cssi/SciSciGPT-SciSciNet huggingface dataset:
Failure of baclofen to modulate discriminative-stimulus effects of cocaine or methamphetamine in rats.

Abstract The effects of baclofen, an agonist at GABA B receptors, were evaluated in rats trained to discriminate 10.0 mg/kg of cocaine or 1.0 mg/kg of methamphetamine from saline under a fixed-ratio 10 schedule of food delivery. Baclofen (0.56–5.6 mg/kg) did not attenuate the discriminative–stimulus effects of the training dose of cocaine or methamphetamine and did not produce any shift in the cocaine and methamphetamine dose–response curves. Higher baclofen doses (3.0–5.6 mg/kg), however, markedly depressed or completely eliminated food-maintained responding. This suggests that previous reports of baclofen-induced decreases in cocaine self-administration behavior are connected, in some way, with either a general suppression of appetitive behaviors or with sedation and locomotor depression, rather than with any pharmacologically specific effect, and not accompanied by changes in subjective response to cocaine, as assessed by discriminative–stimulus measures.
Decentralized acoustic source localization in a distributed sensor network

The purpose of this work is to investigate acoustic source localization algorithms suitable for use with distributed sensor networks. Traditional sensor networks employ a central controller; however centralized data processing in large-scale sensor networks is not always desirable because of the excessive communication and computational complexity it requires. Therefore, fully distributed localization algorithms are considered. The most important aspect of these algorithms is that they be scalable for use in large sensor networks. The scalability is achieved by forming sensor nodes into groups which collaborate to locate sources. Source locations are determined from time of arrival (TOA) information of the acoustic wave front. Two source location solution methods are used: least squares (LS) and Tikhonov regularized inversion (RI). Experimental results validate the accuracy of a distributed localization approach, and the effectiveness of the LS and RI methods are compared. Additionally, important parameters of the distributed localization algorithm are considered.
Poster abstract: Range-based localization in sensor networks: localizability and accuracy

Localizability and accuracy are two fundamental problems in many range-based localization schemes for sensor networks. This poster addresses the two problems theoretically by introducing two new concepts: the effective degree and the lower bound of geometric dilution of precision (GDOP). We prove that the network is not localizable unless the average effective degree is greater than or equal to the dimension of the location space. We further show that the average localization accuracy is approximately inversely proportional to the average degree.
The Effect of Snow on Urban Density Patterns in the United States

It is well known that the metropolitan areas of the American heartland generally exhibit a more spatially concentrated population distribution than do the cities of the Sunbelt. Social scientists have generally attributed this difference to social and historical factors related to city age (i.e., to variation in the timing of cities' growth, and to related differences in their economic and social characteristics). This article seeks to establish the direct explanatory importance of climate itself in determining the population concentration of cities.The data are from Guterbock and Edmonston's Metropolitan Deconcentration Project, and pertain to a large sample of monocentric 1970 Urbanized Areas (UAs) of the United States. Population concentration is measured by the Density Distribution Index (DDI), a size-independent measure based on the parameters of an estimated negative exponential density pattern for each UA.It is shown that regional differences in urban concentration cannot be adequately explained aw...
Simple Techniques for Radiographing the Condyle

Improvement is needed in the techniques for radiographing the condyle. The techniques discussed are designed to reduce distortion and obscurities; the equipment used is inexpensive. Anteroposterior and lateral projections with standard dental X-ray machines, and a lateral condylar technique with a Panorex dental unit are described.
Dynamic mechanical properties of polymer-fluid systems : characterization of poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) hydrogels

Abstract The complex shear moduli of crosslinked poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) hydrogels were measured as a function of water content, temperature and frequency using dynamic mechanical spectroscopy. The effect of increasing water content on both the storage and loss moduli is to lower the temperatures at which mechanical transitions occur. There is a significant decrease in the storage moduli and increase in the loss moduli dispersions with increasing water content. These data could be well correlated by a multiple-mechanism, time-temperature superposition procedure. Between 2% and 28% water content in the copolymer sample, the relaxation spectra and shift function characterizing the glassy-rubbery state transition become independent of water content when properly referenced to the observed transition temperature. At lower temperatures where the β transition occurs, the mechanical viscoelastic spectra depend much more strongly on water content although the shift factors collapse to a single curve when referenced to the observed β transition temperature.
The effects of alcohol in breast milk on infant behavioral state and mother-infant feeding interactions

The short-term impact of infant exposure to alcohol in breast milk on mother-infant interactions and infant arousal was examined. Fourteen mother-infant dyads were tested on 2 occasions that consisted of an alcohol administration and a nonalcohol condition. Mother-infant interactions during feeding were videotaped and coded for dyadic reciprocity, maternal noncontingency, and dyadic conflict. Infants were observed for 1 hr after receiving either plain breast milk or breast milk containing alcohol. Behavioral state, startles, and tremors were recorded every 30 sec. Mother-infant interactions were characterized by higher noncontingency and dyadic conflict in the alcohol condition. After drinking breast milk containing alcohol, infants changed behavioral state more often, startled more, and spent less time in quiet sleep and more time in quiet alert and crying states. These findings suggest that exposure to breast milk containing alcohol may not have a sedating effect, as commonly believed.
Cooperation of nonsyngeneic tolerant lymphocytes: genetic restriction.

