cssi/SciSciGPT-SciSciNet huggingface dataset:
THz time scale structural rearrangements and binding modes in lysozyme-ligand interactions

Predicting the conformational changes in proteins that are relevant for substrate binding is an ongoing challenge in the aim of elucidating the functional states of proteins. The motions that are induced by protein-ligand interactions are governed by the protein global modes. Our measurements indicate that the detected changes in the global backbone motion of the enzyme upon binding reflect a shift from the large-scale collective dominant mode in the unbound state towards a functional twisting deformation that assists in closing the binding cleft. Correlated motion in lysozyme has been implicated in enzyme function in previous studies, but detailed characterization of the internal fluctuations that enable the protein to explore the ensemble of conformations that ultimately foster large-scale conformational change is yet unknown. For this reason, we use THz spectroscopy to investigate the picosecond time scale binding modes and collective structural rearrangements that take place in hen egg white lysozyme (HEWL) when bound by the inhibitor (NAG) 3. These protein thermal motions correspond to fluctuations that have a role in both selecting and sampling from the available protein intrinsic conformations that communicate function. Hence, investigation of these fast, collective modes may provide knowledge about the mechanism leading to the preferred binding process in HEWL-(NAG) 3. Specifically, in this work we find that the picosecond time scale hydrogen-bonding rearrangements taking place in the protein hydration shell with binding modify the packing density within the hydrophobic core on a local level. These localized, intramolecular contact variations within the protein core appear to facilitate the large cooperative movements within the interfacial region separating the α- and β- domain that mediate binding. The THz time-scale fluctuations identified in the protein-ligand system may also reveal a molecular mechanism for substrate recognition.
Interactive forces between lipid bilayers: An evaluation of relative importance of the various force components

Abstract The interactive forces between dipalmitoylphosphatidylcholine bilayers in water were analyzed using a least-squares iterative technique. The decay constant of the hydration repulsive force and the Hamaker constant of the van der Waals attractive force are evaluated for a range of previously determined bending moduli as a measure of the long range fluctuation force. However, in all cases, the strength of the various interactive forces was not deduced to be negligible. It can be concluded that this characterization of these interactive forces results in a more complete determination of the material constant describing these forces.
Identification of alloys using single shot laser ablation inductively coupled plasma time-of-flight mass spectrometry

Single shot laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) has been developed as a method for the rapid identification of alloy samples. This technique provides good accuracy for elemental concentrations greater than 0.1 percent by mass from samples with a range of different matrix compositions. Through the simultaneous measurement of all elements present within a cloud of ablated particles, relative percent composition values are measured that can be directly compared with certified concentrations. Cluster analysis has been used to successfully classify 33 metal alloys based on the measurement of 15 elements. Additionally, cluster analysis was used to identify the samples from a library of standard reference values. For the 15 alloys used to train this method, the correct standard was identified in greater than 99% of measurements. The only failed identification in the training set may have been due to elemental fractionation experienced with a brass sample. For the 18 standards used to validate the technique, samples were identified with a 93% success rate. Misidentifications may have been caused by inaccurate certified data. Several alloys investigated in this study were less than 500 µm in length at their largest dimension and weighed less than one milligram.
Genetic diversity in the gypsy moth fungal pathogen Entomophaga maimaiga from founder populations in North America and source populations in Asia

Entomophaga maimaiga is a naturally occurring fungal pathogen specific to larvae of the gypsy moth, Lymantria dispar. E. maimaiga is thought to be native to Asia where its epizootics can suppress gypsy moth outbreaks. However, in the USA this beneficial fungal pathogen was not observed until 1989, although an isolate of E. maimaiga from Tokyo was released in Massachusetts to control gypsy moths as early as in 1910-1911, and another isolate from Ishikawa Prefecture in Japan was later released in 1985 and 1986 in New York and Virginia. Our objectives were to: (1) test the hypothesis that E. maimaiga populations in the USA have reduced genetic variability due to founder effects compared to the putative ancestral populations in Asia; (2) track the origin of the North American populations of this fungus; and (3) assess whether genetic differences among E. maimaiga isolates are correlated to morphological differences. We compared genetic diversity among 30 E. maimaiga isolates originating from seven states in the USA, five prefectures in Japan, one province of China and one region of far eastern Russia by AFLPs. Among 14 USA isolates, only ten polymorphic AFLP loci were found, whereas 56 polymorphic loci were found among 16 Asian isolates; 29 loci were polymorphic among 12 isolates from Japan alone. Average gene diversity (h) for the polymorphic loci was 0.223 +/- 0.005 for Asia (including Japan), 0.131 +/- 0.006 for Japan only, and 0.041 +/- 0.004 for the USA. Thus, native populations from Asia were more diverse than the USA populations. These results are consistent with the expectation of a population founded from a source population by a small number of individuals. Distance and parsimony analyses of AFLP data showed that the isolates from the USA formed one distinct clade that was most closely related to Japanese isolates collected outside the Tokyo area. No morphological variation of E. maimaiga from different geographical locations was detected.
Diseases and drugs that increase risk of acute large bowel ischemia.

