cssi/SciSciGPT-SciSciNet huggingface dataset:
Overview of the nonclinical quality and toxicology testing for recombinant biopharmaceuticals produced in mammalian cells

Biopharmaceuticals represent significant advances in therapeutic approaches for unmet medical needs, and increasingly, traditional pharmaceutical firms have been incorporating biotechnology capabilities into their product portfolios. There are some differences in the overall safety testing paradigms for small molecules and biopharmaceuticals, this safety testing including both quality and toxicology aspects. These differences are associated with both the manufacturing processes involved and the molecules themselves. For example, for biopharmaceuticals, living cells represent the factories for synthesizing complex molecular entities. As a result of this, safety testing for this class of drugs includes adventitious agent testing (e.g. viral, mycoplasma, transmissible spongiform encephalopathy agents) not normally needed for small molecules. Also, strategies for nonclinical toxicology testing of biopharmaceuticals differ from the paradigms used for small molecules and often need to be defined on a case-by-case basis, primarily taking into consideration species cross-reactivity attributes of the molecule of interest. Certain studies required for small molecules are not applicable to most biopharmaceuticals (i.e. genotoxicity testing, testing for interactions with the hERG channel). This manuscript provides an overview of both the quality and nonclinical toxicology testing for these mammalian-cell-derived products, two elements pivotal to the overall nonclinical assessment of the safety of these biopharmaceutical products.
In vitro protein-binding characteristics of delavirdine and its N-dealkylated metabolite

Abstract This study was performed to determine delavirdine protein-binding characteristics as well as those of its N -dealkylated metabolite ( N -DLV). Initial studies of 36 μM delavirdine and 30 μM N -DLV in solutions of plasma, albumin 4 g%, alpha-1-acid glycoprotein (AAG) 100 mg% or immune globulin (IVIG) 5 g% were conducted. Delavirdine (12, 36 and 73 μM) and N -DLV (10, 30 and 60 μM) were then studied alone and in combination in plasma and various concentrations of albumin. Studies were done in triplicate using equilibrium dialysis. The mean delavirdine fraction unbound ( f u ) in plasma, albumin, IVIG and AAG was 0.013, 0.033, 0.752 and 0.912 while the mean f u of N -DLV in these same protein solutions was 0.139, 0.195, 0.329 and 0.359. In plasma and albumin, a greater f u was observed at higher delavirdine concentrations and no significant changes in f u were noted with the addition of N -DLV. An increase in delavirdine f u was noted as the albumin concentrations decreased. The f u of N -DLV increased significantly as the concentration of albumin decreased as well as with decreasing N -DLV concentration. The potential implications of extensive delavirdine binding to plasma proteins, primarily albumin, are discussed.
Effect of advanced aging on ability of mice to cause regression of an immunogenic lymphoma in response to immunotherapy based on depletion of suppressor T cells.

This study shows that two therapeutic agents, anti-CD4 mAb and vinblastine, capable of causing T-cellmediated regression of an established L5178Y lymphoma in 3-month-old mice, are incapable of causing regression of this tumor in 20- to 22-month-old mice. It is known that both agents are immunoaugmentative because of their ability to destroy tumor-induced CD4+ suppressor T cells preferentially. Therefore, the results indicate, that aged mice, unlike young mice, are not capable of generating therapeutic numbers of CD8+ effector T cells in the absence of suppressor cells.
Selective Lutheran Glycoprotein Gene Expression at the Blood-Brain Barrier in Normal Brain and in Human Brain Tumors

The Lutheran (LU) glycoprotein was shown to be a specific marker of brain capillary endothelium, which forms the blood-brain barrier (BBB) in vivo. A 1.5 kb partial cDNA encoding the bovine LU was isolated from a bovine brain capillary cDNA library. Sequence analysis showed that the bovine and human LU had a 75% and 79% identity in the amino acid and nucleotide sequences, respectively. Northern blot analysis demonstrated a very high level of gene expression of the LU transcript in freshly isolated bovine brain capillaries, but no measurable LU mRNA in whole bovine brain. The high level of LU gene expression was maintained when bovine brain capillary endothelium was grown in tissue culture. Because many BBB specific genes are downregulated in tissue culture and in brain tumors, the expression of the LU mRNA and immunoactive LU protein was investigated in primary and metastatic human brain tumors. Immunocytochemistry of fresh frozen human brain and human brain tumors showed abundant immunostaining of brain capillary endothelium. Northern blot analysis showed the presence of LU transcripts in a panel of primary and metastatic human brain tumors. These studies demonstrated that the LU glycoprotein was a novel new marker of the BBB, and unlike other BBB specific genes, there was a persistent gene expression of the LU glycoprotein both in brain capillary endothelial cells grown in culture and in the endothelium of capillaries perfusing human brain cancer.
Six Dimensional Trajectory Solver for Autonomous Proximity Operations

