cssi/SciSciGPT-SciSciNet huggingface dataset:
Intragenic Suppressing Mutations Correct the Folding and Intracellular Traffic of Misfolded Mutants of Yor1p, a Eukaryotic Drug Transporter

ATP-binding cassette (ABC) transporters play pivotal physiological roles in substrate transport across membranes, and defective assembly of these proteins can cause severe disease associated with improper drug or ion flux. The yeast protein Yor1p is a useful model to study the biogenesis of ABC transporters; deletion of a phenylalanine residue in the first nucleotide-binding domain (NBD1) causes misassembly and retention in the endoplasmic reticulum (ER) of the resulting protein Yor1p-ΔF670, similar to the predominant disease-causing allele in humans, CFTR-ΔF508. Here we describe two novel Yor1p mutants, G278R and I1084P, which fail to assemble and traffic similar to Yor1p-ΔF670. These mutations are located in the two intracellular loops (ICLs) that interface directly with NBD1, and thus disrupt a functionally important structural module. We isolated 2 second-site mutations, F270S and R1168M, which partially correct the folding injuries associated with the G278R, I1084P, and ΔF670 mutants and reinstate their trafficking. The position of both corrective mutations at the cytoplasmic face of a transmembrane helix suggests that they restore biogenesis by influencing the behavior of the transmembrane domains rather than by direct restoration of the ICL1-ICL4-NBD1 structural module. Given the conserved topology of many ABC transporters, our findings provide new understanding of functionally important inter-domain interactions and suggest new potential avenues for correcting folding defects caused by abrogation of those domain interfaces.
Pathway of ATP hydrolysis by monomeric kinesin Eg5.

Kinesin-5 family members including human Eg5/KSP contribute to the plus-end-directed force necessary for the assembly and maintenance of the bipolar mitotic spindle. We have used monomeric Eg5-367 in the nucleotide-free state to evaluate the role of microtubules at each step in the ATPase cycle. The pre-steady-state kinetic results show that the microtubule−Eg5 complex binds MgATP tightly, followed by rapid ATP hydrolysis with a subsequent slow step that limits steady-state turnover. We show that microtubules accelerate the kinetics of each step in the ATPase pathway, suggesting that microtubules amplify the nucleotide-dependent structural transitions required for force generation. The experimentally determined rate constants for phosphate product release and Eg5 detachment from the microtubule were similar, suggesting that these two steps are coupled with one occurring at the slow rate after ATP hydrolysis followed by the second step occurring more rapidly. The rate of this slow step correlates well with...
Correlation of non-random chromosomal aberrations in lymphocytes of prostate cancer patients with specific clinical parameters.

The purpose of this research was to correlate non-random chromosomal aberrations in the peripheral blood lymphocytes (PBLs) of prostate cancer patients with specific clinical parameters. Peripheral blood samples were analyzed from 59 informative prostate cancer patients. Non-random chromosomal alterations detected in the PBLs and their correlation with any specific clinical parameters were analyzed statistically. A comparison was made between specific chromosomal abnormalities in the patients having an early ( or =65 years) age at disease onset, low-grade (Gleason grade or =7) tumors, a low ( or =10 ng/ml) prostate-specific antigen (PSA) level, and androgen-sensitive or -insensitive disease. In examining the specific chromosomal breakpoints, the regions 1p13, 2q21, 3p21, 4q13, 5q31, 6p21, 7p15, 7p13, 7q32, 10p11, 10q26, 11p15, 11p11, 14q12, and 16q12 showed breaks in at least four cases. Chromosome 15 (P=0. 045) was significantly altered in patients having a PSA value greater than or equal to 10, while it (P=0.017) and chromosome 19 (P=0.036) were significantly altered in patients having a PSA value greater than or equal to 20. In addition, chromosomes 5 (P=0.032), 8 (P=0.020), 16 (P=0.009), and 20 (P=0.047) were significantly altered in patients having a Gleason grade greater than 7. Also, chromosomes 2 (P=0.020) and 3 (P=0.044) were significantly altered in patients who had early disease onset. Additionally, chromosome 10 (P=0.041) was significantly altered in patients having metastasis, and chromosomes 4 (P=0.006) and 7 (P=0.028) were significantly altered in patients having androgen-insensitive disease. In spite of the small subset of patients, chromosome 8 (p=0.003) was significantly altered in patients having small cell carcinoma of the prostate. From these results we conclude that non-random chromosomal aberrations present in PBLs of prostate cancer patients can be correlated with specific clinical parameters. These correlations can be used to identify a prostate cancer patient's risk response to therapy.
Long-term dynamics of leafy spurge (Euphorbia esula) and its biocontrol agent, flea beetles in the genus Aphthona