Abstract We have used a previously devised in vivo experimental model to investigate the ability of mouse thymus-dependent (T) and bone marrow-derived (B) lymphocytes to cooperate in immune (humoral) rejection of rat Yoshida ascites sarcoma (YAS). Because of conflicting reports in the literature concerning the effectiveness of T-B cooperation across major histocompatibility complex (MHC) barriers, we explored the interaction of T and B lymphocytes from mutually tolerant animals. Tolerance was achieved by establishing radiation chimeras of B6 → B6D2F 1 and D2 → B6D2F 1 constitutions. Chimeras' erythrocytes and spleen cells were shown by serological analysis to be the donor type. When the chimera was to serve as the tumor host or B-cell source, it was thymectomized prior to irradiation and reconstitution (TIR). Tolerance was evaluated by noting the inability of chimeric spleen cells to effect graft-versus-host damage upon injection into TIR host-type mice and the markedly reduced anti-host-type reactivity in short-term [ 3 H]thymidine-uptake tests. Successful cooperation, manifested by YAS rejection, was seen whenever donor T and host B lymphocytes were syngeneic. Parental (P) T cells enabled F 1 TIR mice to reject YAS, but the reciprocal was not true: F 1 donor T cells did not cooperate with B cells in parental TIR mice. However, when the host B lymphocytes were tolerant P cells, i.e., in a P → F 1 TIR chimera, injected F 1 T lymphocytes did cooperate successfully. The final test of allogeneic T and B cells gave the clear-cut negative answer that, even when tolerant mice are used as sources of lymphocytes, cooperation does not occur. These results therefore confirm that T and B lymphocytes must at least share one MHC haplotype in order to cooperate.
Optimal policies under risk for changing software systems based on customer satisfaction

Abstract The critical nature and impact of decisions regarding software-system changes demand a comprehensive framework for policy analysis. In this paper, we develop a Markov decision process model for the determination of jointly optimal warranty, maintenance and upgrade policies for software systems. The decision maker is the supplier, who needs to establish policies regarding the timing and nature of changes in the sytem. The state of the system is the customer satisfaction index, which is subject to declines of random magnitude, as a consequence of forgone warranty, maintenance and upgrade opportunities that arise randomly in any period. We consider a class of control-limit policies, defined by warranty, maintenance and upgrade thresholds. These thresholds divide the state space into four regions in which the supplier would, given the appropriate opportunity, do nothing, warrant only, warrant and maintain, or warrant, maintain and upgrade. We determine the optimal policies under different criterion functions, develop solution algorithms, provide computational examples, and identify a class of optimal or near-optimal policies of practical interest.
Extracting the hybrid functional mixing parameter from a GW quasiparticle approach

Relying on quasiparticle GW electronic structure calculations we present an approach to obtain an “optimal value” of the so called “mixing parameter,” α, in hybrid functional calculations. We show that when this “optimal” amount of exact exchange (we denote this as αopt) is mixed with the semi-local PBE exchange-correlation functional, the net quasiparticle corrections to the PBE Kohn–Sham eigenvalues attain a minimum value. We employ this approach to perovskite oxide insulators SrTiO3 and PbTiO3 and compare that to the widely studied semiconductor compounds, Si and Ge. A system dependence of the optimal choice of the mixing parameter is revealed.
Pattern Analysis of an Actuarial Strategy for Computerized Diagnosis of Childhood Exceptionality

The construct and predictive validity of a computerized diagnostic decision-making system, known as multidimensional actuarial classification (MAC), is investigated through a unique pattern analysis procedure. The MAC diagnostic system applies a series of actuarial decision rules to differentially classify children's mental retardation, learning disabilities, academic achievement problems, social and behavioral maladjustment, and other related disorders. Using a selected set of the decision routines available through MAC, the computerized system was used to classify 200 children referred for psychological services. A cross-products agreement matrix was constructed from the resultant multidimensional classifications produced for each child and was subjected thereafter to factor pattern analysis. Seven distinct and recognizable patterns emerged, supporting the verity and utility of the systems-actuarial approach to classification of child exceptionality. Moreover, pattern scores indicating the extent of chi...
Separations-based fiber optic sensing

