cssi/SciSciGPT-SciSciNet huggingface dataset:
Error Estimation of Template-Based Protein Structure Models

The tertiary structure of proteins provides rich source of information for understanding protein function and evolution. Computational protein tertiary structure prediction has made significant progress over more than a decade due to the advancement of the techniques and the growth of sequence and structure databases. However, methods for assessing quality of predicted structure models are not well established. Quality assessment of structure models is important for reranking and selecting the best possible models from a pool of models as a post-processing step in structure prediction, and thus many methods are developed in this direction. Recently, it is also recognized that the model-quality assessment is crucial for practical use of a model such as design and interpretation of biochemical experimental data. For such practical application of a computational model, the real-value quality of the model should be predicted, which is different from reranking alternative models. The quality (error) of a model determines its potential practical application, ranging from protein design, designing site-directed mutagenesis experiments, ligand–protein docking prediction, to function prediction from structure. In this chapter, we discuss importance of the real-value error estimation and overview the existing methods.
Daugavet type inequalities for operators on Lp–spaces

Let T be a regular operator from Lp → Lp. Then \(T \bot I{\text{ implies that }}\left\| {I \pm T} \right\|_r \geqslant (1 + \left\| T \right\|_r^p )^{\frac{1}{p}} \), where ∥T∥r denotes the regular norm of T, i.e., ∥T∥r=∥ |T| ∥ where |T| denotes the modulus operator of a regular operator T. For p=1 every bounded linear operator is regular and ∥T∥=∥T∥r, so that the above inequality generalizes the Daugavet equation for operators on L1–spaces. The main result of this paper (Theorem 9) is a converse of the above result. Let T be a regular linear operator on Lp and denote by TA the operator T○χA. Then \(\left\| {I_A \pm T_A } \right\|_r \geqslant (1 + \left\| {T_A } \right\|_r^p )^{\frac{1}{p}} \) for all A with μ(A)>0 if and only if \(T \bot I\).
Lymphoid V(D)J Recombination: Accessibility and Reaction Fidelity in Normal and Ataxia-Telangiectasia Cells

The seven antigen receptor loci are targeted for V(D)J recombination at different times, at different developmental stages, and with B or T lineage specificity. The mechanisms remain undefined. The physical basis for the differential accessibility in this site-specific recombination reaction has been a matter of much speculation. Possibilities have included the processes of transcription (Ferrier et al., 1989; Martin et al., 1991; Schlissel et al., 1991) and DNA replication, and the structural features of DNA methylation and chromatin structure (Mather and Perry, 1983; Persiani and Seising, 1989; Storb and Arp, 1983; Yancopoulos et al., 1986). The relevant order and hierarchy of these parameters in controlling accessibility of the V(D)J recombination activity are poorly understood. Although some studies have raised the possibility that transcription is a requirement for recombination, the temporal resolution of such studies has been limiting. They have not permitted determination of whether transcription and recombination are consequences of a common chromatin change or whether transcription precedes and, thereby, activates recombination.
Development of a Primary Energy Driven Absorption Heat Pump for Domsestic Heating

An absorption heat pump for warm water domestic heating has been developed. It promises economical advantages over conventional heating systems. The project results permit the construction of prototype units.
Blood Cholinesterases as Human Biomarkers of Organophosphorus Pesticide Exposure

The organophosphorus (OP) insecticides were developed before and during World War II. The history of their development has been reviewed (Holmstedt 1963; Karczmar 1970; Ursdin 1970; Koelle 1981). In 1936, Schrader synthesized paraoxon, parathion, and octamethylpyrophosphoramide (OMPA, schradan) in a search for an effective cockroach control agent (Ursdin 1970). Parathion use in agriculture began after World War II. In 1949, a mixer loader was killed by parathion in Lake Placid, FL (Griffiths et al. 1951). Monitoring red blood cell acetyl-cholinesterase (RBC AChE) of exposed workers was begun in 1950 in the Florida citrus industry (Griffiths et al. 1951), perhaps the first use of human blood esterase monitoring in agriculture.
Nanofibers as Bioinstructive Scaffolds Capable of Modulating Differentiation Through Mechanosensitive Pathways for Regenerative Engineering

Bioinstructive scaffolds encode information in the physical shape and size of materials to direct cell responses. Electrospinning nanofibers is a process that offers control over scaffold architecture and fiber diameter, while providing extended linear length of fibers. This review summarizes tissue engineering literature that has utilized nanofiber scaffolds to direct stem cell differentiation for various tissues including musculoskeletal, vascular, immunological and nervous system tissues. Nanofibers are also considered for their extracellular matrix mimetic characteristics that can preserve stem cell differentiation capacity. These topics are considered in the context of focal adhesion and integrin signaling. Regenerative engineering will be enhanced by construction of scaffolds encoded with shape information to cause an attached cell to create the intended tissue at that region. Nanofibers are likely to be a bioinstructive scaffold in future regenerative engineering development as we pursue the Grand Challenges of engineering tissues.
Comorbid conditions are a risk for osteonecrosis of the jaw unrelated to antiresorptive therapy.