Three flea beetle species (Aphthona spp.), first introduced into North America in 1988, have come to be regarded as effective biological control organisms for leafy spurge (Euphorbia esula). The black flea beetles (Aphthona lacertosa and A. czwalinae) in particular have been shown to cause reductions in leafy spurge stem counts in the northern Great Plains, while the brown flea beetle (A. nigriscutis) has persisted and spread, but has not been found to be as effective at controlling leafy spurge. The ability of black flea beetles to control leafy spurge in any given year, however, has been found to vary. To better understand the long-term effects of flea beetle herbivory on leafy spurge, we monitored stem counts of leafy spurge and numbers of black and brown flea beetles at three sites on two National Wildlife Refuges in east-central North Dakota, USA, from 1998 to 2006. Brown flea beetle numbers were observed to be negligible on these sites. Over the 9 years of the study, black flea beetles were seen to spread over the three study sites and leafy spurge stem counts declined substantially on two of the three sites. Even at low densities of spurge, black flea beetle populations persisted, a necessary prerequisite for long-term control. We used structural equation models (SEM) to assess the yearly effects of black flea beetles, soil texture, and refuge site on leafy spurge stem counts over this time period. We then used equations developed from the SEM analysis to explore flea beetle–leafy spurge dynamics over time, after controlling for soil texture and refuge. Yearly effect strength of black flea beetles on leafy spurge was found to be modest, largely owing to substantial spatial variability in control. However, simulation results based on prediction coefficients revealed leafy spurge to be highly responsive to increases in flea beetle populations on average.
WASP: A NEW CONCEPT FOR SEMISUBMERSIBLES

This paper describes an innovative new concept for semisubmersibles that is adaptable to a wide variety of operational objectives and subsystem equipment packages. The WASP (Wave Adaptive Semisubmersible Platform) is a "jack-up semisubmersible" which can be tuned (with minimal ballasting) so as to improve overall stability and motion in any sea condition. Various operational advantages are described for application of the concept to ocean drilling, North Sea tug/supply operations, pipelaying, diver support, or general workover.
Scanning OCT endoscope with 2-axis magnetic micromirror

Micromirrors used to steer optical beams at the tip of an endoscope are an active area of research. MEMS mirrors with various actuation mechanisms have been reported including rotating micromotors, parallel plate electrostatic drive, electrothermal and electrostatic comb drive. This paper presents a two-axis magnetically actuated micromirror designed for an OCT (Optical Coherence Tomography) endoscope. Magnetic actuation allows large angular deflections at low voltage (1-3 V), a significant advantage for patient safety relative to the high voltages used for electrostatic mirrors. Actuation is accomplished with small coils in proximity to the moving mirror, which contains a small permanent magnet. The endoscope scan engine is contained in a 2.8 mm ID plastic tube. The MEMS scan mirror was fabricated by a simple process using an SOI wafer and only 2 photo-steps. The mirror is supported by silicon springs on both axes, and can scan to +/- 20 degrees mechanical on both axes. Both time domain and spectral domain OCT have been used to take cross-sectional tissue images. By operating the 2-axis mirror in a raster scan, a sequence of cross-sections is taken to form a 3-D image. Details of the endoscope design, MEMS fabrication, and sample OCT images are presented.
Non-antibody immunotherapy of cancer

Immunotherapeutic agents have become important additions to the list of anti-cancer treatments; further progress will require more information about how the immune system can respond to tumor cells. Tumor cells can avoid eliciting an immune response through several mechanisms. Understanding these mechanisms may suggest strategies to manipulate tumor cells so that they trigger an effective immune response. Another strategy being developed is to improve the therapeutic index of cytokines so that better anti-tumor effects can be elicited with less toxicity.
Alternative Approaches to Modeling Hereditary Dystonias

Dystonia is a movement disorder characterized by involuntary muscle contractions resulting in abnormal postures. Although common in the clinic, the etiology of dystonia remains unclear. Most dystonias are idiopathic and are not associated with clear pathological brain abnormalities. Attempts to genetically model these dystonias in rodents have failed to replicate dystonic symptoms. This is at odds with the fact that rodents can exhibit dystonia. Because of this discrepancy, it is necessary to consider alternative approaches to generate phenotypically and genotypically faithful models of dystonia. Conditional knockout of dystonia-related genes is 1 technique that may prove useful for modeling genetic dystonias. Lentiviral-mediated small or short hairpin RNA (shRNA) knockdown of particular genes is another approach. Finally, in cases in which the function of a dystonia-related gene is well-known, pharmacological blockade of the protein product can be used. Such an approach was successfully implemented in the case of rapid-onset dystonia parkinsonism, DYT12. This (DYT12) is a hereditary dystonia caused by mutations in the α3 isoform of the sodium potassium adenosine triphosphatase (ATPase) pump (sodium pump), which partially hampers its physiological function. It was found that partial selective pharmacological block of the sodium pumps in the cerebellum and basal ganglia of mice recapitulates all of the salient features of DYT12, including dystonia and parkinsonism induced by stress. This DYT12 model is unique in that it faithfully replicates human symptoms of DYT12, while targeting the genetic cause of this disorder. Acute disruption of proteins implicated in dystonia may prove a generally fruitful method to model dystonia in rodents.
Maternal-infant relationship quality and risk of obesity at age 5.5 years in a national US cohort

