cssi/SciSciGPT-SciSciNet huggingface dataset:
Stochastic Model Predictive Control for Gust Alleviation during Aircraft Carrier Landing

This paper presents a constrained stochastic model predictive control approach for approach and landing on an aircraft carrier. Particularly, we analyze the offset recovery control for an aircraft during the powered approach-to-landing phase commonly associated with carrier based landings in the presence of stochastic wind gusts. A Dryden turbulence model is used to model the gust wind. An augmented stochastic linear time invariant system trimmed at a nominal flight condition is constructed with the gust appearing as an input. Probabilistic constraints are introduced to account for the state and control bounds. An affine disturbance feedback based control is proposed for offset recovery and glideslope regulation. This formulation leads to a tractable, sub-optimal convex approximation of the original stochastic problem and is amenable to fast online optimization solvers. The performance of the proposed approach is evaluated with numerical simulations.
Mythical androids and ancient automatons

Long before the advent of modern robots and artificial intelligence (AI), automated technology existed in the storytelling and imaginations of ancient societies. In her new book, Gods and Robots, Adrienne Mayor draws comparisons between mythical androids and ancient robots and the AI of today.
Priority setting for the introduction of rotavirus vaccine: what evidence was essential?

Rotavirus (RV) diarrhea is the most common cause of severe diarrhea in children worldwide and since 2006, vaccines have been available and recommended by WHO for use in all children. We developed protocols that countries could use to assess the burden of RV disease in their own countries and the cost-effectiveness of a program for vaccine introduction. A decade later and in the setting of extreme tiering of prices so that the poorest countries pay the least for the vaccine, more than 92 countries have introduced this vaccine into their national programs and more than 90 have not. Those countries that introduced determined by protocol that the burden of RV disease was substantial and the cost of vaccine reasonable, especially in low income settings where GAVI subsidizes the vaccines’ purchase. However, elsewhere, WHO's global recommendation has not been enacted leaving a majority of the world’s children still at risk of this severe and sometimes fatal disease. We remain with much to learn about how to encourage countries to make decisions that will improve the health of their own children.
Feedback Linearization of the Rotational Dynamics of a Flock of Target Tracking Visual Sensor Array using Tait-Bryan Parameterization

Abstract Using Tait-Bryan (TB) Parameterization, we revisit the visual sensor pointing control problem as a constrained dynamics on SO(3) from the point of view of a nonlinear multi input multi output (MIMO) system. The attitude of every sensor is assumed to satisfy a constraint, such as the ones proposed by Donders and Listing for the monocular and binocular eyes and the head rotation problems. While studying the problem of controlling the pointing direction of human head, the constraint, proposed by Donders, is that for every human head rotating away from its primary pointing direction, the rotational vectors are restricted to lie on a surface called the Donders’ surface. This paper assumes the existence of Donders’ surfaces for an array of visual sensors in a flock, tasked with the goal of tracking a point target in IR3. We assume that the Donders’ surfaces are described by a quadratic equation on the coordinates of the rotation vector. The inputs to the MIMO system are three external torque triplet, one for each visual sensor. The three output signals from each sensor are chosen as follows. Two of the signals are coordinates of the frontal pointing direction. The third signal measures deviation of the state vector from the Donders’ surface. Thus we have a square system and recent results have shown that this system is feedback linearizable on a suitable neighborhood N of the state space. We estimate a lower bound on the size of N by computing distance between the Donders’ and the associated Singularity surface. Our results are discussed for the monocular and the trinocular cases and a comparison is made from the point of view of the observed singularities. Analysis of the feedback linearizing control problem, from the point of view of ‘three eyed visual sensing’, is new.
Wuli and stance in a Korean heritage language classroom: A language socialization perspective

Abstract This study examines stances evoked by a Korean teacher's use of the pronoun, wuli (we/our), in a heritage language classroom. Close analysis of recorded classroom interaction reveals that the frequent use of “ wuli chingwutul” (our friends), “wuli plus first name”, and wuli for “you” evokes the stance of solidarity between the teacher and students. By mitigating face-threatening acts of directives and imperatives, the teacher's stance-taking works to encourage students’ active engagement. The normalized use of wuli in the teacher's discourse marks its absence for a shift in her stances from solidarity to authority and distance. These contrasting stances serve to socialize students into both pedagogically appropriate classroom behaviors and culturally appropriate linguistic practices. The results highlight ways in which speaker stances make up a significant aspect of language learning and socialization, calling for further studies on how bilingual children interpret and take up various stances in dynamic contexts.
Neuron model with conductance-resistance symmetry

Abstract This paper is to derive a mathematical model for neuron by imposing only a principle of symmetry that two modelers must obtain the same model when one models the conductances of ion channels and the other models the channels' resistances. Conductance-voltage characteristics for ion transport channels and protein gating channels are both derived. They are expressed as products of maximal conductances and opening probabilities for both types of channel. It gives an explanation to the role of spontaneous firing of individual channel pores and to the origin of leak current. The model has a better fit to a classical data than the Hodgkin-Huxley model does. It can also be reduced to a 2-dimensional model qualitatively similar to the FitzHugh-Nagumo equation and be expanded to a model of three ion channels capable of spike bursts.
3D photonics as enabling technology for deep 3D DRAM stacking