Background & Aims Information is limited on risk factors for acute large bowel ischemia (ALBI). We investigated diseases and drugs associated with ALBI. Methods We compared patients hospitalized with ALBI and controls through multivariate analysis of prior outpatient/emergency department/inpatient diagnoses and pharmacy dispensing records. Results There were 379 cases and 1516 controls (median age, 69 y; range, 25–97 y; 74.4% female). Disorders that were diagnosed in more cases than controls, based on univariate analysis ( P 2 -antagonists, immunomodulators, digoxin, clopidogrel/ticlopidine, taxanes/vinca alkaloids, and antibiotics. In all cases, ALBI was associated independently with hypertension (adjusted odds ratio [AOR], 3.21, 95% confidence interval [CI]; 2.28–4.53; P P P = .0218), atrial fibrillation (AOR, 2.21; 95% CI, 1.34–3.64; P = .0019), congestive heart failure (AOR, 1.94; 95% CI, 1.11–3.39; P = .0205), diabetes (AOR, 1.82; 95% CI, 1.31–2.53; P = .0004), antibiotics (AOR, 3.30; 95% CI, 2.19–4.96; P P P = .0012). Analysis of only women revealed similar associations except for diarrhea plus rheumatoid arthritis (AOR, 3.27; 95% CI, 1.07–9.96; P = .0370), irritable bowel syndrome (AOR, 2.72; 95% CI, 1.04–7.14; P = .0424), and female hormones (AOR, 1.88; 95% CI, 1.30–2.73; P = .0009). Conclusions Heterogeneous diseases and drugs increase the risk of ALBI, consistent with multifactorial pathogenesis.
Does theory have value in clinical child psychology

Examines the value and importance of theory in child psychology, particularly with respect to clinical practice. Although it is readily apparent that theory is not an essential element of treatment, the role of theory is to provide a coherent framework for clinical intervention. Theory provides a foundation for understanding the presenting pathology, the factors that affect it, the patient's and therapist's roles within the context of treatment, and the specific intervention strategies to be utilized. Therapeutic commonalities are considered as they may affect treatment outcome, but they are not viewed as the essential factors in efficacy. The value and meaning of eclecticism are also discussed.
Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.
Continuous Free Flow Electrophoresis in an Alternating Two-Dimensional Electric Field

A method of continuous free flow electrophoresis in an alternating two-dimensional electric field is proposed as a basis for continuous separation of biomolecules. Fractionation of species with different electrophoretic mobilities is investigated theoretically. Numerical calculations on particles' trajectories and dispersion are presented.
Correction of Microcytosis Following Elimination of an Occult Source of Aluminum Contamination of Dialysate

A higher prevalence of aluminum-associated microcytic anemia was noted in hemodialysis unit A (n = 67) compared to unit B (n = 39). This finding could not be explained by differences in the aluminum content of reverse osmosis (RO) water or intake of antacids containing aluminum by patients in the two units. An intermittent source of aluminum contamination was suspected when water aluminum and total dissolved solutes (TDS) were measured at several sites in the water treatment facility of unit A. A one-way valve that maintained unidirectional flow in an RO bypass circuit was found missing. Intermittent pressure changes in this circuit altered the direction of water flow causing mixing of partially purified water with RO water. Installation of the valve stopped contaminatioin and resulted in a decrease in plasma aluminum concentration from 183 ± 12 μg/L to 76 ± 7.3 Ag/L, erythrocyte aluminum concentration from 210 ± 31 μg/L to 61 ± 9 μg/L and microcytosis from 58% to 8% in patients (n = 48) when measured 6 months later. Because contamination was missed in spite of water testing at the RO site, these findings underscore the importance of measuring water aluminum and TDS content at the dialysis stations. Frequent water testing at dialysis stations, familiarity with the design of water treatment facilities, and recognition of aluminum overload can lead to early detection and correction if similar types of aluminum contamination should occur.
Effects of dressing type and change interval on intravenous therapy complication rates