Poor quality relationships between mothers and toddlers have been associated with higher risk for childhood obesity, but few prospective studies of obesity have assessed maternal-child relationship quality in infancy. In addition it is not known whether the increased risk is associated with the mother’s or the child’s contribution to the relationship quality. We analyzed data (n = 5650) from the Early Childhood Longitudinal Study, Birth Cohort, a national study of U.S. children born in 2001 and followed until they entered kindergarten. At 9 months of age, the Nursing Child Assessment Teaching Scale (NCATS) was used to assess the quality of observed playtime interactions between mothers and infants, yielding separate scores for maternal and infant behaviors. Obesity (BMI ≥95th percentile) at age 5.5 years was based on measured weight and height. The prevalence (95% confidence interval) of obesity at 5.5 years of age was higher among children in the lowest quartile of maternal NCATS score (20.2% [95% CI: 17.2%, 23.2%]) than in the highest quartile (13.9% [11.3%, 16.5%]), but maternal NCATS score was not significantly associated with obesity after adjustment for race/ethnicity, maternal education and household income. The prevalence of obesity at 5.5 years of age was similar among children in the lowest quartile of infant NCATS score (17.4% [14.4%, 20.3%]) and in the highest quartile (17.6% 14.4%, 20.8%]), and was not changed with covariate adjustment. Maternal-infant relationship quality, assessed by direct observation at 9 months of age in a national sample, was not associated with an increased risk of obesity at age 5.5 years after controlling for sociodemographic characteristics.
Thickness, and a categoric view of type-space functors

We dene the class of thick cats (compact abstract theories, which con- tains in particular semi-Hausdor, Hausdor and rst order cats), and prove that in this class simplicity behaves as in rst order theories. We consider well-known rst order no- tions, such as interpretability or stable dividing/reduct, and propose analogous notions that can be naturally expressed in terms of maps between type-space functors. We prove several desirable properties of the new notions and show the connection between them and their classical counterparts. We conclude with several scattered results concerning cats and simplicity. Introduction. In (Ben03) we dened cats (or compact abstract theo- ries), which may be viewed as a model-theoretic framework with compact- ness but without negation. It is more general than the rst order framework, and can accommodate, for example, various kinds of analytic structures that do not admit a rst order description. In fact, we showed the equivalence of several quite dieren t approaches to the denition of cats, each having its own merits. The rst and most concrete presentation of a cat is via a particular kind of universal domains which are homogeneous and compact in a language without negation. Types, dividing, etc., are dened more or less as usual inside a universal domain. In (Benb) we showed how simplicity can be de- veloped in this context from the assumption that non-dividing has the local character, even though this does not imply that non-dividing extensions always exist. In the rst section of the present paper we introduce the class of thick cats, i.e., cats where indiscernibility is type-denable. We show that the thickness assumption is very mild, and that with this assumption many
THIS LAND IS OURS NOW: Social Mobilization and the Meanings of Land in Brazil. By Wendy Wolford.

(2011). This Land is Ours Now: Social Mobilization and the Meanings of Land in Brazil. By Wendy Wolford. Geographical Review: Vol. 101, No. 2, pp. 292-294.
Further experience with contrast-enhanced CT in head trauma

Abnormal contrast enhancement was seen in 196 (39.8%) of 492 CT scans performed on patients for evaluation of head trauma. It proved most helpful in the diagnosis of isodense subdural hematomas and contusions. The advantages of contrast-enhanced CT scans in the evaluation of head trauma more than compensate for the additional time in performing the examination.
Increased levels of ubiquitin in the 6-OHDA-lesioned striatum of rats.

This thesis describes the utilization of the matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and electrospray ionization (ESI) MS techniques for analysis of complex brain tissue samples. Direct molecular profiling of biological samples using MALDI MS is a powerful tool for identifying phenotypic markers. MALDI MS-profiling of proteins and peptides directly on brain tissue sections was used for the first time to study experimental models of Parkinson’s disease (PD). The mass spectrometer was used to map the peptide and protein expression directly on 12 µm tissue sections in mass-to-charge (m/z) values, providing the capability of mapping specific molecules of the original sample, that is, localization, intensity and m/z ratio. Several protein and peptide expression profile differences were found in the dopamine denervated brains when compared to the corresponding controls, for example, calmodulin, cytochrome c, cytochrome c oxidase, and the neuroimmunophilin protein FKBP-12. The increased expression of FKBP-12 from the profiling experiments was supported by mRNA expression analysis and two-dimensional gel electrophoresis separation analysis. Multiple genetic deficits have linked impaired ubiquitin-conjugation pathways to various forms of familiar PD. This study showed for the first time an increased level of unconjugated ubiquitin specifically in the dorsal striatum of the dopamine depleted PD brain. The strength of the MALDI MS-profiling technique is that a minimum of sample handling and manipulation is necessary pre-analysis. This ensures preservation of the spatial localization of the biomolecules in the tissue section.Biological liquid samples often contain high amounts of salt that is non-compatible with the ESI MS technique. A nano-flow capillary liquid chromatography (nanoLC) system coupled on-line with ESI-MS was used to study the metabolism of the peptide LVV-hemorphin-7 in the brain and blood using in vivo microdialysis. The microdialysis technique provides capabilities for very precise sampling in specific brain regions. The combination of on-line desalting and pre-concentration by nanoLC with ESI MS is a powerful tool to detect minute concentration of metabolic fragments and endogenous biomolecules.The utilization of mass spectrometry in neuroscience applications provides a uniquely advantageous tool for the analysis of complex biochemical events that underlie the pathological symptoms expressed in different disease states. Furthermore, the MALDI-MS profiling technique shows great potential for the future with regards to proteome analysis and drug discovery.
Fluorescence correlation spectroscopy. III. Uniform translation and laminar flow