Objective Osteonecrosis of the jaw (ONJ) is commonly associated with antiresorptive therapy. There have been numerous reports of ONJ unrelated to antiresorptive therapy (ONJuat), confounding risk assessment. This study aimed to determine if ONJuat is associated with one or more particular comorbidities. Study Design This was a retrospective case-control study of patients with ONJuat and delayed healing (DH). Each case was matched for patient age and gender, as well as location of ONJuat or DH lesion to a control patient who had a history of dentoalveolar surgery with uneventful healing and no history of antiresorptive therapy. Comorbidity data included medical conditions and smoking. Results Of the 92 patients identified, 67 (73%) met the criteria for ONJuat and 25 (27%) for DH. The most common trigger for ONJ and DH was extraction (50%). The presence of any comorbidity (i.e., at least 1) was more prevalent in ONJuat than among controls (P = .04), and there were more comorbidities in patients with ONJuat and DH than in controls [M(SD) = 1.94 (1.2) and 2.0 (1.3) vs 1.26 (0.89); both P Conclusions ONJ and DH are not limited to patients with a history of antiresorptive therapy. More comorbidities may signal increased risk for ONJuat and DH.
Experiences of social demand in a simulated gaming environment

Communicating with others is a key motivation for playing digital games, but associated gratifications often require the presence of and interaction with other agents that may be inherently demandi...
A 28-Year-Old High Level Volleyball Player with Sore Shoulder

The vast majority of shoulder injuries in overhead athletes should initially be approached with a conservative treatment. Only significant structural injuries with loss of function deserve early surgical intervention. Every overhead athlete requires a training program that strengthens all elements of the kinetic chain of the throwing motion. To prevent the effects of overtraining or throwing, it is essential to instruct the athlete what to do through specific exercises throughout the year.
The emergence of a half-century of research on humour in advertising: what have we learned? What do we still need to learn?

AbstractThe use of humour in advertising is widespread and research about it has grown rapidly. There are now at least 250 academic works devoted to advertising humour with over 150 articles, disse...
Policies and Interventions to Provide Safety for Pedestrians and Overcome the Systematic Biases Underlying the Failures

Road transport is failing pedestrians more than other road users. For pedestrians, roads are not safe or improving: Globally pedestrian deaths have increased at nearly twice the rate of other road crash deaths (12.9% increase from 2013 to 2016, versus a 6.6% increase for other road users). Pedestrians commonly lack safe crossings, safe speeds, and in many locations, footpaths. This paper briefly identifies successes and failures for pedestrian safety, reviews weaknesses and limitations to actions for pedestrian safety and identifies barriers to effective action. Barriers include current culture on road usage, victim blaming, under-estimation of the pedestrian crash death problem in particular, and other crash data issues. Advocacy, policies and actions are recommended to overcome these barriers and to improve pedestrian safety.
Target-Mediated Drug Disposition-A Class Effect of Soluble Epoxide Hydrolase Inhibitors

Pharmacological target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TMDD can also happen in small-molecule compounds, it has been largely overlooked. In this mini-review, we summarize the occurrence of TMDD that we discovered recently in a series of small-molecule soluble epoxide hydrolase (sEH) inhibitors. Our journey started with an accidental discovery of target-mediated kinetics of 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU), a potent sEH inhibitor, in a pilot clinical study. To confirm what we observed in humans, we conducted a series of mechanism experiments in animals, including pharmacokinetic experiments using sEH knockout mice as well as in vivo displacement experiments with co-administration of another potent sEH inhibitor. Our mechanism studies confirmed that the TMDD of TPPU is due to its pharmacological target sEH. We further expanded our evaluation to various other sEH inhibitors and found that TMDD is a class effect of this group of small-molecule sEH inhibitors. In addition to summarizing the occurrence of TMDD in sEH inhibitors, in this mini-review we also highlighted the importance of recognizing TMDD of small-molecule compounds and its impact in clinical development as well as using pharmacometric modeling in facilitating quantitative understanding of TMDD.
Firm Finances and the Spread of COVID-19: Evidence from Nursing Homes

We find that firms’ financial resources play an important role in mitigating the spread of COVID-19. We study nursing homes – whose residents account for over one-third of all U.S. COVID-19 deaths – at a time when investment in risk mitigation was costly and critical. We find that facilities with less liquidity and those experiencing more severe cash flow shocks had a higher likelihood of COVID-19 reaching residents. These patterns are strongest for financially constrained facilities. We also find higher rates of transmission between staff and residents within liquidity-constrained facilities, which is consistent with these facilities creating a less-effective barrier between groups.
Rarefied particle motions on hillslopes – Part 2: Analysis

