cssi/SciSciGPT-SciSciNet huggingface dataset:
Concentration of Creatine Phosphate, Adenine Nucleotides and Their Derivatives in Electrically Stimulated and Nonstimulated Beef Muscle

The concentration of creatine phosphate (CP), adenosine tri-, di- and monophosphate (ATP, ADP and AMP, respectively), inosine monophosphate (IMP) and inosine in longissimus muscle removed from electrically stimulated (ES) and nonstimulated (NS) beef sides was enzymatically determined. After aging the carcass 7 days, steaks were removed for flavor evaluation. R values (absorbance ratios) were obtained from muscle samples removed over time from both sides. Data indicate more rapid catabolism of CP, ATP, and ADP in ES samples, with subsequent fluctuations in IMP and inosine concentration. At 12 and 24 hr post-stimulation, ES samples had more inosine; however, this difference did not exist after aging. Flavor differences were not observed after the 7-day aging period. R values parallel the degradation of adenine nucleotides and indicate rapid onset of rigor mortis in ES muscle.
Exploiting imperfections in the bulk to direct assembly of surface colloids

We exploit the long-ranged elastic fields inherent to confined nematic liquid crystals (LCs) to assemble colloidal particles trapped at the LC interface into reconfigurable structures with complex symmetries and packings. Spherical colloids with homeotropic anchoring trapped at the interface between air and the nematic LC 4-cyano-4′-pentylbiphenyl create quadrupolar distortions in the director field causing particles to repel and consequently form close-packed assemblies with a triangular habit. Here, we report on complex open structures organized via interactions with defects in the bulk. Specifically, by confining the nematic LC in an array of microposts with homeotropic anchoring conditions, we cause defect rings to form at well-defined locations in the bulk of the sample. These defects source elastic deformations that direct the assembly of the interfacially trapped colloids into ring-like assemblies, which recapitulate the defect geometry even when the microposts are completely immersed in the nematic. When the surface density of the colloids is high, they form a ring near the defect and a hexagonal lattice far from it. Because topographically complex substrates are easily fabricated and LC defects are readily reconfigured, this work lays the foundation for a versatile, robust mechanism to direct assembly dynamically over large areas by controlling surface anchoring and associated bulk defect structure.
Determination of the structural role of the internal guanine-cytosine base pair in recognition of a seven-base-pair sequence cross-linked by bizelesin.

Bizelesin (formerly U77,779, The Upjohn Co.) is a bifunctional DNA cross-linking antitumor antibiotic consisting of two open-ring homologs of the (+)-CC-1065 cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one (CPI) subunits connected by a rigid linking moiety. Previous studies have shown that Bizelesin most often forms an interstrand cross-link through the N3 of two adenines 6 base pairs (bp) apart (inclusive of the modified adenines). However, gel electrophoresis studies have also indicated that Bizelesin forms 7-bp cross-links in specific sequences. In most of these sequences the cross-linked adenines represent the only possible cross-link site (i.e., no 6-bp site is available); however, in several sequences, a 7-bp sequence is selected in overwhelming preference to a possible 6-bp sequence. In this study, we demonstrate the unique requirement for a G.C base pair within this sequence and the critical presence of the exocyclic 2-amino group of guanine. In a subsequent two-dimensional 1H-NMR study that concentrates on the 7-bp cross-link formed with the sequence 5'-TTAGTTA-3', the role of the central G.C base pairs in the formation of a 7-bp cross-link is probed. 1H-NMR analysis coupled with restrained molecular dynamics (rMD) provides evidence for distortion around the covalently modified adenines. Because of this distortion, the modified bases are twisted toward the center of the duplex adduct, effectively reducing the cross-linked distance. The rMD study also indicates that a hydrogen bond is formed between the exocyclic amine of the central guanine and the carbonyl of the ureylene linker. On the basis of the observation of the distortion in the duplex and the hydrogen bonding between the drug and DNA, it is possible to speculate on the role of the central G.C bases in this sequence preference and propose a mechanism by which Bizelesin forms a 7-bp rather than a 6-bp cross-link with this sequence.
RB Tumor Suppressive Function in Response to Xenobiotic Hepatocarcinogens

Diverse etiologic events are associated with the development of hepatocellular carcinoma. During hepatocarcinogenesis, genetic events likely occur that subsequently cooperate with long-term exposures to further drive the progression of hepatocellular carcinoma. In this study, the frequent loss of the retinoblastoma (RB) tumor suppressor in hepatocellular carcinoma was modeled in response to diverse hepatic stresses. Loss of RB did not significantly affect the response to a steatotic stress as driven by a methionine- and choline-deficient diet. In addition, RB status did not significantly influence the response to peroxisome proliferators that can drive hepatomegaly and tumor development in rodents. However, RB loss exhibited a highly significant effect on the response to the xenobiotic1,4-Bis-[2-(3,5-dichloropyridyloxy)] benzene. Loss of RB yielded a unique proliferative response to this agent, which was distinct from both regenerative stresses and genotoxic carcinogens. Long-term exposure to 1,4-Bis-[2-(3,5-dichloropyridyloxy)] benzene yielded profound tumor development in RB-deficient livers that was principally absent in RB-sufficient tissue. These data demonstrate the context specificity of RB and the key role RB plays in the suppression of hepatocellular carcinoma driven by xenobiotic stress.
Penetration of insecticides through the isolated midgut of insects and mammals