We extend fluorescence correlation spectroscopy to systems that undergo translation or laminar flow in a sample cell. We include theoretical and experimental results; we consider uniform and nonuniform velocity profiles. Concentration correlation analysis extracts microscopic rate parameters from measurements of the spontaneous concentration fluctutations, which occur even at equilibrium. Fluorescence is one of the most sensitive means of monitoring these fluctuations. Analysis of flowing or translating systems (1) offers a method of measuring number concentrations of selected species, for example, of aggregates or polymers, (2) provides a nonperturbing velocity probe, (3) sometimes allows one to circumvent photolytic degradation, (4) has proved extremely helpful in testing and aliging apparatus for fluorescence correaltion measurement and in verifying theoretical analyses, and (5) may be required for interpretation of results obtained on systems in motion, even though that motion is undesired or initially unsuspected. We include both theoretical and experimental results for combined Poiseuille flow and diffusion in the geometry which is of most practical interest. Theoretical expressions for the much simpler cases of nondiffusive Poiseuille flow as well as uniform flow or translation with or without diffusion constitute limiting cases which are displayed explicitly.
A Holistic Schema Matcher

The capability of matching the schemas of the databases has led to its wide use in e-commerce, data integration, and data warehousing. In this paper we develop a holistic schema matcher, which provides a match between two schemas by combining the match results from the element-level techniques as well as instance-level techniques. The experimental results demonstrate good performance of the proposed matcher.
Novel Mesoporous Silicates with Two-Dimensional Mesostructure Direction Using Rigid Bolaform Surfactants

In this paper we describe how pore-structure modification can be achieved in a highly ordered fashion through the use of bolaform surfactants containing a rigid unit in the hydrophobic chain. The silicate mesophase, SBA-8, synthesized using bolaform surfactants at room temperature, is a two-dimensional (2-D) pore structure with a centered rectangular lattice (space group cmm, 1 1000 m2/g). The unit cell parameter of the silicate mesostructure can be varied by adding gemini surfactants or by changing reaction temperature; a 2-D silicate mesophase (Mα, a/b > √3) and high quality hexagonal MCM-41 (p6mm, a/b = √3) can be obtained. Hydrothermal transformation of SBA-8 into MCM-41 takes place, confirming the intermediate nature of the SBA-8 mesophase.
Prey use among sympatric lizard species in lowland rain forest of Nicaragua

The diets of 17 lizard species (seven families) studied simultaneously in a Caribbean lowland forest of Nicaragua were compared. Lizards varied in body size over nearly one order of magnitude. Twelve species for which there were adequate samples separated by prey types and most diet overlaps were low. A pseudocommunity analysis on volumetric diet data revealed significant guild struc- ture in the assemblage. At each nearest neighbour rank in niche space, observed overlaps were higher than expected based on chance alone when all values in the consumer-resource matrix were randomized. There was no difference between observed and pseudocommunity overlaps with zero positions in the consumer- resource matrix retained (conserved-zero overlaps) indicating that the zero struc- ture of the community matrix was important in maintaining structure and that lizards were converging on key resources. Individual prey size varied among species and mean prey size was significantly correlated with body size of lizard species. A phylogenetic analysis revealed no relationship between similarity in prey use (dietary overlap) and evolutionary relationships - more closely related species did not eat more similar prey types. Based on this analysis of Nicaraguan lizard diets and comparisons with other New World tropical lizard assemblages, it is suggested that factors contributing to the organization of tropical lizard assemblages are complex including historical differences in morphology (size), prey types and sizes, habitat structure and species interactions.
Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence

Abstract Postnatal day-14 (P14) infant rats remained naive or were implanted with osmotic minipumps infusing saline or fentanyl (50 μg kg −1 h −1 ). Fentanyl was administered 72 h later for measurement of antinociception in the tail-flick test. The potency of fentanyl was 3.0-fold lower in fentanyl-infused compared to saline-infused P17 rats. Fentanyl-infused P17 rats injected with naloxone underwent withdrawal characterized by increases in spontaneous activity, wall climbing, diarrhea, abdominal stretching, forepaw treading/tremors, wet-dog shakes, jumping, ptosis, rhinorrhea and hypothermia. Other naive, saline-infused and fentanyl-infused P17 rats not challenged with fentanyl or naloxone were housed until maturing into P42 juveniles. Fentanyl's potency was equal among each treatment group. However, morphine's potency was reduced in juveniles tolerant to fentanyl as infants. Morphine was also less potent in P90 adults tolerant to fentanyl as infants. Thus, chronic opiate exposure during infancy may affect the developing central nervous system, and desensitize animals and humans to opiate analgesia throughout life.
Novel polyviologens: Photochromic redox polymers with film‐forming properties

Several novel polyamides containing the N,N′-dialkyl-4,4′-dipyridinium (“viologen”) system were made by interfacial condensation of N,N′-bis(aminoalkyl)-4,4,-dipyridinium salts with di-, tri-, or tetrafunctional acid chlorides. These materials are useful redox polymers which turn deeply colored when reduced chemically or electrically, or when exposed to light.
Apparent absorptance for diffusely and specularly reflecting spherical cavities

The apparent absorptance of a cavity α cavity, is defined as the fraction of energy flux emitted by a black-body surface stretched across the cavity opening that is absorbed by the cavity walls. Because of multiple reflections among the cavity walls, α cavity will exceed the surface absorptance, α . Such an effect, called the cavity effect, is employed in the design of receiver/reactors for solar furnaces to capture the solar radiation. The cavity effect for partial enclosures has been analyzed for specific configurations, among them: cylindrical, conical, spherical, rectangular-groove and V-groove cavities. These problems have been solved for specularly and diffusely reflecting cavity walls. Little information is presently available which describes the particular case of specularly reflecting spherical cavities with a circular opening. Such cavities offer several intriguing advantages over the conventional heavily insulated enclosures made of ceramic materials when applied for solar furnace receivers at moderate to high (2000 K and above) temperatures. Specular spherical geometries have also significant importance in modelling radiant heat transport through the void spaces across a porous material, and the apparent surface emittance was analytically derived for a differential element of a sphere. In the present study, the apparent absorptance of a spherical cavity with a circular opening is calculated for cavity walls having both specular and diffuse reflectance components.
Electrophysiology of newt skin: responses to salt-depletion, aldosterone, arginine vasotocin and epinephrine.

Abstract 1. 1. Newts ( Taricha granulosa ), salt-depleted by 3 weeks' immersion in distilled water, showed significantly higher in vitro integumental short-circuit current (SCC) than control newts immersed in dilute saline. 2. 2. Isolated, in vitro preparations of newt skin responded to aldosterone (10 −6 M), arginine vasotocin (10 −9 –10 −8 M), and epinephrine (10 −7 –10 −5 M) by increasing SCC. 3. 3. The hormonal response of the skin of this salamandrid urodele, as judged from in vitro (Ussing chamber) measurements, is similar to that seen in classical anuran (“frog skin”) preparations.
The statistical distribution of magnetotelluric apparent resistivity and phase

SUMMARY The marginal distributions for the magnetotelluric (MT) magnitude squared response function (and hence apparent resistivity) and phase are derived from the bivariate complex normal distribution that describes the distribution of response function estimates when the Gauss‐ Markov theorem is satisfied and the regression random errors are normally distributed. The distribution of the magnitude squared response function is shown to be non-central chi-squared with 2 degrees of freedom, with the non-centrality parameter given by the squared magnitude of the true MT response. The standard estimate for the magnitude squared response function is biased, with the bias proportional to the variance and hence important when the uncertainty is large. The distribution reduces to the exponential when the expected value of the MT response function is zero. The distribution for the phase is also obtained in closed form. It reduces to the uniform distribution when the squared magnitude of the true MT response function is zero or its variance is very large. The phase distribution is symmetric and becomes increasingly concentrated as the variance decreases, although it is shorter-tailed than the Gaussian. The standard estimate for phase is unbiased. Confidence limits are derived from the distributions for magnitude squared response function and phase. Using a data set taken from the 2003 Kaapvaal transect, it is shown that the bias in the apparent resistivity is small and that confidence intervals obtained using the non-parametric delta method are very close to the true values obtained from the distributions. Thus, it appears that the computationally simple delta approximation provides accurate estimates for the confidence intervals, provided that the MT response function is obtained using an estimator that bounds the influence of extreme data.
Some improvements to the Shenoy-Shafer and Hugin architectures for computing marginals

Abstract The main aim of this paper is to describe two modifications to the Shenoy-Shafer architecture with the goal of making it computationally more efficient in computing marginals of the joint valuation. We also describe a modification to the Hugin architecture. Finally, we briefly compare the traditional and modified architectures by solving a couple of small Bayesian networks, and conclude with a statement of further research.
Endoscopic Brow-lift in the Male Patient