Abstract. We examine a theoretical formulation of the probabilistic physics of rarefied particle motions and deposition on rough hillslope surfaces using measurements of particle travel distances obtained from laboratory and field-based experiments, supplemented with high-speed imaging and audio recordings that highlight effects of particle–surface collisions. The formulation, presented in a companion paper (Furbish et al., 2021a), is based on a description of the kinetic energy balance of a cohort of particles treated as a rarefied granular gas, as well as a description of particle deposition that depends on the energy state of the particles. Both laboratory and field-based measurements are consistent with a generalized Pareto distribution of travel distances and predicted variations in behavior associated with the balance between gravitational heating due to conversion of potential to kinetic energy and frictional cooling due to particle–surface collisions. For a given particle size and shape these behaviors vary from a bounded distribution representing rapid thermal collapse with small slopes or large surface roughness, to an exponential distribution representing approximately isothermal conditions, to a heavy-tailed distribution representing net heating of particles with large slopes. The transition to a heavy-tailed distribution likely involves an increasing conversion of translational to rotational kinetic energy leading to larger travel distances with decreasing effectiveness of collisional friction. This energy conversion is strongly influenced by particle shape, although the analysis points to the need for further clarity concerning how particle size and shape in concert with surface roughness influence the extraction of particle energy and the likelihood of deposition.
Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease.

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.
Pushing-Down Tensor Decompositions over Unions to Promote Reuse of Materialized Decompositions

From data collection to decision making, the life cycle of data often involves many steps of integration, manipulation, and analysis. To be able to provide end-to-end support for the full data life cycle, today's data management and decision making systems increasingly combine operations for data manipulation, integration as well as data analysis. Tensor-relational model (TRM) is a framework proposed to support both relational algebraic operations (for data manipulation and integration) and tensor algebraic operations (for data analysis). In this paper, we consider joint processing of relational algebraic and tensor analysis operations. In particular, we focus on data processing workflows that involve data integration from multiple sources (through unions) and tensor decomposition tasks. While, in traditional relational algebra, the costliest operation is known to be the join, in a framework that provides both relational and tensor operations, tensor decomposition tends to be the computationally costliest operation. Therefore, it is most critical to reduce the cost of the tensor decomposition task by manipulating the data processing workflow in a way that reduces the cost of the tensor decomposition step. Therefore, in this paper, we consider data processing workflows involving tensor decomposition and union operations and we propose a novel scheme for pushing down the tensor decompositions over the union operations to reduce the overall data processing times and to promote reuse of materialized tensor decomposition results. Experimental results confirm the efficiency and effectiveness of the proposed scheme.
Chemical modification of aldehyde dehydrogenase by a vinyl ketone analogue of an insect pheromone

A major component of the sex pheromone from the tobacco budworm moth Heliothis virescens is a C16 straight-chain aldehyde with a single unsaturation at the eleventh position. The sex pheromones are inactivated when metabolized to their corresponding acids by insect aldehyde dehydrogenase. During this investigation it was demonstrated that the C16 aldehyde is a good substrate for human aldehyde dehydrogenase (EC 1.2.1.3) isoenzymes E1 and E2 with Km and Kcat. values at pH 7.0 of 2 microM and 0.4 mumol of NADH/min per mg and of 0.6 microM and 0.24 mumol of NADH/min per mg respectively. A vinyl ketone analogue of the pheromone inhibited insect pheromone metabolism; it also inactivated human aldehyde dehydrogenase. Total inactivation of both isoenzymes was achieved at stoichiometric (equal or less than the subunit number) concentrations of vinyl ketone, incorporating 2.1-2.6 molecules/molecule of enzyme. Substrate protection was observed in the presence of the parent aldehyde and 5′-AMP. Peptide maps of tryptic digests of the E2 isoenzyme modified with 3H-labelled vinyl ketone showed that incorporation occurred into a single peptide peak. The labelled peptide of E2 isoenzyme was further purified on h.p.l.c. and sequenced. The label was incorporated into cysteine-302 in the primary structure of E2 isoenzyme, thus indicating that cysteine-302 is located in the aldehyde substrate area of the active site of aldehyde dehydrogenase. Affinity labelling of aldehyde dehydrogenase with vinyl ketones may prove to be of general utility in biochemical studies of these enzymes.
Adsorption of Gases in Nanomaterials: Theory and Simulations

Physical adsorption (physisorption) is the study of atoms or molecules weakly bound to material surfaces. Physisorption-related investigations raise critical questions concerning phase transitions, fractals, wetting transitions, two-dimensional superfluidity, and Van der Waals interactions. This chapter focuses on adsorption of gases (e.g. Ar, Kr, H2, CO2, and CH4) in nanomaterials, and in particular the authors describe equilibrium properties of the gases adsorbed in carbon nanotubes, graphene and Metal Organic Frameworks (MOFs). The adsorption potential used for developing the theoretical model for studying physisorption involves the summing of two-body interactions, and several important properties of adsorbates can be obtained via simulations, namely equilibrium properties, thermal characteristics, selectivity, wetting features, and structure and phase of the adsorbed monolayer. Applications of physisorption include the separation of cryogenic gases, their storage and their use as a surface characterization tool.
Assembly and intracellular trafficking of GABAA receptors.