Abstract 1. 1. The rates of intestinal penetration of 5 insecticides (DDT, dieldrin, carbaryl, malathion, and nicotine) in 3 animals ( Blaberus discoidalis, Manduca sexta , and Mus musculus ) were studied. Data presented illustrate both total penetration (through the midgut) and partial penetration (bound to midgut). 2. 2. The partition coefficients of the insecticides were determined. A correlation between intestinal penetration and partition coefficient was evident in both insect species but not in mice. 3. 3. Penetration of insecticides through the midgut was found to be by passive transport. 4. 4. Rate constants and half-time penetration rates were calculated. A correlation between these constants and partition coefficients was found in insects but not in the mouse. 5. 5. Penetration was similar for the insecticides whether utilizing an ‘open’ system (perfusion) or a ‘closed’ system.
A Role for Old Yellow Enzyme in Ergot Alkaloid Biosynthesis

Ergot alkaloids, secondary metabolites produced by filamentous fungi, elicit a diverse array of pharmacological effects. The biosynthesis of this class of natural products has not been fully elucidated. Here we demonstrate that a homologue of Old Yellow Enzyme encoded in the Aspergillus fumigatus ergot gene cluster catalyzes reduction of the alpha,beta unsaturated alkene of chanoclavine-I aldehyde 3. This reduction, which yields dihydrochanoclavine aldehyde, facilitates an intramolecular reaction between a secondary amine and aldehyde to form the D ring of the ergot alkaloid structural framework.
An Experimental Radiopaque Composite Material

Numerous physical properties of a new reinforced resin were found to be similar to those obtained with earlier composite material formulations.
Prenatal diagnosis of congenital myotonic dystrophy and counseling of the pregnant mother: Case report and literature review

The molecular basis of the myotonic dystrophy (MD) kinase gene is expansion of the CTG repeat at the 3'-untranslated region of the MD gene. Variability of the CTG repeat size in different tissues of affected individuals has been demonstrated. The objective of this report was to examine and review the feasibility of prenatal diagnosis of congenital myotonic dystrophy (CMD) in pregnant women with MD using CTG repeat sizes in amniocytes or villi. We present a case of a pregnant woman with MD who underwent prenatal diagnosis of MD using amniocytes. The repeat size in the amniocytes was smaller than the repeat size in the maternal leukocytes and smaller than the repeat size in the infant blood. The infant had CMD. We also reviewed the literature for reports on MD cases that were prenatally tested for CTG repeat size using amniocytes or chorionic villi. Data were tabulated based on the number of maternal CTG repeats, prenatal procedure [amniocentesis or chorionic villus sampling (CVS)], CTG repeat size in fetal tissue, fetal/infant blood, and pregnancy outcome. Twenty-seven pregnancies at risk for MD that underwent prenatal diagnosis were reported. Eleven (40.7%) of the 27 pregnancies underwent amniocentesis, and 16 (59.3%) underwent CVS. Fourteen patients (61%) demonstrated an increase in CTG repeat size in the amniocytes or villi compared with the maternal repeat size. Nine (33%) of the 27 pregnancies were terminated because of CMD risk. The outcomes of 11 (40.7%) pregnancies were consistent with diagnosis of CMD. CMD was diagnosed in fetuses demonstrating expansion or contraction of the CTG mutation in the amniocytes. Prenatal diagnosis of MD is possible by using mutation analysis on maternal and fetal DNA and detection of the CTG repeat expansion. Prenatal diagnosis of CMD is more complex. The possible lack of correlation between CTG repeat size in amniocytes, villi, and other fetal tissues is a potential limitation in prenatal diagnosis and counseling of CMD using CTG repeat size. Thus, prenatal diagnosis of CMD should be based on a combination of factors, including maternal pregnancy history, clinical findings, and cautious interpretation of maternal and fetal DNA analysis.
Prioritizing development goals in low-income developing countries

Abstract This paper outlines a systematic approach to prioritizing the multiple and often conflicting development goals and objectives in a typical low-income developing country (LDC). First, a hierarchy of development goals and objectives is developed from an extensive review of the literature. Then, Analytic Hierarchy Process (AHP) is utilized to analyze the judgement elicited from World Bank experts and a priority structure established reflecting the perceived importance of these development goals and objectives. This methodology can assist development planners in LDCs in formulating developement plans consistent with national objectives.
Measurement and prediction of diagnostic performance during radiology training.