3D stacking improves bandwidth, energy, and latency of DRAMs by exploiting shorter and more abundant wiring in three dimensions. While future stacks are predicted to provide tens of DRAM layers, TSV pitches are bound to stop decreasing due to physical limitations, requiring either large area overheads or energy for higher pin data rates to preserve bandwidth scaling. In addition, deep 3D DRAM stacks increase the average number of TSVs hops to reach the appropriate DRAM layer. Recent advances in vertical silicon-photonic interconnects now allow diameters of 1-2μm which results in high bandwidth density for optics. In this paper, we explore the benefits and architectural implications of vertical optical interconnects in terms of area, power, and performance. We propose a hierarchical approach to stacking 3D DRAM to tens of layers by utilizing sub-stacks which are optically-interconnected to a memory interface on the processor die. Our results show that photonics could be a key enabler for deep-3D DRAM offering at least 2× interconnect area savings compared to TSVs for the same bandwidth with comparable performance and less power.
Ciências da Educação, Escolarização e Abjeção: diferença e construção da desigualdade

Neste artigo, traco uma historia das ciencias dirigidas a escola na virada do seculo XX e hoje, focando primordialmente os EUA, e exploro os gestos dubios de esperanca e medo como uma historia do presente. Considero os temas de salvacao da educacao progressista americana na pedagogia escolar, no cosmopolitismo da crianca que envolve seu gesto de oposto da abjecao e da exclusao nas novas sociologias da comunidade e da vida da familiar urbana. Retorno aos temas da salvacao, da educacao e da comunidade urbana nas reformas contemporâneas num cosmopolitismo do presente que dirige a atencao as qualidades da crianca associadas a aprendizagem ao longo da vida que existe em relacao aos medos daquela crianca que vive fora do espaco cultural desse cosmopolitismo.
By Any Other Name: On the Merits of Moving Beyond Forensics

This essay argues that the interscholastic speaking and debating activity that calls itself forensics has effectively lost the battle for its own name. As students of and experts in rhetoric and performance, members of the forensics community should be the first to recognize the importance of an undisputed name. Yet the community continues to call itself by a name that medical science has overtaken. The resulting confusion does the community no favors and weakens the activity within the academy. The essay concludes that it might be time for a new name that the activity can claim for its own.
Financial Impact of Cancer Treatment

Advances in cancer prevention, screening and early detection, diagnosis, treatment, and care delivery have yielded significant improvements in survival for cancer patients and decreases in cancer-related treatment toxicity. However, these advances have been accompanied by an increasing financial burden to patient and their caregivers. Financial toxicity, which draws a parallel between the side effects of cancer treatment and the side effects of undue financial distress, is increasingly recognized as being common and a source of significant morbidity and decreased health-related quality of life for head and neck cancer (HNC) patients and their caregivers. This chapter will (1) define financial toxicity following cancer treatment, (2) estimate its incidence in HNC patients, (3) highlight key risk factors in HNC patients, (4) describe various tools for its measurement, (5) discuss the impact of financial toxicity on HNC patients, and (6) review resources on financial toxicity for patients and caregivers. Knowledge gaps and research opportunities to improve the delivery of patient-centered cancer care that is attentive to the complex issue of financial toxicity will be explored at the conclusion.
Manual wheelchair propulsion cost across different components and configurations during straight and turning maneuvers

AimManeuvering manual wheelchairs is defined by changes in momentum. The amount of effort required to maneuver a wheelchair is dependent on many factors, some of which reflect the design and config...
Online access to male factor infertility care: the challenge of finding a specialist.

Objective To investigate internet search results available to couples searching for a male factor infertility specialist. Design Cross-sectional. Setting Online search engine. Patient(s) The phrase “male infertility specialist ” was searched in Google for 50 states and Washington D.C. The top 10 results (i.e., first page) of each search were evaluated for website content. Intervention(s) None. Main Outcome Measure(s) The first page of each search was evaluated for provider type (urology vs. obstetrics and gynecology), level of training (fellowship vs. none), male factor fertility information provided, and procedures offered. We compared search position rank (1–10) to determine the likelihood of finding an urologist versus a practitioner in obstetrics and gynecology. Result(s) A total of 419 results were identified; the majority were obstetrics and gynecology-related (N = 229, 54.7%). Urology-related results appeared higher than obstetrics and gynecology-related results (median, 4 vs. 5). Andrology fellowship-trained urologists were identified in 153 (36.5%) results. Among 229 obstetrics and gynecology results, 152 unique practices were identified. A small portion (N = 38, 16.6%) of these practices had a fellowship-trained urologist identified on the website. Most obstetrics and gynecology websites did not mention vasectomy reversal (N = 116, 76.3%) or varicocele repair (N = 93, 61.2%). A minority of practices offered referral to urologists for sperm extraction (N = 23, 15.1%) or offered sperm retrieval themselves (N = 23, 15.1%). Conclusion(s) When searching online for a male factor infertility specialist, most results identified obstetrics and gynecology physicians. A large proportion of obstetrics and gynecology websites lacked information on male factor fertility treatments and did not offer these treatments. These data indicate the need for a more robust online presence of male reproductive urologists to optimize online access.
THE 10830 Å HELIUM LINE AMONG EVOLVED STARS IN THE GLOBULAR CLUSTER M4