Abstract : Many future space mission will require that proximity operations be accomplished reliably, precisely and efficiently without a pilot in the loop. This thesis examines one element of an autonomous proximity operations controller, the trajectory planner. The trajectory planner uses a modified gradient search to find a locally optimal trajectory from the initial state to the target state that does not violate any of the mission constraints. The mission constraints are defined as the maximum time of flight for the operation, the maximum closing velocity allowed, and the obstacles in close proximity to the chase and target craft. The obstacles in this space are not assumed to be stationary; therefore, the planner must be able to develop a solution that, although not guaranteed globally optimal, meets all mission constraints in real time. This will enable the autonomous controller to avoid obstacles moving rapidly with respect to it and to correct for failed actuators. The Clohessy-Wiltshire equations for relative position and quaternions for relative attitude are used to define a state space relationship solver the initial state and the final state as a function of time. The trajectory between then uses these equations to find the minimum fuel solution to the problem of maneuvering to a target position and attitude while evading moving obstacles. Example results and simulations are included for various initial conditions and maneuvering constraints. The trajectory planner algorithm can find a trajectory from any initial state to any final state which satisfies the input constraints and uses minimum fuel.
Comparisons between DSMC and the Navier-Stokes equations for reentry flows

A detailed comparison is made between Navier-Stokes and DSMC calculations for flows near the continuum limit to assess the accuracy of the continuum equations in this regime. Meaningful comparisons require the use of similar physical models. This necessitates the inclusion of a separate rotational energy equation and use of slip boundary conditions. Inclusion of slip boundary conditions resulted in improved agreement between surface properties. Moreover, good agreement was obtained for the various temperatures in the nonequilibrium portion of the flow field that does not contain the shock region. Departures are noted in the shock region and in regions where thermal diffusion effects are important.
Advection–diffusion around a curved obstacle

Advection and diffusion of a substance around a curved obstacle is analyzed when the advection velocity is large compared to the diffusion velocity, i.e., when the Peclet number is large. Asymptotic expressions for the concentration are obtained by the use of boundary layer theory, matched asymptotic expansions, etc. The results supplement and extend previous ones for straight obstacles. They apply to electrophoresis, the flow of ground water, chromatography, sedimentation, etc.
The Effects of Processing on Interply Bond Strength of Thermoplastic Composites

The double cantilevered beam (DCB) Mode I fracture toughness test was selected to characterize the interply (autohesive) bonding of the prepreg plies during ther moplastic composite consolidation. AS4 graphite fiber/P1700 polysulfone amorphous thermoplastic prepreg was selected for study. The fractured AS4/P1700 DCB specimens were healed in a special fixture under different combinations of temperature, pressure, and time. The healed DCB specimens were refractured and the critical strain energy release rates (GIC) were measured. Pressure was found to be a key factor governing the healing process. Temperature and time dependencies of the interply bond development were also observed.
Effect of glutathione on oxymyoglobin oxidation.

The oxidation of oxymyoglobin (OxyMb) to metmyoglobin (MetMb) is responsible for fresh meat discoloration. Glutathione (GSH) is an important tripeptide reductant that can protect lipid and protein ...
Making sense of multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome (MODS) continues to be a leading cause of morbidity and mortality in critical care units. The best defense against patients developing this complex syndrome is prevention and identification of persons at risk for developing MODS. Prevention begins with the critical care nurse's understanding of the etiology of the syndrome and the specific goals that guide interventions aimed toward ameliorating or preventing the critical care patient from developing MODS.
Lattice vibrational study of the phase transition in the plastic crystal adamantane (C10H16)

Abstract Using the Raman technique we have studied the lattice vibrations of the prototype plastic crystal adamantane (C 10 H 16 ). The measurements, as a function of temperature through the phase transition (208K), show splittings in certain lines. At room temperature using hydrostatic pressure, we also induced a phase transition. The transition is detected by Raman measurements, and we observe splittings of the very same vibrational lines. This indicates that the pressure induced phase transition yields the same crystal structure as the low temperature structure. Some analysis of the pressure and temperature derivatives of the vibrational modes is presented.
Positron annihilation in positronium negative ions

The positron annihilation rate of positronium negative ions was calculated as 2.08613 ns−1 by using a 946 term Hylleraas-type wave function.
[Comment on] Bottom water

I read with great interest your writeup on the ‘Mysteries of Bottom Water’ in the March issue of The Oceanography Report (Eos, March 1, 1983, p. 83). I can recall the time, not so very long ago, when some very prominent physical oceanographers dismissed the notion advanced by paleo-oceanographers that the deep ocean environment is far from steady. It is nice to see them come around, some of them even to start to pay attention to what paleo-oceanographers have to say.
Topological “vector gluons”

A topological representation for individual quark chirality is proposed which eliminates spin lines from the classical surface and provides “chiral entropy” through patch-boundary lines that correspond to chirality reversal. The effect on quark spin makes it appropriate to describe such a patch-boundary line as a “topological vector gluon”. The chiral entropy index is equal to the number of “vector gluons”.
The Self: Metaphysical not Political