Objective To report our experience with the endoscopic brow-lift in male patients at a university-affiliated outpatient surgery center. Methods Retrospective case series. Results From 1995 to 2007, a total of 244 endoscopic brow-lift procedures were performed, 21 of which involved men. Thirteen of the male patients had receding hairlines or some degree of baldness. Two male patients had postoperative complications; 1 male patient had temporal branch neurapraxia that resolved; and 1 male patient had in-office scar revision. Conclusions We have found that the endoscopic brow-lift procedure is well suited for male facial rejuvenation. Furthermore, our combined stair-step approach and suture suspension technique provides consistent results and high satisfaction regardless of the patient's hairline.
Variable damping impedance control of a bilateral telerobotic system

Stiffness and damping control in a telerobotic system allows the master and slave dynamics to be defined by the user. However, many requirements for good teleoperation produce conflicting choices of desired dynamic parameters. Rather than selecting a compromise value for the damping of the master and slave, it is proposed that these values be functionally dependent on sensed and commanded values of force and velocity, with no previous knowledge of the environment required. A strategy is proposed which provides better quality teleoperation under a variety of circumstances than is achievable with constant dynamics. It is shown that tracking in free space and along a surface by the slave can be maintained while impact forces are minimized. The algorithms have been implemented on a 7-DOF Robotics Research Corporation manipulator with a 6-DOF Kraft master hand controller, and the impact and tracking performance is illustrated.
The FK506-Binding Immunophilin FKBP51 Is Transcriptionally Regulated by Progestin and Attenuates Progestin Responsiveness

FKBP51 and FKBP52 are large molecular weight FK506-binding immunophilins that have diverse biochemical functions. Best studied is the role that they play as components of steroid hormone receptors. Differential display and gene array screens have identified FKBP51 as a progestin-inducible gene. Here we demonstrate progestin enhancement of FKBP51 mRNA and protein in T-47D cells. FKBP51 mRNA and protein levels were increased 3-fold by 20 nM R5020. Induction of FKBP51 mRNA was unaffected by 1 g/ml cycloheximide but was blocked by the progestin receptor (PR) antagonist RU486 (1 M). Reporter plasmids containing 3.4 kb and 427 bp of 5-flanking sequences of the human FKBP51 protein gene (FKBP5) exhibited regulation by progestin in T-47D cells. A construct containing 19 bp of upstream sequence demonstrated diminished basal activity and no stimulation by R5020. To test whether elevated FKBP51 affects progestin responsiveness, HepG2 cells were transfected with human FKBP51, PR, and mouse mammary tumor virus-luciferase plasmids, and treated with R5020 (0.03–10 nM). Expression of FKBP51 increased the EC50 for PR transactivation by 3.2-fold. Expression of FKBP51 from squirrel monkey, a New World primate with naturally occurring progestin resistance, increased the EC50 more dramatically (11.7-fold vs. control). Expression of FKBP51 bearing a double-point mutation in the tetratricopeptide repeat domain had no effect on PR transactivation. These results suggest that increased expression of FKBP51 by progestin may attenuate progestin responsiveness in hormone-conditioned cells. Furthermore, overexpression of FKBP51 in the squirrel monkey may be a contributing cause of progesterone resistance in this species. (Endocrinology 144: 2380 –2387, 2003)
High‐throughput sequencing for biology and medicine

Advances in genome sequencing have progressed at a rapid pace, with increased throughput accompanied by plunging costs. But these advances go far beyond faster and cheaper. High-throughput sequencing technologies are now routinely being applied to a wide range of important topics in biology and medicine, often allowing researchers to address important biological questions that were not possible before. In this review, we discuss these innovative new approaches—including ever finer analyses of transcriptome dynamics, genome structure and genomic variation—and provide an overview of the new insights into complex biological systems catalyzed by these technologies. We also assess the impact of genotyping, genome sequencing and personal omics profiling on medical applications, including diagnosis and disease monitoring. Finally, we review recent developments in single-cell sequencing, and conclude with a discussion of possible future advances and obstacles for sequencing in biology and health.
Proprioceptive Hair Cells on the Neck of the Squid Lolliguncula brevis: A Sense Organ in Cephalopods for the Control of Head-To-Body Position

Decapod cephalopods, such as cuttlefishes and squids, have a distinct neck region that allows movements (roll, pitch and yaw) of the head relative to the body. This paper describes the structure, innervation and central pathways of proprioceptive hair cells on the neck of the squid Lolliguncula brevis that sense such movements and control head-to-body position. These hair cells exist on the dorsal side of the neck underneath the nuchal cartilage, close to the animal's midline on either side of the nuchal crest. On each side, the hair cells can be divided into an anterior and a posterior group of 25-35 and 70-80 cells, respectively. An individual hair cell carries up to 300 kinocilia of equal length (about 30 $\mu $ m), arranged in up to seven rows. The hair cells of the left and right anterior group are morphologically polarized in the medial direction, whereas the hair cells of the left and right posterior group are polarized in the anterior direction. The hair cells are primary sensory cells. They are innervated by a branch of the postorbital nerve and project ipsilaterally into the ventral part of the ventral magnocellular lobe. Efferent synaptic contacts are present at the base of the hair cells. In behavioural tests the influence of the neck hair cells on head position control was investigated. During imposed body rolls, a unilateral deafferentation of the cells caused an asymmetric change of the compensatory head roll response and elicited a head roll offset to the operated side. Bilateral deafferentation of the cells elicited a downward head pitch offset. This offset was superimposed on the compensatory head pitch response during imposed body pitch.
Grid computing environments