A novel separations-based fiberoptic sensor (SBFOS) is described for remote analysis that incorporates capillary electrophoresis (CE). High sensitivity is possible with laser induced fluorescence detection and a unique and powerful element of selectivity is afforded by the exceptional separation power of CE. Speed of analysis and the possibility of remote control are further attributes which render the system useful for sensing applications. Details are given in this report for a SBFOS that employs a single-fiber optical configuration and a single buffer reservoir CE arrangement. The fiberoptic probes the outlet of a short separation capillary in a simple frontal mode of operation. Design considerations and the results of preliminary evaluations of the separation and detection characteristics of the SBFOS are presented.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
A Jackknife and Voting Classifier Approach to Feature Selection and Classification

With technological advances now allowing measurement of thousands of genes, proteins and metabolites, researchers are using this information to develop diagnostic and prognostic tests and discern the biological pathways underlying diseases. Often, an investigator's objective is to develop a classification rule to predict group membership of unknown samples based on a small set of features and that could ultimately be used in a clinical setting. While common classification methods such as random forest and support vector machines are effective at separating groups, they do not directly translate into a clinically-applicable classification rule based on a small number of features.We present a simple feature selection and classification method for biomarker detection that is intuitively understandable and can be directly extended for application to a clinical setting. We first use a jackknife procedure to identify important features and then, for classification, we use voting classifiers which are simple and easy to implement. We compared our method to random forest and support vector machines using three benchmark cancer ‘omics datasets with different characteristics. We found our jackknife procedure and voting classifier to perform comparably to these two methods in terms of accuracy. Further, the jackknife procedure yielded stable feature sets. Voting classifiers in combination with a robust feature selection method such as our jackknife procedure offer an effective, simple and intuitive approach to feature selection and classification with a clear extension to clinical applications.
Characterization of AE from fatigue crack growth in steel bridge components

Early detection of fatigue crack-growth in steel structures is an ongoing challenge. Furthermore, characterization of the different stages of the fatigue lifecycle using NDE techniques is particularly difficult. AE systems have been shown to serve as early damage detection mechanisms in bridge structures. This technology, however, is fraught with noise problems and complex datasets that are difficult to interpret. This paper attempts to design and implement a data mining scheme that can classify raw AE datasets into discrete clusters using an improved variant of the popular k-means clustering algorithm. The datasets are then augmented with the class label found during clustering, and a series of rules are inferred using a C4.5 decision tree classification algorithm. An implementation of the data mining scheme is coded in MATLAB®, with data from PAC® AE systems as the input. In order to validate this procedure, data from a pencil lead break test with a concurrent noise source is fed into the data mining program. Classification using the decision tree is compared to manual classification of the pencil lead break hits. The resulting decision tree is then applied to a similar dataset in order to evaluate the generality of the resulting rule sets. Once validated, the data mining program is applied to data belonging to a steel fatigue crack-growth test. Results of this classification are discussed, and possible improvements to the data mining scheme are suggested.
Myelin Basic Protein-primed T Helper 2 Cells Suppress Microglial Activation via AlphaVBeta3 Integrin: Implications for Multiple Sclerosis

Multiple sclerosis (MS) is the most common autoimmune demyelinating disease in human and T helper type 2 (Th2) cells have been shown to be beneficial for this disease. However, mechanisms by which Th2 cells ameliorate disease in MS are poorly understood. Microglial activation plays an important role in the pathogenesis of MS and other neurodegenerative disorders. Here, we delineate that Th2 cells are capable of suppressing microglial activation via cell-to-cell contact. After polarization of MBP-primed Th1 cells to Th2 by gemfibrozil and other drugs, we observed that MBP-primed Th2 cells dose dependently inhibited the production of interleukin-1β (IL-1β) and nitric oxide (NO) in LPS-stimulated microglia via cell-to-cell contact. Similarly, Th2 cells also suppressed the microglial inflammatory response in the presence of different pathological stimuli of Alzheimer's disease (AD), Parkinson's disease (PD), and HIV associated dementia (HAD). Interestingly, Th2 cells expressed higher levels of alphaV (αV) and beta3 (β3) integrins as compared to Th1 cells, and functional blocking antibodies against αV and β3 integrins impaired the ability of Th2 cells to suppress microglial activation. Furthermore, we demonstrate that microglia expressed the beta subunit of PDGF receptor (PDGFRβ) and that neutralization of PDGFRβ abrogated the ability of Th2 cells to suppress microglial inflammation. Activation of microglial cAMP response element-binding (CREB) by Th2 cells, suppression of CREB activation by neutralization of either αV and β3 integrins on Th2 cells or PDGFRβ on microglia, abrogation of anti-inflammatory activity of Th2 cells by siRNA knockdown of microglial CREB, highlights the importance of αVβ3 and PDGFRβ in guiding the anti-inflammatory activity of Th2 cells via activation of CREB, which may be responsible for beneficial effect of Th2 cells in MS and other related disorders.
Time-optimal Trajectories for an Omni-directional Vehicle

