cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular Basis of Catalytic Chamber-Assisted Unfolding and Cleavage of Human Insulin by Human Insulin Degrading Enzyme.

Insulin is a hormone vital for glucose homeostasis, and insulin-degrading enzyme (IDE) plays a key role in its clearance. IDE exhibits a remarkable specificity to degrade insulin without breaking the disulfide bonds that hold the insulin A and B chains together. Using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to obtain high mass accuracy, and electron capture dissociation (ECD) to selectively break the disulfide bonds in gas phase fragmentation, we determined the cleavage sites and composition of human insulin fragments generated by human IDE. Our time-dependent analysis of IDE-digested insulin fragments reveals that IDE is highly processive in its initial cleavage at the middle of both the insulin A and B chains. This ensures that IDE effectively splits insulin into inactive N- and C-terminal halves without breaking the disulfide bonds. To understand the molecular basis of the recognition and unfolding of insulin by IDE, we determined a 2.6-A resolution insulin-bound IDE structure. Our structure reveals that IDE forms an enclosed catalytic chamber that completely engulfs and intimately interacts with a partially unfolded insulin molecule. This structure also highlights how the unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity (∼100 nm) for insulin. In addition, this structure shows how IDE utilizes the interaction of its exosite with the N terminus of the insulin A chain as well as other properties of the catalytic chamber to guide the unfolding of insulin and allowing for the processive cleavages.
Allosteric effects of RuvA protein, ATP, and DNA on RuvB protein-mediated ATP hydrolysis.

A detailed characterization of RuvB protein-mediated ATP hydrolysis in the presence of RuvA protein has provided (a) the steady-state kinetic parameters of ATP hydrolysis within a RuvAB complex and (b) several insights into the mechanism of ATP hydrolysis and its coupling to translocation on DNA. In general, the RuvA protein increases the kcat and decreases the Km for the RuvB ATPase activity. DNA has a much greater effect on the kinetics of ATP hydrolysis when RuvA is present, consistent with a role of RuvA in facilitating the interaction between RuvB and DNA. Mechanistic clues come from deviations from normal steady-state kinetic behavior. A previously described burst of ATP hydrolysis, corresponding to two ATPs per RuvB hexamer [Marrione & Cox (1995) Biochemistry 34, 9809−9818], is still observed in the presence of RuvA protein. This suggests a functional asymmetry in the RuvB hexamer. There is a gradual attenuation of ATP hydrolysis when RuvB protein, alone or in the presence of RuvA protein, hydrolyz...
Excitatory Amino Acid Receptor Interactions of a Novel α-Phosphinic Acid Analogue of α-Methylaspartic Acid

An α-phosphino analogue of α-methylaspartate has been synthesized. The compound may not interact with excitatory amino acid receptors directly, as assessed by direct in vitro radioreceptor binding methods; however, it possesses weak anticonvulsant activity and exhibits an excitant action in vitro that is apparently not mediated by a N-methyl-D-aspartate receptor.
Contributions of walter A. Pons, to development of methodology for mycotoxins

Walter Pons began work on mycotoxins in 1963, well prepared by 20 years’ experience in the Analytical Section of the SURDD, USDA. His first paper on aflatoxin methodology, presented at the fall meeting of the AOCS in 1964, was rated as one of the 3 best. In this paper, he introduced acetone as the extraction solvent for aflatoxins, moved away from the lengthy, exhaustive Soxhlet extraction to the far more rapid equilibrium shaker extraction and introduced lead acetate to precipitate major interfering impurities. He early saw the need for the calibration of reference aflatoxin standards and for their availability. He prepared and supplied more than 3,000 aflatoxin standards, used worldwide, as a public service of USDA before such standards were available commercially. Walter Pons pioneered in every aspect of development of analytical methodology for aflatoxins. He was instrumental in development of objective densitometric methods for determination of aflatoxins in diverse commodities, including milk, eggs and mixed feeds; in multimycotoxin methodology; in application of minicolumns for the rapid estimation of aflatoxins in various agricultural commodities; and, most recently, in application of high pressure liquid chromatography to the precise objective determination of aflatoxins. Many of Walter’s contributions resulted from the generous gift of his time. He organized symposia, presented seminars, participated in workshops and responded freely and enthusiastically to numerous requests from analysts for assistance.
The metamorphosis of communication, the knowledge revolution, and the maintenance of a contemporary perspective during the 21st century.

Objective To define and discuss elements of the escalation in scientific data availability and their importance to neurosurgery. Methods This multifactorial essay describes the evolution of communication methodologies, the information revolution, and the advent and effect of Internet communication with its potential effect on the practice of neurosurgery, professional assemblies, journals, and the infrastructure of the discipline. Practical and philosophical viewpoints are rendered to assess the existing and developing availability of information to the neurosurgical community. Conclusion Knowledge must be discerned from information. The individual does not have the luxury of detachment and must remain consistently, intellectually, and actively involved in the adaptations required to stay truly informed and current.
If you are good you can have a cookie: How memories of childhood food rules link to adult eating behaviors.