Publisher Summary The chapter focuses on the assembly and intracellular trafficking of GABA A receptors. γ-Aminobutyric acid type A (GABAA) receptors provide channels for fast inhibitory postsynaptic currents in the central nervous system (CNS) of vertebrates. For GABA A receptors, the assembly pathway is much less understood. The observation that, in a single neuron, only a subset of the available GABA A receptor subunits is oligomerized into receptors, suggests a highly selective process. Presumably, complementary sites on the surfaces of neighboring subunits must enable their specific, high-affinity association. As for the nAChR, the ordered arrangement of five subunits to form a central channel adds an additional layer of complexity to the assembly of GABA A receptors. Some of the subunit associations that seem to be involved in this process are examined in the chapter. Following assembly in the endoplasmic reticulum (ER), GABA A receptors are targeted to the plasmalemma, where they cluster in postsynaptic membranes and are activated by the presynaptic release of GABA. The reason that receptor clustering is a prerequisite for the establishment of fast inhibitory postsynaptic currents, there is considerable interest in this process. Alternatively, surface GABA A receptors may participate in an endocytic cycle. Ligand-induced GABA A receptor endocytosis has been implicated in the synaptic remodeling that may underlie physical dependence on benzodiazepines and related drugs.
Successful implementation of a rural extracorporeal photopheresis program for the treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease in a rural hospital

Objective Extracorporeal photopheresis (ECP) is currently standard therapy for cutaneous T-cell lymphoma (CTCL) and Graft-versus-host disease (GVHD). Of the many challenges associated with outpatient ECP treatments, commuter travel to capable facilities can fragment and compromise the patient care. In 2008, our hospital implemented an ECP program providing patients to a treatment center over 120 minutes away. This study was undertaken to describe our experience with the establishment of a regional ECP program. Methods A retrospective review using a standardized template was performed of patients treated from May 2008 to 2012. The response to treatment was analyzed after a minimum of eight procedures. A partial response to treatment in individuals with CTCL, was more than 50% skin improvement, and GVHD, a reduction in steroid dose by 50%, liver function test improvement or documented improvement in skin findings. Results Of the 34 patients treated, 11 were for CTCL and 23 for GVHD. 95.8% of the 1,071 planned procedures were successfully. The average procedure time was 186 min for the UVAR-XTSTM and 93 min for the CELLEXTM. Patients travelled a median of 65.7 miles (range 4–133 miles). The median duration of therapy was 6 months (range 2–23) for CTCL and 5 months (range 1–27) for GVHD. A clinical benefit was observed in 7 of 11 (63.6%) patients with CTCL and in 15 of 23 (65.2%) with GVHD. Conclusion Our regional ECP program was a viable option in improving access to care for patients requiring treatment for CTCL and chronic GVHD. J. Clin. Apheresis, 2015. © 2015 Wiley Periodicals, Inc.
Optimizing the “demographic dividend” in young developing countries: The role of contractual savings and insurance for financing education

Many developing regions are facing a youth bulge, meaning that young people comprise the highest proportion of the population. These regions are at risk of losing what could be a tremendous opportunity for economic growth and development if they do not capitalize on this young and economically productive population - also referred to as the "demographic dividend," defined as the increase in economic growth that tends to follow increases in the ratio of the working-age population - essentially the labor force - to dependents. Nations undergoing this population transition have the opportunity to capitalize on the demographic dividend if the right social, economic, and human capital policies are in place. In particular, sub-Saharan Africa, the Middle East, and North Africa are at risk of losing the demographic dividend. These regions face high youth unemployment, low primary school completion, and low secondary school enrollment. This results in an undereducated and unskilled segment of the population. The prohibitive costs of education prevent young people from finishing school, thereby entering the labor market unprepared. This article presents a case for youth-focused financial inclusion programs as one of the antidotes to the masses of poor, undereducated, and low-skilled young people swelling the labor markets of poor developing countries.
Orientalism and Islam: Alexis de Tocqueville and Colonization

The stature of Alexis de Tocqueville (1805–59) as a political thinker has varied during the last century and a half. The rapid acknowledgment of the importance of his writings immediately on their publication, and the warmth and extent of his voluminous correspondence with both French and foreign, especially British, distinguished individuals, including John Stuart Mill and Nassau Senior, testify to the admiration for his intellectual brilliance and appreciation of his acumen and even prophetic insight on political affairs. That admiration was officially and explicitly shown by his election in 1838 to the Academie des Sciences Morales et Politiques and in 1841 to the illustrious French Academy after the second of his volumes on Democracy in America had been published the previous year. If that admiration and high regard seemed to have ebbed, as all literary reputations do from time to time, for a while in the early twentieth century, it has in recent years swelled in full flood as analysts of different points of view and with diverging interpretations have seen him as an astute observer of politics or discussed his relevance for understanding the nature and problems of democracy and of social and political development. His works have not only been considered in scholarly fashion; they have also been used for ideological reinforcement, or ransacked by politicians for polemical purposes or by those seeking aphoristic nuggets for verbal impact. Tocqueville's ambition was not confined to brilliantly written, influential original publications on political and social issues, now regarded as masterpieces.
Macular pigment in donor eyes with and without AMD: a case-control study.