According to communitarian antiliberals, liberalism is fatally marred by a false metaphysics of the self. Liberalism, communitarians charge, regards the self as atomistic, isolated, presocial, ahistorical, “Cartesian,” Crusoeesque, essentially independent of other selves—in Michael Sandel's felicitous word, “unencumbered.” In reality, the self is constituted by relationships with others, hence by its contingent history. The self is fundamentally historical and social, and a true metaphysics of the self would, in the words of George Fletcher, take “relationships as logically prior to the individual.” Sandel puts it thus: “Can we view ourselves as independent selves, independent in the sense that our identity is never attached to our aims and attachments? I do not think we can….”
L∞-convergence of collocation and galerkin approximations to linear two-point parabolic problems

Two semidiscrete collocation approximations using smooth cubic splines are developed as approximations to the solution of two-point linear parabolic boundary value problems.L∞-convergence results are presented for these two approximations as well as the piecewise linear Galerkin approximation. Several computational examples are given to illustrate the convergence results and demonstrate the applicability of the method.
Exercise dependence: a systematic review

Abstract Background and Purpose: The purpose of this paper was to review the equivocal literature examining exercise dependence and deprivation. Method: A comprehensive literature search yielded 77 exercise dependence and 11 exercise deprivation studies, spanning 29 years (range=1970 to 1999), were reviewed. Results and conclusions: The research was characterized by three general approaches: (a) comparing exercisers to eating disorder patients, (b) comparing “excessive” to “less excessive” exercisers, and (c) comparing exercisers to nonexercisers. Study results have been inconclusive due, in part, to a lack of experimental research, inconsistent or nonexistent control groups, discrepant operational criteria for exercise dependence, and/or invalidated or inappropriate measures of exercise dependence. More systematic theory based research is required to understand the precipitating and perpetuating factors associated with exercise dependence, as well as effective treatment regimens.
Serum Biomarkers to Differentiate Benign and Malignant Mammographic Lesions

Background Mammographic screening has increased detection of earlier-stage breast cancers and has decreased mortality from breast cancer. A Breast Imaging-Reporting and Data System (BIRADS) 4 classification prompts a biopsy that most often reveals benign disease. Our objective was to determine if serum protein-expression profiles could be used to differentiate between benign and malignant mammographic lesions. Study Design After IRB approval, women undergoing an image-guided biopsy for a BIRADS category 4 lesion were recruited. Serum was collected prebiopsy and labeled retrospectively after final pathology was reviewed. Serum was incubated with weak cation exchange magnetic beads and assayed in duplicate for analysis on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) instrumentation (Bruker Daltonics). Spectra were analyzed using ClinProTools 2.0 software (Bruker Daltonics), and classifications determined using a genetic-clustering algorithm. Results In a 14-month period, 260 subjects were recruited into this study. Sera from 92 subjects were randomly selected to form benign (n = 46) and cancer (n = 46) cohorts. The MALDI-TOF spectra analysis yielded 273 peaks, with 14 peaks expressed differentially (p Conclusions MALDI-TOF protein-expression profiles generated from BIRADS 4 sera could be used to distinguish between benign and malignant mammographic lesions.
Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy

The aim of this study was to conduct a quantitative review of prostate cancer studies to pool relative risk (RR) estimates on the association between prostate cancer and vasectomy, in an attempt to determine whether there is an association, and if so, its magnitude. Random-effects models were examined along with a linear model for time since vasectomy. The pooled RR estimate was 1.37 (95% CI=1.15-1.62) based on five cohort studies and 17 case-control studies. The RR estimate varied by study design with the lowest risk for population-based case-control studies. No difference was seen in risk by age at vasectomy. A linear trend based on the 16 studies reporting time since vasectomy suggested an 10% increase for each additional 10 y or a RR of 1.32 (95% CI=1.17-1.50) for 30 y since vasectomy. When null effects were assumed for the six studies not reporting information, the linear RR for the 22 studies was 1.07 (1.03-1.11) and 1.23 (1.11-1.37) for 10 and 30 y since vasectomy, respectively. These results suggest that men with a prior vasectomy may be at an increased risk of prostate cancer, however, the increase may not be causal since potential bias cannot be discounted. The overall association was small and therefore could be explained by bias. The latency effect shown here for time since vasectomy should be examined further.
Present effect of penicillin on experimental peritonitis in dogs.

Summary These experiments indicate that penicillin remains a remarkably effective antimicrobial agent for the repression of experimental peritonitis in dogs. Providing these conclusions may be transferred to humans, penicillin may remain a drug of considerable importance in the treatment of peritonitis of gastrointestinal origin. Because of its relatively low degree of toxicity, which permits administration of large quantities of the drug, penicillin still closely approximates an ideal antibiotic. These experiments also indicate that an animal without an omentum will withstand peritonitis poorly, even with the administration of a dose of penicillin which would save a significant number of animals in which the omentum had not been removed. These data emphasize the urgency of early surgical correction of abdominal conditions likely to lead to peritonitis, such as intestinal obstruction, appendicitis, and the like, in infants and young children who have not developed a satisfactory omentum, and in adults who have had their omentum resected or effectively removed by adhesions. Surgical removal of the primary lesion would seem to hold the only chance of survival under these circumstances.
In situ monitoring of zeolite crystallization by electrical conductivity measurement: New insight into zeolite crystallization mechanism