Abstract Objective: The aim of this study was to determine whether memories of parental rules about food during childhood are linked to adult eating behaviors. Method: An adult community sample (N=122) (56% female, 44% male) with a mean age of 44.6 years completed self-report measures of weight and dieting history, current eating patterns, and recollection of different types of rules about food from their parents. Three types of food rules were assessed: (a) rules which restrict intake of certain foods, (b) rules which encourage food intake, and (c) rules where food is used to reward or punish behavior. Results: Binge eating and dietary restraint in adulthood are significantly related to participants' recollection of their parents using food to control their behavior in childhood. These results held true regardless of body mass index (BMI), ethnicity, age, or childhood weight status. Discussion: This study suggests that some childhood food rules may have a long-lasting impact on eating behaviors. Further research on the impact of using food to reward and punish children's behavior is needed to inform recommendations to parents regarding the use of food for behavioral control.
Aggregation state and reducing power of the samarium diiodide–DMPU complex in acetonitrile

Abstract The aggregation state of SmI2 and the reducing power of SmI2 and its DMPU complex were investigated employing vapor pressure osmometry (VPO) and cyclic voltammetry (CV), respectively. The aggregation number for SmI2 in acetonitrile was found to be 1.03±0.07 over the entire concentration range studied indicating that SmI2 is monomeric. The CV study showed that DMPU enhances the reducing power of SmI2 in acetonitrile but that the resulting complex is not as powerful as the SmI2–HMPA complex in THF. The CV study also showed that solvent could alter the reducing power of SmI2.
Hematopoietic stem cell trafficking: Regulated adhesion and attraction to bone marrow microenvironment

Hematopoiesis takes place preferentially within bone cavities, suggesting that bone-derived factors contribute to blood formation. Hematopoietic stem and progenitor cells (HSPCs) can be mobilized from the bone marrow parenchyma to the circulation by various agonists whose common downstream action leads to alteration in the expression or function of the chemokine CXCL12 and adhesion molecules mediating migration. Granulocyte colony-stimulating factor (G-CSF), the most prevalent drug used to mobilize HSPCs, dramatically suppresses osteoblast function. Recent studies suggest that G-CSF-mediated suppression requires signals from the sympathetic nervous system (SNS). This review summarizes emerging concepts thought to contribute to stem cell migration.
Two-stepping into the icehouse: East Antarctic weathering during progressive ice-sheet expansion at the Eocene–Oligocene transition

In conjunction with increasing benthic foraminiferal δ 18 O values at the Eocene–Oligocene transition (EOT; ca. 34 Ma), coarse-grained ice-rafted debris (IRD; >425 μm) appears abruptly alongside fossil fish teeth with continentally derived neodymium (Nd) isotope ratios (e Nd ) in Kerguelen Plateau (Southern Ocean) sediments. Increased Antarctic weathering flux, as inferred from two steps to less radiogenic e Nd values, coincides with two steps in benthic foraminiferal δ 18 O values. These results indicate that two distinct surges of weathering were generated by East Antarctic ice growth during the EOT. Weathering by ice sheets during a precursor glaciation at 33.9 Ma did not produce significant IRD accumulation during the first e Nd shift. Glacial weathering was sustained during a terrace interval between the two steps, probably by small high-elevation ice sheets. A large increase in weathering signals the rapid coalescence of small ice sheets into an ice sheet of continental proportions ca. 33.7 Ma. Rapid ice sheet expansion resulted in a suppression of weathering due to less exposed area and colder conditions. Parallel changes in Antarctic weathering flux and deep-sea carbonate accumulation suggest that ice-sheet expansion during the EOT had a direct impact on the global carbon cycle; possible mechanisms include associated changes in silicate weathering on the East Antarctic craton and enhanced fertilization of Southern Ocean waters, both of which warrant further investigation.
Levels and Distribution of the Calcium‐Modulated Proteins S100 and Calmodulin in Rat C6 Glioma Cells

To understand better the mechanisms involved in the transduction of a calcium signal into an intracellular response via multiple calcium-modulated proteins, we have examined the calcium-modulated proteins, S100 and calmodulin, and their intracellular targets in rat C6 glioma cells. Subconfluent, confluent, and postconfluent C6 cells contain predominantly, if not exclusively, the S100 beta polypeptide. The level of S100 beta in C6 cells increases approximately 20-fold from subconfluency to postconfluency whereas the level of calmodulin increases only about two-fold. The subcellular distribution of S100 beta and calmodulin in mitotic cells is similar. However, the subcellular distribution of these proteins in interphase cells is different and appears to change with cell density. Gel overlay analysis demonstrated that the S100- and calmodulin-binding protein profiles are significantly different and that some of the binding proteins appear to change in intensity with cell density. These data demonstrate that S100 beta is the predominant S100 polypeptide in C6 cells and suggest that changes in S100 beta and S100 beta-binding proteins may be involved in regulating S100-mediated intracellular processes in C6 cells. Our studies also suggest that the levels of S100 and calmodulin may be differentially regulated in C6 cells.
The counterdiffusion of adsorbed hydrocarbons in porous glass