PURPOSE To determine whether there is an association between the density of macular pigment in the human retina and the risk of age-related macular degeneration (AMD). METHODS Retinas from 56 donors with AMD and 56 controls were cut into three concentric regions centered on the fovea. The inner, medial, and outer regions covered the visual angles 0 degrees to 5 degrees, 5 degrees to 19 degrees, and 19 degrees to 38 degrees, respectively. The amounts of lutein (L) and zeaxanthin (Z) extracted from each tissue sample were determined by high-performance liquid chromatography. RESULTS L and Z levels in all three concentric regions were less, on average, for the AMD donors than for the controls. The differences decreased in magnitude from the inner to medial to outer regions. The lower levels found in the inner and medial regions for AMD donors may be attributable, in part, to the disease. Comparisons between AMD donors and controls using the outer (peripheral) region were considered more reliable. For this region, logistic regression analysis indicated that those in the highest quartile of L and Z level had an 82% lower risk for AMD compared with those in the lowest quartile (age- and sex-adjusted odds ratio = 0.18, 95% confidence interval = 0.05-0.64). CONCLUSIONS The results are consistent with a theoretical model that proposes an inverse association between risk of AMD and the amounts of L and Z in the retina. The results are inconsistent with a model that attributes a loss of L and Z in the retina to the destructive effects of AMD.
False-positive reaction to the regitine test for pheochromocytoma: report of a case.

Excerpt Regitine (preparation C-7337) or 2-{[N-(m-hydroxyphenyl)-p-toluidino] methyl}-2-imidazoline methanesulfonate lowers the blood pressure in patients with hypertension caused by a pheochromocy...
A selective sigma-2 receptor ligand antagonizes cocaine-induced hyperlocomotion in mice.

Cocaine functions, in part, through agonist actions at sigma-1 (σ1) receptors, while roles played by sigma-2 (σ2) receptors are less established. Attempts to discriminate σ2 receptor-mediated effects of cocaine in locomotor hyperactivity assays have been hampered by the lack of potent and selective antagonists. Certain tetrahydroisoquinolinyl benzamides display high σ2 receptor affinity, and excellent selectivity for binding to σ2 over σ1 receptors. The behavioral properties of this structural class of σ ligands have not yet been investigated. The present study evaluated 5-bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide, 1, a ligand shown by others to bind preferentially to σ2 over σ1 receptors, as well as dopamine D2 and D3 sites. First, we determined binding to monoamine transporters and opioid receptors, and noted 57-fold selectivity for σ2 receptors over the serotonin transporter, and >800-fold selectivity for σ2 receptors over the other sites tested. We then examined 1 in locomotor activity studies using male CD-1® mice, and saw no alteration of basal activity at doses up to 31.6 µmol/kg. Cocaine produced a fivefold increase in locomotor activity, which was attenuated by 66% upon pretreatment of mice with 1 at 31.6 µmol/kg. In vivo radioligand binding studies also were performed, and showed no occupancy of σ1 receptors or the dopamine transporter by 1, or its possible metabolites, at the 31.6 µmol/kg dose. Thus, ligand 1 profiles behaviorally as a σ2 receptor-selective antagonist that is able to counteract cocaine's motor stimulatory effects. Synapse 68:73–84, 2014. © 2013 Wiley Periodicals, Inc.
125I-iodinated benzazepines bind to melanin: implications for the noninvasive localization of pigmented melanomas.

Abstract Both the 5-R and the 5-S enantiomers of [ 125 I]2,3,4,5-tetrahydro-8-iodo-3-methyl-5-phenyl-1 H -3-benzazepin-7-ol bind to melanin. The interaction between the 5-R enantiomer and melanin permits visualization of melanomas in mice with a noninvasive imaging procedure. Two lines of evidence suggest that the interaction between iodinated ligands and melanin is not related to the D-1 dopamine receptor, a known target for the 5-R enantiomer: first, melanin binds both enantiomers of the 125 I-iodinated benzazepine while the D-1 receptor binds only the 5-R enantiomer; second, the melanin binding site displays only a 5-fold difference in affinity towards the R- and S-enantiomers of SCH 23390 while the D-1 receptor displays a 100-fold difference in affinity towards these two molecules. Because both enantiomers of the iodinated benzazepine bind to a human pigmented melanoma, we propose that such compounds may be of use in the diagnosis of pigmented melanoma: in addition, we discuss the possible application of these molecules as a supplement to existing technology for the localization of pigmented melanomas.
Endometrial Cancer—current state of the art therapies and unmet clinical needs: The role of surgery and preoperative radiographic assessment

Endometrial carcinoma is the fourth most common cancer among women in the United States. Surgical pathologic staging has been the standard of care since 1988, which consists of analysis of collected peritoneal fluid, hysterectomy/oophorectomy, and pelvic and para-aortic lymphadenectomy. In 2005, it was further recommended that essentially all women with endometrial cancer who choose to undergo surgery have pelvic and para-aortic lymph node analysis. Despite this recommendation, there still remains controversy as to whether all patients with endometrial cancer should undergo full lymph node dissection. In this review, we assess the evidence surrounding this controversy and conclude that women with endometrial cancer should undergo complete lymphadenectomy at the time of surgery. Furthermore, we evaluate the evidence regarding laparoscopic surgical staging as a safe and effective alternative to the more invasive traditional laparotomy. Finally, for those patients who a gynecologic oncologist is not readily available to perform a complete lymph node dissection, we evaluate the various imaging studies and their utility as preoperative triage modalities.
Affinity chromatographic purification of serum retinol-binding protein using 4-substituted aminoretinoids.