Grid aspects that form grid computing environments (GCEs) are not cleanly defined, although there is an operational definition stemming from the work areas of the GCE research group of the Global Grid Forum. We describe the two major areas covered by this research group today. First we discuss programming the grid and follow with a discussion of portals that control the user view of the grid. Together they provide a linked component model for the middleware and user interface to the grid.
A Statistical Model for Lost Language Decipherment

In this paper we propose a method for the automatic decipherment of lost languages. Given a non-parallel corpus in a known related language, our model produces both alphabetic mappings and translations of words into their corresponding cognates. We employ a non-parametric Bayesian framework to simultaneously capture both low-level character mappings and high-level morphemic correspondences. This formulation enables us to encode some of the linguistic intuitions that have guided human decipherers. When applied to the ancient Semitic language Ugaritic, the model correctly maps 29 of 30 letters to their Hebrew counterparts, and deduces the correct Hebrew cognate for 60% of the Ugaritic words which have cognates in Hebrew.
Isohormones of Chorionic Gonadotropin Produced by Cloned Cell Lines in Culture

Chorionic gonadotropin (CG) synthesized by human choriocarcinoma cells in culture was fractionated by isoelectric focusing on polyacrylamide gel and examined for biological (B) and immunological (I) activity. Two isohormones of CG with isoelectric points (pI's) of 3.0 and 4.5 were found in the culture medium from each of three clonal lines studied. The isohormones of CG with pI 3.0 had a B/I ratio of 2.5 while the isohormone with pI 4.5 had a B/I ratio of 0.5. The relative proportions of these two isohormones correlated with the B/I ratios previously found for the unfractionated CG from the same clones.
Pricing of multi-product bundles to match supply and demand

In this paper we provide a framework to price bundles that contain multiple products in a way to match supply and demand, more specifically we extend the framework developed by Schlamensee (1984) who considers the case of a bundle that contains two products. In Schmalensee (1984) the correlation structure among reservation prices (maximum price that a customer pays to acquire a product) for the two products within each consumer is analyzed by assuming that buyer’s reservation price pairs follow a bivariate normal distribution. We extend this two-product bundle framework into a multi-product bundle case by modeling the reservation prices within each consumer follow a multivariate normal distribution. We then analyze the implications of using multivariate normal distribution on several pricing aspects of the bundle and finally develop rules to price the bundle in order to match supply and demand, rather than the standard objectives such as profit maximization or cost minimization.
Sequential Analysis of Mothers’ and Fathers’ Reassurance and Children’s Postoperative Distress

Objective Children experience distress after surgery. Associations exist between parent reassurance (e.g., ‘‘It’s OK’’) and child distress, but little is known about the causal direction of these interactions. This study examined sequential relations between mothers’ and fathers’ reassurance and children’s distress. Methods 146 families with 2- to 11-year-olds undergoing elective surgery participated. Timeevent coding and time-window sequential analysis examined whether reassurance preceded or followed child distress. Secondary analyses examined the relation of child sex and parent anxiety with the reassurance/distress contingency. Results Reassurance was positively correlated with distress; however, nonverbal distress was less likely to start following reassurance and was also more likely to continue following reassurance. Mothers were more likely to reassure following boys’ verbal distress, and mothers with higher anxiety were more likely to reassure following nonverbal distress. Conclusions Whereas parental reassurance may prevent the start of child distress, it might maintain ongoing child distress.
The reproductive performance of Border Leicester ewes in contrasting photoperiodic environments

Border Leicester ewes were kept in three contrasting photoperiodic environments, the rhythm at latitude 30° 32′ S (group 1) - 12 h light: 12 h dark interrupted by 6 weeks of continuous light (group 2 a ) and 12 h light: 12 h dark (group 2 b ) - from August 1972 to September 1973. In group 1 all ewes exhibited oestrus compared with 87·5% and 57·1% in groups 2( a ) and 2( b ) respectively. The mean number of oestrous periods per ewe ranged from 4·4 in group 1 to 3·0 in group 2( a ) and 1·0 in group 2( b ). It is concluded that the non-fluctuating light rhythm had an adverse effect on the reproductive potential of the treated groups and that Border Leicester ewes are dependent on a fluctuating light rhythm for normal reproductive function.
Vegetation-climate interactions in the warm mid-Cretaceous