Summary Experimental results are presented for the counterflow of binary mixtures of both adsorbing (ethylene, propylene and isobutane) and non-adsorbing (nitrogen and argon) gases through microporous unconsolidated Vycor glass plugs. The adsorbed surface flow increased the transfer rate relative to the Knudsen type transport. The data suggest that the flow of one of the gases in the adsorbed layer did not interfere with the counter flow of other gas.
Glenoid revision: a gambler’s choice

Abstract Glenoid revision can be a diagnostic and technical challenge. It is imperative that the cause of the failure be identified preoperatively. Loosening of the glenoid is the most common reason for revision surgery. The status of the rotator cuff, glenoid version, glenoid bone stock, instability, and infection are factors that should be considered when attempting to identify the etiology of glenoid loosening. When possible, the glenoid should be reimplanted at the time of revision surgery. However, a staged procedure consisting of glenoid removal and bone grafting is usually performed if there is severe glenoid erosion that precludes reimplantation with subsequent glenoid reimplantation if clinically indicated.
Evaluating a rule against possible instances.

This investigation is concerned with a reasoning task in which subjects are given a sentence expressing a material implication and are asked to select those instances which would have to be examined in order to determine the truth or falsity of the sentence. A model is developed to describe the process of evaluating the sentence against possible instances. Two sources of differences among subjects are incorporated into the model: differences in interpretation of the sentence, and differences in interpretation of the reversibility of the stimulus cards which are the instances. This evaluation model is then combined with a model previously developed by P. C. Wason and P. N. Johnson-Laird to explain the process which subjects employ to select the instances which they believe must be examined. Predictions derived from the combined model were tested in an experiment which used an expanded version of a set of ‘therapeutic’ procedures developed by Wason and Johnson-Laird. Subjects were found to make initial selections and to modify their choices in ways consistent with the model's predictions. The results are briefly discussed in terms of the ambiguity of aspects of the task when the stimulus materials are arbitrary symbols without reference to a realistic context.
Low-Spatial Coherence Chaotic Cavity Laser for Speckle-Free Full-Field Imaging

We demonstrate electrically-pumped semiconductor-based chaotic microcavity lasers. The cavity shape is designed to maximize the number of lasing modes, providing emission with low spatial coherence and high-power per mode for high-speed, speckle-free full-field imaging applications.
The evolving treatment of dry eye

Palliative treatments that historically have been the mainstay of therapy for dry eye continue to improve and are still appropriate therapy while we await new advances to control the underlying cause of dry eye disease. The approach of tear supplementation and tear preservation continues to be useful. The goal of tear stimulation or enhancement is elusive, but it may be nearer with the advent of P2Y2 agonists. The recognized importance of inflammation in producing dry eye through lacrimal gland and ocular surface damage is leading us to novel strategies to immunomodulate the disease and to restore hormonal balance to the ocular surface-lacrimal gland homeostatic cycle. It has taken 20 years of investigation to reach this threshold. The next 3 years should see promising treatments approved for dry eye disease.
New unified matrix upper bound on the solution of the continuous coupled algebraic Riccati equation

Abstract In this paper, a unified matrix upper solution bound is established for the continuous coupled algebraic Riccati equation arising from the optimal control of a Markovian jump linear system. In particular, the issue of rank deficiency with the control matrices is addressed because it may cause problems to some existing matrix upper solution bounds. The results of this paper not only apply to this rank deficient case but also contain those existing results as special cases.
Laser-Assisted Dry Etching Of Semiconducting Materials

The use of laser assisted chemistry for dry etching of semiconductors is described. Both direct laser-driven etching of GaAs and laser-enhanced plasma etching of Si are given as examples.
Teenage Heart Murmurs

The first-time appearance of a murmur in an adolescent can create a substantial amount of anxiety in the parents and the teenager. The appropriate evaluation and diagnosis is very important in decision-making regarding sports participation in this population. Accurate identification of the innocent murmurs can obviate the need for echocardiography. Identification of a pathologic murmur may reduce morbidity and, possibly, mortality in critical lesions such as hypertrophic cardiomyopathy. This article discusses the physiology and characteristics of different murmurs, and outlines an approach to cardiac murmurs in adolescents.
Strategic Responses to Resource Dependence Among Transnational NGOs Registered in the United States

Many of the world’s largest and most impactful transnational NGOs are registered in the United States where they engage in significant fundraising activities to support their global operations. Their reliance on the external environment for financial support exposes them to resource dependence and the possibility of external control. However, as civil society organizations organized as firms, transnational NGOs attempt to maintain operational independence from the donors upon which they rely for funding. This article contributes to resource dependence theory by identifying the strategies that transnational NGOs employ in response to resource dependence, explaining the emergence of strategic response, and exploring the conditions under which NGOs are capacitated to preserve organizational autonomy. The responses transnational NGOs employ include alignment, subcontracting, perseverance, diversification, commercialization, funding liberation, geostrategic arbitrage, specialization, selectivity, donor education, and compromise. Elements of this strategic repertoire empower NGOs to resist external control, even circumventing and influencing donor preferences. Findings are based on in-depth, face-to-face interviews with top organizational leaders from a diverse sample of transnational NGOs registered in the United States.
Táticas oligopolísticas para controlar mercados e o crescimento das CTNs na indústria de material elétrico do Brasil

