cssi/SciSciGPT-SciSciNet huggingface dataset:
An efficient solution methodology to study the response of a beam on viscoelastic and nonlinear unilateral foundation: Static response

Abstract Many engineering materials and foundations such as soils demonstrate nonlinear and viscoelastic behaviour. Yet, it is challenging to develop static and dynamic models of systems that include these materials and are able to predict the behaviour over a wide range of loading conditions. This research is focused on a specific example: a pinned–pinned beam interacting with polyurethane foam foundation. Two cases, when the foundation can react in tension and compression as well as only in compression, are considered. The model developed here is capable of predicting the response to static as well as dynamic forces, whether concentrated or distributed. Galerkin’s method is used to derive modal amplitude equations. In the tensionless foundation case, the contact region changes with beam motion and the estimation of the co-ordinates of the lift-off points is embedded into the solution procedure. An efficient solution technique is proposed that is capable of handling cases where there are multiple contact and non-contact regions. Depending on the loading profiles a high number of modes may need to be included in the solution and to speed up computation time, a convolution method is used to evaluate the integral terms in the model. The adaptability of the solution scheme to complicated loading patterns is demonstrated via examples. The solution approach proposed is applicable to dynamic loadings as well and in these cases the automated treatment of complicated response patterns makes the convolution approach particularly attractive. The influence of various parameters on the static response is discussed.
A Further Assessment of Treatment Effects in the Florida Area Cumulus Experiment through Guided Linear Modeling

Abstract The Florida Area Cumulus Experiment (FACE) was a two-stage program dedicated to assessing the potential of “dynamic seeding” for enhancing convective rainfall in a fixed target area. FACE-1 (1970–76) was an exploratory cloud seeding experiment that produced substantial indications of a positive treatment effect on rain at the ground, and FACE-2 (1978–80) was a confirmatory experiment that did not confirm the treatment effect results of FACE-1. This article presents some new analyses of both the FACE-1 and FACE-2 data in an effort to better understand the role of meteorological and treatment factors on rainfall in the days selected for experimentation in Florida. The analyses rely upon a guided exploratory linear modeling of the natural target area rainfall and the potential treatment effects. In particular, a conceptual model of natural Florida rainfall is utilized to guide the construction of the exploratory linear model. After the form of the model is selected it is fitted to both the FACE-1 an...
The nature of Japan's comparative advantage, 1965-80

Abstract This paper compares the dynamic factor proportions theory to the product cycle theory in explaining Japan's comparative advantage for the 1965-80 period. Three tests were used: (1) domestic Japanese relative prices of more and less competitive export commodities; (2) trends in capital-labour ratios, skill ratios, RD (3) price elasticities over time of Japan's exports. The results suggest that: (1) the product cycle must be considered along with the factor proportions theory for the pre-oil shock period; (2) the product cycle theory is superior for the post-oil shock period.
Identification and cloning of the Na/HCO3− cotransporter (NBC) in human corneal endothelium

Abstract Fluid secretion by the corneal endothelium is associated with the net flux of HCO 3 − from basolateral (stromal) to apical (anterior chamber) sides of the tissue. In this study we asked if Na + /HCO 3 − cotransporter (NBC-1) protein expression and functional activity are present in freshly isolated human corneal endothelium. Immunoblot analysis using a polyclonal antibody to NBC-1 showed a single band at ∼130 kDa. Indirect immunofluorescence indicated that NBC-1 is expressed on the basolateral, but not apical side of human corneal endothelium. RT-PCR was used to determine whether the kidney or pancreatic isoform of NBC-1 is expressed. Using the specific primers for pNBC and kNBC isoforms, RT-PCR showed that only pNBC could be detected in human corneal endothelium. The product was cloned and confirmed by sequencing. Full-length NBC-1 was also cloned from human corneal endothelium. This clone (hcNBC) is 100% identical to the longer, more common form of NBC [pNBC; 1079 amino acids (aa); 122 kDa in human heart, pancreas and prostate]. To test for functional activity of NBC-1, freshly isolated endothelium was loaded with the pH sensitive fluorescent dye BCECF and HCO 3 − fluxes were measured. HCO 3 − fluxes were Na + -dependent, electrogenic and H 2 -DIDS sensitive. We conclude that the long isoform of the sodium bicarbonate cotransporter (pNBC-1) is expressed on the basolateral side of fresh human corneal endothelium (hcNBC). The shorter form, kNBC, could not be detected. As in bovine corneal endothelium, hcNBC is instrumental in loading HCO 3 − into endothelial cells from the basolateral membrane.
Solid-State Characterization of the Nuclear and Electronic Environments in a Boron−Fluoride Co-doped TiO2 Visible-Light Photocatalyst