Helium is a pivotal element in understanding the multiple main sequences and extended horizontal branches observed in some globular clusters. Here we present a spectroscopic study of helium in the nearby globular cluster Messier 4 (M4). We have obtained spectra of the chromospheric He i 10830 Å line in 16 red horizontal branch (RHB), red giant branch, and asymptotic giant branch stars. Clear He i absorption or emission is present in most of the stars. Effective temperature is the principal parameter that correlates with 10830 Å line strength. Stars with K do not exhibit the helium line. RHB stars, which are the hottest stars in our sample, all have strong He i line absorption. A number of these stars show very broad 10830 Å lines with shortward extensions indicating outflows as high as 80–100 km s−1 and the possibility of mass loss. We have also derived [Na/Fe] and [Al/Fe] abundances to see whether these standard tracers of “second generation” cluster stars are correlated with He i line strength. Unlike the case for our previous study of ω Cen, no clear correlation is observed. This may be because the sample does not cover the full range of abundance variations found in M4, or simply because the physical conditions in the chromosphere, rather than the helium abundance, primarily determine the He i 10830 Å line strength. A larger sample of high-quality He i spectra of both “first” and “second” generation red giants within a narrow range of and luminosity is needed to test for the subtle spectroscopic variations in He i expected in M4.
Stacking faults and alternate crystal structures for the shape-memory alloy NiTi

We use ab initio calculations to study the role of stacking faults in connecting the high-temperature B2 and the theoretically predicted low-temperature B33 NiTi phases. In contrast with prior work, we describe the $\mathrm{B}2\ensuremath{\rightarrow}\mathrm{B}33$ phase transformation in terms of alternate bilayer shifts by $\frac{1}{2}$ [100] on the ${(011)}_{\mathrm{B}2}$ plane, obtaining a viable pathway; the same mechanism could also work with the B19 parent phase. We then examine B33-like structures built from alternate stacking sequences of B19 bilayers, constructed to have monoclinic tilt angles close to the experimentally reported NiTi B19\ensuremath{'} martensite, and find four low-energy stacking-fault variants with energies 5.8--8.5 meV/atom above the calculated B19\ensuremath{'} martensite structure, suggesting that such structures might appear as a part of the NiTi martensite phase at low temperatures. Investigating further the occurrence of specific coordinated planar shifts in NiTi systems, we report a dynamically stable NiTi B27 phase and find that it is only 1.2 meV/atom above the calculated B33 ground-state structure, thus having a potential to also play a role in NiTi martensitic phase transformation.
Mechanics of pressure cells

The accurate measurement of a stress field in a solid medium requires an understanding of the interaction between the pressure gage and the surrounding material. In this paper, the effects of shape and stiffness of the pressure gage are analyzed with a view to the prediction of pertinent static-calibration factors. The stress fields around isolated gages are evaluated as a means of estimating when closely spaced pressure cells might interact. The results of experiments performed with miniature semiconductor-type pressure transducers are presented. Good correlation between the experimental results and analytical predictions is obtained.
Utility of Bronchoscopy with Bronchoalveolar Lavage among Hematologic Transplant Recipients in the Era of Noninvasive Testing.

BACKGROUND Pulmonary complications are common among hematologic stem cell transplant (HSCT) recipients. Their evaluation can be pursued through bronchoscopy with bronchoalveolar lavage (BAL) and a variety of available noninvasive studies, which include newer molecular markers for detecting a variety of infectious agents. OBJECTIVE The objective of this study is to evaluate the diagnostic yield of BAL among HSCT patients relative to the yield of noninvasive testing. METHOD This is a retrospective analysis of HSCT recipients who underwent both BAL and noninvasive testing at a cancer center in 2013 and 2014. RESULTS There were 210 diagnostic results among 98 HSCT recipients. There were 84 unique findings on noninvasive testing that were not evident on BAL, and 36 unique findings on BAL that were not evident on noninvasive testing. Noninvasive testing tended to yield bacterial and viral infections more commonly, while BAL yielded mycobacterial isolates more commonly. CONCLUSION While both noninvasive testing and BAL are helpful in this population, each appeared more precise than the other with individual lung diseases. Bronchoscopy with BAL and noninvasive testing should be considered complementary strategies in the workup of pulmonary complications among HSCT patients.
State-Owned Enterprises Play a Smaller, But Still Strategic, Role in China's External Sector

China’s external sector has been the engine behind the country’s robust economic growth over the past four decades. By 2016, China’s total merchandise trade accounted for 16.1% of the world total, compared to 0.6% in 1978 when its economic reforms were initiated. China’s rapid trade growth was attributable to a series of interrelated factors. This briefing focuses on one of those factors—China’s declining dependence on state-owned enterprises (SOEs) in much, but not all, of its trade activity. Using the latest data, and starting from 1995 when official trade statistics became more reliable, this briefing (a) describes SOEs’ declining influence in China’s trade and (b) highlights prominent sectoral exceptions where Chinese SOEs still affect global market conditions.
Pre-Operative Chemoradiotherapy With or Without Induction Chemotherapy for Operable Locally-Advanced Esophageal Cancer.