Abstract Retinol-binding protein has been purified from rabbit serum by a new affinity chromatographic phase. Human retinol-binding protein has been shown to bind with vitamin A derivatives and certain other terpenoids. Consequently, this affinity method is based upon the ability of the protein to reversibly bind to β-ionone and employs a derivatized affinity ligand while preserving the integrity of the β-ionone molecule via substitution at the allylic 4-position. Purification is relatively simple when compared with other known methods and the yield from serum is similar to other schemes. The protein is obtained in the apo-form and retains the ability of the native protein to bind retinol.
Corticotropin-releasing factor receptor densities vary with photoperiod and sociality.

Abstract Life in social groups relies on prosocial behaviors as well as on reduction of antisocial behaviors such as aggression and territoriality. The mechanisms supporting variation in behaviors that give rise to group living (sociality) are largely unknown. Female meadow voles exhibit natural seasonal variation in sociality: females are aggressive and territorial in summer, while in winter they share burrows and nest in mixed-sex groups. This behavioral shift is paralleled in the lab by day length-dependent variation in partner preference formation and social huddling. We exploit natural variation in meadow vole sociality in order to examine changes in neural pathways that coincide with environmental and behavioral variations. Mounting evidence suggests that the corticotropin-releasing factor system, encompassing multiple peptides and two receptor subtypes (CRF 1 and CRF 2 ), may play an important role in regulating social behaviors. We report day-length dependent variation in CRF 1 and CRF 2 receptor binding in female meadow voles, and relate these findings to previously collected oxytocin receptor (OTR) binding data and behavioral data for the same individuals. CRF 1 receptor binding was greater in summer-like long day lengths (LD), particularly in the hippocampus, while CRF 2 receptor binding was greater in winter-like short day lengths (SD) in the cingulate cortex and hippocampus. OTR varied with day length in the bed nucleus of the stria terminalis, nucleus accumbens, and hippocampus. SD voles huddled more extensively than LD voles, and greater huddling time was associated with more CRF 1 receptor binding and less CRF 2 receptor binding in subregions of the lateral septum. CRF 2 receptor associations with behavior mirrored those of OTR in the lateral septum. Finally, estradiol treatment affected density of CRF receptors in multiple brain regions. CRF receptors and their ligands are promising candidates for enhancing understanding of the regulation of non-sexual social behavior between group living peers.
Age, Growth, and Fecundity of the Quillback (Carpiodes cyprinus) and Highfin (C. velifer) Carpsuckers in an Ohio Stream

Abstract An analysis of age, growth, and fecundity was carried out on 208 quillback (Carpiodes cyprinus) and 32 highfin (C. velifer) carpsuckers collected from Four Mile Creek, Ohio, May-October, 1972. Back-calculations of growth indicated that C. cyprinus grows more rapidly than C. velifer, reaching its maximum size at age X. Males in both species were generally larger than females at each annulus, though the actual differences in length and weight were highly variable. The respective length-weight relationships for C. cyprinus and C. velifer were, respectively: log W = -4.06042 + 2.78559 log TL; and log W = -4.05206 + 2.80837 log TL; where W = wet weight (g) and TL = total length (mm). Monthly (May-October) condition coefficients for C. cyprinus ranged from 1.13 to 1.37 for males and 1.20 to 1.24 for females. Values for C. velifer (ages IV-VIII) ranged from 1.24 to 1.39. Fecundity of four C. velifer (ages V-VII) ranged from 41,644 to 62,355 ova per individual. The fecundity estimates (Fec) (range = 15,2...
On the correctness of the Krivine machine

We provide a short proof of the correctness of the Krivine machine by showing how it simulates weak head reduction.
Derogating black sheep: Individual or group protection?

What motivates people to derogate unfavorable ingroup members more harshly than comparably unfavorable outgroup members? Researchers investigating the black sheep effect maintain that this differential derogation is a means of group protection. In contrast, we argue that derogating unfavorable ingroup members may be an individual protection strategy whereby target devaluation distances an unfavorable other from the self as a means of limiting the threat of being associatively miscast. Participants read an article describing an unfavorable ingroup or outgroup target, and then received two means of responding to the target: target devaluation and group disidentification. Importantly, group disidentification was considered to be a uniquely individualistic distancing strategy. We found that both response options substituted for one another, depending on the order of presentation. Substitutability, we argue, suggests that the primary motive behind ingroup derogation in our study was distance augmentation, an individual protection strategy.
Response to Tomsak, R. PDE5 inhibitors and permanent visual loss (Int J Impot Res 2005; 17: 547-549).