We describe the synthesis of a visible light absorbing boron−fluoride co-doped TiO2 photocatalyst by a sol−gel methodology and its structural characterization using magnetic resonance techniques. The formation of photoactive sites was induced by pyrolysis under anaerobic conditions at temperatures of 400 to 500 °C, followed by a short exposure to air or oxygen gas and rapid cooling. 11B solid-state nuclear magnetic resonance analysis of B/F−TiO2 shows that the chemical environment of the photochemically active B/F co-doped TiO2 can be described as tetrahedrally coordinated BO4 units (δ = −1.4 ppm). 19F NMR indicates that fluorine species form part of the Ti coordination sphere and are of the form TiO5F (δ = −152 ppm). Similarly, X-ray photoelectron spectroscopy indicates that fluorine is found at lattice positions forming O−Ti−F fragments. Electron paramagnetic resonance spectroscopy, coupled to spectral simulation of the sample calcined at 485 °C, shows that the radicals formed in this material are mainl...
Monoamine oxidase in the brain of European corn borer larvae, Ostrinia nubilalis (Hübner)

Abstract Monoamine oxidase (MAO) activity was demonstrated in intact brains of larvae from the European corn borer, Ostrinia nubilalis using 2-(2′-benzothiazolyl)-5-stryl-3-(4′-phthalhydrazidyl) tetrazolium chloride (BSPT). With tryptamine as the substrate, MAO specific activity was restricted to mitochondria within perineurial cells. The basic BSPT methodology was modified by the substitution of 2% dimethylsulfoxide for dimethylformamide in the incubation medium. This yielded increased permeability of the brain to the incubation medium, presumably by disrupting the integrity of the blood-brain barrier. A discussion of possible reasons for the previous inability to demonstrate insect neuronal MAO activity is presented.
Acoustic Characterization of Compact Jet Engine Simulator Units

Two dual-stream, heated jet, Compact Jet Engine Simulator (CJES) units are designed for wind tunnel acoustic experiments involving a Hybrid Wing Body (HWB) vehicle. The newly fabricated CJES units are characterized with a series of acoustic and flowfield investigations to ensure successful operation with minimal rig noise. To limit simulator size, consistent with a 5.8% HWB model, the CJES units adapt Ultra Compact Combustor (UCC) technology developed at the Air Force Research Laboratory. Stable and controllable operation of the combustor is demonstrated using passive swirl air injection and backpressuring of the combustion chamber. Combustion instability tones are eliminated using nonuniform flow conditioners in conjunction with upstream screens. Through proper flow conditioning, rig noise is reduced by more than 20 dB over a broad spectral range, but it is not completely eliminated at high frequencies. The low-noise chevron nozzle concept designed for the HWB test shows expected acoustic benefits when installed on the CJES unit, and consistency between CJES units is shown to be within 0.5 dB OASPL.
Metal etch process defects

In this paper, four major defects for metal etch process will be introduced and discussed. The defect sources related to chamber condition are identified as well. These defects are classified into four types: (1) flake type metal residue, induced by chamber polymer, (2) ball type particle, resulted from the chamber wall arcing during process, (3) on film particle, found during post-etch and photo resist strip processes, (4) metal broken, came from local arcing on wafer. All of these defects would result in metal line bridge and yield loss. In order to reduce the particle contamination, the paper proposes a protection method for chamber parts by using so called `linear' to cover most of chamber parts. The liner could adapt to chamber shape and clean easily. Experimental data shows that it can successfully reduce flake type metal residue, ball type particle. For the on film particle and metal broken, a new routine monitor method is also created.
Simulation in critical care and trauma education and training

Purpose of review To review theory and practice of simulation technology in critical care and trauma training. Recent findings Simulators provide a safe and realistic environment in which active learning, enhanced by repetition and feedback, can take place. Simulation and computer-based education address the needs of knowledge and skill acquisition across a continuum of professional development. Summary Simulation appears poised to revolutionize education, training, and credentialing in critical care, surgery, and anesthesiology. However, advances in computing and technology have outpaced the evaluative and validation studies of simulation-based education.
Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-Kα and pandinustoxin-Kα

The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca(2+)-activated K+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors.
Moral atmosphere: An educational bridge between moral judgment and action

The child's orientation toward the community can play a major role in linking the child's moral judgment to action.
A mathematical model for the economic justification of setup time reduction

Abstract A justification model for setup time reduction is presented. The model includes inventory carrying cost, setup cost, storage cost, setup time reduction cost, and quality cost. The level of setup time reduction which yields the lowest total cost indicates the extent to which setup time reduction is economically justified. A case study is presented based on one machine and one product. Results indicate that unlimited setup time reduction is not always justified based on the analysis of one product. However, a greater level of reduction is justified if the lot size is reduced appropriately as setup time is reduced.
MASS SPECTRAL CHARACTERIZATION OF SOME NUCLEOSIDE PHOSPHATES AND PHOSPHORAMIDATES

Seven new synthetic nucleotide analogues have been characterized as their trimethylsilyl derivatives by recording their electron impact mass spectra. These spectra are consistent with their expected structures, most of which possess a cyclic phosphate or phosphoramidate group.
Adjuvant irradiation for cervical lymph node metastases from melanoma.