A maioria das explicacoes convencionais da rapida expansao das corporacoes transnacionais (CTNs) nos paises em desenvolvimento atribui seu crescimento a eficiencia superior das CTNs em relacao a seus competidores domesticos. Uma interpretacao alternativa focaliza as estruturas industriais do oligopolio que estao associadas ao investimento transnacional e o poder de mercado das CTNs. Este trabalho explora algumas taticas de mercado e extramercado empregadas pelas CTNs para protegerem sua vantagem monopolistica nos paises hospedeiros. Usando o exemplo da industria de material eletrico do Brasil, o artigo considera as consequencias economicas de sete formas de conduta de CTN: diretorias entrosadas, indulgencia mutua, controle de canais de suprimento, subsidiacao mutua e predacao, conluio formal e informal, vinculos politicos formais e comportamento de aquisicao das CTNs. Conclui-se que nem as barreiras a entrada determinadas pela eficiencia, nem as determinadas pela tecnologia sao completamente satisfatorias para explicar o crescimento da participacao do mercado transnacional; ao menos no caso da industria de material eletrico do Brasil, o poder de mercado associado ao comportamento da CTN e igualmente, ou talvez mais, importante.
Magnetic and spectroscopic characteristics of ZnMnO system

We report on the observation of room-temperature ferromagnetism in epitaxial (Zn,Mn)O films grown by a pulsed-laser deposition technique using high-density targets. The X-ray, microscopic, spectroscopic and magnetic properties of target material containing 6 at.% of Mn and films were compared. The target shows the presence of large clusters exhibiting paramagnetic behavior. However, ferromagnetic properties were observed in (Zn,Mn)O films grown at a substrate temperature of 500 °C and with an oxygen partial pressure of 1 mTorr. Although, crystalline quality of the film improves with increasing substrate temperature, the ferromagnetism becomes weaker.
PARENTAL IMMUNIZATION REFUSAL

Parental vaccine refusal is raising concern and has received considerable attention worldwide. Although the most prevalent and consistent predictor for vaccine refusal remains adverse events follow immunization (AEFI). Other causes exist that could increase risk when combined. Awareness regarding immunization refusal risk factor and adopt a practice to address parent’s concerns to reduce risk, including clinic base education, academic detailing and reminder recall interventions have been show to increase knowledge and vaccine coverage. The purpose of this review is to examine the state of science on immunization refusal and gain knowledge about the nature and origins of parent’s concerns, attitudes, beliefs and behavior; and how that might impact on global health and immunization practices. Nursing theory and model are examined. Strategies that can be implemented by the Advanced Practitioner Register Nurse (APRN) to address parental concerns; thus increase knowledge and intentions to vaccinate their children are explored. Index Terms – Beliefs, attitudes, immunization refusal, knowledge, vaccine, vaccine program.
Immunohistochemical detection of p53 protein as a prognostic indicator in prostate cancer

Mutation of the p53 gene is the most common genetic alteration in human cancers. The mutant p53 protein is more stable than the wild type and can be detected by immunohistology. The objective of the current study was to evaluate the immunohistological detection of p53 protein in prostate cancer and its utility as a prognostic indicator. We used a monoclonal anti-p53 antibody and immunostained primary prostate adenocarcinomas (stages A1 to D1) from 109 patients with a mean follow-up of 3.8 years (range, 1.3 to 9.3 years). Immunoreactivity for p53 was seen in 23 cancers (21%). There were 12 instances of progression (14%) among the p53-negative cancers versus seven (30%) among the p53-positive group. Survival analysis using three univariate statistical tests showed that p53 reactivity (P < .03), Gleason score (P < .01), and stage (P < .05) had significant effects on time to progression of prostate cancer. Multivariate analyses showed that Gleason score was significant with all three tests; p53 reactivity was significant with the Wilcoxon test but only approached significance by the log rank and Cox tests. When the analyses included only patients with Gleason scores 2 to 7 (N = 94), univariate analyses showed that p53 reactivity was strongly related to progression of prostate cancer (P < .007). Stage also was significant (P < 0.04), but Gleason score was not. Multivariate analyses showed only p53 reactivity to be significant (P < .007). In conclusion, mutation of the p53 gene may be involved in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of prostate cancer and appears to be an independent prognostic indicator that is particularly valuable among the low to intermediate grade cancers.
Locating Object Boundaries in Textured Environments