Purpose/objective(s) Following presentation of the CALGB 80803 trial, which demonstrated notably high pathologic complete response (pCR) rates with induction FOLFOX followed by chemoradiotherapy (CRT), our institution more routinely incorporated induction chemotherapy (IC) into the management of LA-EC patients. However, improvements in progression-free (PFS) or overall survival (OS) with this regimen compared to pre-operative CRT alone have not yet been shown. We hypothesized IC-CRT would lead to an improvement in OS and PFS when compared to CRT. Materials/methods Patients with operable LA-EC were eligible for analysis if they received CRT between 2013-2019. The cohort was stratified into two groups, IC-CRT vs. CRT. The Kaplan-Meier method was used to estimate OS and PFS. The cumulative incidences of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. The impact of treatment group on pathologic response and surgical outcomes were assessed by Chi-square. Results 95 patients were included for analysis (IC-CRT n = 58; CRT n = 37). Baseline characteristics included median Karnofsky Performance Status 80, median weight loss 5% (IQR 0-9%), with the majority being adenocarcinoma histology (81%), T3-T4 (60%), N+ (79%), located in the distal esophagus or gastroesophageal junction (89%). Patients receiving IC-CRT were more likely to have been treated after 2016 (64% vs 38%, P = 0.021). IC was most commonly FOLFOX (74%) for a median of 3 (IQR 1-3) cycles. CRT was delivered to a median dose of 50 Gy in 25-28 fractions. Surgery was attempted in 60% and 68% of the IC-CRT and CRT cohorts, respectively. Median follow-up was 26 months. ICRT and CRT were associated with similar 2-year OS (66% [95% CI 51-78%] vs 70% [95% CI 52-83%]) and PFS (47% [95% CI 33-59%] vs 48% [95% CI 30-63%]). In the adenocarcinoma subset (n = 77), 2-year OS was 69% (95% CI 52-81%) in the IC-CRT cohort vs 61% (95% CI 40-77%) with CRT. 2-year PFS was 46% (95% CI 31-60%) and 38% (95% CI 20-56%), respectively. IC-CRT was not associated with an OS or PFS benefit among any patient subgroup. Recurrence rates were similar between the cohorts (47%) and first recurrence was most commonly DM (61% IC-CRT vs 65% CRT). Patients receiving IC-CRT compared to CRT had numeric but not statistically significant improvement in pCR (45% vs 29%, P = 0.24) and N-stage regression (72% vs 58%, P = 0.28). There was no difference in the rate of R0 resection, hospitalization, surgical complications, or treatment-related death with use of IC-CRT. Conclusion IC-CRT was not associated with improved OS or PFS in this small and perhaps underpowered cohort study. Further investigations are needed to explore the impact of IC-CRT on quality of life, symptom burden, and to see if meaningful trends develop with time.
Landslide Generated Water Wave Model

A numerical model is developed for simulating the development and propagation of landslide generated water waves in reservoirs. The numerical model is based upon a finite difference representation of the depth averaged hydrodynamic equations. The landslide is formulated as a moving boundary condition, propagating into the reservoir and accelerating the fluid due to physical displacement and viscous drag. Arbitrary reservoir geometry and landslide parameters can be considered. The numerical model results are compared with experimental results obtained on a 1:120 undistorted scale physical model of Libby Dam and Lake Koocanusa in Montana. Landslides were considered reflecting a wide range of landslide volumes and velocities. The wave heights predicted by the numerical model are in good agreement with the wave heights observed in the physical model.
Regulatory Responses to Investor Irrationality: The Case of the Research Analyst

An extensive body of behavioral economics literature suggests that investors do not behave with perfect rationality. Instead, investors are subject to a variety of biases that may cause them to react inappropriately to information. The policy challenge posed by this observation is to identify the appropriate response to investor irrationality. In particular, should regulators attempt to protect investors from bad investment decisions that may be the result of irrational behavior?This article considers the appropriate regulatory response to investor irrationality within the concrete context of the research analyst. Many commentators have argued that analyst conflicts of interest led to biases reports and recommendations that distorted analyst behavior. In the wake of the analyst scandals, regulators have responded - most recently by mandating increased independence. This response can be understood as an effort to make investor reliance reasonable.The article questions this mission. In particular, the article challenges the role of regulators in identifying appropriate sources of investment information or determining when investor behavior is rational. This fallibility of regulatory oversight coupled with the costs of regulation suggest that regulators should exercise caution, particularly in light of the market's capacity to discipline investor decisions.
Mathematical Modeling in Engineering Design Projects