BACKGROUND The risk of regional disease recurrence after surgery alone for lymph node metastases from melanoma is well documented. The role of adjuvant irradiation remains controversial. METHODS The medical records of 160 patients with cervical lymph node metastases from melanoma were reviewed retrospectively. Of these, 148 (93%) presented with clinically palpable lymph node metastases. All patients underwent surgery and radiation to a median dose of 30 grays (Gy) at 6 Gy per fraction delivered twice weekly. Surgical resection was either a selective neck dissection in 90 patients or local excision of the lymph node metastasis in 35 patients. Only 35 patients underwent a radical, modified radical, or functional neck dissection. RESULTS At a median follow-up of 78 months, the actuarial local, regional, and locoregional control rates at 10 years were 94%, 94%, and 91%, respectively. Univariate analysis of patient, tumor, and treatment characteristics failed to reveal any association with the subsequent rate of local or regional control. The actuarial disease-specific (DSS), disease-free, and distant metastasis-free survival (DMFS) rates at 10 years were 48%, 42%, and 43%, respectively. Univariate and multivariate analyses revealed that patients with four or more involved lymph nodes had a significantly worse DSS and DMFS. Nine patients developed a treatment-related complication requiring medical management, resulting in a 5-year actuarial complication-free survival rate of 90%. CONCLUSIONS Adjuvant radiotherapy resulted in a 10-year regional control rate of 94%. Complications for all patients were rare and manageable when they did occur. The authors recommend adjuvant irradiation for patients with extracapsular extension, lymph nodes measuring 3 cm in size or larger, the involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a selective therapeutic neck dissection. Cancer 2003;97:1789–96. © 2003 American Cancer Society. DOI 10.1002/cncr.11243
Time dependent temperature distribution in pulsed Ti:sapphire lasers

An expression is derived for the time dependent temperature distribution in a finite solid state laser rod for an end-pumped beam of arbitrary shape. The specific case of end pumping by circular (constant) or Gaussian beam is described. The temperature profile for a single pump pulse and for repetitive pulse operation is discussed. The particular case of the temperature distribution in a pulsed titanium:sapphire rod is considered.
Intracranial reinforcement: Performance decrements as a function of stimulus parameters

Rats, on ad lib food and water schedules, ran a maze for intracranial stimulation with an independent variable of different intensities or durations of the reinforcer. The performance decrement of the first trial of a set of massed trials, sometimes seen with intracranial reinforcement, was found to be a function of the values of the brain stimulation with some rats.
Upper bound analysis of oblique cutting: improved method of calculating the friction area

This paper describes further development of the upper bound analysis of oblique cutting with nose radius tools described previously by Adibi-Sedeh et al. [1] by incorporation of an improved method for calculating the friction area at the chip-tool interface. Previously, the friction area was obtained from the shear surface area assuming that the ratio of these areas is the same as in orthogonal machining. Our results showed that this led to overestimation of the effect of friction on the chip flow angle, thereby resulting in smaller changes in the chip flow angle with inclination angle as compared to experimental data. In the new approach, the chip-tool contact length is obtained from the length of the shear surface assuming that the ratio of the lengths is the same as in orthogonal machining and the friction area is calculated using this length. The chip flow angle predicted using the new approach shows much better agreement with experimental data. In particular, the dependence of the chip flow angle on the inclination angle is accurately reproduced. Upper bound analysis of oblique cutting using this new model for the friction area provides an elegant explanation for the relative influence of the normal and equivalent rake angles on the cutting force.
Brand extension and customer loyalty: evidence from the lodging industry

Excerpt] Building and successfully managing strong brands is considered to be one of the key drivers of success in the hotel industry. CEOs of hotel companies that own brands recognize that brand equity drives stock price and shareholder value. This sentiment is echoed on Wall Street, as the following comment indicates: "Lodging is a brand-equity business—(that) is the backbone of expansion. By building equity in its brand, a lodging company is able to “sell” its name to hotel owners and franchisors, and also able to reach consumers, thereby generating the demand to support expansion." Consumers often base their hotel-stay decisions on their perception of a specific hotel’s brand name. The United States now has over 200 hotel brands competing for business, more than in any other product category. Many of these brands are extensions of existing brand names. Brand extension is the practice of introducing a new brand (differentiated by market segment) using a well-established brand name as leverage.
Photonic crystal vertical-cavity lasers

Photonic crystal confinement in vertical cavity surface-emitting lasers (VCSELs) is a robust and reliable technology for achieving operation in the fundamental lateral mode and is potentially applicable to a variety of materials systems and operating wavelengths. We demonstrate photonic crystal VCSELs operating in a single transverse mode with over 30 dB side mode suppression and over 1 mW of output power. These lasers have been subjected to a post-process technique to introduce the etched holes making up the photonic crystals that surround a centralized defect in which lasing occurs. We also show that coupling between adjacent defects in a photonic lattice is possible, further increasing the power available in the devices.
Ocean–Atmosphere Interactions in the Tropical and Subtropical Atlantic Ocean