Detection of object boundaries is an important step in the analysis of an image. In the presence of a textured background, local edge operators generate many edges that do not correspond to the object boundaries. However, edges along the object boundaries link in elongated segments. An efficient algorithm to perform such linking is described and experimental results of a working program are presented.
Pirh2 E3 Ubiquitin Ligase Modulates Keratinocyte Differentiation through p63

p63, a homolog of the tumor-suppressor p53, is essential for the development of the epidermis and limbs. p63 is highly expressed in the epithelial cell layer and acts as a molecular switch that initiates epithelial stratification. However, the mechanisms controlling p63 protein levels are still far from being fully understood. Here, we demonstrate a regulatory protein for p63 activity. We found that Pirh2 (p53-induced RING-H2) E3 ubiquitin ligase physically interacts with p63 and targets p63 for polyubiquitination and subsequently proteasomal degradation. We also found that ectopic expression of Pirh2 in HaCaT cells suppresses cell proliferation. Consistent with this, we found that along with altered expression of ΔNp63 protein, ectopic expression of Pirh2 promotes, whereas knockdown of Pirh2 inhibits, keratinocyte differentiation. Collectively, our data suggest that Pirh2 has a physiologically relevant role in keratinocyte differentiation through the posttranslational modification of p63 protein.
Variability of uterine cervical anatomy in the white‐tailed gnu (Connochaetes gnou)

Examination of the reproductive anatomy of six female white-tailed gnu revealed duplex uterus with varying degrees of cervical division. The division ranged from 36 to 100% of the length of the cervix, with one animal exhibiting double external ossa. This variability in reproductive anatomy could be important in artificial insemination or embryo transfer procedures in this species.
Dual tachycardia in the setting of amiodarone-induced hyperthyroidism

A 65-year-old male with dilated cardiomyopathy (left ventricular ejection fraction 30%) presented with incessant wide complex tachycardia (WCT). His history included paroxysmal atrial fibrillation treated chronically with amiodarone. WCT was refractory to intravenous amiodarone and required multiple cardioversions. …
Intracellular pH in mammalian stages of Trypanosoma cruzi is K+-dependent and regulated by H+-ATPases.

Regulation of intracellular pH (pHi) was investigated in Trypanosoma cruzi amastigotes and trypomastigotes using 2′,7′-bis-(carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF). pHi was determined to be 7.33±0.08 and 7.35±0.07 in amastigotes and trypomastigotes, respectively, and there were no significant differences in the regulation of pHi between the two stages. Steady-state pHi, recovery of pHi from acidification, and H+-efflux were all decreased markedly by the H+-ATPase inhibitors N,N′-dicyclohexylcarbodi-imide (DCCD), diethylstilbestrol (DES) and N-ethylmaleimide (NEM) supporting a significant role for a plasma membrane H+-ATPase in the regulation of pHi. pHi was maintained at neutrality over a range of external pH (pHe) from 5–8 in parasites suspended in a buffer containing Na+ and K+ (standard buffer) but was acidified at low pHe in the absence of these cations (choline buffer). The pHi of trypomastigotes decreased significantly when they transformed into amastigotes. The rate of recovery of pHi by acidified parasites was similar in Na+-free buffer and standard buffer but was slower in the absence of K+ (K+-free or choline buffer) and parasites suspended in choline buffer were acidic by 0.25 pH units as compared with controls. Ba2+ and Cs+ decreased the pHi of parasites suspended in standard but not choline buffer suggesting the presence of an inward directed K+ channel. The pHi of amastigotes and trypomastigotes suspended in Cl−-free buffer was decreased by 0.13 and 0.2 pH units, respectively, supporting the presence of a chloride conductive channel. No evidence of pH regulation via a Na+/H+ or Cl−/HCO3− exchanger was found. These results are consistent with the presence of a plasma membrane H+-ATPase that regulates pHi and is supported by K+ and Cl− channels.
Modeling the sensitivity to variability relationship in perimetry

Abstract Purpose Studies in glaucoma patients show that standard automated perimetry results increase in variability as sensitivity decreases. However, the reasons for this change are unclear. This study presents the principle of Divergent Dysfunction as a possible explanation for this change in variability, and incorporates it into a model that can be used to simulate perimetry. Methods A computer program was written to simulate visual field test results based on the model, using a Full Threshold testing strategy. The validity of the simulation was tested by comparing it with normal sensitivity values, and with test–retest data from 63 participants evaluated five times each over the course of 1 month. The effect on the simulated data of varying parameters of the model was investigated, such as changing the magnitude of variability and the percentages of false positive and negative responses. Results The correlation between subject and simulated test–retest data was 0.987. Several factors were found to affect the sensitivity–variability relationship for the simulated data, most notably the rate of sensitivity decline, the percentage of false positives, and the starting luminance of the test procedure. Conclusions The principle of Divergent Dysfunction presented here provides a plausible explanation for the sensitivity–variability relationship for standard automated perimetry in glaucomatous eyes. The model and resultant simulation program aim to provide an intuitive demonstration of the principle, which can also be used to examine the effectiveness of different testing strategies. These findings have great implications for future clinical research.
Diagnosis and Management of Precancerous Cervical Lesions