Abstract. Vegetation-climate interactions are thought to have amplified polar warmth during past warm periods. Here, we explore the vegetation-climate interactions in the mid-Cretaceous using a fully coupled ocean-atmosphere general circulation model with a dynamic vegetation component. We run simulations with 1x, 10x and 16x pre-industrial atmospheric CO2. Results show that forests expand from mid-latitudes to high latitudes as CO2 increases from 1x to 10x and 16x, mainly due to the CO2-induced warming. This expansion of mid-to-high latitude forests are largely supported by the distribution of mid-Cretaceous fossil woods and coal deposits. Globally, the presence of vegetation increases mean annual temperature and precipitation by 0.9 °C and 0.11 mm day−1 relative to bare ground. High-latitude warming induced by the presence of vegetation (∼1.9 °C) is less than half of that reported in previous studies. The weaker warming here is mainly due to less pronounced albedo feedbacks, and to a less extent, reduced poleward heat transport via weakening of the meridional overturning circulation. Our results suggest that other mechanisms in addition to high atmospheric CO2 and high-latitude vegetation are required to maintain the polar warmth.
Biologically Inspired Hierarchical Model for Feature Extraction and Localization

Some of the most important problems of computer vision are feature extraction and subsequent localization of those features in a new image. Since it is computationally prohibitive to search for the features over all possible locations and scales, it is necessary to design an algorithm that can selectively focus on and process information from only some regions within the image. In this work we present such an algorithm that is biologically inspired and performs a hierarchical search, from coarse to fine, in order to minimize the computational costs. The algorithm is very robust to non-linear image transformations such as changes in scale, rotation, skew, addition of noise, and changes in brightness and contrast. We demonstrate the computational efficiency as well as the effectiveness of the algorithm on several real world images.
A dynamic crash model for energy absorption in braided composite materials - Part II: Implementation and verification

A dynamic crash model is developed and implemented to model the failure behavior and energy absorption of braided composite structures. Part I describes the development and theoretical foundation of a viscoplastic material model that captures the rate-dependent behavior present in braided composite materials. Part II presents the implementation of the model into a finite element model program and the experimental results for tubes crushed from quasi-static to 4000 mm/s rates used to verify the model. Energy absorption decreases sharply with an increase in crush rate, which is reflected in this model. Design concepts are also introduced to increase energy absorption in braided composites.
Upland Movement Patterns and Habitat Selection of Adult Eastern Spadefoots (Scaphiopus holbrookii) at Cape Cod National Seashore

Abstract There is a paucity of empirical results regarding many aspects of the movement ecology and upland habitat use and preferences of the Eastern Spadefoot Toad (Scaphiopus holbrookii), an ephemeral, wetland-breeding anuran that is rare throughout a number of states in the northern portion of its range. We radio-tracked 45 adult Eastern Spadefoots in a coastal dune ecosystem at Cape Cod National Seashore, Massachusetts, United States and assessed a number of attributes related to the upland movement ecology and habitat preferences of this species. The mean maximum distance that we found for each of the 19 successfully tracked individuals, immediately post-breeding from the breeding wetlands, was 130.4 ± 28.0 m with a range of 3 – 449 m. Paired logistic regression results indicated that individuals selected areas closer to deciduous shrub edges and areas with greater percent cover of 1) ground-running pitch pine (Pinus rigida) branches at a 1-m scale, 2) deciduous shrubs at a 1-m scale, and 3) reindeer...
Upgrading transport protocols using untrusted mobile code

In this paper, we present STP, a system in which communicating end hosts use untrusted mobile code to remotely upgrade each other with the transport protocols that they use to communicate. New transport protocols are written in a type-safe version of C, distributed out-of-band, and run in-kernel. Communicating peers select a transport protocol to use as part of a TCP-like connection setup handshake that is backwards-compatible with TCP and incurs minimum connection setup latency. New transports can be invoked by unmodified applications. By providing a late binding of protocols to hosts, STP removes many of the delays and constraints that are otherwise commonplace when upgrading the transport protocols deployed on the Internet. STP is simultaneously able to provide a high level of security and performance. It allows each host to protect itself from untrusted transport code and to ensure that this code does not harm other network users by sending significantly faster than a compliant TCP. It runs untrusted code with low enough overhead that new transport protocols can sustain near gigabit rates on commodity hardware. We believe that these properties, plus compatibility with existing applications and transports, complete the features that are needed to make STP useful in practice.
Patient‐Regulated Methadone Dose and Optional Counseling in Methadone Maintenance

The authors evaluated the effects on retention and other outcomes of three approaches in a methadone maintenance program. At the time of admission, 300 chronic opioid users were randomly assigned to standard treatment, patient-regulated dose, or optional counseling. Retention of the optional counseling group exceeded that of the other two groups, but the difference was only of borderline significance. Allowing patients to regulate their methadone dose did not lead to a general escalation of dose. Subjects in optional counseling saw their counselors less than half as often as those in the standard treatment with two mandatory sessions per month. Illicit drug use and social performance in the twelfth month did not differ significantly among the three subgroups that remained in treatment. The findings support patient participation in decisions about methadone dose and the frequency of counseling.