Using a prospective study design, we compared the incidence rates in 807 patients of phlebitis, malfunction, cellulitis, and septicemia for short-term Teflon catheters with dressings changed every 24 or 48 hr, or using a polyurethane dressing changed every 48 hr. The study utilized either a standard dressing, which consisted of a small piece of dry sterile gauze, or a polyurethane dressing. The risk of phlebitis at 48 hr was significantly greater in the daily dressing change group as compared with the group that had dressings changed every 48 hr or with those using the polyurethane dressing (p less than 0.05). At 72 hr, there was also significantly less phlebitis using the standard dressing changed every 48 hr (p less than 0.05). The risk of malfunction was significantly greater at 24 hr for the polyurethane dressing compared with the other two groups (p less than 0.05). These findings indicate that adoption of a 48-hr dressing change interval using a standard dressing could result in less phlebitis and significant cost savings to a university-based institution.
The effect of high pressure processing on the morphology of polyethylene films tested by differential scanning calorimetry and X-ray diffraction and its influence on the permeability of the polymer

This study investigated the influence of high-pressure processing on the morphology and permeability of low-density polyethylene (LDPE) films used for food packaging. This was done by monitoring the crystallinity, melting temperature (Tm), and oxygen transmission rate (OTR) of the materials before and after the pressure treatments. A first set of pouches made from the LDPE films were filled with 95% ethanol then pressured at 200, 400, 600, and 800 MPa for 5 and 10 min at 25 and 75°C. The crystallinity and Tm of the films were measured using differential scanning calorimetry (DSC). X-ray diffraction (XRD) was also used to determine the crystallinity. A second set of LDPE pouches were similarly made but a half of them were filled with 95% ethanol and the other half filled with distilled water. These second set of pouches were pressured at 200, 600, and 800 MPa then their OTR tested. Results of the DSC experiments showed that the Tm increased with increasing pressure intensity but the crystallinity changes were not detectible. The XRD method on the other hand, showed significant (P < 0.05) crystallinity increases with increasing pressure treatments. The gas permeability analyses showed decreasing OTR's with increasing high-pressure intensity treatments. The OTR in the pouches filled with the 95% ethanol was slightly lower than that of the pouches filled with water. These findings allowed us to better anticipate the behavior of LDPE films used to package high-pressure processed foods. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Rapid, oxygen-dependent microbial Mn(II) oxidation kinetics at sub-micromolar oxygen concentrations in the Black Sea suboxic zone

Abstract Microbial Mn(II) oxidation kinetics in response to oxygen concentration were assessed in suboxic zone water at six sites throughout the Black Sea. Mn(II) oxidation rates increased asymptotically with increasing oxygen concentration, consistent with Michaelis–Menten enzyme kinetics. The environmental half-saturation constant, KE, of Mn(II) removal (oxidation) varied from 0.30 to 10.5 μM dissolved oxygen while the maximal environmental rate, VE−max, ranged from 4 to 50 nM h−1. These parameters varied spatially and temporally, consistent with a diverse population of enzymes catalyzing Mn oxide production in the Black Sea. Coastally-influenced sites produced lower KE and higher VE−max constants relative to the Western and Eastern Gyre sites. In the Bosporus Region, the Mn(II) residence time calculated using our KE and VE−max values with 0.1 μM oxygen was 4 days, 25-fold less than previous estimates. Our results (i) indicate that rapid Mn(II) oxidation to solid phase Mn oxides in the Black Sea’s suboxic zone is stimulated by oxygen concentrations well below the 3–5 μM concentration reliably detected by current oceanographic methods, (ii) suggest the existence of multiple, diverse Mn(II)-oxidizing enzymes, (iii) are consistent with shorter residence times than previously calculated for Mn(II) in the suboxic zone and (iv) cast further doubt on the existence of proposed reactions coupling solid phase Mn oxide production to electron acceptors other than oxygen.
Experimental mechanistic insight into the BINOL-catalyzed enantioselective conjugate addition of boronates to enones

Abstract The diol-catalyzed enantioselective conjugate addition of boronic acids and boronate esters has seen significant development in the last decade. However, no experimental mechanistic studies related to this transformation have been reported to date. Hammett plot-based analysis of reaction rates has been performed with aryl substitution both at the carbonyl and at the olefin of an enone electrophile. The resulting trends indicate that C–C bond formation is the likely rate limiting step.
Engineering Youth Service System Infrastructure: Hawaii's Continued Efforts at Large-Scale Implementation Through Knowledge Management Strategies