A common mobile robot design consists of three 'omniwheels' arranged at the vertices of an equilateral triangle, with wheel axles aligned with the rays from the center of the triangle to each wheel. Omniwheels, like standard wheels, are driven by the motors in a direction perpendicular to the wheel axle, but unlike standard wheels, can slip in a direction parallel to the axle. Unlike a steered car, a vehicle with this design can move in any direction without needing to rotate first, and can spin as it does so. The shortest paths for this vehicle are straight lines. However, the vehicle can move more quickly in some directions than in others. What are the fastest trajectories? We consider a kinematic model of the vehicle and place independent bounds on the speeds of the wheels, but do not consider dynamics or bound accelerations. We derive the analytical fastest trajectories between configurations. The time-optimal trajectories contain only spins in place, circular arcs, and straight lines parallel to the wheel axles. We classify optimal trajectories by the order and type of the segments; there are four such classes, and there are no more than 18 control switches in any optimal trajectory.
Attractive Invariant Manifolds under Approximation. Inertial Manifolds

A class of nonlinear dissipative partial differential equations that possess finite dimensional attractive invariant manifolds is considered. An existence and perturbation theory is developed which unifies the cases of unstable manifolds and inertial manifolds into a single framework. It is shown that certain approximations of these equations, such as those arising from spectral or finite element methods in space, one-step time-discretization or a combination of both. also have attractive invariant manifolds. Convergence of the approximate manifolds to the true manifolds is established as the approximation is refined. In this part of the paper applications to the behavior of inertial manifolds under approximation are considered. From this analysis deductions about the structure of the attractor and the flow on the attractor under discretization can be made.
The cannabinoid receptor antagonist SR-141716 does not readily antagonize open-field effects induced by the cannabinoid receptor agonist (R)-methanandamide in rats.

Abstract This study examined the effects of the cannabinoid CB 1 receptor agonist (R)-methanandamide and the CB 1 receptor antagonist SR-141716 on open-field behaviors in rats. Animals were examined after administration of (R)-methanandamide (dose range 10 to 30 mg/kg) plus vehicle, and the two drugs in combination; the dose range of SR-141716 was 0.3 to 5.6 mg/kg. Injections were given intraperitoneally 20 min prior to initial testing. Additional exposures to the open-field arena occurred for the groups treated with 30 mg/kg (R)-methanandamide at 60 and 120 min post administration. There was a dose-related suppression of ambulation (horizontal activity) and rearing (vertical activity) after (R)-methanandamide administration. Coadministration of SR-141716 did not counteract the suppression induced by 10 and 18 mg/kg (R)-methanandamide but rather tended to augment it, especially with regard to ambulation using SR-141716 doses of 1 mg/kg and up. The latency to leave the starting area in the center of the field was significantly elevated by 30 mg/kg (R)-methanandamide. This effect was completely blocked by SR-141716. With increasing doses of SR-141716, there was an increase in grooming and scratching. Generally, the strongest effects occurred 20 min post administration with the exception of grooming, which reached maximum at 60 min post. Differences in the number of circlings, vocalizations, urination, and defecation generally did not differ clearly among treatments. These results coupled with previous open-field data examining combinations of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and SR-141716 [Pharmacol. Biochem. Behav. 73 (2002) 911] underscore pharmacological differences between (R)-methanandamide and Δ 9 -THC revealed by their interactions with SR-141716.
Mutants partially defective in excision repair at five autosomal loci in Drosophila melanogaster.

Primary cell cultures derived from mutants in seventeen different genes were analyzed for their ability to excise pyrimidine dimers from DNA. Five of these mutagen-sensitive mutants [mus(2)205A1, mus(3)302D1, mus(3) 304D3, mus(3)306D1, mus(3)308D2] display a significantly reduced excision capacity relative to control cultures. In addition, two of the five [mus(3)306D1, mus(3)308D2] are defective in the accumulation of single-strand breaks normally seen after ultraviolet irradiation. This study, therefore, brings the total number of Drosophila mutants known to be defective in excision repair to seven. The results are discussed relative to other genetic and biochemical properties of these mutants.
Making methods choices

Abstract This article is a further discussion of methodological paradigms in evaluation research. More specifically, this article is a response to the attacks on paradigmatic perspectives made by Reichardt and Cook in the opening chapter of their edited book Qalitative and Quantitative Methods in Evaluation Research. They “suggest that part of this current debate over qualitative and quantitative methods is not centered on productive issues and so is not being argued in as logical a fashion as it should be.” For better or worse paradigm debates are, by their nature, only partly subject to logical analysis. Paradigms — methodological or otherwise — involve values, world view, empirical tendencies, and patterned responses. Because their central arguments rest entirely on a logical foundation, Reichardt and Cook may have done precisely what they accuse others of doing: “obscuring issues and unnecessarily creating schisms between the two methodtypes.”
Detection of Variable Gaseous Absorption Features in the Debris Disks Around Young A-type Stars