Faculty evaluations of residents' diagnostic performance in radiology subspecialty rotations were examined in two studies in order to ascertain whether the relative capabilities of residents change during training and to predict residents' diagnostic performance using a three-dimensional form perception test. In the first study, numeric ratings by faculty members were averaged to provide interpretive/diagnostic scores for each of 16 residents in each of 5 consecutive half-years. Sixty-seven percent of the relative differences among residents' diagnostic proficiencies persisted during training. The magnitude of these unchanging differences between individuals in diagnostic performance strongly favors resident selection based upon diagnostic potential. An additional 22% of the relative differences correlated with an abrupt change in the rank order of residents in diagnostic performance at the beginning of the second year of residency. This rearrangement of ranks may have resulted from an abrupt change in th...
Organ weights, T-cell proliferation, and graft vs host capabilities of hypothyroidic chickens

Thiouracil-induced hypothyroidism reduced the thymus weights of young chickens. Thyroid weights were greater in thiouracil-fed (TF) chicks, and the circulating levels of triiodothyronine and thyroxine were lower. Thiouracil treatment resulted in higher relative adrenal weights and serum corticosterone concentrations. Absolute weights of adrenals were equivalent between control and TF groups. The TF chicks showed depressions of total white blood cell counts and numbers of lymphocytes. Monocyte and granulocyte numbers were unchanged from those of controls. Thiouracil treatment lowered the phytohemagglutinin M responsiveness of peripheral blood leukocytes (PBL). On the other hand, the PBL from TF chicks produced the higher graft vs host (GvH) response. Therefore, while the hypothyroidic state impaired cycling activity in T cells, this condition did not significantly influence a functional parameter of T cells, the GvH response.
Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence.

Purpose: We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence.Materials and Methods: Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety.Results: A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change −19.0 versus −14.5, p = 0.0165), reduced average daily urinary frequency (mean change −2.3 versus −1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire...
Novel hydroxypropyl-guar gellable lubricant eye drops for treatment of dry eye

Objective| The objective of this review is to evaluate the safety and efficacy of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar (Systane® Ultra [PEG/PG with HP-guar], Alcon Laboratories, Inc., Fort Worth, TX, USA) lubricant eye drops in reducing the signs and symptoms of dry-eye disease.
STREPTOCOCCAL INFECTION IN NORMAL AND SPLENECTOMIZED MONKEYS.

SummaryAerosol challenge with staphy-lococci produced no demonstrable disease in rhesus monkeys. Intravenous challenge was followed by definite clinical and laboratory evidence of infection. Toxoid immunization did not alter the course of infection. No significant differences were noted between splen-ectomized and normal monkeys in all parameters measured.The technical assistance of Maurice Marietti, Joann Sparks and Joseph Hackett is gratefully acknowledged.
Extension of Belyaev--Zelevinski method for rotation as intrinsic nuclear excitation

Abstract The method of Belyaev-Zelevinski is extended and it is extended and it is shown how more complicated forms of the rotational energy can be obtained in lowest order.
Intermittent explosive disorder and other psychiatric co-morbidity among court-referred and self-referred aggressive drivers

We assessed possible Axis I and Axis II disorders in two groups of aggressive drivers (n=20, court-referred; n=10, self-referred) and 30 non-aggressive driver controls, using the SCID and SCID-II. Aggressive drivers were more likely than controls to be positive for any Axis I and Axis II disorders. They were also more likely to meet the criteria for Intermittent Explosive Disorder (IED), current or past alcohol or substance abuse or dependence and Antisocial PD and Borderline PD. The self-referred aggressive drivers were more likely than court-referred aggressive drivers to meet the criteria for a current or past Anxiety Disorder. Re-analysis of aggressive driver data on the basis of presence or absence of IED revealed differences only in Axis II disorders: those with IED were more likely to meet the criteria for any Axis II disorder and Antisocial PD.
Testing linear models of sea-floor topography

Stochastic models can generate profiles that resemble topography by taking uncorrelated, zero-average noise as input, introducing some correlation in the time series of noise, and integrating the resulting correlated noise. The output profile will depict a nonstationary, randomly rough surface. Two models have been chosen for comparison: a fractal model, in which the noise is correlated even at large distances, and an autoregressive model of order 1, in which the correlation of the noise decays rapidly. Both models have as an end-member a random walk, which is the integration of uncorrelated noise. The models have been fitted to profiles of submarine topography, and the sample autocorrelation, power spectrum and variogram have been compared to the theoretical predictions. The results suggest that a linear system approach is a viable method to model and classify sea-floor topography. The comparison does not show substantial disagreement of the data with either the autoregressive or the fractal model, although a fractal model seems to give a better fit. However, the amplitudes predicted by a nonstationary fractal model for long wavelengths (of the order of 1000 km) are unreasonably large. When viewed through a large window, ocean floor topography is likely to have an expected value determined by isostasy, and to be stationary. Nonstationary models are best applied to wavelengths of the order of 100 km or less.
Postirradiation processes in the induction of recessive lethals by ionizing radiation.