Response to Tomsak, R. PDE5 inhibitors and permanent visual loss ( Int J Impot Res 2005; 17 : 547–549)
Design, construction, and operation of an actively controlled deep-sea CO2 enrichment experiment using a cabled observatory system

Abstract We describe the design, testing, and performance of an actively controlled deep-sea Free Ocean CO 2 Enrichment (dp-FOCE) system for the execution of seafloor experiments relating to the impacts of ocean acidification on natural ecosystems. We used the 880 m deep MARS (Monterey Accelerated Research System) cable site offshore Monterey Bay, California for this work, but the Free Ocean CO 2 Enrichment (FOCE) system concept is designed to be scalable and can be modified to be used in a wide variety of ocean depths and locations. The main frame is based on a flume design with active thruster control of flow and a central experimental chamber. The unit was allowed to free fall to the seafloor and connected to the cable node by remotely operated vehicle (ROV) manipulation. For operation at depth we designed a liquid CO 2 containment reservoir which provided the CO 2 enriched working fluid as ambient seawater was drawn through the reservoir beneath the more buoyant liquid CO 2 . Our design allowed for the significant lag time associated with the hydration of the dissolved CO 2 molecule, resulting in an e-folding time, τ , of 97 s between fluid injection and pH sensing at the mean local T =4.31±0.14 °C and pH T of 7.625±0.011. The system maintained a pH offset of ~0.4 pH units compared to the surrounding ocean for a period of ~1 month. The unit allows for the emplacement of deep-sea animals for testing. We describe the components and software used for system operation and show examples of each. The demonstrated ability for active control of experimental systems opens new possibilities for deep-sea biogeochemical perturbation experiments of several kinds and our developments in open source control systems software and hardware described here are applicable to this end.
Cognitive Load Theory and Library Research Guides

Online library research guides are instructional tools that most libraries provide for their patrons. With greater flexibility in Web programming and new products like Springshare's Libguides, librarians have multiple venues for guide creation. This paper seeks to assist research guide editors in assessing their guides based on cognitive load theory. This theory is based on the idea that cognitive capacity for learning is limited and that techniques can be developed to help learners avoid cognitive overload. Addressing the three main sources of cognitive load gives librarians a framework in which to create meaningful and useful research guides.
Secobarbital-mediated Inactivation of Cytochrome P450 2B1 and Its Active Site Mutants PARTITIONING BETWEEN HEME AND PROTEIN ALKYLATION AND EPOXIDATION

Secobarbital (SB) is a relatively selective mechanism-based inactivator of cytochrome P450 2B1, that partitions between epoxidation and heme and protein modification during its enzyme inactivation. The SB-2B1 heme adduct formed in situ in a functionally reconstituted system has been spectrally documented and structurally characterized as N-(5-(2-hydroxypropyl)-5-(1-methylbutyl)barbituric acid)protoporphyrin IX. The SB-protein modification has been localized to 2B1 peptide 277-323 corresponding to the active site helix I of cytochrome P450 101. The targeting of heme and this active site peptide suggests that the 2B1 active site topology could influence the course of its inactivation. To explore this possibility, the individual SB epoxidation, heme and protein modification, and corresponding molar partition ratios of the wild type and seven structural 2B1 mutants, site-directed at specific substrate recognition sites, and known to influence 2B1 catalysis were examined after Escherichia coli expression. These studies reveal that Thr-302 is critical for SB-mediated heme N-alkylation, whereas Val-367 is a critical determinant of 2B1 protein modification, and Val-363 is important for SB epoxidation. SB docking into a refined 2B1 homology model coupled with molecular dynamics analyses provide a logical rationale for these findings.
A microcomputer-based system for feed control, temperature control and temperature recording in an experimental fish hatchery.

Abstract An automatic feed delivery system and complementary temperature control and recording system designed to save labor and improve the efficiency of an experimental fish rearing facility is described. A microcomputer with a 6502 type microprocessor accepts an instruction array of feeding times and amounts, as well as upper and lower temperature limits for activation of an alarm and a heater, respectively. Feed is released by solenoid-actuated devices constructed from common materials and components. All other peripheral devices (real-time clock, disk drive input-output control and temperature sensors) are commercially available. The BASIC program for control of feeding and temperature is available upon request.
Analysis of a RanGTP-regulated gradient in mitotic somatic cells