Hawaii's Child and Adolescent Mental Health Division provides a unique illustration of a youth public mental health system with a long and successful history of large-scale quality improvement initiatives. Many advances are linked to flexibly organizing and applying knowledge gained from the scientific literature and move beyond installing a limited number of brand-named treatment approaches that might be directly relevant only to a small handful of system youth. This article takes a knowledge-to-action perspective and outlines five knowledge management strategies currently under way in Hawaii. Each strategy represents one component of a larger coordinated effort at engineering a service system focused on delivering both brand-named treatment approaches and complimentary strategies informed by the evidence base. The five knowledge management examples are (a) a set of modular-based professional training activities for currently practicing therapists, (b) an outreach initiative for supporting youth evidence...
Human vaginal leukocytes and the effects of vaginal fluid onlymphocyte and macrophage defense functions

Summary OBJECTIVES : The purpose of this study was to quantify, characterize, and further define the role ofvaginal white blood cells in defense mechanisms and human immunodeficiency virus infection. STUDY DESIGN : Vaginal lavages were obtained from five healthy women throughout three menstrualcycles. Lymphocyte subpopulations, macrophages, and granulocytes were characterized and quantified by an immunohistologic technique. Vaginal lavage fluid was added to peripheral blood mononuclear cells, and effects on cell viability, lymphocyte proliferation, macrophage phagocytosis, and expression of various cell surface molecules critical to immunologic functions were assessed. Data were analyzed by Student's t test. RESULTS : Few lymphocytes were found at any stage of the menstrual cycle; however, granulocytes andmacrophages were abundant at menstruation and present at low levels through the proliferative phase. Vaginal lavage fluid collected during menses, at midcycle, and after coitus suppressed mitogen-induced lymphocyte proliferation but had no effect on surface expression of human leukocyte antigen or CD4 antigens, or on macrophage function. Likewise, low pH ( CONCLUSION : White blood cells, including lymphocytes and macrophages, are infrequently present incervicovaginal secretions of healthy women except during menses; the vaginal environment may effect their function.
A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex

Early sensory experience instructs the maturation of neural circuitry in the cortex. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties

Objective and Design: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain.¶Materials and Methods: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine α-monooxygenase (PAM) isolated from Xenopus laevis skin.¶Results: CDB (10 to 100 mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50 mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-1 activity (IC50 ≅ 17 μM) while having only a weak inhibitory activity on both COX-2 and PAM activity.¶Conclusions: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.
Lung dose for minimally moving thoracic lesions treated with respiration gating.

Purpose: To evaluate incidental doses to benign lung tissue for patients with minimally moving lung lesions treated with respiratory gating. Methods and Materials: Seventeen lung patient plans were studied retrospectively. Tumor motion was less than 5 mm in all cases. For each patient, mid-ventilation (MidVen) and mid-inhalation (MidInh) breathing phases were reconstructed. The MidInh phase was centered on the end-of-inhale (EOI) phase within a 30% gating window. Planning target volumes, heart, and spinal cord were delineated on the MidVen phase and transferred to the MidInh phase. Lungs were contoured separately on each phase. Intensity-modulated radiotherapy plans were generated on the MidVen phases. The plans were transferred to the MidInh phase, and doses were recomputed. The evaluation metric was based on dose indices, volume indices, generalized equivalent uniform doses, and mass indices for targets and critical structures. Statistical tests were used to establish the significance of the differences between the reference (MidVen) and compared (MidInh) dose distributions. Results: Statistical tests demonstrated that the indices evaluated for targets, cord, and heart differed by within 2.3%. The index differences in the lungs, however, are in excess of 6%, indicating the potentially achievable lung sparing and/or dose escalation. Conclusions: Respiratory gating isaclinical optionfor patientswith minimally moving lunglesions treated at EOI. Gating will be more beneficial for larger tumors, since dose escalation in those cases will result in a larger increase in the tumor control probability. 2010 Elsevier Inc. Gating, 4D, Dose, IMRT, Lung, Motion management.
Divergent Evolution in Enolase Superfamily: Strategies for Assigning Functions

Nature's strategies for evolving catalytic functions can be deciphered from the information contained in the rapidly expanding protein sequence databases. However, the functions of many proteins in the protein sequence and structure databases are either uncertain (too divergent to assign function based on homology) or unknown (no homologs), thereby limiting the utility of the databases. The mechanistically diverse enolase superfamily is a paradigm for understanding the structural bases for evolution of enzymatic function. We describe strategies for assigning functions to members of the enolase superfamily that should be applicable to other superfamilies.
Inhibition of proteoglycan synthesis influences regeneration of goldfish retinal axons on polylysine and laminin.