Over the past five decades, the Pap smear for cervical cancer screening has become standard of care across the United States and other countries, and its implementation in the routine gynecologic examination has dramatically reduced the rates of invasive cervical cancer. As we have come to understand the nuances of this routine screening and are increasingly better able to identify precancerous cervical lesions, we have also developed improved screening and treatment modalities. This progress has led to ever-changing diagnostic and management guidelines. Over the last several years, the American Society for Colposcopy and Cervical Pathology (ASCCP) has revised its guidelines for cervical cancer screening and issued new recommendations for treatment and management of cervical dysplasia. In addition, investigators across the world are exploring improved methods of screening, treatment, and identification of precancerous cervical lesions. Such methods include optimizing HPV testing, genotyping HPV and identifying associations with cervical dysplasia, and optimizing the timing and efficacy of treatment. This article will review and critically evaluate the literature published within the past year with regard to the diagnosis and management of precancerous cervical lesions.
β-Secretase Cleavage at Amino Acid Residue 34 in the Amyloid β Peptide Is Dependent upon γ-Secretase Activity

The amyloid β peptides (Aβ) are the major components of the senile plaques characteristic of Alzheimer's disease. Aβ peptides are generated from the cleavage of amyloid precursor protein (APP) by β- and γ-secretases. β-Secretase (BACE), a type-I transmembrane aspartyl protease, cleaves APP first to generate a 99-amino acid membrane-associated fragment (CT99) containing the N terminus of Aβ peptides. γ-Secretase, a multi-protein complex, then cleaves within the transmembrane region of CT99 to generate the C termini of Aβ peptides. The production of Aβ peptides is, therefore, dependent on the activities of both BACE and γ-secretase. The cleavage of APP by BACE is believed to be a prerequisite for γ-secretase-mediated processing. In the present study, we provide evidence both in vitro and in cells that BACE-mediated cleavage between amino acid residues 34 and 35 (Aβ-34 site) in the Aβ region is dependent on γ-secretase activity. In vitro, the Aβ-34 site is processed specifically by BACE1 and BACE2, but not by cathepsin D, a closely related aspartyl protease. Moreover, the cleavage of the Aβ-34 site by BACE1 or BACE2 occurred only when Aβ 1– 40 peptide, a γ-secretase cleavage product, was used as substrate, not the non-cleaved CT99. In cells, overexpression of BACE1 or BACE2 dramatically increased the production of the Aβ 1–34 species. More importantly, the cellular production of Aβ 1–34 species induced by overexpression of BACE1 or BACE2 was blocked by a number of known γ-secretase inhibitors in a concentration-dependent manner. These γ-secretase inhibitors had no effect on enzymatic activity of BACE1 or BACE2 in vitro. Our data thus suggest that γ-secretase cleavage of CT99 is a prerequisite for BACE-mediated processing at Aβ-34 site. Therefore, BACE and γ-secretase activity can be mutually dependent.
Generalized, basis-independent kinematic surface fitting

Kinematic surfaces form a general class of surfaces, including surfaces of revolution, helices, spirals, and more. Standard methods for fitting such surfaces are either specialized to a small subset of these surface types (either focusing exclusively on cylinders or exclusively on surfaces of revolution) or otherwise are basis-dependent (leading to scale-dependent results). Previous work has suggested re-scaling data to a fixed size bounding box to avoid the basis-dependence issues. We show that this method fails on some simple, common cases such as a box or a cone with small noise. We propose instead adapting a well-studied approximate maximum-likelihood method to the kinematic surface fitting problem, which solves the basis-dependence issue. Because this technique is not designed for a specific type of kinematic surface, it also opens the door to the possibility of new variants of kinematic surfaces, such as affinely-scaled surfaces of revolution.
Nonlinear energy transfer in gravity–capillary wave spectra, with applications

The energy flux in gravity-capillary wave spectra has been obtained using Hasselmann's (1962) perturbation analysis for a homogeneous Gaussian sea. As expected, resonant interactions now appear at second order, and a third-order perturbation analysis shows that energy is redistributed from waves with intermediate wavelengths (in the neighbourhood of 1·7 cm) toward gravity and capillary waves. Numerical computations are also obtained for the energy flux and the interaction time of a sharply peaked spectrum consisting of wavenumbers concentrated around a single wavenumber, superposed on a smooth background spectrum. The range of validity of the inviscid results is discussed.
Oceanic micronektonic/macrozooplanktonic community structure and feeding in ice covered Antarctic waters during the winter (AMERIEZ 1988)

Fifty-seven species of oceanic micronekton and macrozooplankton were collected under pack ice during the winter in the vicinity of the Weddell-Scotia Confluence with a modified opening-closing Tucker trawl. The majority of the 57 species did not vertically migrate and lived deeper during the winter than during the spring or fall. However, despite the short day length, several of the most common mesopelagic fish and crustaceans did migrate. Fish moved into shallower depths at night but apparently most did not continue into the near-freezing upper mixed layer, leaving that zone to the migratory crustaceans. In the upper 1000 m, the dominant species were, in order of decreasing biomass, Euphausia superba, the cnidarian Atolla wyvillei, the ctenophore Beroe sp., and the mesopelagic fish Electrona antarctica, Bathylagus antarcticus and Gymnoscopelus braueri. Thysanoessa macrura and Salpa thompsoni were biomass subdominants. The majority of the dominant species showed little seasonal differences in biomass. However, the biomass of gelatinous species varied considerably with A. wyvillei and Beroe sp. being most abundant and S. thompsoni least abundant during the winter. Incidence of food in the stomachs in several important species was low, suggesting a low impact on their Zooplankton prey. Specimens of S. thompsoni had high quantities of food in their guts but this species was uncommon so its net impact would also have been low. Euphausia superba and the three common mesopelagic fish had significantly lower stomach fullness ratings during the winter than during the fall, suggesting an overall decrease in feeding activity of dominant species during the winter.
The computation of relative motion with increased precision