Electrical conductivity of zeolite synthesis mixtures during zeolite crystallization has been measured in situ, and the results show that the onset of zeolite crystallization is accompanied by an abrupt increase in measured conductivity. Leading up to the onset of crystallization, however, electrical conductivity may gradually increase or decrease, depending on whether high- or low-silica synthesis mixtures are used. These results show promise that in situ electrical conductivity measurement can be a new tool for mechanistic studies of zeolite crystallization as well as for practical use in monitoring the process of large scale zeolite synthesis.
Severity Risk Adjusting Relating to Obstetric Outcomes DRG Assignment, and Reimbursement

Obstetric risk has important implications for reporting and benchmarking quality in today's managed health care environment. Administrative data, including diagnosis related group (DRG) information collected by hospitals, is used by payers and governmental groups for reimbursement, monitoring quality, and setting financial rates. Obstetric conditions that affect the patient experience are coded but do not often contribute to the overall DRG assignment. This strategy, therefore, may provide comparisons that are misleading to consumers and payers. Additionally, financial rates often do not provide adequate reimbursement for the cost incurred in caring for high-risk patients. Finally, risk prediction strategies have historically been used to both identify vulnerable patients for early management and make more equitable comparisons of groups of patients.
On the Relative Strengths of Bacillus Spore Signatures in the Terahertz (THz)Versus the Mid-Infrared

We have recently extended our studies of the infrared signatures of Bacillus bacterial spores from the mid-infrared to the far-infrared (sometimes called the terahertz, THz) spectral domain. The ultimate goal is to use such signatures to distinguish different strains of spores from unknowns as well as from one another. Five different strains of Bacillus were prepared by culturing the spores, washing repeatedly in sterile water and drying them onto windows that are simultaneously transparent in both the mid- and far-infrared. The strains include B. globigii BG-01, B. thuringiensis subsp kurstaki ATCC 35866, B. subtilis ATCC 49760, B. subtilis ATCC 6051, and B. atrophaeus ATCC 49337. Using different combinations of hardware in the Fourier transform infrared (FTIR) spectrometer, essentially continuous spectral coverage was obtained from ~8 to 6,000 cm-1. Preliminary results indicate that any THz signatures are at least 25 times weaker (based on p-p noise) than the strongest mid-IR amide I bands near 1657 cm-1.
Retrospective Study Comparing Two Materials Commonly Used in the LFS Technique for CCLR

Cranial cruciate ligament rupture (CCLR) is the most common cause of degenerative joint disease (DJD) in the stifle of adult dogs. Over the last several years, a new generation of nonabsorbable, multifilament, polyblend polyethylene orthopedic suture materials have been evaluated for use in the lateral fabellar suture (LFS) technique for surgical treatment of CCLR. This retrospective study compared the short-term outcome of 16 dogs that were treated using the LFS technique using either a proprietary polyblend polyethylene orthopedic suture material (FW) or monofilament nylon leader line (NLL). The FW was significantly more likely to fail compared with the NLL (P = 0.0379). Specifically, the FW was 14.667 times likelier to fail than the NLL. When one and two strands of NLL were compared with FW, the FW was 6 times more likely to fail than one strand of NLL and 32 times more likely to fail than two strands of NLL. To the authors’ knowledge, this is the first study comparing the two materials used in the LFS...
Cultivating Institutional Transformation and Sustainable STEM Diversity in Higher Education through Integrative Faculty Development

An urgent need to broaden diversity and support the preparation of students and faculty members along proactive pathways to research and success can be facilitated by targeted faculty development and formalization of policies built on institutional commitment, engagement, and accountability. Involvement of the faculty in building institutional diversity will recognize equity-building initiatives as valid forms of faculty scholarship and as one way to address the growing public problem of educational disparities in the STEM fields. We propose systemic, institutional transformation centered on a foundation of faculty engagement, empowerment, and reward that reflects intentionality and accountability for developing diverse institutional communities.
Sextual activity

Ajzen's TRA constructs were found as predictors of sexting behaviors and intentions.Attitudes, subjective norms, and intentions were predictors of sexting behaviors.Attitudes and subjective norms predicted sexting intentions among non-sexters.Majority have previously sexted, and nearly half have sexted in the past 30days.Educators, health educators, and parents can use results to reduce risks of sexting. Purpose: To determine predictors of sexting behaviors among college students. Participants: Participants were 697 undergraduates at a midsized, Midwestern public university. Methods: A 111-item instrument measured participants' sextual activity (i.e., range of different sexting behaviors) regarding constructs from the Theory of Reasoned Action (attitudes, subjective norms, behavioral intentions, behaviors), global self-esteem levels, and selected demographics. Results: Predictors of sexting behaviors among selected undergraduate students include attitudes toward sexting, subjective norms, and behavioral intentions. Predictors of intentions to sext include attitudes toward sexting, and subjective norms. Conclusions: Social norms and personality traits can help predict whether or not young adults will sext and the scope of their sexting behaviors. Many college students sext for many different reasons and those who have sexted before are likely to sext again. Further, many of those who have not sexted intend to do so given the right circumstance. Recommendations for future research are discussed.
Electromagnetic nucleon-to-delta transition in chiral effective-field theory.