Studies on x-ray induced recessive lethal mutations in Paramecium suggest at least two post-irradiation processes. These include loss of premutational damage by what can best be looked upon a metabolic repair of localized chromosome lesions, and conversion of remaining damage to mutation at the time of DNA synthesis. Little if any mutation can be produced by irradiation of G2 and early prophase, suggesting that repair of chromosome lesions is remarkably efficient during one or both of these periods. (C.H.)
Internal Family Systems: A Parts Party Intervention

Few therapeutic models look at the internal and external system as well as the Internal Family Systems (IFS) model developed by Richard Schwartz (1995). Internally, the individual parts of a person...
Operative failure in the era of focused parathyroidectomy: a contemporary series of 845 patients.

Hypothesis Focused parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IPM) may lead to higher failure rates because of missed multiglandular disease. Design Retrospective review of prospectively collected data. Setting Tertiary referral center. Patients From September 8, 1993, through January 30, 2009, a total of 845 consecutive patients with sporadic primary hyperparathyroidism underwent focused parathyroidectomy guided by IPM at a single institution. Main Outcome Measures Parathyroid hormone dynamics and perioperative data were analyzed for factors affecting outcome. Operative failure was defined as hypercalcemia with elevated parathyroid hormone levels within 6 months after parathyroidectomy. Detailed intraoperative data from the failed operations were also reviewed. Results Of 723 patients followed up for at least 6 months, 702 (97.1%) had successful parathyroidectomy, and 21 (2.9%) had failed parathyroidectomy. The major cause of operative failure was the surgeon's inability to find the abnormal parathyroid gland (16 of 21 patients [76.2%]). In the remaining patients, IPM results were false-positive in 5 of 21 patients (23.8%) or 0.7% overall. Among the cohort, IPM correctly identified missed multiglandular disease in 33 of 38 patients (86.8%). Patients having operative failure were more likely to have a history of thyroidectomy or parathyroidectomy and were less likely to have correct findings on technetium Tc 99m sestamibi or ultrasonographic localizing studies compared with patients having operative success. Conclusion Inability of the surgeon to find the abnormal parathyroid gland—not missed multiglandular disease—is the main cause of operative failure in focused parathyroidectomy guided by IPM.
Developmental emergence of fear learning corresponds with changes in amygdala synaptic plasticity

Mother-infant attachment is facilitated in altricial rodents through unique neural mechanisms that include impaired neonatal fear conditioning until the time that pups first begin to leave the nest (sensitive period). Here, we confirmed the developmental emergence of odor fear conditioning in neonatal rat pups, and examined synaptic plasticity of inputs to the basolateral amygdala in vitro. Coronal slices through the amygdala were obtained from sensitive ( 10, < 19 days) period pups. Field potentials were recorded in the basolateral amygdala in response to stimulation of either the external capsule (neocortical inputs) or fibers from the cortical nucleus of the amygdala (olfactory inputs). The effects of tetanic stimulation were examined in each pathway. In both pathways, tetanic stimulation induce significant long-term synaptic plasticity in post-sensitive period pups, but no significant plasticity in sensitive period pups incapable of learning odor aversions. GABAA receptor blockade in post-sensitive period slices reverts synaptic plasticity to sensitive period characteristics. The results suggest that sensitive period deficits in fear conditioning may be related to impaired amygdala synaptic plasticity and the immature state of GABAergic inhibition and/or it modulation in the neonatal amygdala.
Laminated plate design using genetic algorithms and parallel processing

Abstract The use of a parallel computer in the stacking sequence optimization of a composite laminate via a genetic algorithm is studied. Results are obtained for a graphite-epoxy plate under buckling, strain, and ply contiguity constraints. Two parallelization schemes for the optimization problem are proposed and compared. Results are presented showing the computation time as a function of the number of processors, illustrating the benefits and drawbacks of both schemes. A new technique for design population visualization is also developed as a tool for monitoring the performance of the genetic algorithm.
Electrophoretic Deposition of Gallium with High Deposition Rate

In this work, electrophoretic deposition (EPD) is reported to form gallium thin film with high deposition rate and low cost while avoiding the highly toxic chemicals typically used in electroplating. A maximum deposition rate of ~0.6 μm/min, almost one order of magnitude higher than the typical value reported for electroplating, is obtained when employing a set of proper deposition parameters. The thickness of the film is shown to increase with deposition time when sequential deposition is employed. The concentration of Mg(NO3)2, the charging salt, is also found to be a critical factor to control the deposition rate. Various gallium micropatterns are obtained by masking the substrate during the process, demonstrating process compatibility with microfabrication. The reported novel approach can potentially be employed in a broad range of applications with Ga as a raw material, including microelectronics, photovoltaic cells, and flexible liquid metal microelectrodes.
150mV sub-threshold Asynchronous multiplier for low-power sensor applications