Abstract Previous studies have shown that goldfish retinal axons regenerating in vivo transport increased radioactivity in the glycosaminoglycan (GAG) components of proteoglycans (PGs). During this enhanced transport, the ratio of chondroitin sulfate (CS) to heparan sulfate (HS) was 60/40. In the present investigation, PG synthesis was inhibited during in vitro axon growth from regenerating goldfish retinal explants. Explants growing on either poly- l -lysine (PLYS) or poly- l -lysine + laminin (PLYS + LN) incorporated 35 SO 4 into proteoglycan-bound CS and HS in an approximate 2/1 ratio. Addition of 4-methylumbelliferyl β- d -xyloside (β-xyloside) to the culture medium reduced the sulfate radioactivity in proteoglycan-bound CS and HS by 89 and 71%, respectively, on PLYS and by 89 and 72% on PLYS + LN. Morphological evaluation of explants revealed that β-xyloside treatment reduced both the number of retinal axons per explant and their growth rate on PLYS; on PLYS + LN this treatment reduced the number of axons, but had no effect on growth rate. This study suggests that retinal ganglion cell PGs containing CS and/or HS GAG chains are required for both the initiation and the maintenance of axonal outgrowth on artificial polycationic substrata such as PLYS, but only for the initiation of outgrowth on laminin.
Preparation of Adult Drosophila Eyes for Thin Sectioning and Microscopic Analysis

Drosophila has long been used as model system to study development, mainly due to the ease with which it is genetically tractable. Over the years, a plethora of mutant strains and technical tricks have been developed to allow sophisticated questions to be asked and answered in a reasonable amount of time. Fundamental insight into the interplay of components of all known major signaling pathways has been obtained in forward and reverse genetic Drosophila studies. The fly eye has proven to be exceptionally well suited for mutational analysis, since, under laboratory conditions, flies can survive without functional eyes. Furthermore, the surface of the insect eye is composed of some 800 individual unit eyes (facets or ommatidia) that form a regular, smooth surface when looked at under a dissecting microscope. Thus, it is easy to see whether a mutation might affect eye development or growth by externally looking for the loss of the smooth surface ('rough eye' phenotype; Fig. 1) or overall eye size, respectively (for examples of screens based on external eye morphology see e.g.1). Subsequent detailed analyses of eye phenotypes require fixation, plastic embedding and thin-sectioning of adult eyes. The Drosophila eye develops from the so-called eye imaginal disc, a bag of epithelial cells that proliferate and differentiate during larval and pupal stages (for review see e.g. 2). Each ommatidium consists of 20 cells, including eight photoreceptors (PR or R-cells; Fig. 2), four lens-secreting cone cells, pigment cells ('hexagon' around R-cell cluster) and a bristle. The photoreceptors of each ommatidium, most easily identified by their light sensitive organelles, the rhabdomeres, are organized in a trapezoid made up of the six "outer" (R1-6) and two "inner" photoreceptors (R7/8; R8 [Fig. 2] is underneath R7 and thus only seen in sections from deeper areas of the eye). The trapezoid of each facet is precisely aligned with those of its neighbors and the overall anteroposterior and dorsoventral axes of the eye (Fig. 3A). In particular, the ommatidia of the dorsal and ventral (black and red arrows, respectively) halves of the eye are mirror images of each other and correspond to two chiral forms established during planar cell polarity signaling (for review see e.g. 3). The method to generate semi-thin eye sections (such as those presented in Fig. 3) described here is slightly modified from the one originally described by Tomlinson and Ready4. It allows the morphological analysis of all cells except for the transparent cone cells. In addition, the pigment of R-cells (blue arrowheads in Fig. 2 and 3) can be used as a cell-autonomous marker for the genotype of a R-cell, thus genetic requirements of genes in a subset of R-cells can readily be determined5,6.
HIV and Cardiovascular Disease: The Impact of Cigarette Smoking

The era of combination antiretroviral therapy (cART) has resulted in longer life expectancy for HIV-infected individuals, leaving them at greater risk of developing chronic illnesses such as cardiovascular disease (CVD). Tobacco use is an important modifiable risk factor for CVD events; however, our ability to promote successful cessation among people living with HIV/AIDS (PLWHA) remains limited. Barriers such as co-occurring substance use disorders, mental health conditions, and low socioeconomic status present many challenges to sustained smoking abstinence. Additional strategies must be implemented to improve quit rates in the HIV-infected population and further research is needed to inform approaches. In this article, we examine the contribution of HIV and cigarette smoking to CVD risk, and summarize the data on smoking behaviors and efforts to improve tobacco cessation among PLWHA.
Electron-electron interactions in cathode objective lenses.