We present medium resolution (R = 60,000) absorption measurements of the interstellar Ca II K line observed towards five nearby A-type stars (49 Ceti, 5 Vul, ι Cyg, 2 And, and HD 223884) suspected of possessing circumstellar gas debris disks. The stars were observed on a nightly basis during a six night observing run on the 2.1-meter Otto Struve telescope at the McDonald Observatory, Texas. We have detected nightly changes in the absorption strength of the Ca II K line observed near the stellar radial velocity in three of the stars (49 Ceti, i Cyg and HD 223884). Such changes in absorption suggest the presence of a circumstellar (atomic) gas disk around these stars. In addition to the absorption changes in the main Ca II K line profile, we have also observed weak transient absorption features that randomly appear at redshifted velocities in the spectra of 49 Ceti, 5 Vul, and 2 And. These absorption features are most probably associated with the presence of falling evaporated bodies (exo-comets) that liberate evaporating gas on their approach to the central star. This now brings the total number of systems in which exocomet activity has been observed at Ca II or Na I wavelengths on a nightly basis to seven (β Pic, HR 10, HD 85905, β Car, 49 Ceti, 5 Vul, and 2 And), with 2 And exhibiting weaker and less frequent changes. All of the disk systems presently known to exhibit either type of short-term variability in Ca II K line absorption are rapidly rotating A-type stars (V sin i > 120 km s-1). Most exhibit mid-IR excesses, and many of them are very young (< 20 Myr), thus supporting the argument that many of them are transitional objects between Herbig Ae and "Vega-like" A-type stars with more tenuous circumstellar disks. No mid-IR excess (due to the presence of a dust disk) has yet been detected around either 2 And or HD 223884, both of which have been classified as λ Bootis-type stars. This may indicate that the observed changes in gas absorption for these two stars may not be due to circumstellar activity, but may instead be associated with the stars' episodic mass loss and passage though low-density interstellar clouds.
Immunopathogenesis of inflammatory bowel disease: current concepts.

Purpose of reviewAccording to the current paradigm, ulcerative colitis and Crohn's disease occur in genetically predisposed individuals because of dysregulated immune responses against intraluminal bacterial antigens. Data have recently accumulated supporting alternative hypotheses for the pathogene
Genetic counseling and women.

T he practice and profession of genetic counseling, still in its youth, has matured and developed during the past quarter century in response to technological, psychological, societal, economic, and cultural factors. Concerns regarding the ethical, legal, and social implications (ELSI) of the Human Genome Project (HGP) have been articulated in the professional literature and the popular press. Research and educational programs designed to address these concerns in order to anticipate and prevent negative ramifications of genome research for individuals and society have taken a variety of forms. A priority of the ELSI program is to address the effect of the massive amount of new genetic information and related technologies on mainstream medical practice, particularly for clinical genetics and primary care.l Although many scholars and practitioners have stated that the HGP does not raise new ethical issues or dilemmas, the magnitude of the clinical and societal applications of the scientific and technologic discoveries are bringing these to light in a more extensive manner. * Philosophical exploration of the practice of genetic counseling in light of new technologies has fostered a fresh look at the counseling process, practice standards, and service delivery with an emphasis on gender issues and women’s roles.3 Therefore, in this article, I discuss some basic assumptions about genetic counseling and points to consider vis-a-vis the work of Carol Gilligan on women’s psychologic theory and a care-based ethic4
Synthesis of 13C‐ and 14C‐labeled 1192U90, an ortho‐amino benzamide with a preclinical atypical antipsychotic profile

Three isotopic forms of potential antipsychotic agent 1192U90 (2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide) were synthesized : one containing 13 C-isotopes and two containing 14 C-isotopes. The compound in which the ortho-amino benzamide ring is completely 13 C-labeled was prepared in a four-step sequence starting from [ 13 C 6 ]aniline. The 14 C-labeled compounds were prepared by methods analogous to those previously described for the unlabeled material. The key step involved the condensation of 3-(4-(4-aminobutyl)-1-piperazinyl)-1,2-benzisothiazole with isatoic anhydride. The first 14 C-labeled compound (3) was prepared from 14 C-labeled 3-(4-(4-aminobutyl)-1-piperazinyl)-1,2-benzisothiazole, while the second compound (4) derived its isotopic label from [ 14 C]isatoic anhydride. Compound 3 had a specific activity of 26.55 mCi/mmol, a radiochemical purity of 99.3%, and a radiochemical yield of 3.4% based on 9. Compound 4 had a specific activity of 22.67 mCi/mmol and a radiochemical purity of 99.2%.
Liquid crystalline supramolecular polymers formed via complementary nucleobase pair interactions