While engineering students are required to complete a number of mathematics courses, some engineering students and practitioners believe that they do not use the mathematics that they learned from their courses in engineering projects. This study investigates engineering students’ use of mathematics through observations of two teams of students working on extensive design projects. The case studies presented in this chapter provide insights into situations when engineering students engage in modeling behavior and also explore ambiguity and precision in engineering design. These insights can inform engineering education as we help engineering students become more aware of the ways that mathematics is used in engineering. Additionally, understanding the ways that mathematics and mathematical thinking is used in professional applications can help us motivate and contextualize mathematics instruction as well as determine what should be taught to students in both college and pre-college settings.
Kings as Wardens and Wardens as Kings: Post-Rana Ties between Nepali Royalty and National Park Staff

This article locates Nepali national park staff (game scouts, rangers and park wardens) in the context of their historical ties with monarchy. The pre-andolan (1951-90) accounts by park staff show how their individual and collective identities were shaped through encounters with royalty, which informed their everyday practices. The social relations, professional goals, and familial desires envisioned by government servants were linked to their perceived closeness with the Nepali kings and through specific events such as royal hunts. Historically, park staff ave displayed particularly strong regard and allegiances for the royal family since Nepali kings sanctioned much of Nepal's early conservation efforts and because monarchs espoused close ties with these officials in the setting up of national parks.
Higher or Basic Education? The Composition of Human Capital and Economic Development

No country has achieved sustained economic development without investment in education. But do all types of human capital affect growth identically? And which types of schooling – secondary or tertiary – should public policy promote? This paper develops an analytical framework to address these questions. It shows how the composition of human capital stock determines a country's development. Hence, promoting the "wrong" type of schooling can have little effect on development. In addition, the paper helps in understanding why empirical studies have failed to find a significant relationship between schooling and growth.
Performance of Medical Graduates Within and Outside Nigeria

The objective of this report is to provide a summary of the outcome of Nigerian Medical Graduates globally. Since the establishment of the first medical school at the University College Hospital, Ibadan, at least four generations of medical schools have been created. With approximately 306 health training institutions and ~ 26 medical schools, www.who.int/hrh/wdms/ media/Nigeria.pdf, Nigeria graduates approximately 2300 medical doctors each year. Nigeria has one of the largest stocks of human resources for health in Africa comparable only to Egypt and South Africa. In 2005, there were about 39, 210 doctors and 124, 629 nurses registered in the country, which translates into about 39 doctors and 124 nurses per 100, 000 populations as compared to the Sub-Sahara African average of 15 doctors and 72 nurses per 100, 000 populations[2]. Between 2005 and 2007 requests for certificate of good standing (a surrogate for migration), were 2, 341, 2, 989 and 3, 567 respectively. While many graduates remain in-country, migration occurs in a significant percentage. Based on one study, the most common country of migration is the U.S.A ( 20%), United Kingdom ( 9%) and Ireland ( 5%). In the U.S. most Nigerian physicians in clinical practice, are in a private practice, whereas a small minority is engaged in academic medicine. Curriculum reform in medical schools will be important to adequately prepare medical graduates for practice within and outside Nigeria.
Regions of ion energization observed during the Galaxy‐15 substorm with TWINS

Ions in the plasma sheet are measured by the energetic neutral atom imagers on the Two Wide-Angle Imaging Neutral-Atom Spectrometers (TWINS) spacecraft. A line of sight (LOS) projection is used to determine the location of the ions that dominate the measured spectrum, assuming that the equatorial plane is the hottest region along the LOS. We verify reasonable agreement between ion spectral shapes measured using this remote measurement technique and in situ measurements from the Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft during two moderate geomagnetic storms. Conditions for reliable use of this technique to determine ion spectra and effective ion temperatures are identified. The technique is applied to the substorm interval associated with the loss of communication with the Galaxy-15 satellite. During this interval, localized and broad regions of ion energization are observed, demonstrating that magnetic reconnection and current disruption may have played a role during this very extreme event. These observations demonstrate the ability of this technique to cast local ion spectra measurements in a global context.
Thermal imaging by infrared near-field microscopy

Heat dissipation is a major concern in integrated circuit (IC) design. Mapping the temperature distribution of ICs plays a very important role in detecting fabrication and material defects and also verifying the temperature distribution predicted by thermal simulations. We describe a non-invasive, affordable and easy to maintain thermal imaging system capable of measuring devices under normal operating conditions. The operating principle of our thermal imaging system is based on the application of near-field scanning optical microscopy (NSOM) to IR thermography.
High-Blocked Heterojunction and Schotiky Barrier Solar Cells