We perform a relativistic chiral effective-field theory calculation of the pion electroproduction off the nucleon (e{sup -} N {yields} e{sup -} N {pi}) in the {Delta}(1232)-resonance region. After fixing the three low-energy constants, corresponding to the magnetic (M1), electric (E2), and Coulomb (C2) {gamma} N {Delta} couplings, our calculation provides a prediction for the momentum-transfer and pion-mass dependence of the {gamma} N {Delta} form factors. The prediction for the pion-mass dependence resolves the discrepancy between the recent lattice QCD results and the experimental value for the ''C2/M1 ratio'' at low Q{sup 2}.
NOTES ON THE EXCAVATION OF A NEST OF MELOPHORUS BAGOTI LUBBOCK IN THE NORTHERN TERRITORY, AUSTRALIA (HYMENOPTERA: FORMICIDAE)

A dormant nest of the red honey ant, Melophorus bagoti, was excavated in Alice Springs, Northern Territory, Australia in August 1987. The nest had 160 chambers, reached a depth of 1.75 m, and contained 2,849 workers and mobile repletes and a dealate queen. Aborigines are familiar with this honey ant, but do not normally eat its repletes.
Failures of the interpolation lemma in quantified modal logic

Beth's Definability Theorem, and consequently the Interpolation Lemma, fail for the version of quantified S5 that is presented in Kripke's [6]. These failures persist when the constant domain axiom-scheme ∀x□φ ≡ □∀xφ is added to S5 or, indeed, to any weaker extension of quantificational K.§1 reviews some standard material on quantificational modal logic. This is in contrast to quantified intermediate logics for, as Gabbay [6] has shown, the Interpolation Lemma holds for the logic CD with constant domains and for several of its extensions. §§2—4 establish the negative results for the systems based upon S5. §5 establishes a more general negative result and, finally, §6 considers some positive results and open problems. A basic knowledge of classical and modal quantificational logic is presupposed.Let me briefly review the relevant model theory for quantified modal logic. Further details can be found in [3] or [7].The language is obtained from the language for classical first-order logic with identity by adding a unary operator □ for necessity. The atomic formula ‘Ex’ is used as an abbreviation for ‘∃y(y = x)’ and may be read as ‘x exists’.
Slow-slip phenomena in Cascadia from 2007 and beyond: A review

Recent technological advances combined with more detailed analyses of seismologic and geodetic observations have fundamentally changed our understanding of the ways in which tectonic stresses arising from plate motions are accommodated by slip on faults. The traditional view that relative plate motions are accommodated by a simple cycle of stress accumulation and release on “locked” plate-boundary faults has been revolutionized by the serendipitous discovery and recognition of the significance of slow-slip phenomena, mostly in the deeper reaches of subduction zones. The Cascadia subduction zone, located in the Pacific Northwest of the conterminous United States and adjacent Canada, is an archetype of exploration and learning about slow-slip phenomena. These phenomena are manifest as geodetically observed aseismic transient deformations accompanied by a previously unrecognized class of seismic signals. Although secondary failure processes may be involved in generating the seismic signals, the primary origins of both aseismic and seismic phenomena appear to be episodic fault slip, probably facilitated by fluids, on a plate interface that is critically stressed or weakened. In Cascadia, this transient slip evolves more slowly and over more prolonged durations relative to the slip in earthquakes, and it occurs between the 30- and 40-km-depth contours of the plate interface where information was previously elusive. Although there is some underlying organization that relaxes nearly all the accrued plate-motion stresses along the entirety of Cascadia, we now infer that slow slip evolves in complex patterns indicative of propagating stress fronts. Our new understanding provides key constraints not only on the region where the slow slip originates, but also on the probable characteristics of future megathrust earthquakes in Cascadia. Herein, we review the most significant scientific issues and progress related to understanding slow-slip phenomena in Cascadia and highlight some of their societal implications. We provide a comprehensive review, from the big picture as inferred from studies of regional-scale monitoring data to the details revealed by innovative, focused experiments and new instrumentation. We focus on what has been learned largely since 2007, when several major investments in monitoring and temporary deployments dramatically increased the quality and quantity of available data.
Differential Vibration of the Feet and Trunk of Humans

At vibrational frequencies below four or five Hz most subjects preferred that the footrest move in phase with and at the same amplitude as the seat. At higher frequencies most subjects preferred a stationary footrest.
Phentermine and topiramate extended-release: a new treatment for obesity and its role in a complications-centric approach to obesity medical management.