We report on the effect of placement of nucleobase units, thymine or N6-(4-methoxybenzoyl)-adenine onto the ends of the mesogenic and fluorescent core: bis-4-alkoxy-substituted bis(phenylethynyl)-benzene (AA and BB type monomers). While the addition of these bulky polar groups significantly reduces the range of liquid crystalline behavior, mixing two complementary nucleobase-containing monomer units together yields stable thermotropic liquid crystalline phases. Here, we focus on the effect of non-stoichiometric mixing of AA + BB monomers. Hydrogen bonding is shown to play an important role in the formation of these LC phases consistent with the formation of oligomeric or polymeric hydrogen bonding aggregates. Differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) have been used in our studies, revealed greater stability of LC phase formation for the 1:1 mixture.
A contralateral repeated bout effect attenuates induction of NF-κB DNA binding following eccentric exercise

We investigated the existence of contralateral repeated bout effect and tested if the attenuation of nuclear factor-kappa B (NF-κB; an important regulator of muscle inflammation) induction followin...
“We’ll only see parts of each other’s lives:” The role of mundane talk in maintaining nonresidential parent–child relationships:

Research on relational maintenance shows that mundane day-to-day talk is important in sustaining relationships. This study explores how absence associated with the visitation process shapes nonresidential parents’ communication with their children. Participants’ open-ended responses indicate that several factors facilitate and constrain interaction with their children during absence including their philosophy about communication boundaries, technology, and their relationship with the other parent. Participants who have limited interactions struggle to “know” their children, while those with frequent interaction with their children have access to the mundane stories of their children’s lives, which helps to maintain the relationships. This research suggests that the process of updating about what occurs during absence may be central to maintaining relationships.
DISTINCT SUBCLASSES OF SMALL GTPASES INTERACT WITH GUANINE NUCLEOTIDE EXCHANGE FACTORS IN A SIMILAR MANNER

The Ras-related GTPases are small, 20- to 25-kDa proteins which cycle between an inactive GDP-bound form and an active GTP-bound state. The Ras superfamily includes the Ras, Rho, Ran, Arf, and Rab/YPT1 families, each of which controls distinct cellular functions. The crystal structures of Ras, Rac, Arf, and Ran reveal a nearly superimposible structure surrounding the GTP-binding pocket, and it is generally presumed that the Rab/YPT1 family shares this core structure. The Ras, Rac, Ran, Arf, and Rab/YPT1 families are activated by interaction with family-specific guanine nucleotide exchange factors (GEFs). The structural determinants of GTPases required for interaction with family-specific GEFs have begun to emerge. We sought to determine the sites on YPT1 which interact with GEFs. We found that mutations of YPT1 at position 42, 43, or 49 (effector loop; switch I), position 69, 71, 73, or 75 (switch II), and position 107, 109, or 115 (alpha-helix 3–loop 7 [α3-L7]) are intragenic suppressors of dominant interfering YPT1 mutant N22 (YPT1-N22), suggesting these mutations prevent YPT1-N22 from binding to and sequestering an endogenous GEF. Mutations at these positions prevent interaction with the DSS4 GEF in vitro. Mutations in the switch II and α3-L7 regions do not prevent downstream signaling in yeast when combined with a GTPase-defective (activating) mutation. Together, these results show that the YPT1 GTPase interacts with GEFs in a manner reminiscent of that for Ras and Arf in that these GTPases use divergent sequences corresponding to the switch I and II regions and α3-L7 of Ras to interact with family-specific GEFs. This finding suggests that GTPases of the Ras superfamily each may share common features of GEF-mediated guanine nucleotide exchange even though the GEFs for each of the Ras subfamilies appear evolutionarily unrelated.
Plantar pressure distribution in Type 2 diabetic patients without peripheral neuropathy and peripheral vascular disease

Aims To evaluate the distribution of plantar pressure during walking on a level gradient in patients with Type 2 diabetes mellitus without any microvascular and macrovascular complications and to compare them with non-diabetic control subjects. Methods A group of 15 patients with Type 2 diabetes mellitus without either peripheral neuropathy or peripheral vascular disease (PVD), as well as without both diabetic retinopathy and nephropathy, was compared with a group of 15 non-diabetic subjects matched for age, sex, body weight and height. The plantar pressure and duration of plantar pressure were measured on big toe, 1st, 3rd and 5th metatarsal heads, and on the heel of both feet by Force Sensing Resistors sensors. The static contact plantar surface was measured by method of Harris footprints. Results The diabetic group showed a significant increase in peak plantar pressure at the level of the big toe [right foot 205 +/- 94 vs. 101 +/- 39 kPa (mean +/- SD), P = 0.01; left foot 165 +/- 61 vs. 104 +/- 43 kPa, P = 0.05] and 5th metatarsal head (right foot 160 +/- 68 vs. 97 +/- 32 kPa, P = 0.05; left foot 174 +/- 65 vs. 91 +/- 42 kPa, P = 0.02) with a significantly prolonged duration of plantar pressure at each step. Under the heel, the peak plantar pressure was significantly lower in the diabetic group (right foot 187 +/- 54 vs. 321 +/- 91 kPa, P = 0.05; left foot 184 +/- 63 vs. 298 +/- 110 kPa, P = 0.05). No significant differences were noted under 1st and 3rd metatarsal heads. The contact plantar surface was significantly reduced in the diabetic group compared with control subjects (right foot 118.2 +/- 10.8 vs. 141.5 +/- 12.7 cm2, P = 0.05; left foot 127.5 +/- 8.7 vs. 140.0 +/- 11.1 cm2, P = 0.05). Conclusions We observed an anterior displacement of weight-bearing during walking on a level gradient as well as a reduced static contact plantar surface in diabetic patients without evidence of any complications compared with the non-diabetic control group. This could be a premature sign of peripheral neuropathy, which is not evaluated on clinical examination or quantitative sensory testing used in clinics.
Generation, characterization, and application of broadband coherent femtosecond visible pulses in dispersion micromanaged holey fibers