Abstract The impact of electron–electron interactions on the electron-optical performance of imaging cathode objective lenses is evaluated.Three types of cathode objectives are considered: decelerating and accelerating electrostatic, and combined magnetic lenses.The beam blur is calculated for field sizes ranging from 50 μm ×50 μm to 500 μm ×500 μm and total beam currents ranging from 200 nA to 20 μA .The functional dependence of the beam blur upon electron beam current and current density is elucidated in detail.
Energetic particle fluxes in magnetron sputter deposition of a-Si:H

Reactive d.c. magnetron sputtering of a silicon target in a plasma of Ar plus H 2 produces high-quality a-Si:H films. This paper reports a study of the growth flux using mass spectrometry, plasma probes, and computer simulations to determine the identity, flux, energy distribution, and angular distribution of all incident species. Spectroscopic ellipsometry is used to deduce the bulk density of the films. The average energy delivered to the growing film is found to depend on the angle between the target normal and the substrate. The density of unhydrogenated a-Si films increases from 0.94 to 0.97 as the incident energy increases from 13 to 21 eV per deposited Si. The distributions of sputtered particles, of ions, and of fast H affect the film properties and merit continued study.
SOME EFFECTS OF GAMMA IRRADIATION ON THE GYPSY MOTH, PORTHETRIA DISPAR

Pupae and larvae of the gypsy moth, Porthetria dispar (L.), were irradiated with a cobalt-60 gamma source. The effect of various dosages on pupal survival, adult longevity, mating success, egg numbers, egg viability, and F1 survival are reported. The irradiation of pupae more than 9 days old with 20,000 r resulted in very few crippling defects of the treated insects and reduced egg hatch to a low level.
The effect of frequency on electric field induced surface force in red blood cell membrane

The use of electric field induced surface force acting on a red blood cell membrane to explain the observed sphering and hemolysis of the cell when exposed to the field is discussed. The frequency of the applied sinusoidal field inversely affects the field strengths at which sphering and hemolysis occur. Increase in frequency decreases the magnitude of the surface force. The effect appears to be the result of an /spl alpha/-dispersion of the dielectric property of the cell membrane. >
‘Children of the HMM’: Modeling Longitudinal Customer Behavior at Hulu.Com

Stand-alone marketing models are well-suited to deal with different behavioral features such as variation in transaction frequency (customer heterogeneity with latent classes), recency and attrition (“buy ‘till you die” models), and more general changes in customer transaction rates (hidden Markov models, HMMs). We unite these modeling approaches in a integrative framework as special cases or “children” of the HMM. We then selectively constrain the general model to assess the impact of each component on model performance. Instead of selecting latent-state models primarily using likelihood-based criteria, we favor a multi-faceted empirical evaluation using summaries of posterior predictive distributions; thus focusing model checking on managerially relevant features of the data, such as reach, frequency, and “streakiness.”We apply our methods to daily viewing incidence data from Hulu.com, a leading U.S. online streaming video provider. We find that increasing model complexity can improve some aspects of model performance (as expected) but worsen others in non-obvious ways. For instance, only models allowing back-and-forth movements among latent states can capture streakiness (a pattern of growing importance given the increasing availability of digital media data); but as a trade-off, these models still perform worse than their simpler counterparts in both forecasting and capturing other audience measurement criteria. Finally, using machine-learning classification techniques, customers are grouped based on similar model fit and features of their past consumption patterns. This allows researchers and managers to portend the “winning model” prior to having to fit the models for all customers. We discuss the generality of the methods and findings for different mixes of patterns of customer behavior.
Easy bruising in a patient with secondary amenorrhea.