A simple formula is given for the current voltage characteristics of abrupt heterojunctions with a blocking barrier for the majority carriers in the highly doped region: The meaning of the denominator, which acts as a shape factor of the characteristic, is discussed. This description replaces the one related to the exponential AkT-factor and can be directly interpreted as function of physical junction parameters, such as s.,μn and space-charge-, e.g. donor- density.
Building Models for Keratin Disorders

Palmoplantar keratoderma is a hallmark of pachyonychia congenita (PC) and focal non-epidermolytic palmoplantar keratoderma (FNEPPK). By generating keratin 16 (Krt16)–deficient mice, Lessard and Coulombe, as described in this issue, have generated a mouse model to replicate these palmoplantar lesions. Studies using this model may provide novel insights into the molecular mechanisms responsible for the formation of palmoplantar lesions in PC and FNEPPK patients.
A measure of the proportion of treatment effect explained by a surrogate marker.

Les essais randomises impliquant des criteres principaux dont l'occurrence est rare, ou dont la mesure est penalisee par des temps de survenue importants, s'averent onereux. C'est la raison de l'interet croissant porte aux methodes consistant a remplacer le veritable critere clinique par un critere de substitution, disponible plus precocement. Cependant, ces criteres de substitution doivent etre correctement valides. A cet egard, une mesure quantitative specifique a chaque essai de la proportion de l'effet traitement expliquee par le critere de substitution s'avere un concept utile. Freedman et al. (1992) ont ainsi suggere de mesurer la qualite de la substitution en calculant le rapport des coefficients de regression associes a l'effet traitement dans deux modeles separes, ajustes on non par le critere de substitution. Cette mesure se revele helas extremement variable. sans compter qu'il n'y a aucune garantie que chacun des deux modeles soit approprie. En nous inspirant d'une idee formulee par Tsiatis et al. (1995), nous proposons, pour le calcul de cette proportion expliquee. des methodes alternatives qui requierent moins d'hypotheses sous-jacentes au niveau de l'estimation et permettent davantage de flexibilite au niveau de la modelisation. A partir de donnees issues d'un essai en ophtalmologie, et en utilisant egalement un certain nombre de simulations, nous comparons les estimations obtenues a l'aide de ces nouvelles mesures. lesquelles semblent de fait presenter moins de variabilite.
The Role of ILT Mutations in Individual Subunits

The concurrent mutation of three hydrophobic residues (V369I, I372L, and S376T) in the N-terminus of the S4 segment of Shaker K+ channel slows down the kinetic of channel activation by a ∼6-fold factor and shifts the conductance-voltage (G-V) curve to 115 mV (Smith-Maxwell et al., 1998). We sought to determine the effect of the ILT mutations in heterotetrameric concatemerized channels with different stoichiometries to gain insights into the mechanisms of action of the ILT mutations. The channels were expressed in Xenopus oocytes and studied using cut-open oocyte voltage clamp and patch clamp techniques. The G-V curve of a concatemer with the ILT mutations in only one subunit (wtILT/3wt) is centered at ∼8 mV compared with ∼115 mV for the homotetramers Shaker ILT, while the homotetramer concatemerized Shaker zH4 Δ(6-46) (4wt) as a V1/2 of −20 mV. The slope of the G-V curve is reduced. The kinetics of activation and deactivation are similar between 4wt and wtILT/3wt. The ILT mutations were introduced on the single wild type voltage sensor of a heterotetramer having three subunits with the four gating charges neutralized (wtILT/3mut; mut = R362Q/R365Q/R368N/R371Q). The G-V of the wtILT/3mut heterotetramer is right shifted (V1/2 ∼43 mV) compared with the wtILT/3wt and its slope is even more reduced. The number of closed states estimated from the Cole-Moore shift with an exponential function raised to a power n was slightly higher for wtILT/3wt than that of 4wt [9.5±2(9) vs. 7.5±1.5(8), P=0.05]. However, wt/3mut and wtILT/3mut have the same estimates [n=1.58±0.4(5) vs. 1.8±0.7(7), P=0.5]. wtILT/3wt has the same single channel conductance than Shaker ILT. We conclude that a single ILT wild type subunit is not sufficient for fully modifying the concerted step as in homotetramers. (Support: NIHGM30376 and NSERC fellowship to DGG)
High-content Analysis of Antibody Phage-display Library Selection Outputs Identifies Tumor Selective Macropinocytosis-dependent Rapidly Internalizing Antibodies