Submillimeter-scale dispersion micromanagement (DMM) is discussed and used to generate coherent and stable femtosecond visible pulses (bandwidth up to 50 nm and scalable center wavelength in the range of 385-625 nm) in tapered holey fibers as short as 10 mm. The longitudinal variation of the phase-matching conditions for Cherenkov radiation and four-wave mixing explains the results well. We compare the broadband noise of the visible pulses generated through a DMM holey fiber, a tapered fiber, and long holey fibers and find that DMM holey fibers offer the lowest noise for visible pulse generation. We discuss the importance of the distance scale of the DMM and show ultrabroadband visible pulse (180 nm) generation by submillimeter-scale DMM, which can be compressed to a 11 fs duration. We further apply DMM to polarization-maintaining holey fibers and show different center-wavelength visible pulse generation by changing the input polarization. With DMM flexibility, a strong f-2f beat signal for carrier-envelope phase stabilization is obtained by simply mixing the visible pulse generated by a DMM holey fiber with the second harmonic of the input pulse.
Two compound replication origins in Saccharomyces cerevisiae contain redundant origin recognition complex binding sites.

While many of the proteins involved in the initiation of DNA replication are conserved between yeasts and metazoans, the structure of the replication origins themselves has appeared to be different. As typified by ARS1, replication origins in Saccharomyces cerevisiae are <150 bp long and have a simple modular structure, consisting of a single binding site for the origin recognition complex, the replication initiator protein, and one or more accessory sequences. DNA replication initiates from a discrete site. While the important sequences are currently less well defined, metazoan origins appear to be different. These origins are large and appear to be composed of multiple, redundant elements, and replication initiates throughout zones as large as 55 kb. In this report, we characterize two S. cerevisiae replication origins, ARS101 and ARS310, which differ from the paradigm. These origins contain multiple, redundant binding sites for the origin recognition complex. Each binding site must be altered to abolish origin function, while the alteration of a single binding site is sufficient to inactivate ARS1. This redundant structure may be similar to that seen in metazoan origins. The replication of eukaryotic chromosomes initiates at multiple origins during each S phase. These DNA replication origins are best understood in the budding yeast Saccharomyces cerevisiae, in which they were initially recognized by their ability to promote the autonomous replication of plasmids. For this reason, they are referred to as autonomously replicating sequence (ARS) elements (29, 55). The paradigm S. cerevisiae replication origin is ARS1. It has a modular structure that spans about 120 bp and includes a small essential region, domain A, and three small accessory sequences, B1, B2, and B3, mutations in which reduce but do not abolish activity (40). Domain A, which encompasses the essential match to the 11-bp ARS consensus sequence (ACS), is the core of the binding site for the S. cerevisiae replication initiator protein, the origin recognition complex (ORC). The six-subunit ORC complex also contacts and protects DNA in the B1 element, and some mutations in B1 compromise ORC binding in vitro (3, 37, 50, 52). The B3 element contains a binding site for the transcriptional activator-repressor Abf1p, which can be replaced by the binding sites for the transcriptional regulators Rap1p and Gal4p (40). The precise role of the B2 element has not been defined, although at least one of its functions is likely to be unwinding the DNA duplex to allow entry of the replication machinery (38, 41).
Functional Correlates of Lower Cognitive Test Scores in Essential Tremor

Although motor features have been the defining element of essential tremor (ET), lower neurocognitive test scores are increasingly being recognized. However, the clinical correlates, if any, of these lower test scores remain largely unexplored. The aim of this study was to determine whether cognitive test scores in ET have any functional correlates. The Modified Mini Mental Status Examination (MMSE), Katz Activities of Daily Living (ADL) scale and Lawton Instrumental (I) ADL scale were administered to 95 cases. The Katz ADL score (rho = 0.26, P = 0.01) and Lawton IADL score (rho = 0.32, P = 0.001) were correlated with MMSE scores, such that poorer cognitive performance indicated greater dysfunction. Furthermore, cognitive test scores were a better predictor of functional disability than was tremor severity. Poorer cognitive performance in ET was associated with greater functional deficit. Cognition should enter the clinical dialog with ET patients as an issue of clinical significance.
Pharmacokinetics of high-dose oral calcitriol: results from a phase 1 trial of calcitriol and paclitaxel.