A 33-year-old woman presented with amenorrhea and weight gain of 27.2–31.8 kg, despite diet and exercise, as well as progressively worsening acne. Symptoms began subsequent to a spontaneous abortion 5 years earlier and had become especially concerning during the past year. There was no notable family medical history. The patient did not report taking any prescription or over-the-counter medication and denied tobacco, alcohol, or illicit drug use. She had a blood pressure of 144/86 mmHg, heart rate of 88 beats/min, temperature of 37.1 °C, and was 1.8 m tall and weighed 105.7 kg (body mass index, 33.4). The results of a physical examination were otherwise normal. Initial laboratory evaluation results included a negative point-of-care urine human chorionic gonadotropin test and concentrations within reference intervals for thyroid-stimulating hormone (TSH),2 prolactin, leutinizing hormone (LH), and follicle-stimulating hormone (FSH) (Table 1). Further testing revealed a low estradiol concentration (20 pg/mL, reference interval, 24–706 pg/mL), as well as increased total testosterone [96 ng/dL (DPC, Siemens, Malvern PA), reference interval, 10–80 ng/dL] and dehydroepiandrosterone-S (DHEA-S) (594 μg/dL, reference interval, <340 μg/dL) (Table 1). She was diagnosed with polycystic ovary syndrome (PCOS) and treated with metformin, which she did not tolerate, and local creams for her acne were ineffective. View this table: Table 1. Laboratory values on the initial and return visits. Approximately 1 year later, the patient presented with continuing amenorrhea and complained of mood swings and depression as well as easy bruising and hirsutism. She was referred to an endocrinologist for further evaluation. Laboratory testing at this time included a basic metabolic panel. All measurands were within reference intervals, as were concentrations of TSH, LH, and FSH (Table 1). A random 17-hydroxyprogesterone (17-OHP) was within reference intervals, and estradiol was at the lower limit of the reference interval (28 pg/mL). Prothrombin time and partial thromboplastin time were both within reference intervals. Total testosterone (132 ng/dL) and …
Survival and Metabolic Activity of Microencapsulated Bifidobacterium longum in Stirred Yogurt

: Live cells of Bifidobacterium longum, microencapsulated in K-carrageenan, were added to stirred yogurt after fermentation (pH 4.6) and stored at 4.4 °C for 30 d. Cell enumeration indicated no decline of encapsulated cell number in yogurt samples, while there was significant reduction in nonencapsulated cell population (89.3% for B. longum B6 and 91.8% for B. longum ATCC 15708). Ion-exchange high-performance liquid chromatography showed comparable amounts of lactic and acetic acids in all samples, indicating little metabolic activity by bifidobacteria in experimental yogurts. Consumer sensory analysis of blackberry-flavored yogurts revealed that samples containing encapsulated bifidobacteria had a grainy texture. Results suggested that microencapsulation protected bifidobacteria from the low pH of yogurt.
Group Threat and Social Control: Race, Perceptions of Minorities and the Desire to Punish

This research examines the individual-level and contextual correlates of punitive attitudes in the United States. Prior research suggests that the demographic composition and economic conditions of geographic areas influence public support for punitive policies. Yet, these findings rest on assumptions about individual perceptions of minority groups as threatening. This work builds on the threat framework by measuring the concept of "perceived threat" and examining the association between aggregate social conditions, perceived threat and punitive sentiments. Analysis of newly collected data suggests that individual perceptions of African Americans as threatening to economic resources is a strong predictor of punitive attitudes. In addition, respondents residing in areas with higher unemployment rates and places that experienced a recent increase in the size of the African American population are more punitive. The latter effect is largely mediated by perceptions of African Americans as threatening to material resources for white respondents. The results agree with racial threat perspectives on social control, but we go beyond extant research by unpacking the micro-level processes that are central to the threat hypothesis.
Hemoproteins Designed from Scratch for O2 Transport, Co, No Signaling, Oxidoreductase and Cytochrome P450 Oxygenase Catalysis

We have designed and engineered a non-natural heme binding protein maquette with diverse heme ligations (bis-his, his-cys, single cys) and dramatically different spectroscopic and redox properties. Hemoproteins in nature perform diversified functions such as oxygen storage, oxygen transport, CO, NO signaling, gene regulation, drug metabolism. Hemoproteins achieve these diversified functions by modifying the redox properties of heme prosthetic group and by altered ligating amino acid to the central Fe metal or by use of different tetrapyrroles or by the nature of amino acids in the vicinity of heme. We have successfully designed a single chain tetra-helix bundle hemoproteins with bis-his, his-cys and single cys ligations, all display native absorption spectra of neuroglobin, CooA (transcription activator), other CO sensing enzymes and cytochrome P450 respectively. All these designed proteins form stable oxyferrous state with natural and synthetic iron porphyrins. These protein maquettes are readily expressable in E.coli. and holds great promise for doing P450 kind of reactions.
Analytical model for the electric field distribution in SOI RESURF and TMBS structures

A simple analytical model for the electric field distribution in silicon-on-insulator (SOI) reduced surface field (RESURF) structures is developed. The model applies for uniform and linearly graded doping profiles. It is also applicable to trench MOS barrier Schottky (TMBS) rectifiers, which have a similar structure. The results are valuable for breakdown voltage, tunneling, hot carrier, and other electric field dependent analyses.
Growth Hormone Increases Regional Coronary Blood Flow and Capillary Density in Aged Rats