A 4-bit Asynchronous multiplier was designed in the sub-threshold regime. The multiplier, using asynchronous completion detection, is more tolerant to process variation than conventional synchronous sub-threshold circuits and operates with a supply voltage as low as 150mV. The average energy per computation was simulated at 1.13pJ. The minimum energy voltage was simulated at 350mV, with an average micro-pipelined frequency of 11.3 kHz.
Profile of Acute Tolerance to Three Sedative Anxiolytics

Acute tolerance, defined as a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours, is pronounced following single doses of diazepam or pentobarbital. Both of these lipid-soluble drugs produce an early peak behavioral impairment and subsequent rapid recovery component that is followed by a much slower blood-drug rise time. These pronounced early peak effects were not shared by alcohol, and contribute significantly to the lack of correlation between impairment and DPL.
Cryptorchidism in meningomyelocele

investigation, we do not know if these PFT abnormalit ies will persist. Several other childhood illnesses which affect pulmonary function are related to adult chronic lung disease. 11 We do not know if increased or decreased therapy for JRA will alter these abnormal PFT results. Finally, we can only speculate that specific therapy for these pulmonary function abnormalities might improve the patients' health. Certainly, in J R A patients who report exercise intolerance, pulmonary function tests including oximetry with exercise should be obtained to see if pulmonary involvement, and not solely joint discomfort, is restricting the patients' exercise.
Measurement of low hysteretic losses in CVD prepared Nb3Ge

Abstract Very low hysteretic losses have been measured in CVD prepared Nb 3 Ge. An apparent correlation between second phase content and low losses has been found as well as a reduction in hysteretic loss by appropriate surface treatment.
Amygdala volume in patients receiving chronic corticosteroid therapy.

Background Hippocampal volume reduction and declarative memory deficits are reported in humans and animals exposed to exogenous corticosteroids. The amygdala is another brain structure involved in the stress response that has important interactions with the hypothalamic-pituitary-adrenal axis. To our knowledge, no studies in animals or humans have examined the impact of exogenous corticosteroid administration on the amygdala. We assessed amygdala volume in patients receiving chronic prescription corticosteroid therapy and control subjects with similar medical histories not receiving corticosteroids. Methods Fifteen patients on long-term prednisone therapy and 13 control subjects of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging. Amygdala volume was manually traced and compared between groups using a two-way analysis of variance (ANOVA). Correlations between amygdala volume, age, and corticosteroid dose/duration were assessed using Pearson's correlation coefficient. Results Compared with control subjects, corticosteroid-treated patients had significantly smaller amygdala volumes. Right amygdala volume correlated significantly with age in control subjects and with duration of corticosteroid therapy in patients. Conclusions Patients receiving chronic corticosteroid therapy had smaller amygdala volumes than control subjects that correlated with duration of corticosteroid therapy. These findings suggest that corticosteroid exposure may be associated with changes in the amygdala as well as hippocampus.
Modulation of the activities of HN protein of Newcastle disease virus by nonconserved cysteine residues

Comparisons of the sequences of the hemagglutinin-neuraminidase (HN) protein from thirteen different strains of Newcastle disease virus (NDV) show that while 12 cysteine residues are conserved in all strains, two cysteine residues are variably present (Sakaguchi et al. (1989) Virology 169, 260-272). One of these residues, at amino acid 6, is in the cytoplasmic domain. The other cysteine is at amino acid 123 in the ectodomain and is responsible for disulfide-linked HN dimers detected in some NDV strains (McGinnes and Morrison (1994) Virology 200, 470-483). To explore the role of these nonconserved residues in the structure and function of the protein, cysteine residues at amino acid 6 and 123 in the HN protein of the AV strain of NDV were mutated individually and in combination by site specific mutagenesis to serine and tryptophan, respectively. Proteins with mutations in either residue (C6S or C123W) or in both residues (C6S,123W) were transported to the cell surface. However, all three mutants had reduced attachment, neuraminidase, and fusion promotion activities. All three mutant proteins also showed an alteration in an antigenic site specific for oligomers of HN protein while all other antigenic sites were present at wild type levels. These results suggest that the nonconserved cysteine residues in the HN sequence may modulate the biological activities of the protein by affecting the oligomeric structure of the protein.
Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy

Optimal four-dimensional imaging requires high spatial resolution in all dimensions, high speed and minimal photobleaching and damage. We developed a dual-view, plane illumination microscope with improved spatiotemporal resolution by switching illumination and detection between two perpendicular objectives in an alternating duty cycle. Computationally fusing the resulting volumetric views provides an isotropic resolution of 330 nm. As the sample is stationary and only two views are required, we achieve an imaging speed of 200 images/s (i.e., 0.5 s for a 50-plane volume). Unlike spinning-disk confocal or Bessel beam methods, which illuminate the sample outside the focal plane, we maintain high spatiotemporal resolution over hundreds of volumes with negligible photobleaching. To illustrate the ability of our method to study biological systems that require high-speed volumetric visualization and/or low photobleaching, we describe microtubule tracking in live cells, nuclear imaging over 14 h during nematode embryogenesis and imaging of neural wiring during Caenorhabditis elegans brain development over 5 h.
Method for Automatic, Continuous Blood Sampling with Remote Alarm for Clogged Catheters