Abstract A 110-yr simulation is conducted using a specially designed coupled ocean–atmosphere general circulation model that only allows air–sea interaction over the Atlantic Ocean within 30°S–60°N. Since the influence from the Pacific El Nino–Southern Oscillation (ENSO) over the Atlantic is removed in this run, it provides a better view of the extratropical influences on the tropical air–sea interaction within the Atlantic sector. The model results are compared with the observations that also have their ENSO components subtracted. The model reproduces the two major anomalous patterns of the sea surface temperature (SST) in the southern subtropical Atlantic (SSA) and the northern tropical Atlantic (NTA) Ocean. The SSA pattern is phase locked to the annual cycle. Its enhancement in austral summer is associated with atmospheric disturbances from the South Atlantic during late austral spring. The extratropical atmospheric disturbances induce anomalous trade winds and surface heat fluxes in its northern flank...
Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin.

Mutations of the TSC1 and TSC2 genes give rise to the clinical disorder of tuberous sclerosis characterized by the development of hamartomas predominantly affecting the central nervous system, kidney, skin, lung, and heart. The function of the gene products, hamartin and tuberin, is not well understood but we have previously suggested a role in vesicular transport. To define the subcellular compartment(s) involved with these two proteins, biochemical characterization of hamartin and tuberin was performed in primary tissues and cell lines. Fractionation of cell lysates identified both proteins in the cytosolic, microsomal, and cytoskeletal compartments. In each of these fractions, hamartin and tuberin formed a stable complex in coimmunoprecipitation analyses. Further, they colocalized extensively in discrete, vesicular structures in the cytoplasm. Within the microsomal compartment, hamartin and tuberin behaved as peripheral membrane proteins that associate with the cytosolic leaflet of membranous domains. Immunoisolation of tuberin-bound vesicles using magnetic beads showed an enrichment of rap1, rab5, and caveolin-1, all of which have been found in specialized lipid microdomains, caveolae. Our data suggest that hamartin and tuberin are multicompartmental proteins that partially reside in caveolin-1-enriched structures and potentially affect their signaling.
Rayleigh laser guide stars for extremely large telescopes

Rayleigh laser guide star technology is discussed here with particular attention paid to the effects of laser pulse length, a parameter that becomes more significant to the design when telescope apertures are greater than 10 meters. After reviewing the relative return signal for Rayleigh versus sodium laser guide stars, a brief review of the pulse length characteristics of sodium lasers is given. Only one of the proposed sodium laser systems is pulsed while the others are CW. To insure star-like sources at the wavefront sensor with FWHM < 1.0 arcsec, lasers that will be most useful for Extremely Large Telescopes must have a short pulse format whereas CW lasers will be of little to no use. A relatively simple Rayleigh laser guide star method is described for Ground Layer Adaptive Optics (GLAO). This method provides a way to average out the effects of high altitude turbulence with a single Rayleigh laser guide star leaves intact the wavefront sign needed to correct ground-layer wavefront perturbations.
Computer-aided preform design in forging of an airfoil section blade

Abstract This study attempts to establish systematic procedures for the preform design in forging of an airfoil section blade as a two-dimensional plane-strain problem. Forward loading and backward tracing simulations by the finite element method are used. A circular shape is selected as an original stock, and a side-pressed preform of the circular shape is adopted in view of preliminary simulations using rectangular preforms. The optimal slope angle of the die parting line and the position of the preform within the die, which satisfy the final design condition of flashless forging, are determined from the results of the simulations.
Factors influencing adverse perinatal outcomes in pregnancies achieved through use of in vitro fertilization.

Objective To determine the associations of specific components of IVF treatment with abnormal perinatal outcomes. Design Case-control study. Setting University-based and community-based infertility centers. Patient(s) All viable pregnancies achieved through IVF procedures performed between January 1999 and March 2004. Intervention(s) None. Main Outcome Measure(s) Infertility etiology, gonadotropin exposure, embryo manipulation, and quality. Result(s) Of 455 viable pregnancies identified during the study period, 435 met inclusion criteria. While adjusting for maternal age, race, parity, body mass index, infertility center, and year of IVF procedure, multiple gestations were associated with a 12-fold increased risk of poor perinatal outcome compared to singletons. Ovarian hyperstimulation syndrome significantly increased the risk more than 3-fold (odds ratio=3.14; 95% confidence interval, 1.08–9.14), while endometrial thickness was found to have a significant protective effect (odds ratio=0.89; 95% confidence interval, 0.80–0.99). We found no effect of etiology of infertility, dose or type of medication used for stimulation, use of embryo-manipulation techniques, or quality on perinatal outcome. Conclusion(s) These data confirm and quantify the risk of perinatal morbidity associated with multiple births. After adjusting for multiple births, ovarian hyperstimulation syndrome and suboptimal endometrial development are associated with adverse outcomes in pregnancies achieved through IVF. Our findings suggest that it may be the endometrium rather than the embryo that influences fetal growth and perinatal outcomes after IVF.
Social networks in borderline personality disorder.