The RanGTPase cycle provides directionality to nucleocytoplasmic transport, regulating interactions between cargoes and nuclear transport receptors of the importin-beta family. The Ran-importin-beta system also functions in mitotic spindle assembly and nuclear pore and nuclear envelope formation. The common principle underlying these diverse functions throughout the cell cycle is thought to be anisotropy of the distribution of RanGTP (the RanGTP gradient), driven by the chromatin-associated guanine nucleotide exchange factor RCC1 (refs 1, 4, 5). However, the existence and function of a RanGTP gradient during mitosis in cells is unclear. Here we examine the Ran-importin-beta system in cells by conventional and fluorescence lifetime microscopy using a biosensor, termed Rango, that increases its fluorescence resonance energy transfer signal when released from importin-beta by RanGTP. Rango is predominantly free in mitotic cells, but is further liberated around mitotic chromatin. In vitro experiments and modelling show that this localized increase of free cargoes corresponds to changes in RanGTP concentration sufficient to stabilize microtubules in extracts. In cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle formation but is largely dispensable once the spindle has been established. Consistent with previous reports, we observe that the Ran system also affects spindle pole formation and chromosome congression in vivo. Our results demonstrate that conserved Ran-regulated pathways are involved in multiple, parallel processes required for spindle function, but that their relative contribution differs in chromatin- versus centrosome/kinetochore-driven spindle assembly systems.
NMDA Receptor Characteristics in the Brain of Fetal Guinea Pigs Following In Utero Hypoxia and Recovery. † 201

Previous studies have shown that in utero hypoxia results in brain cell membrane dysfunction and alters N-methyl-D-aspartate (NMDA) receptor characteristics in fetal guinea pigs. The present study tests the hypothesis that modification of brain cell membrane function during in utero hypoxia persists following recovery. Six pregnant guinea pigs at term were exposed to 7% oxygen for 1 hour. Brain tissue obtained from fetal guinea pigs immediately after in utero hypoxia was compared to that of fetuses exposed to hypoxia but allowed to recover in utero for 24 hours. ATP and phosphocreatine (PCr) levels were determined biochemically as indices of brain tissue energy metabolism. ATP and PCr levels were significantly higher in the recovery group compared to the hypoxic group(5.22±0.95 vs. 1.5±0.02 and 3.73±0.28 vs. 0.66±0.17 μ mol/g brain, respectively, p<0.01). Brain cell membrane Na+,K+-ATPase activity was measured as an index of brain cell membrane function. The recovery group demonstrated a significantly higher activity of Na+,K+-ATPase compared to the hypoxic group(35.1±4.0 vs. 25.2±7.0 μ moles Pi/mg protein/hr, p<0.05).3[H]MK-801 binding (2.5-50 nM) in the presence of glutamate and glycine was performed as an index of NMDA receptor modification. Receptor number(Bmax) in the recovery group was similar to the hypoxic group(1.28±0.04 vs 1.25±0.18 pmol/mg protein). In addition receptor dissociation constant (Kd) was similar in the two groups (5.61±0.30 vs 4.94±0.84 nM). This preliminary data show that following recovery from in utero hypoxia, brain cell energy metabolism and brain cell membrane function improve, but that hypoxia-induced alterations in NMDA receptor characteristics persist. We speculate that alterations in the NMDA receptor following in utero hypoxia may contribute to delayed brain cell injury despite recovery of cellular energy metabolism and cell membrane function.
Structure, characterization, and expression of the gene encoding the mouse Mel1a melatonin receptor.

Recently, a distinct family of G protein-coupled receptors has been cloned that mediates the biological effects of melatonin. Of two sub-types cloned from mammals (Mel1a and Mel1b), the Mel1a receptor appears to mediate the circadian and reproductive effects of the hormone. We now report the cloning, characterization, and expression of the gene encoding the Mel1a receptor in mice. The receptor gene is composed of two exons, separated by an intron of greater than 13 kilobases. Exon 1 encodes the entire 5'-untranslated region and the coding region through the first cytoplasmic loop. Exon 2 encodes the rest of the coding region and the entire 3'-untranslated region. 5'-Rapid amplification of complementary DNA ends and ribonuclease protection analyses show that the major transcription start site is 103 nucleotides upstream of the translation start codon. Sequence analysis of 1.1 kilobases of the 5'-flanking region reveals that it does not contain TATA or CAAT boxes. The 5'-flanking region drives luciferase ex...
Determination of superoxide dismutase and glutathione peroxidase activities in blood of healthy pediatric subjects.

Abstract Background: Given the growing requirement of antioxidant enzymes measurements in laboratory and the increasing role of SOD/GPx ratio in the balance of reactive oxygen species (ROS), the aim of our study was to contribute to define reference values of enzyme activities in Italian healthy children, by determining SOD in erythrocytes and GPx in whole blood. Methods: SOD (E.C.1.15.1.1) and GPx (E.C.1.11.1.9) activities were spectrophotometrically assayed in erythrocytes with commercial kits. SOD activity was expressed as the amount of protein causing a 50% inhibition of formazan dye (505 nm), employing xanthine and xanthine oxidase to generate superoxide radicals. Units of GPx activity were calculated following NADPH oxidation at 340 nm using cumene hydroperoxide as the substrate. Results: Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were assayed in blood of 45 healthy pediatric subjects (26 males and 19 females between 0 and 14 years of age). We found no significant differences in blood antioxidant enzymes both in all population and when we distributed the subjects for age classes and sex. Conclusion: the definition of pediatric values of antioxidant enzyme activities in blood of healthy children may be useful in monitoring SOD and GPx in physiologic and pathologic conditions, also for future therapeutic trials.