An inexpensive blood sampling system is described that includes a remote alarm triggered by a decrease in rate of blood withdrawal. Additional modifications include design of a reliable sampling catheter and of a method for quickly and atraumatically replacing clogged catheters. This system has been used to collect continuous, integrated blood samples every 15 min for up to 72 h from cows. The alarm system is also useful for monitoring any flow in which minimum rate is critical, e.g., for column chromatography.
Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP

Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.
Controlling the Selectivity of Competitive Nitroaldol Condensation by Using a Bifunctionalized Mesoporous Silica Nanosphere-Based Catalytic System

A series of bifunctionalized mesoporous silica nanosphere-based (MSN) heterogeneous catalysts for the nitroaldol (Henry) reaction have been synthesized. A common 3-[2-(2-aminoethylamino)ethylamino]propyl (AEP) primary group and three different secondary groups, ureidopropyl (UDP), mercaptopropyl (MP), and allyl (AL) functionalities, were incorporated to these mesoporous silica materials by introducing equal amounts of AEP-trimethoxysilane with UDP-, MP-, or AL-trialkoxysilane precursors to our previously reported co-condensation reaction. Structures and relative concentrations of the functional groups were detailed by solid-state NMR and other spectroscopic techniques. The AEP group served as a catalyst, and the other secondary groups provided different noncovalent interactions to reactants and thereby controlled the reaction selectivity. By varying the secondary group in these bifunctionalized MSN catalysts, we investigated the selectivity of a nitroaldol reaction of two competing benzaldehydes reacting ...
Impaired marrow osteogenesis is associated with reduced endocortical bone formation but does not impair periosteal bone formation in long bones of SAMP6 mice.

We used the SAMP6 osteoporotic mouse to examine the link between marrow osteogenic potential and in vivo cortical bone formation. SAMP6 marrow supported less in vitro osteogenesis than marrow from SAMR1 controls; SAMP6 mice had a corresponding deficit in endocortical mineralizing surface. This marrow/endocortical defect did not affect the periosteum, where SAMP6 mice had normal to enhanced bone formation. Introduction: With aging, there may be a reduction in the number or proliferative capacity of bone marrow osteoprogenitors that may contribute to age-related decreases in bone formation. To examine the link between the ability of the marrow to support osteogenesis and age-related changes in bone formation, we measured in vitro and in vivo indices of osteogenesis in a model of osteoporosis, the senescence-accelerated mouse SAMP6. Materials and Methods: Femora and tibias from SAMP6 and SAMR1 (control) mice were harvested at 2, 4, 6, and 12 months of age (168 bones total). Bone marrow cells were cultured under osteogenic conditions and stained for alkaline phosphatase (ALP) and alizarin red. Dynamic indices of bone formation were assessed histologically from calcein labels. Results: ALP+ and alizarin red-positive areas were significantly less in cultures from SAMP6 bones versus SAMR1 (p < 0.05), indicating less osteogenic potential. For example, SAMP6 tibial cultures had 21% less ALP+ area and 36% less alizarin red-positive area than SAMR1. Marrow from tibias had 2-fold greater osteogenesis than femoral marrow (p < 0.001). SAMP6 mice had a deficit in endocortical mineralizing surface across all age groups (p < 0.05), but no deficit in mineral apposition rate. Last, despite the marrow and endocortical deficits, SAMP6 mice had normal or slightly increased periosteal bone formation, consistent with their larger bone size. Conclusion: SAMP6 bone marrow supports less in vitro osteogenesis than SAMR1, consistent with a lower concentration of marrow osteoprogenitors in SAMP6. SAMP6 mice have less endocortical mineralizing surface than SAMR1 at all ages but no detectable deficit in mineral apposition rate, which suggests a reduction in osteoblast number but normal function. Periosteal bone formation is unimpaired in SAMP6 mice, indicating that the marrow/endocortical defect does not affect the periosteal surface.
Cyrano's nose: Variations on the theme of response

Abstract This essay responds to three articles in this issue on response to student writing. The author analyzes the consensus view of responding to student writing in order to highlight missing or misconceived elements of current theory, and then offers a speculative outline for a more comprehensive study of response. With this sketch in mind, she offers two variations on the theme of response, depicting it as “critical” and as “artful.”
The Costs of Speaking Truth to Power: How Professionalism Facilitates Credible Communication

This article examines how information or policy analysis can be credibly communicated between the bureaucracy and Congress. To investigate this issue, I develop a signaling model which shows that under certain circumstances-specifically when professionalized bureaucrats can impose observable costs on themselves that their politically inclined counterparts are unwilling to incur-credible communication between the bureaucracy and Congress is possible. A contribution of this article is that it provides a theoretical underpinning for the importance of professionalism and neutral competence in the bureaucracy as a means of promoting good governance.
Probing nanoscale self-assembly of nonfluorescent small molecules inside live mammalian cells.