The interpersonal dysfunction that characterizes borderline personality disorder (BPD) has generally been studied using broad global measures, leading to a lack of precision. We report on a novel methodology using social network analysis (SNA) to quantify interactions with others in the patient’s social world. We assessed the social networks of 22 clinical patients, diagnosed with either BPD (N = 11) or no personality disorder (No PD; N = 11). The social networks of patients with BPD contained a greater number of former romantic partners, and a greater number of relationships that had been terminated. Mixed model analyses found that the No PD group reported higher levels of positive relationships (e.g., trust, social support) with more central members of their social networks, whereas the BPD group did not discriminate among members of their networks. Results suggest deficits in social cognition for positive relations, but not for negative relations such as interpersonal conflict.
Arthroscopic repair of large rotator cuff tears using the double-row technique: an analysis of surgeon experience on efficiency and outcomes

Background: Arthroscopic rotator cuff repair is one of the most commonly performed procedures in the orthopaedic specialty. The goal of this study was to evaluate the effect(s) of surgical experience on efficiency and patient outcomes after double-row rotator cuff repair. Methods: A retrospective review of 69 consecutive patients with large rotator cuff tears who underwent double-row arthroscopic rotator cuff repair by 1 surgeon from the start of practice was conducted. We divided the patients into 2 cohorts: group 1, early (first 18 months of study period) (n ¼ 35), and group 2, recent (final 12 months of study period) (n ¼ 34). Outcome measures including American Shoulder and Elbow Surgeons score, Penn Shoulder Score, and range of motion were assessed preoperatively and at final follow-up. In addition, we compared the operative times between the groups. Results: At a mean follow-up of 13.25 months, both cohorts showed significant improvement (P <.001) in American Shoulder and Elbow Surgeons scores (from 47.9 to 76.5 and from 43.6 to 79.4 in groups 1 and 2, respectively) and Penn Shoulder Scores (from 45.8 to 80 and from 38.7 to 79.6 in groups 1 and 2, respectively) postoperatively. The magnitude of change and final scores were similar between the groups. Similar improvements in range of motion were noted in both groups. Patients in group 1 had a statistically significantly longer mean operative time than those in group 2 (116 minutes vs 99.7 minutes, P ¼ .036). Conclusion: Double-row rotator cuff repair provides predictable improvement in pain and function. It can be performed effectively early in a surgeon’s career. However, with experience, efficiency is improved. Level of evidence: Level III, Retrospective Case-Control Design, Treatment Study. 2013 Journal of Shoulder and Elbow Surgery Board of Trustees.
THE EARNINGS PERFORMANCE OF THE CONSUMER FINANCE INDUSTRY

CONSUMER FINANCE HAS COME to play a major role in America's economic life since the end of World War II. Consumer finance companies' have entered the ranks of "big business" and have become increasingly important from an investor standpoint. This article examines the postwar profitability of the consumer finance industry in terms of (1) an analysis of the composite earnings record of the principal units in the industry, (2) a comparison of this record with the composite performance of the major industrial enterprises in the nation, and (3) a comparison with the performance of the primary industries in the manufacturing and trade sectors of the economy. To make the interindustry comparison, this study uses a substantial body of data already compiled for 33 industry groups.2 Therefore, the procedures employed in developing the 33-industry data have been adopted in both selecting the sample and compiling the financial information for the consumer finance industry.
Identification of predictive biomarker signatures in melanoma tumors associated with response to tumor-infiltrating lymphocyte (TIL) therapy