In this study, we examined the effects of age and growth hormone replacement on both coronary blood flow and capillary density. Blood flow was measured by using [(14)C]-iodoantipyrine in three groups of anesthetized Brown Norway x Fischer 344 rats: young vehicle-treated animals (6 months; n = 13), old vehicle treated animals (30 months; n = 9), and old animals treated with bovine growth hormone (200 microg/kg) twice a day for 30 days (30 months; n = 7). Capillary density was measured by color segmentation analysis of sections stained for platelet endothelial cell adhesion molecule-1. In all regions examined, coronary blood flow decreased with age, and growth hormone administration resulted in an increase in flow compared to vehicle-treated animals. Capillary density decreased with age in the apex and the left ventricular middle segment. In response to growth hormone administration, capillary density increased significantly in the apex but not in other regions of the heart. Our results demonstrate that growth hormone enhances regional myocardial blood flow in the aged heart and suggest that part of this effect could be due to an increase in capillary density.
Ligand-directed nanobialys as theranostic agent for drug delivery and manganese-based magnetic resonance imaging of vascular targets

Although gadolinium has been the dominant paramagnetic metal for MR paramagnetic contrast agents, the recent association of this lanthanide with nephrogenic systemic fibrosis, an untreatable disease, has spawned renewed interest in alternative metals for MR molecular imaging. We have developed a self-assembled, manganese(III)-labeled nanobialys (1), a toroidal-shaped MR theranostic nanoparticle. In this report, Mn(III) nanobialys are characterized as MR molecular imaging agents for targeted detection of fibrin, a major biochemical feature of thrombus. A complementary ability of nanobialys to incorporate chemotherapeutic compounds with greater than 98% efficiency and to retain more than 80% of these drugs after infinite sink dissolution, point to the theranostic potential of this platform technology.
Is Judicial Review Compatible with Democracy

In this Article, I take up the controversial question of whether judicial review is compatible with democratic theory and seek to make two new contributions to the field. First, I reexamine the long-running dispute between Ronald Dworkin and Jeremy Waldron over the democratic legitimacy of judicial review, including Waldron’s latest response in a recent issue of the Yale Law Journal. After identifying two distinct objections that Waldron raises to Dworkin's theory of judicial review, I seek to show that that the first of these objections proves unsound and that the second is only sustainable if one accepts an understanding of “democracy” that is both unappealing on its face and inconsistent with current practice in the United States and elsewhere. Second, after identifying the alternative theory of democracy that appears to underlie Dworkin’s views, I briefly sketch out a constructive argument in support of judicial review based on the judiciary’s unique institutional posture. While my argument has important similarities to other theories that have been put forth by Dworkin, John Hart Ely, and Christopher Eisgruber, among others, it is unique in its focus on the requirement that judges issue written opinions for each decision and on the effect this requirement has on judicial decision making as compared to legislative deliberations. This leads to a fairly expansive view of the proper scope for judicial review in a democratic government, which I then defend against several common criticisms.
Selection criteria for antifungals: the right patients and the right reasons

The increasing number of new antifungal agents and their range of licensed indications mean that clinicians now have several pharmacological options for combating fungal infections. This paper briefly reviews the current available agents and seeks to introduce evidence that will help ensure optimal treatment for each type of fungal infection.
The lattice-Boltzmann method for simulating gaseous phenomena

We present a physically-based, yet fast and simple method to simulate gaseous phenomena. In our approach, the incompressible Navier-Stokes (NS) equations governing fluid motion have been modeled in a novel way to achieve a realistic animation. We introduce the lattice Boltzmann model (LBM), which simulates the microscopic movement of fluid particles by linear and local rules on a grid of cells so that the macroscopic averaged properties obey the desired NS equations. The LBM is defined on a 2D or 3D discrete lattice, which is used to solve fluid animation based on different boundary conditions. The LBM simulation generates, in real-time, an accurate velocity field and can incorporate an optional temperature field to account for the buoyancy force of hot gas. Because of the linear and regular operations in each local cell of the LBM grid, we implement the computation in commodity texture hardware, further improving the simulation speed. Finally, textured splats are used to add small scale turbulent details, achieving high-quality real-time rendering. Our method can also simulate the physically correct action of stationary or mobile obstacles on gaseous phenomena in real-time, while still maintaining highly plausible visual details.