Encke's method as modified by Potter to increase the accuracy of orbit computations of gravitationally interacting bodies is applied to the problem of relative motion of non-interacting space vehicles. This technique is then combined with a simple transformation of the independent variable to arrive at a system of equations from which the relative motion may be determined with increased precision.
Connections of the mesencephalic locomotor region (MLR) III. Intracellular recordings.

The responses of neurons in the area of the cat mesencephalic locomotor region (MLR) following stimulation of the entopeduncular nucleus (EN) were recorded intracellularly. At the end of each experiment a precollicular-postmamillary brainstem transection was performed and stimulation of the recording site(s) was employed to induce locomotion on a treadmill. This procedure was assumed to establish that intracellularly studied cells in the vicinity of a locomotion-inducing site were MLR neurons. About 10% of MLR neurons were found to respond to stimulation of the EN at short latencies. Stimulation of MLR efferent pathways was used to identify output neurons by antidromic activation. Very few MLR output neurons were found to receive EN projections (i.e. to respond at short latency following EN stimulation). These experiments support previous results describing a sparse projection from the EN to the MLR. This projection appears to be functionally varied (EPSP, IPSP and EPSP-IPSP responses were observed in MLR neurons following EN stimulation) and to exert its major influence on interneurons, not on output neurons, of the MLR.
Attaching uncertainty to deterministic spatial interpolations

Abstract Deterministic spatial interpolation algorithms such as the natural neighbor interpolation (NNI) or the Cressman interpolation schemes are widely used to interpolate environmental features. In particular, the former have been applied to digital elevation models (DEM’s), the latter to weather data and pollutant exposure. However, they are unsatisfying in that they fail to provide any uncertainty assessment. Such schemes are not model-based; rather, they provide a set of rules, usually geometrically motivated, by which point-level data is interpolated to a grid. We distinguish this setting from the case where the deterministic model is essentially a mapping from inputs to outputs in which case a joint model can be formulated to assign uncertainty. In our setting we have no inputs, only an interpolated surface at some spatial resolution. We propose a general approach to handle the non model-based setting. In fact, the approach can be used to assign uncertainty to any supplied surface regardless of how it was created. We first formulate a useful notion of uncertainty and then show, with additional external validation data, that we can attach uncertainty using a convenient version of a data fusion model. We also clarify the distinction between this setting and the more usual case where we are trying to build an explanatory model to explain an environmental surface. We discuss two settings for such interpolation, one where the surface is presumed to be continuous such as elevation or temperature and the other where the surface would be discontinuous such as with precipitation where, at any location, there would be a point mass in the distribution at 0. We work within a hierarchical Bayesian framework and illustrate with a DEM within the Cape Floristic Region of South Africa.
Jury Verdicts How Much Difference Does One Juror Make

This study examined the following question: How well will a predictor of an individual juror's decision preference predict the verdict of the jury to which that individual belongs? A simulation study or "thought experiment " was performed. Using basic probability theory and the social decision scheme model of the jury decision-making process, it was possible to determine how strongly a juror characteristic would be related to his or her jury's verdict from a knowledge of how strongly that characteristic was related to his or her own personal verdict preference. For 12-person juries, the predictor accounted for less than 5% as much variance in juries' behavior as it did in jurors' behavior, regardless of the overall rate of conviction for jurors or the strength with which individual decisions were predicted. Although decreasing the jury size tended to increase this percentage, it remained quite small, even for dyads. Quite similar results were found when alternative decision schemes were employed. It was a...
Measurements of materials with high dielectric constant and conductivity at ultrahigh frequencies

THE principles for measuring dielectric properties of materials at ultrahigh frequencies are well established.1,2 They are based on measurement of voltage standing wave ratio (VSWR) and location of the standing wave pattern, which results from reflection of electromagnetic waves in front of the sample; see Fig. 1. Transmission line or wave guide sections, depending upon frequency, are used to obtain the necessary 1-dimensional field propagation. The complex reflection factor p, obtained from the measurement as indicated, is related to the dielectric properties of the sample. This relationship permits expressions of the dielectric properties directly, in terms of the observed quantities W = 1 ? ?/1 + ? (inverse of VSWR) and l0 = x0 + ?/4. For the two most important special cases, sample loaded with either infinite or zero impedance, the relations given in Fig. 2 hold.2 ?? is the complex dielectric constant of the sample, ? its permittivity, and tan ? characterizes the dielectric losses. It is assumed that the dimensions of the transmission line are unchanged in the sample section, as indicated in Figs. 1 and 2.
Effect of Use Value Assessment on Property Tax Rates