Adoptive cell therapy using expanded autologous TIL is a promising immunotherapy for metastatic melanoma. However, we still know relatively little about the types of T cells in TIL mediating tumor regression, and there have been no biomarker studies on the actual tumors used to expand TIL to identify factors predictive of clinical response. The purpose of this study was to identify immune biomarkers in tumors used to expand TIL and determine their power to predict an eventual response to TIL therapy. We performed immunohistochemistry (IHC) for a number of parameters (e.g., CD8, CD4, CD3, FoxP3, and PD-1) on formalin-fixed paraffin-embedded (FFPE) tumor samples from 48 patients that expanded TIL and were eventually treated as well as FFPE samples from 39 patients from which TIL did not successfully expand. We found a correlation between the percentage of CD8+ cells in the original tumor by IHC and the CD8 content of the final expanded TIL product of these patients (p=0.046, r2=0.283, Spearman correlation coefficient). We also found highly significant differences in CD8, CD4 and CD3 staining in tumors between TIL growers and non-growers (p<0.0001). Although the percentages of total, peri-tumoral or intra-tumoral CD8, PD-1 and FoxP3 in the original tumor for TIL expansion could not predict tumor response (CR/PR vs. SD/PD), increased peri-tumoral and total CD4 staining had an inverse trend towards predicting CR/PR (p=0.067 and p=0.082, respectively). Interestingly, when we combined CD8 and FoxP3 staining and developed a scoring system that considered the location and extent of staining, we found that patients who had a lower CD8 and FoxP3 score in peri-tumoral and/or intra-tumoral areas had significantly shorter overall survival in both univariate (HR= 3.657, p=0.041) and multivariate (HR=3.514, p=0.048) Cox proportional hazards analysis. We also performed gene expression analysis on RNA isolated from the same tumor samples using a new NanoString nCounter™ technology. This revealed significant differences in a number of immune system-related genes in tumors of TIL growers and non-growers, such as CD3e and CD3δ, STAT4, TRAFs, CD27, ICOS, IL-21R, TNF-α, FoxP3, and CCR8. There were also differences in gene expression in tumors of responding and non-responding patients treated with TIL, such as BATF3 and IRAK1. Our data suggests that IHC analysis together with gene profiling of archived FFPE tumor samples is useful to develop predictive biomarker signatures to select patients for TIL therapy and identify those who will have a survival benefit for stratification in future clinical trials.
For-profit hospital status and rehospitalizations at different hospitals: an analysis of Medicare data.

Higher-than-expected rehospitalization rates have come to be an indicator of quality-of-care problems. This study of 16 222 Medicare beneficiaries rehospitalized within 30 days of an acute care hos...
Optimal sleep-wakeup algorithms for barriers of wireless sensors

The problem of sleep wakeup has been extensively studied for the full coverage model, where every point in the deployment region is covered by some sensor. Since the sleep-wakeup problem is NP-Hard for this model, several heuristics exist. For the model of barrier coverage, however, where sensors are deployed to form an impenetrable barrier for detecting moving objects (a flagship application of wireless sensor networks), design of an optimal sleep-wakeup algorithm is open. In this paper, we solve this open problem by proposing optimal algorithms not only for the often-used case of equal lifetime but also for the much harder case when sensor lifetimes are different. We prove the optimality of both algorithms. Our algorithms can be used to maintain not just barrier coverage but fault tolerant connectivity, as well, while maximizing the network lifetime. We use simulation to show that for random deployments, even when a minimal number of sensors have been deployed, our optimal algorithms can increase the network lifetime by 500% (from 10 weeks to more than a year). Finally, we show that using our optimal algorithms increases the network lifetime six times longer than that achievable using an existing sleep wake-up algorithm called Randomized Independent Sleeping (RIS).
Characterization of PINK1 processing, stability, and subcellular localization

Mutations found in PTEN-induced putative kinase 1 (PINK1), a putative mitochondrial serine/threonine kinase of unknown function, have been linked to autosomal recessive Parkinson's disease. It is suggested that mutations can cause a loss of PINK1 kinase activity and eventually lead to mitochondrial dysfunction. In this report, we examined the subcellular localization of PINK1 and the dynamic kinetics of PINK1 processing and degradation. We also identified cytosolic chaperone heat-shock protein 90 (Hsp90) as an interacting protein of PINK1 by PINK1 co-immunoprecipitation. Immunofluorescence of PINK1 protein and mitochondrial isolation show that the precursor form of PINK1 translocates to the mitochondria and is processed into two cleaved forms of PINK1, which in turn localize more to the cytosolic than mitochondrial fraction. The cleavage does not occur and the uncleaved precursor stays associated with the mitochondria when the mitochondrial membrane potential is disrupted. Metabolic labeling analyses show that the PINK1 processing is rapid and the levels of cleaved forms are tightly regulated. Furthermore, cleaved forms of PINK1 are stabilized by Hsp90 interaction as the loss of Hsp90 activity decreases PINK1 level after mitochondrial processing. Lastly, we also find that cleaved forms of PINK1 are degraded by the proteasome, which is uncommon for mitochondrial proteins. Our findings support a dual subcellular localization, implying that PINK1 can reside in the mitochondria and the cytosol. This raises intriguing functional roles that bridge these two cellular compartments.
CONCENTRATION OF THE GONADOTROPIC HORMONE IN PREGNANT MARE'S SERUM

The gonadotropic hormone of the blood of the pregnant mare has been greatly concentrated by adsorption on active aluminum hydroxide followed by elution. The preparations so obtained gave demonstrable gonadotropic effects within 100 hours in 21 day old female mice following three subcutaneous injections of 0.001 mg. in 1 cc. of physiological saline. As is well known, other gonadotropic substances do not cause conspicuous development of the male gonads but injections of comparatively large doses of these preparations into immature male rats caused marked development of the testes, which in 10 days were trebled in weight. An astonishing increase in the weight of the seminal vesicles resulted, for these organs were approximately 75 times heavier than in controls.
Scaled Gradients on Grassmann Manifolds for Matrix Completion

