for the constrained hardware/software partitioning (assignment and scheduling) problem is presented. The key feature of the algorithm is the adaptive objective mechanism governed by the combination of global and local measures. As hardware area minimization and latency constraints present contradictory objectives, a global time-criticality (GC) measure selects an objective function in accordance with feasibility. In addition to global consideration, local characteristics of the nodes are emphasized by classifying nodes into local phase (LP) types. A local phase 1 node (extremity) has an obvious preference for an implementation on the basis of its area/time requirements. A local phase 2 node (repeller) is a repeller to an implementation on the basis of relative preferences of other nodes. At each iteration, the global and local criteria are superimposed by a threshold mechanism so as to determine the best implementation. The algorithm has quadratic complexity in the number of nodes and has shown promising behaviour on the examples tested. >
SPERM HARVESTING AND POSTMORTEM FATHERHOOD

The motives and consequences of harvesting sperm from brain dead males for the purpose of effecting post mortem fatherhood are examined. I argue that sperm harvesting and post mortem fatherhood raise no harms of a magnitude that would justify forbidding the practice outright. Dead men are not obviously harmed by the practice; children need not be harmed by this kind of birth; and the practice enlarges rather than diminishes the reproductive choices of surviving partners. Certain ethical and legal issues nevertheless require attention. As a matter of consistency with other harvesting protocols, there ought to be a mechanism for respecting the wishes of men who when alive do not wish to become fathers post mortem. Mechanisms governing entitlement to harvest and use sperm will also be required. I note that the law is unlikely to recognize the paternity of children born from harvested sperm, though there may be reasons to recognize that paternity in some instances.
The use of specialized laboratory facilities for science in elementary schools: A call for research

The reforms call for elementary science that engages students in meaningful and relevant learning opportunities for all students. While science lab facilities are common to middle and high school, in elementary schools, science is typically taught in the regular classroom. Elementary schools across the nation, however, have devoted financial and other resources to establishing separate laboratory facilities for science. How do these facilities support the delivery models for elementary science instruction and aid in meeting the vision of the reforms? The lack of research in this area should be addressed to enable districts to make informed decisions about whether to allocate funds to establishing separate facilities or equipping regular classrooms for elementary science instruction.
Multi-wavelength pumping technique for up-conversion single-photon detectors

We propose a multi-wavelength pumping technique to improve temporal resolution of up-conversion single-photon detectors. By using two-wavelength pumping we doubled the date rate of a quantum system beyond its original limitation.
Analogous Pacific and Atlantic Meridional Modes of Tropical Atmosphere-Ocean Variability*

From observational analysis a Pacific mode of variability in the intertropical convergence zone (ITCZ)/cold tongue region is identified that possesses characteristics and interpretation similar to the dominant ‘‘meridional’’ mode of interannual‐decadal variability in the tropical Atlantic. The Pacific and Atlantic meridional modes are characterized by an anomalous sea surface temperature (SST) gradient across the mean latitude of the ITCZ coupled to an anomalous displacement of the ITCZ toward the warmer hemisphere. Both are forced by trade wind variations in their respective northern subtropical oceans. The Pacific meridional mode exists independently of ENSO, although ENSO nonlinearity projects strongly on it during the peak anomaly season of boreal spring. It is suggested that the Pacific and Atlantic modes are analogous, governed by physics intrinsic to the ITCZ/ cold tongue complex.
Promoter-specific transactivation of hepatitis B virus transcription by a glutamine- and proline-rich domain of hepatocyte nuclear factor 1.

Abstract The cloned transcription factor hepatocyte nuclear factor 1 (HNF1) transactivates transcription from the hepatitis B virus (HBV) large surface antigen promoter but does not influence the transcriptional activities of the other three HBV promoters. This indicates that this transcription factor can differentially influence the activities of the HBV promoter. By using a transient-transfection system, the major domain of the HNF1 polypeptide involved in transcriptional activation of the large surface antigen promoter in the human hepatoma cell line HepG2.1 has been mapped to a region that is rich in glutamine and proline residues (9 of 18) and is different from the previously identified regions of this factor responsible for in vitro transcriptional activation of a promoter containing human albumin promoter HNF1 binding sites. The human albumin promoter HNF1 binding site mediates transcriptional activation through the same HNF1 polypeptide domain as the HBV large surface antigen promoter HNF1 binding site in transient-transfection assays with HepG2.1 cells, suggesting that HNF1 may possess multiple transcriptional activation domains.
Multi-Area Reliability -- A New Approach

Transmission interconnections can improve power system reliability, and this reliability improvement can be measured by the change in loss of load probabilities (LOLP's) . This paper presents a new method for evaluating loss of load proba bilities for an interconnected multi-area system. This method is based upon a reduced set of demand-supply feasibility conditions. This reduced set of feasibility conditions are used to directly define the infeasible region without iterative state space decomposition. LOLP's are then evaluated by attributing the probabilities of infeasible states to the appropriate reliability indices. The simulation results of a sample four-area system with 9,068,544 capacity states are presented in this paper. The computational efficiency of the proposed method is also illustrated in this paper.
Surgical Neuropathology Update: A Review of Changes Introduced by the WHO Classification of Tumours of the Central Nervous System, 4th Edition