Many forms of antibody-based targeted therapeutics, including antibody drug conjugates, utilize the internalizing function of the targeting antibody to gain intracellular entry into tumor cells. Ideal antibodies for developing such therapeutics should be capable of both tumor-selective binding and efficient endocytosis. The macropinocytosis pathway is capable of both rapid and bulk endocytosis, and recent studies have demonstrated that it is selectively up-regulated by cancer cells. We hypothesize that receptor-dependent macropinocytosis can be achieved using tumor-targeting antibodies that internalize via the macropinocytosis pathway, improving potency and selectivity of the antibody-based targeted therapeutic. Although phage antibody display libraries have been utilized to find antibodies that bind and internalize to target cells, no methods have been described to screen for antibodies that internalize specifically via macropinocytosis. We hereby describe a novel screening strategy to identify phage antibodies that bind and rapidly enter tumor cells via macropinocytosis. We utilized an automated microscopic imaging-based, High Content Analysis platform to identify novel internalizing phage antibodies that colocalize with macropinocytic markers from antibody libraries that we have generated previously by laser capture microdissection-based selection, which are enriched for internalizing antibodies binding to tumor cells in situ residing in their tissue microenvironment (Ruan, W., Sassoon, A., An, F., Simko, J. P., and Liu, B. (2006) Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection. Mol. Cell. Proteomics. 5, 2364–2373). Full-length human IgG molecules derived from macropinocytosing phage antibodies retained the ability to internalize via macropinocytosis, validating our screening strategy. The target antigen for a cross-species binding antibody with a highly active macropinocytosis activity was identified as ephrin type-A receptor 2. Antibody-toxin conjugates created using this macropinocytosing IgG were capable of potent and receptor-dependent killing of a panel of EphA2-positive tumor cell lines in vitro. These studies identify novel methods to screen for and validate antibodies capable of receptor-dependent macropinocytosis, allowing further exploration of this highly efficient and tumor-selective internalization pathway for targeted therapy development.
Binding the elderly: A prospective study of the use of mechanical restraints in an acute care hospital.

Little information exists on the use of mechanical restraints among nonpsychiatric inpatients. This prospective study evaluates their use among consecutive medical and surgical admissions to an acute care hospital. Daily direct observation of patients and hospital record review provided data on potential predictors of restraint, reasons for their application, complications, and outcome. Cox regression analysis was used to calculate relative risk of restraint while adjusting for duration of hospitalization as well as other variables. Restraints were applied to 37 (17%) of the 222 study patients. Restrained patients were eight times more likely to die during hospitalization (24% v 3%; P less than 0.01). Abnormal mental status exam, diagnosis of dementia, surgery, and presence of monitoring and support devices (eg, intravenous lines) were statistically significant independent predictors of restraint. Mechanical restraint is a common occurrence among nonpsychiatric inpatients particularly those with impaired mentation, requirement for surgery, or intensive medical intervention. Identification of medical and surgical patients at risk for restraint may reduce the use of these devices by concentrating surveillance and prevention on this group.
Accelerated junctional escape. A clinical and electrocardiographic study.

During the routine interpretation of electrocardiograms, 49 cases of spontaneously occurring accelerated, or borderline accelerated, junctional escape complexes (escape intervals of 1200 ± 20 msec) were encountered. Forty-seven of the 49 patients whose cardiograms demonstrated the accelerated junctional escapes had the clinical setting recognized to be associated with the more protracted accelerated junctional rhythm, nonparoxysmal junctional tachycardia. In addition, five patients demonstrated nonparoxysmal junctional tachycardia immediately preceding or subsequent to the cardiograms demonstrating accelerated junctional escape. It is suggested, therefore, that the two arrhythmias, i.e., accelerated junctional escape and nonparoxysmal junctional tachycardia, may be of similar clinical significance. The determinants of the length of the manifest escape interval could be assessed in those cases where two or more junctional escape complexes occurred in sequence, allowing the true interectopic interval to be ascertained. The dominant role of the rate of atrioventricular conduction and the sequence of ventricular and junctional activation in determining the length of the manifest escape interval was apparent.
Microscopically controlled surgery (Mohs' chemosurgery) for treatment of verrucous squamous cell carcinoma of the foot (epithelioma cuniculatum)

In two cases of epithelioma cuniculatum, a rather rare form of verrucous carcinoma of the plantar surface of the foot, the lesions were excised by means of microscopically controlled surgery (Mobs' chemosurgery) with successful results, both clinically and cosmetically. Although the tumor is generally slow-growing and often mistaken for a plantar wart, it can cause extensive local destruction. Metastasis has been reported and may be related to anaplastic transformation caused by radiotherapy. In certain cases, amputation may possibly be avoided through the use of microscopically controlled surgery.
A spliced intron accumulates as a lariat in the nucleus of T cells

The vast majority of mammalian genes are interrupted by non-coding segments of DNA termed introns. Introns are spliced out of RNA transcripts as lariat structures, and then are typically debranched and rapidly degraded. Here, we described an unusual spliced intron from the constant region of the T cell receptor-beta (TCR-beta) locus that is relatively stable in mammalian cells. This intron, IVS1C beta 1, accumulates as a set of lariat RNA structures with different length tails in the nucleus of T cells. The accumulation of this spliced intron is developmentally regulated during murine thymocyte ontogeny. The property of stability appears to be evolutionarily conserved since the human version of this intron also accumulates in T cells. The stability is selective since other spliced TCR-beta introns do not detectably accumulate in T cells. The unusual stability of this intron does not depend on T cell specific factors since non-T cells transfected with TCR-beta gene constructs also accumulate spliced IVS1C beta 1. The discovery of a mammalian intron that accumulates as a lariat in vivo provides an opportunity to elucidate mechanisms that regulate intron debranching, stability, and nuclear localization.
Gender differences in defined contribution pension decisions