This paper describes gradient methods based on a scaled metric on the Grassmann manifold for low-rank matrix completion. The proposed methods significantly improve canonical gradient methods, especially on ill-conditioned matrices, while maintaining established global convegence and exact recovery guarantees. A connection between a form of subspace iteration for matrix completion and the scaled gradient descent procedure is also established. The proposed conjugate gradient method based on the scaled gradient outperforms several existing algorithms for matrix completion and is competitive with recently proposed methods.
Highly Robust Error Correction byConvex Programming

This paper discusses a stylized communications problem where one wishes to transmit a real-valued signal (a block of pieces of information) to a remote receiver. We ask whether it is possible to transmit this information reliably when a fraction of the transmitted codeword is corrupted by arbitrary gross errors, and when in addition, all the entries of the codeword are contaminated by smaller errors (e.g., quantization errors). We show that if one encodes the information as where is a suitable coding matrix, there are two decoding schemes that allow the recovery of the block of pieces of information with nearly the same accuracy as if no gross errors occurred upon transmission (or equivalently as if one had an oracle supplying perfect information about the sites and amplitudes of the gross errors). Moreover, both decoding strategies are very concrete and only involve solving simple convex optimization programs, either a linear program or a second-order cone program. We complement our study with numerical simulations showing that the encoder/decoder pair performs remarkably well.
9‐cis and all‐trans retinoic acid induce a similar phenotype in human teratocarcinoma cells

Abstract Prior work has shown that all-trans retinoic acid (t-RA) treatment of the human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1) induces a neuronal phenotype and other cell lineages. This study sought to explore the potential of 9-cis retinoic acid (9-cis RA) as a differentiation-inducing agent of this multipotent cell. Findings reported here show that 9-cis RA induced a phenotype similar to t-RA treatment of NT2/D1 cells. This similarity extended to their effects on the nuclear receptors retinoic acid receptor-β (RAR-β) and retinoid X receptor-α (RXR-α). Both retinoids prominently augmented RAR-β expression and transactivated a reporter plasmid containing putative RAR response elements (RAREs) with direct repeats separated by five nucleotides (DR5). Both retinoids had no appreciable effect on RXR-α expression and both minimally transactivated a reporter plasmid containing putative RXR response elements (RXREs) with direct repeats separated by one nucleotide (DR1). These studies suggest that 9-cis RA and t-RA activate common events during retinoid-mediated NT2/D1 differentiation. This hypothesis was supported by the finding that NT2/D1 cells rendered refractory to t-RA (NT2/D1-R1) were also resistant to 9-cis RA. To discover alterations that could confer retinoid-refractoriness, retinoid receptor expression was examined in NT2/D1-R1 cells. In contrast to NT2/D1, the NT2/D1-R1 cell was found to have reduced RXR-α expression at the level of total cellular RNA. These studies establish the effectiveness of 9-cis RA as a differentiation agent of human TC cells and demonstrate that retinoids with different nuclear receptor affinities can induce similar phenotypes in NT2/D1 cells. In addition, the findings in the retinoid resistant NT2/D1-R1 cell implicate a role for specific retinoid receptors in this human TC differentiation program.
Controlling water uptake of sugar based epoxy resins

Epoxy resins made from natural materials have numerous advantages over those made from petroleum derived chemicals. Isosorbide and its isomers, isomannide and isoidide, can react similarly to bisphenol A to produce diglycidyl ethers that may be used as epoxy resins. These materials have comparable mechanical properties to bisphenol A based epoxies when produced under similar conditions. However, the sugar derived epoxies take up a significant amount of water, which is detrimental to their use in many applications. Modification of these materials with hydrophobic molecules may be an effective method of reducing water uptake.
The NYU Silver School of Social Work's Zelda Foster Studies Program: Selected Works From the Leadership Fellowship.

The articles in this special issue celebrate the capstone projects of the first two cohorts of an 18-month Leadership Fellowship; one component of New York University Silver School of Social Work's...
Assessment of DNA extracted from FTA cards for use on the Illumina iSelect BeadChip.

As FTA® cards provide an ideal medium for the field collection of DNA we sought to assess the quality of genomic DNA extracted from this source for use on the Illumina BovineSNP50 iSelect BeadChip which requires unbound, relatively intact (fragment sizes ≥ 2 kb), and high-quality DNA. Bovine blood and nasal swab samples collected on FTA cards were extracted using the commercially available GenSolve kit with a minor modification. The call rate and concordance of genotypes from each sample were compared to those obtained from whole blood samples extracted by standard PCI extraction. An ANOVA analysis indicated no significant difference (P > 0.72) in BovineSNP50 genotype call rate between DNA extracted from FTA cards by the GenSolve kit or extracted from whole blood by PCI. Two sample t-tests demonstrated that the DNA extracted from the FTA cards produced genotype call and concordance rates that were not different to those produced by assaying DNA samples extracted by PCI from whole blood. We conclude that DNA extracted from FTA cards by the GenSolve kit is of sufficiently high quality to produce results comparable to those obtained from DNA extracted from whole blood when assayed by the Illumina iSelect technology. Additionally, we validate the use of nasal swabs as an alternative to venous blood or buccal samples from animal subjects for reliably producing high quality genotypes on this platform.
Scalability and Performance Improvements in the Fermilab Mass Storage System