Introduction: Weight-management options include lifestyle modifications, bariatric surgery and, until recently, limited pharmacotherapy. Phentermine and topiramate extended-release (phentermine/topiramate ER) has recently been approved in the USA for chronic weight management in obese adults and overweight adults with weight-related co-morbidities in conjunction with a reduced-calorie diet and increased physical activity. Areas covered: This review describes the pharmacology and clinical trials data for phentermine/topiramate ER and its role in a complications-centric approach to medical care of the overweight and obese patient. Expert opinion: Phentermine/topiramate ER is an effective and safe weight-loss medication that can produce and sustain approximately 10% loss of body weight. This is a landmark development in the pharmacotherapy of obesity. By offering an effective medical option to complement lifestyle and surgical approaches, phentermine/topiramate ER enables a comprehensive medical model for ob...
Morphine does not stimulate prolactin release during lactation.

The ability of morphine to stimulate prolactin and growth hormone (GH) release was investigated in male rats and in female rats during diestrus, proestrus and lactation. In agreement with previous reports, acute morphine administration produced an increase in circulating levels of prolactin in male and in diestrous and proestrous female rats. In contrast to these results, morphine administration (10 or 15 mg/kg, s.c.; 5 mg/kg, i.v.; 5 or 10 micrograms, i.c.v.) did not produce an increase in prolactin levels in lactating dams. Morphine stimulates prolactin release in part by decreasing dopamine turnover in the tuberoinfundibular neurons in the median eminence. In order to assess the functional activity of these neurons during lactation, haloperidol (0.1 or 0.5 mg/kg, i.v.) was given to lactating dams. There was a significant increase in prolactin levels following haloperidol administration, suggesting that these dopaminergic neurons are participating in the modulation of prolactin release during lactation. In contrast to the insensitivity of the lactating rat to morphine stimulation of prolactin release, the intraventricular administration of two other opiate receptor agonists, beta-endorphin (10 or 20 micrograms) and [D-Ala-D-Leu]enkephalin (DADLE; 5 or 10 micrograms), produced significant increases in circulating levels of this hormone. The GH response to morphine, beta-endorphin and DADLE was also measured in these same rats. All these opiate receptor agonists stimulated GH release in male rats and in female rats during diestrus and proestrus as well as during lactation. These observations suggest that the suckling stimulus during lactation renders the rat refractory to morphine stimulation of prolactin release, possibly as a result of down-regulation of the mu-opiate receptor subtype.
Audio-visual speech recognition for a vowel discrimination task

Dept. of Electrical and Computer Engineering Dept. of Electrical and Computer EngineeringOld Dominion University The University of Texas at AustinNorfolk, VA 23529 Austin, TX 78712ABSTRACTAmong the various methods which have been proposed to improve the robustness and accuracy of AutomaticSpeech Recognition (ASR) systems, lipreading has received very little attention. In this paper, we providemotivation for the use of lipreading. A novel speaker dependent lipreading system is developed, which useshidden Markov modeling, a well known and highly successful technique for audio-based ASR. It is used
Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP and Müllerian inhibiting substance.

Abstract In addition to causing Mullerian duct regression in fetal males, Mullerian inhibiting substance (MIS) inhibits the expression of the bifunctional cytochrome P450, C17 hydroxylase/C 17–20 lyase (Cyp17), the enzyme that catalyzes the committed step in sex steroid synthesis. To investigate the paracrine effects of MIS on steroidogenic activity, we have performed assays with microsomes from mouse MA-10 Leydig cells. With microsomes from untreated MA-10 cells, progesterone was largely metabolized by 5α-reductase and subsequently converted by 3-keto steroid reductases to allopregnanolone and epiallopregnanolone. Addition of cAMP to the cells shifted microsomal steroid production to the Cyp17 product androstenedione and its 5α,3β-reduced form, epiandrosterone. Microsomes from MIS-treated cells were less active with the progesterone substrate than those of untreated cells but co-treatment of the cells with both MIS and cAMP mitigated the cAMP-induced shift of the microsomes to androstenedione production. Quantitative analyses of steroid production by Cyp17 showed that cAMP decreased the amount of 17-hydroxyprogesterone produced relative to the androstenedione, suggesting that cAMP signaling lowers the efficiency of the Cyp17 hydroxylase activity or else increases the efficiency of its lyase activity. Addition of MIS to the cAMP-treated cells partially reversed this effect, as well. These results indicate that cAMP induces MA-10 cells to switch from producing 5α-reduced progesterone metabolites to producing androstenedione and its metabolites by increasing Cyp17 expression and its relative lyase activity, both of which are inhibited by MIS.
Diagnosis, treatment, and management of breast cancer in previously augmented women.