Abstract Context.—The World Health Organization (WHO) recently published its 4th edition of the classification of tumors of the central nervous system, incorporating a substantial number of important changes to the previous version (WHO 2000). The new WHO classification introduces 7 changes in the grading of central nervous system neoplasms, ranging in significance from minor to major, in categories of anaplastic oligoastrocytomas, meningiomas, choroid plexus tumors, pineal parenchymal tumors, ganglioglioma, cerebellar liponeurocytoma, and hemangiopericytomas. The 4th edition also introduces 10 newly codified entities, variants, and patterns, as well as 1 new genetic syndrome. A number of established brain tumors are reorganized, including medulloblastomas and primitive neuroectodermal tumors, in an attempt to more closely align classification with current understanding of central nervous system neoplasia. Objective.—To summarize and discuss the most significant updates in the 4th edition for the practici...
K-way partitioning under timing, pin, and area constraints

Circuit partitioning is a very extensively studied problem. Our proposed methodology easily extends to multiple constraints that are very dominant in the design of large scale VLSI systems. In this paper we formulate the problem as a nonlinear program (NLP). The NLP is solved for the objective of minimum cutset size under the constraints of pins, area, and timing. We have tested the unified framework for area, timing, and pin constraints. The NLP is solved using the commercial LP/NLP solver MINOS. We have done extensive testing using large scale RT level benchmarks and have shown that our methods can be used for exploring the design space for obtaining constraint satisfying system designs. We also provide extensions for solving system design problems where a choice between multiple technologies, packaging components, performance, cost, yield, and more can be the constraints for design related decisions.
Effects of land-cover change on spatial pattern of forest communities in the Southern Appalachian Mountains (USA)

Understanding the implications of past, present and future patterns of human land use for biodiversity and ecosystem function is increasingly important in landscape ecology. We examined effects of land-use change on four major forest communities of the Southern Appalachian Mountains (USA), and addressed two questions: (1) Are forest communities differentially susceptible to loss and fragmentation due to human land use? (2) Which forest communities are most likely to be affected by projected future land cover changes? In four study landscapes, maps of forest cover for four time periods (1950, 1970, 1990, and projections for 2030) were combined with maps of potential forest types to measure changes in the extent and spatial pattern of northern hardwoods, cove hardwoods, mixed hardwoods, and oak-pine. Overall, forest cover increased and forest fragmentation declined in all four study areas between 1950 and 1990. Among forest community types, cove hardwoods and oak-pine communities were most affected by land-cover change. Relative to its potential, cove hardwoods occupied only 30– 40% of its potential area in two study landscapes in the 1950s, and oak-pine occupied 50% of its potential area; cove hardwoods remained reduced in extent and number of patches in the 1990s. Changes in northern hardwoods, which are restricted to high elevations and occur in small patches, were minimal. Mixed hardwoods were the dominant and most highly connected forest community type, occupying between 47 and 70% of each study area. Projected land-cover changes suggest ongoing reforestation in less populated regions but declining forest cover in rapidly developing areas. Building density in forest habitats also increased during the study period and is projected to increase in the future; cove hardwoods and northern hardwoods may be particularly vulnerable. Although increases in forest cover will provide additional habitat for native species, increases in building density within forests may offset some of these gains. Species-rich cove hardwood communities are likely to be most vulnerable to future land-use change.
Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532.

Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In this study, we investigated the effect of GR on telomerase activity and on the efficacy of its inhibition by BIBR 1532. Breast cancer MDA-MB 231 and MCF-7 cells were cultured in DMEM (Dulbecco’s modified eagle’s media) with 0, 1 or 4.5 g/l of glucose. The telomerase activity was measured via quantitative Real-Time PCR, and the two telomerase subunits were semi-quantified by RT-PCR. Proliferation test and mitochondrial metabolism were assessed via tetrazolium salt reduction and cell counts; apoptosis was assessed via caspase-3 quantification and flow cytometry. A decrease in the telomerase activity of more than 75% was associated with a significant reduction in the mRNA expression of its catalytic subunit hTERT (Reverse Transcriptase) and a decrease in the mitochondrial metabolism by more than 80% under restricted glucose conditions. In addition, GR increased the effect of BIBR 1532. Glucose deprivation induces apoptosis via BIBR 1532-mediated telomerase inhibition in triple negative breast cancer cells, as assessed by caspase-3 measurements and Annexin analysis. Taken together, our results suggest that the effect of BIBR 1532 is potentiated by GR to induce triple negative breast cancer cell death.
Digital video microscopy for the undergraduate histology laboratory

An undergraduate histology course was profoundly changed through the introduction of digital video microscopy. Students have access to a networked, Macintosh-based imaging laboratory where they can digitally capture, enhance, analyse, and media output microscope originated images. By increasing the access to image information, students are able to assume a more active inquiry mode in a microscope-based course. The technology allowed students to increase intellectual sharing among themselves and to leave ‘digital legacies’ for future classes.