5M /'ANY states are using or contemplating using use value in place of ad valorem assessment and taxation to influence urban expansion and land use [2]. This note attempts to provide quantitative estimates of the impact of use value assessment on the property tax base and tax rate. Although New Hampshire data are used in this analysis, the approach is sufficiently general to be applicable elsewhere. The impact of use value assessment depends on (1) the amount of total property valuation that qualifies for use value assessment, (2) the amount of eligible assessed valuation that participates in the program, and (3) the amount of taxes that are abated on the participating valuation. Because a use value assessment law does not currently exist in New Hampshire, these variables were either estimated from a cross-sectional sample or assigned values and varied parametrically. The amount of property valuation qualifying for use value assessment was estimated for each town (municipality) in the state. The estimating procedure consisted of first estimating the qualifying valuation for a sample of towns and then projecting the results of the sample to all towns in the state. Qualifying valuation was defined as the valuation of nonurban property. The amount of qualified valuation that enrolls or participates in a use value tax program depends on the economic incentives of the program. The impact of use value assessment was computed for five levels of participation, which varied from 10 to 90 percent of the qualified valuation. The amount of tax abatement on the participating valuation is the major incentive of a use value assessment tax program. The impact of use value assessment was computed for three levels of abatement; these varied from 30 to 75 percent of current taxes under the present system of ad valorem taxation. These variables were combined in a model designed to provide quantitative estimates of the immediate impact of use value assessment
An analysis of alternative slot auction designs for sponsored search

Billions of dollars are spent each year on sponsored search, a form of advertising where merchants pay for placement alongside web search results. Slots for ad listings are allocated via an auction-style mechanism where the higher a merchant bids, the more likely his ad is to appear above other ads on the page. In this paper we analyze the incentive, efficiency, and revenue properties of two slot auction designs: "rank by bid" (RBB) and "rank by revenue" (RBR), which correspond to stylized versions of the mechanisms currently used by Yahoo! and Google, respectively. We also consider first- and second-price payment rules together with each of these allocation rules, as both have been used historically. We consider both the "short-run" incomplete information setting and the "long-run" complete information setting. With incomplete information, neither RBB nor RBR are truthful with either first or second pricing. We find that the informational requirements of RBB are much weaker than those of RBR, but that RBR is efficient whereas RBB is not. We also show that no revenue ranking of RBB and RBR is possible given an arbitrary distribution over bidder values and relevance. With complete information, we find that no equilibrium exists with first pricing using either RBB or RBR. We show that there typically exists a multitude of equilibria with second pricing, and we bound the divergence of (economic) value in such equilibria from the value obtained assuming all merchants bid truthfully.
Simplicial families of drawings

In this paper we present a method for helping artists make artwork more accessible to casual users. We focus on the specific case of drawings, showing how a small number of drawings can be transformed into a richer object containing an entire family of similar drawings. This object is represented as a simplicial complex approximating a set of valid interpolations in configuration space. The artist does not interact directly with the simplicial complex. Instead, she guides its construction by answering a specially chosen set of yes/no questions. By combining the flexibility of a simplicial complex with direct human guidance, we are able to represent very general constraints on membership in a family. The constructed simplicial complex supports a variety of algorithms useful to an end user, including random sampling of the space of drawings, constrained interpolation between drawings, projection of another drawing into the family, and interactive exploration of the family.
Designing Bayesian Sampling Plans with Adaptive Progressive Hybrid Censored Samples

This paper studies the acceptance sampling for exponential distributions with type-I and type-II adaptive progressive hybrid censored samples. Algorithms are proposed for deriving Bayesian sampling plans. We compare the performance of the proposed sampling plans with the sampling plans of Lin and Huang (2012). The numerical results indicate that the proposed sampling plans outperform the sampling plans of Lin and Huang (2012).
Tutors and small groups in problem‐based learning: Lessons from the literature

Group size, teacher skills, problem types, and student behaviors are central concerns to PBL planners and teachers. In implementing problem-based curricula, decisions about each of these dimensions have implications for the others.
Narrow and broadband low-noise amplifiers at higher frequency using FDSOI CMOS technology

This work demonstrates the successful implementation of two single-stage low-noise amplifiers (LNAs) using 0.18 /spl mu/m fully depleted silicon on insulator (FDSOI) CMOS technology. These two amplifiers utilize a metal T-gate n-MOSFET device for improved RF performance. The narrowband LNA has a measured gain of 8.2 dB, a noise figure (NF) of 1.5 dB and input referred third order intercept point (IIP3) value of 12.8 dBm at 3.2 GHz. The broadband LNA has yielded a gain of 7.6-4.5 dB and a NF of 2.8-3.0 dB across 5-10 GHz. The measured IIP3 is 15.4 dBm at 8 GHz. The narrowband amplifier consumes 28.5 mW and the broadband amplifier consumes 54.5 mW of power, both at Vgs = 0.75 V and Vds = 1.0 V. These two amplifiers have demonstrated the feasibility of FDSOI CMOS technology for phased array applications.