: Augmentation mammaplasty is rapidly becoming one of the most frequently performed cosmetic surgeries. However, as the augmented patient population ages, major concerns associated with the screening, diagnosis and treatment of breast cancer are being realized. Although current evidence convincingly indicates that breast implants do not play a role in inducing localized or systemic disease, particularly breast cancer, recent studies have shown implants not only reduce the sensitivity of mammography, but interfere with mammographic detection, possibly leading to delayed breast cancer diagnosis. In addition, the risk for local recurrence, as well as unfavorable cosmetic results, breast fibrosis, and capsular contracture following radiation therapy as part of breast-conserving therapy in previously augmented patients are of great concern. Given the overall lack of treatment consensus, paucity of literature, and increasing number of augmented breast cancer patients, we provide a retrospective review of the diagnosis, treatment, and follow-up of 12 augmented patients from 1998 to 2004 who developed breast cancer. Eight of 12 augmented patients presented with a palpable mass on physical examination, which prompted further mammographic evaluation. Abnormalities in the remaining four individuals were detected on routine mammographic screening. Pathology staging results were available for all 12 patients. Breast-conserving therapy was used to treat six patients and adequate negative pathologic margins were obtained in all patients. The remaining six patients were treated with mastectomy due to multifocal disease, inadequate margins, or proximity to the implant capsule. Thus far, one patient has had local recurrence and one patient has had distant recurrence after initial surgery. No evidence of local or systemic recurrence, infection, contracture, poor cosmetic outcome, or other complications has been detected in the remaining 10 patients as of the most recent follow-up. Based on this small cohort of augmented women, the presence of implants led to an increased proportion of palpable tumors, in spite of routine screening mammography. Consistent with other studies, although our results suggest a tendency toward delayed diagnosis in augmented women relative to age-matched controls, this did not appear to influence the overall prognosis.
Diastolic dysfunction in cardiac transplant recipients: an important role in the response to increased afterload.

We evaluated the hemodynamic and functional response to acute elevations in left ventricular (LV) afterload in 22 recent recipients of cardiac transplants to determine whether abnormalities in LV diastolic function influence the response to this intervention. In seven patients (group 1) LV ejection fraction decreased significantly from baseline values (≥5%) during methoxamine infusion, whereas in 15 patients (group 2) LV ejection fraction was maintained. Peak filling rate was lower in group 1 versus group 2 (3.36 ± 0.46 vs 4.23 ± 0.68 end-diastolic volumes/sec, p < 0.01). In addition, patients in group 1 did not have LV dilatation during methoxamine (percentage change in end-diastolic counts, −3.4 ± 6.9%) and had a large increase in pulmonary artery wedge pressure. In contrast, patients in group 2 had LV dilatation (percentage change in end-diastolic counts, +10.7 ± 14.7%) and a smaller increase in pulmonary artery wedge pressure. There was a relationship between the baseline peak filling rate and the change in LV ejection fraction during methoxamine (r = 0.65, p = 0.001). Therefore in a subset of cardiac transplant patients, abnormalities in LV filling can have an impact on the response to increased afterload.
Workshop - modeling software the alloy way

Software engineering educators struggle to make formal design methods both accessible to and meaningful for students; the lack of appropriate engineering tools is especially problematic. One tool that addresses these problems is Alloy from Daniel Jackson's Software Design Group at MIT. Alloy has a formal mathematical foundation, making it useful for high-level system modeling, and for exploring the consequences of design decisions. This workshop will focus on using Alloy to teach formal modeling. While the workshop will partly tutorial, the goal is to help computing educators develop the skills, knowledge, and motivation to use Alloy in software engineering classes.
Cognitive Integration of Social and Environmental Beliefs

This paper examines the extent to which acceptance of dominant social beliefs and conflicting environmental beliefs by individuals helps to explain inconsistencies among environmental attitudes and behaviors. Specifically, it is hypothesized that individuals who demonstrate consistency in their acceptance of key social and environmental beliefs will also demonstrate greater consistency in their environmental attitudes and behaviors. Data from a mail survey of Washington state residents are used to examine this issue. The results suggest modest support for the hypothesis as higher correlations among environmental attitudes and behavior occur for groups who evidence greater integration of important social and environmental beliefs.
Decision Making with Prostate Cancer: A Multiple-Objective Model with Uncertainty

A patient who has been diagnosed with prostate cancer must make a difficult treatment decision. The available alternatives have varying cure rates and probabilities of side effects over a period of many years. This paper describes a well-informed, objective, and personalized model for comparing treatments to help a patient make the best treatment decision.
Prostate Cancer Detection: Lessons Learned in the Cleveland Clinic Experience with Focus on the Negative Biopsy

Twelve biopsy cores using an 18-gauge needle allow histological examination of only 0.04 % of an average-size prostate (Fleshner et al. J Urol. 158:505–8, 1997). Recognizing that repeat biopsy is positive in 20–35 % of cases, especially if saturation biopsy is performed, it is clear that any biopsy technique involves significant sampling error. As a referral center that often ends up being the final common pathway for large numbers of patients with suspicion of prostate cancer following one, two, or often many more prior negative biopsies, we have had the opportunity to explore the issues in depth.
A Comparison of Regional Scale Effects of In-Cloud Conversion of SO 2 to SO 4 = in an Eight Layer Diabatic Model with a Single Layer Model