Objectives The data reported are from a trial designed to determine, in patients with advanced cancer, the maximum tolerated dose and pharmacokinetics of calcitriol when administered with paclitaxel, an agent whose antitumor activity in in vitro and in vivo studies has been shown to be enhanced by calcitriol. An additional goal was to evaluate the relationship between calcitriol dose and hypercalcemia. Methods Calcitriol was given orally for 3 consecutive days each week, and paclitaxel (80 mg/m2) was given intravenously weekly. Thirty-six patients were treated in cohorts composed of 3 to 9 patients, at escalating dose levels of calcitriol. The starting dose of calcitriol was 4 μg for 3 consecutive days each week, and the maximum dose administered was 38 μg for 3 consecutive days each week. The preparation of calcitriol used in this trial was a commercially available caplet (0.5 μg per caplet). Serum calcitriol concentrations were measured by radioimmunoassay. Detailed assessments of calcitriol pharmacokinetics were performed in 26 patients. Results There was substantial interpatient variation in peak serum calcitriol concentrations (Cmax), time to reach Cmax, and area under the concentration versus time curve (AUC). Serum calcitriol AUC was not proportional to calcitriol dose (P = .0014). AUC for the 24-hour period after calcitriol administration [AUC (0–24)] at 38 μg was only 4 times that at 4 μg, instead of the 9.5-fold increase expected for a proportional relationship. Calcitriol plasma concentrations of 600 to 1440 pg/mL were achieved. No dose-limiting toxicity occurred in this trial. Conclusions Despite variability in absorption, very high doses of calcitriol can be safely administered with paclitaxel. The high calcitriol serum concentrations achieved in this study approach those that, both in vitro and in vivo, potentiate the cytotoxicity of taxanes and platinum analogs. Clinical Pharmacology & Therapeutics (2002) 72, 648–659; doi: 10.1067/mcp.2002.129305
Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs. To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected. For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN. Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.
Pregnancy following homologous prepubertal ovarian transplantation in the dog

In several canine models of hereditary human disease the homozygote dogs die prior to puberty, or have substantially reduced fertility. To create a clinically healthy animal that can be bred, but can also transmit the gene of interest, a model of homologous ovarian transplantation in prepubertal dogs was developed. Six dog leukocyte antigen (DLA) identical littermates underwent transplantation of ovarian cortical strips (n = 2) or the entire ovary (n = 4). Immunosuppression was maintained with cyclosporine and MMF in the immediate post-operative period and cyclosporine alone thereafter. All 6 dogs entered puberty and normal semiannual estrus cycles as demonstrated by both physical changes and increasing serum progesterone. Four dogs were bred to a proven stud male, and one became pregnant. Three viable fetuses with observable heartbeats were detected on ultrasound examination. Although the dog eventually aborted the litter, this work represents the first pregnancy achieved following a prepubertal ovarian transplant in the dog.
Sequence‐Based Design of α/β‐Peptide Foldamers That Mimic BH3 Domains

The design of molecules that bind tightly and selectively to a specific site on a protein constitutes a fundamental challenge in molecular recognition. Finding high-affinity ligands for protein surfaces that bind to other proteins has proven to be particularly difficult.[1] Foldamers, oligomers with discrete folding propensities,[2] represent an unconventional source of ligands for protein-recognition surfaces,[3] but realizing this potential requires that we learn how to design sequences that contain unnatural building blocks and effectively mimic one of the surfaces involved in a given protein-protein interaction. Here we show that systematic backbone modification throughout a natural protein-binding domain, a process we refer to as sequence-based design, can expeditiously generate foldamers that bind tightly and selectively to target protein surfaces.
Adult recipients of umbilical cord blood transplants after nonmyeloablative preparative regimens.

Abstract We report the outcome of 13 patients with advanced malignancies who underwent nonmyeloablative conditioning therapy followed by infusion of partially matched unrelated cord blood cells. The median age of these patients was 49 years, and their median weight was 65.7 kg. The median nucleated cell dose infused was 2.07 × 107/kg. Eight of the 13 patients demonstrated donor chimerism between 4 weeks and 6 months, and subsequent conversion to full donor chimerism was achieved in 5 patients. Three patients were alive and free of disease at 158 to 1054 days, with a median survival of 288 days after transplantation. The 100-day event-free survival is 69%, and overall survival is 77%. At 1 year, the event-free and overall survival was 43%. Treatment-related mortality observed within the first 100 days after transplantation was low: 1 previously extensively pretreated patient died of multiorgan failure. This result provides a basis for further exploring this potentially curative approach to selected patients who lack matched related or unrelated hematopoietic stem cell donors.