Like cellular proteins that form fibrillar nanostructures, small hydrogelator molecules self-assemble in water to generate molecular nanofibers. In contrast to the well-defined (dys)functions of endogenous protein filaments, the fate of intracellular assembly of small molecules remains largely unknown. Here we demonstrate the imaging of enzyme-triggered self-assembly of nonfluorescent small molecules by doping the molecular assemblies with a fluorescent hydrogelator. The cell fractionation experiments, fluorescent imaging, and electron microscopy indicate that the hydrogelators self-assemble and localize to the endoplasmic reticulum (ER) and are likely processed via the cellular secretory pathway (i.e., ER–Golgi–lysosomes/secretion). This work, as the first example of the use of correlative light and electron microscopy for probing the self-assembly of nonfluorescent small molecules inside live mammalian cells, not only establishes a general strategy to provide the spatiotemporal profile of the assemblies...
Data from the deep: implications for the GIS community

The traditional home of GIS in terms of managing,mapping, modelling and making decisions based on spatial data has been in the land-based sciences and professions. This has resulted in a concentration of GIS on land-based 'application domains' (sets of GIS applications with common properties and data formats), with a relatively homogeneous group of users and applications addressing the solutions of largely related problems. This atmosphere has tended to obscure the essential nature of GIS as an ubiquitous, heterogeneous tool, having utility far beyond land-based problems. We must consider remedying this if we expect GIS to play an increasingly important role in Earth system science or global change research. We therefore propose the expansion of a largely landbased GIS research agenda to the development of systems focusing more on the marine environment, for there are many ways that GIS may be improved by tackling the problems associated with oceanographic data. The discussion is confined largely to deep ...
The nyctohemeral rhythm of plasma prolactin: effects of ganglionectomy, pinealectomy, constant light, constant darkness or 6-OH-dopamine administration.

In male rats maintained on a 12 hlight-dark schedule (6 AM-6 PM), there is a nyctohemeralcycle of plasma prolactin which consistsof a nadir at 11:30 AM and an apogee at approximately11:30 PM. In rats exposed to constant darkness,this rhythm persists for 7 days. Seven days ofconstant light, however, reverses this diurnal variationsuch that plasma prolactin levels peak at 11:30AM and reach a nadir at approximately 11:30 PM. Inanimals maintained on a 12 h light-dark cycle,ganglionectomy and lateral ventricular injections of6-OH-dopamine (250 μg) also appear to reverse thediurnal variation of plasma prolactin, whereas asingle injection of 6-OH-dopamine (250 μg) into thethird ventricle decreases plasma prolactin values atall time intervals but does not alter the diurnalrhythm. Both sites of 6-OH-dopamine administrationmarkedly deplete hypothalamic dopamine andnorepinephrine, but injection of 6-OH-dopamineinto the lateral ventricle destroys the catecholaminergicterminals in the pineal, whereas injectionof 6-OH-...
Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C.

We have previously shown that the activity of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) is required for nerve growth factor (NGF)-induced activation of NF-κB and cell survival ((2002) J. Biol. Chem. 277, 28010–28018). Herein we demonstrate that NGF induces co-association of IRAK with atypical protein kinase C iota (PKC) and that the iota PKC·IRAK complex is recruited to the p75 neurotrophin receptor. Recruitment of IRAK to the receptor was dependent upon the activity of the iota PKC. Moreover, transfection of kinase-dead iota PKC blocked both NGF- and IL-1-induced IRAK activation and the activity of NF-κB. Hence, iota PKC lies upstream of IRAK in the κB pathway. Examining the primary structure of IRAK, we identified three putative PKC phosphorylation sites; iota PKC selectively phosphorylated peptide 1 (RTAS) within the death domain domain at Thr66, which is highly conserved among all IRAK family members. Mutation of Thr66 to Ala impaired the autokinase activity of IRAK and reduced its association with iota PKC but not TRAF6, resulting in impaired NGF- as well as IL-1-induced NF-κB activation. These findings provide insight into the underlying mechanism whereby IRAK regulates the κB pathway and reveal that IRAK is a substrate of iota PKC.
Lessons from SARS and H1N1/A: Employing a WHO–WTO forum to promote optimal economic-public health pandemic response

No formal system exists to review trade restrictions imposed during international public health emergencies rapidly. Failure to put one in place creates disincentives for surveillance and reporting, thereby undermining protection efforts. The 2003 SARS outbreak exposed weaknesses in global governance that caused uncoordinated public health and economic responses. New International Health Regulations (IHR), applied first during the 2009 H1N1 influenza outbreak, demonstrated improvement. Yet they failed to allow for management of public health emergencies in a way that balanced threats to health and those to economies and trade. Establishment of a joint WHO-WTO committee to adjudicate these conflicts might better achieve that balance.
Volunteer Macroinvertebrate Monitoring: Tensions Among Group Goals, Data Quality, and Outcomes