Abstract This paper considers gender differences in allocation of household wealth to defined contribution pensions. Using data from the 1989 Survey of Consumer Finances , we estimate the coefficient of relative risk aversion based on the allocation of wealth into defined contribution pensions. Unlike previous studies, we consider the problem in the context of the household’s overall portfolio. We find that women exhibit greater relative risk aversion in their allocation of wealth into defined contribution pension assets.
An automated turbidimetric method for total sulfur in plant tissue and sulfate sulfur in soils

Abstract An automated turbidimetric method has been developed for the rapid and accurate determination of sulfate. The method is practical and useful for accurately measuring total sulfur in plant tissues, and extractable sulfate in soils. The principle of intermittent reagent addition is used which eliminates drift and sensitivity changes caused by coating of BaSO4 on tubing and cell walls. Also, the appropriate chemistry is used to minimize interactions of the wash with the sample at a sampling rate of 30/H. The sensitivity of the method is excellent with a working range of 0 to 15 ppm sulfur for soils. For plant digests the sample solutions are diluted to 0–35 ppm S. The precision as determined by repeated analysis of a soil sample extract was 0.58% RSD with a mean of 9.26 pg/g extractable SO= 4‐S. On another soil sample using a different extractant and extraction procedure the RSD was 0.64%, mean of 9.26 μg/g. Multiple automated sulfur analyses on a plant tissue digest resulted in an RSD of 0.41% for ...
Time encoded fast neutron/gamma imager for large standoff SNM detection

Passive detection of special nuclear material (SNM) at long range or under heavy shielding can only be directly achieved by observing the penetrating neutral particles that it emits: gamma rays and neutrons in the MeV energy range. The ultimate SNM standoff detector system would have sensitivity to both gamma and neutron radiation, a large area and high efficiency to capture as many signal particles as possible, and good discrimination against background particles via directional and energy information. We are exploring the use of time-modulated collimators that may lead to practical gamma-neutron imaging detector systems that are highly efficient with the potential to exhibit simultaneously high angular and energy resolution. We will present results from a large standoff SNM detection demonstration using a prototype high sensitivity time encoded modulation imager.
An examination of electric servo-guns for the resistance spot welding of complex stack-ups

In this program, the capabilities of medium-frequency direct current (MFDC) electric servo resistance welding guns for the welding of complex stack-ups were investigated. Capabilities of interest from these guns include the ability to apply forge forces and currents, as well as the ability to sequence the current and forging profiles. The complex stack-up under study included a 1-mm outside sheet attached to two 2-mm sheets. Work was done using design of experiment (DOE) techniques. The experiment included a range of processing variations deliverable from the MFDC servo-gun, as well as two electrode variations (materials and sizes). Heat balance during resistance welding of this stack-up was found to be dominated by the electrode variations. As electrode variations are not considered a solution for automotive complex stack-up applications, a best practice was defined from the DOE that included similar-sized class 2 electrodes. This best practice included short overall weld times, a moderate forge force, a significant (40 %) increase in current during forging, and a weld time relative to the forging portion of the weld schedule. This yielded nugget penetrations of roughly 50 % into the thin attached sheet. It was noted that, at these penetrations, indentations on both sides of the joint reached 0.45 mm and that process variations could be used to trade off penetrations with overall indentations.
Mixed‐mode separation of polycyclic aromatic hydrocarbons (PAHs) in electrokinetic chromatography

A mixed-mode separation technique has been developed and optimized for the separation of the 16 Environmental Protection Agency (EPA) priority polycyclic aromatic hydrocarbons (PAHs). The procedure utilized two different buffer additives as pseudo-stationary phases with different selectivities towards the analytes. Sodium dioctyl sulfosuccinate (DOSS) displayed selectivities for PAHs which were somewhat similar to the C18 phase in reversed-phase high performance liquid chromatography (HPLC). High acetonitrile content required for an effective separation prevented the formation of micelles as confirmed by fluorescence spectroscopy. Consequently, the separation could be attributed to the solvophobic association of the PAH molecules with hydrophobic chains of the DOSS surfactant. In another mode of separation, sulfobutylether-beta-cyclodextrin (SB-beta-CD) separated the 16 PAHs on the formation of inclusion complexes with the PAHs, and exhibited different selectivities for the PAHs compared to DOSS. SB-beta-CD and DOSS were then combined in the running buffer to form a mixed pseudo-stationary phase for the separation of the 16 PAHs. Due to the different selectivities of SB-beta-CD and DOSS for the PAHs, the separation of the 16 PAHs was appreciably improved compared to that using DOSS or SB-beta-CD alone. All the 16 PAHs were baseline-resolved using an optimized running buffer containing 22.5 mM DOSS, 15 mM SB-beta-CD, 15% acetonitrile and 5 mM hydroxypropyl-beta-cyclodextrin in 6 mM borate at pH 9.