A multilayer and single layer regional scale models have been used in a short term assessment during two frontal storms in October, 1977. A comparison with observed values has been made of results of the model assessments for SO4 air concentrations using an in-cloud SO 4 = wet deposition conversion, an in-rain conversion and no in-cloud or in-rain conversion in the multilayer model. Also an assessment using in-rain conversion using a single layer model was compared with observations. The results were mixed in that the multilayer model with no in-cloud or in-rain conversion yielded the best SO 4 = air concentration patterns while the multilayer model using in-cloud conversion yielded the best fit to observed wet deposition of SO 4 = . Further work is necessary since only 35% of the SO2 emission in emissions northeast United States were used in this study.
Effects of elevated atmospheric CO2 on net ecosystem CO2 exchange of a scrub–oak ecosystem

We report the results of a 2-year study of effects of the elevated (current ambient plus 350 μmol CO2 mol−1) atmospheric CO2 concentration (Ca) on net ecosystem CO2 exchange (NEE) of a scrub–oak ecosystem. The measurements were made in open-top chambers (OTCs) modified to function as open gas-exchange systems. The OTCs enclosed samples of the ecosystem (ca. 10 m2 surface area) that had regenerated after a fire, 5 years before, in either current ambient or elevated Ca. Throughout the study, elevated Ca increased maximum NEE (NEEmax) and the apparent quantum yield of the NEE (φNEE) during the photoperiod. The magnitude of the stimulation of NEEmax, expressed per unit ground area, was seasonal, rising from 50% in the winter to 180% in the summer. The key to this stimulation was effects of elevated Ca, and their interaction with the seasonal changes in the environment, on ecosystem leaf area index, photosynthesis and respiration. The separation of these factors was difficult. When expressed per unit leaf area the stimulation of the NEEmax ranged from 7% to 60%, with the increase being dependent on increasing soil water content (Wsoil). At night, the CO2 effluxes from the ecosystem (NEEnight) were on an average 39% higher in elevated Ca. However, the increase varied between 6% and 64%, and had no clear seasonality. The partitioning of NEEnight into its belowground (Rbelow) and aboveground (Rabove) components was carried out in the winter only. A 35% and 27% stimulation of NEEnight in December 1999 and 2000, respectively, was largely due to a 26% and 28% stimulation of Rbelow in the respective periods, because Rbelow constituted ca. 87% of NEEnight. The 37% and 42% stimulation of Rabove in December 1999 and 2000, respectively, was less than the 65% and 80% stimulation of the aboveground biomass by elevated Ca at these times. An increase in the relative amount of the aboveground biomass in woody tissue, combined with a decrease in the specific rate of stem respiration of the dominant species Quercus myrtifolia in elevated Ca, was responsible for this effect. Throughout this study, elevated Ca had a greater effect on carbon uptake than on carbon loss, in terms of both the absolute flux and relative stimulation. Consequently, for this scrub–oak ecosystem carbon sequestration was greater in the elevated Ca during this 2-year study period.
Alleviating the Constant Stochastic Variance Assumption in Decision Research: Theory, Measurement, and Experimental Test

Analysts often rely on methods that presume constant stochastic variance, even though its degree can differ markedly across experimental and field settings. This reliance can lead to misestimation of effect sizes or unjustified theoretical or behavioral inferences. Classic utility-based discrete-choice theory makes sharp, testable predictions about how observed choice patterns should change when stochastic variance differs across items, brands, or conditions. We derive and examine the implications of assuming constant stochastic variance for choices made under different conditions or at different times, in particular, whether substantive effects can arise purely as artifacts. These implications are tested via an experiment designed to isolate the effects of stochastic variation in choice behavior. Results strongly suggest that the stochastic component should be carefully modeled to differ across both available brands and temporal conditions, and that its variance may be relatively greater for choices made for the future. The experimental design controls for several alternative mechanisms (e.g., flexibility seeking), and a series of related models suggest that several econometrically detectable explanations like correlated error, state dependence, and variety seeking add no explanatory power. A series of simulations argues for appropriate flexibility in discrete-choice specification when attempting to detect temporal stochastic inflation effects.
A fully Bayesian hidden Ising model for ChIP-seq data analysis

S UMMARY Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a powerful technique that is being used in a wide range of biological studies including genome-wide measurements of protein–DNA interactions, DNA methylation, and histone modifications. The vast amount of data and biases introduced by sequencing and/or genome mapping pose new challenges and call for effective methods and fast computer programs for statistical analysis. To systematically model ChIP-seq data, we build a dynamic signal profile for each chromosome and then model the profile using a fully Bayesian hidden Ising model. The proposed model naturally takes into account spatial dependency and global and local distributions of sequence tags. It can be used for one-sample and two-sample analyses. Through model diagnosis, the proposed method can detect falsely enriched regions caused by sequencing and/or mapping errors, which is usually not offered by the existing hypothesis–testing-based methods. The proposed method is illustrated using 3 transcription factor (TF) ChIP-seq data sets and 2 mixed ChIP-seq data sets and compared with 4 popular and/or well-documented methods: MACS, CisGenome, BayesPeak, and SISSRs. The results indicate that the proposed method achieves equivalent or higher sensitivity and spatial resolution in detecting TF binding sites with false discovery rate at a much lower level.