Volunteer monitoring of natural resources is promoted for its ability to increase public awareness, to provide valuable knowledge, and to encourage policy change that promotes ecosystem health. We used the case of volunteer macroinvertebrate monitoring (VMM) in streams to investigate whether the quality of data collected is correlated with data use and organizers’ perception of whether they have achieved these outcomes. We examined the relation between site and group characteristics, data quality, data use, and perceived outcomes (education, social capital, and policy change). We found that group size and the degree to which citizen groups perform tasks on their own (rather than aided by professionals) positively correlated with the quality of data collected. Group size and number of years monitoring positively influenced whether a group used their data. While one might expect that groups committed to collecting good-quality data would be more likely to use it, there was no relation between data quality and data use, and no relation between data quality and perceived outcomes. More data use was, however, correlated with a group’s feeling of connection to a network of engaged citizens and professionals. While VMM may hold promise for bringing citizens and scientists together to work on joint conservation agendas, our data illustrate that data quality does not correlate with a volunteer group’s desire to use their data to promote regulatory change. Therefore, we encourage scientists and citizens alike to recognize this potential disconnect and strive to be explicit about the role of data in conservation efforts.
Energy management for solar battery charging station

This paper presents a new system architecture for a low cost photovoltaic (PV) battery charging station that can balance: 1) the charging time of each individual battery and 2) the total charging time of all batteries in the system. The control strategy for the new system first charges each individual battery to either the same voltage or same state of charge (SOC) level and then charges multiple batteries in parallel simultaneously. As the paper demonstrates, this method can increase solar energy exploitation so that the total charging time of all batteries is decreased. Experimental results of a prototype of the system validate the effectiveness of the proposed control strategy.
The New Lung Cancer Staging System

The International Association for the Study of Lung Cancer (IASLC) has conducted an extensive initiative to inform the revision of the lung cancer staging system. This involved development of an international database along with extensive analysis of a large population of patients and their prognoses. This article reviews the recommendations of the IASLC International Staging Committee for the definitions for the TNM descriptors and the stage grouping in the new non-small cell lung cancer staging system.
SPT: a stochastic tunneling algorithm for global optimization

A stochastic approach to solving unconstrained continuous-function global optimization problems is presented. It builds on the tunneling approach to deterministic optimization presented by Barhen and co-workers (Bahren and Protopopescu, in: State of the Art in Global Optimization, Kluwer, 1996; Barhen et al., Floudas and Pardalos (eds.), TRUST: a deterministic algorithm for global optimization, 1997) by combining a series of local descents with stochastic searches. The method uses a rejection-based stochastic procedure to locate new local minima descent regions and a fixed Lipschitz-like constant to reject unpromising regions in the search space, thereby increasing the efficiency of the tunneling process. The algorithm is easily implemented in low-dimensional problems and scales easily to large problems. It is less effective without further heuristics in these latter cases, however. Several improvements to the basic algorithm which make use of approximate estimates of the algorithms parameters for implementation in high-dimensional problems are also discussed. Benchmark results are presented, which show that the algorithm is competitive with the best previously reported global optimization techniques. A successful application of the approach to a large-scale seismology problem of substantial computational complexity using a low-dimensional approximation scheme is also reported.
Reversible dioxygen binding to hemerythrin.

A combination of conventional quantum chemical methods and a recently developed mixed quantum mechanical/molecular mechanical (QM/MM) method (QSite) is used to determine the different energetic components involved in reversible binding of O2 to hemerythrin. The use of an accurate quantum chemical description of the active site and the inclusion of effects from the surrounding protein environment are both essential to achieve reversibility and thus to model accurately the binding of O2 to the carboxylate-bridged diiron center in the protein. The major contributions from the protein environment stabilizing dioxygen binding are (1) the van der Waals interaction between the bound dioxygen and the protein atoms and (2) an increase in the hydrogen bonding energy of an imidazole group, ligated to one of the iron atoms, and a neighboring carboxylate side chain in the second coordination sphere. The protein strain energy for this system is negligible. The calculated total O2 binding free energy is in good agreemen...
Enhanced Functionality of Nanotube Atomic Force Microscopy Tips by Polymer Coating

To stabilize nanotube-modified atomic force microscopy tips and extend their functionality, a method for conformal polymer coating of the tips and removal of the polymer from just the probing nanotube end is described. Expressions quantifying stabilization of the tips against buckling and bending due to stresses encountered while imaging are developed. Electrical conductivity of the probes is demonstrated by their use in scanned conductance microscopy, where a substantial sensitivity advantage over standard tips is realized and explained. Further advantages of these electrically insulated (save for the tip) probes are discussed, including their proposed application in bioelectrochemical research.