By 2009 the Fermilab Mass Storage System had encountered two major challenges: the required amount of data stored and accessed in both tiers of the system (dCache and Enstore) had significantly increased and the number of clients accessing Mass Storage System had increased from tens to hundreds of nodes and from hundreds to thousands of parallel requests. To address these challenges Enstore and the SRM part of dCache were modified to scale for performance, access rates, and capacity. This work increased the amount of simultaneously processed requests in a single Enstore Library instance from about 1000 to 30000. The rates of incoming requests to Enstore increased from tens to hundreds per second. Fermilab is invested in LTO4 tape technology and we have investigated both LTO5 and Oracle T10000C to cope with the increasing needs in capacity. We have decided to adopt T10000C, mainly due to its large capacity, which allows us to scale up the existing robotic storage space by a factor 6. This paper describes the modifications and investigations that allowed us to meet these scalability and performance challenges and provided some perspectives of Fermilab Mass Storage System.
Innovation in India: A review of past research and future directions

The rapid economic growth that India enjoyed following the start of its economic reforms in 1991 has led to a growing scholarly interest in Indian organizations and management practices. In this paper, we bring together extant yet dispersed research on one important and salient element of Indian economic growth: innovation. We organize and review the substantive innovation research in India based on its scope and focus, and find that it has yielded unique insights about India’s innovation systems and processes at both the institutional and firm levels. Three interesting trends emerge from this review of the literature. First, a growing body of research has started identifying innovation phenomena unique to India, such as “frugal innovation” and the related notion of “jugaad.” Second, a discernible arc in Indian innovation research can be observed, that is, a shift from a focus on the role of the state to the role of MNEs and Indian businesses in innovation. Finally, unlike much innovation research elsewhere, there appears to be significant interest in innovation that serves the need of the poor. We conclude with directions for future research on innovation within the Indian context.
On the Transfer of Chirality, Thermodynamic Stability, and Folding Characteristics of Stereoisomeric Gated Baskets

We have prepared and characterized chiral and gated baskets (P/M)-2, each containing a twisted P or M platform and three amidopyridine gates at the rim. Racemic (P/M)-2 was found (1H NMR and IR spectroscopy) to stay monomeric in CDCl3 at 298.0 K with the gates forming a seam of intramolecular N–H···N hydrogen bonds. In particular, the amidopyridine gates assume a unidirectional orientation, as directed by the twisted platform, that is, the P-shaped cup sets the amidopyridine gates in a counterclockwise (–) orientation of intramolecular N–H···N hydrogen bonds (VT 1H/13C NMR and M06-2X/6-31G*). The folded form of spacious (355 A3) and chiral (P/M)-2 undergoes an unfolding process in the presence of the polar [D6]DMSO solvent; specifically, with around 25 vol.-% of [D6]DMSO, the N–H···N hydrogen bonds at the rim are broken, thereby allowing a stochastic rotation of the amidopyridine gates about the rim. Interestingly, the thermal stability of folded (P/M)-2 is good with only a small fraction of unfolded state(s) forming at 104 °C in o-xylene.
Crystalline Two‐Dimensional DNA‐Origami Arrays

Nanotechnology aims to organize matter with the highest possible accuracy and control. Such control will lead to nanoelectronics, nanorobotics, programmable chemical synthesis, scaffolded crystals, and nanoscale systems responsive to their environments. Structural DNA nanotechnology1 is one of the most powerful routes to this goal. It combines robust branched DNA species with the control of affinity and structure2 inherent in the programmability of sticky ends. The successes of structural DNA nanotechnology include the formation of objects,3 2D crystals,4 3D crystals,5 nanomechanical devices,6 and various combinations of these species (e.g., ref. 7). DNA origami8 is arguably the most effective way of producing a large addressable area on a 2D DNA surface. This method entails the combination of a long single strand (typically M13 single-stranded form, 7249 nucleotides) with about ~250 staple strands to define its shape and patterning. With a pixilation estimated at about 6 nm,8 it is possible to build patterns with about 100 addressable points within a definable shape in an area of about 10,000 nm2. Many investigators have sought unsuccessfully to increase the useful size of 2D origami units by forming crystals of individual origami tiles.0 Here, we report the 2D crystallization of origami tiles to yield a 2D array with dimensions 2–3 microns on an edge. This size is likely to be large enough to connect bottom-up methods of patterning with top-down approaches.