cssi/SciSciGPT-SciSciNet huggingface dataset:
Implementation of the Federal Performance Framework under Presidents Obama and Trump: A Comparative Analysis of Agency Strategic Plans

Strategic plans are a foundational element of the Federal Performance Framework introduced by the U.S. Office of Management and Budget (OMB) in 2012 to encourage agency implementation of the GPRA M...
Combined immune checkpoint blockade and radiotherapy induces durable remission in relapsed natural killer/T-cell lymphoma: a case report and review of the literature.

Extranodal natural killer/T-cell lymphoma is a rare, aggressive non-Hodgkin lymphoma that is treated upfront mostly with L-asparaginase containing regimens. Relapsed extranodal natural killer/T-cell lymphoma is associated with a poor prognosis, and there is no established standard of care. We report the case of a 72 year-old white male with a distant extranasal relapse of extranodal natural killer/T-cell lymphoma that has been managed successfully with a combination of radiation and immune checkpoint blockade with pembrolizumab. Pseudoprogression with new skin and bone lesions on positron emission tomography imaging was encountered during this Caucasian patient’s immunotherapy and was successfully managed with supportive care and continuation of immune checkpoint blockade. The patient has been in complete clinical, radiologic, and molecular remission for close to 3 years and has not had any immune-related adverse effects. Pseudoprogression is a clinical challenge that can be encountered while patients are treated with immunotherapy, and astute clinical acumen is needed for accurate management. We believe this is the longest duration of response to immune checkpoint blockade in relapsed extranodal natural killer/T-cell lymphoma reported to date in literature. There is a strong biologic rationale in combining radiation with immunotherapy. The optimal timing, dose, and duration of radiation combined with immunotherapy in extranodal natural killer/T-cell lymphoma need to be prospectively evaluated.
Changes in Prostate-Specific Antigen Testing Relative to the Revised US Preventive Services Task Force Recommendation on Prostate Cancer Screening.

Importance In April 2017, the US Preventive Services Task Force (USPSTF) published a draft guideline that reversed its 2012 guidance advising against prostate-specific antigen (PSA)–based screening for prostate cancer in all men (grade D), instead endorsing individual decision-making for men aged 55 to 69 years (grade C). Objective To evaluate changes in rates of PSA testing after revisions in the USPSTF guideline on prostate cancer screening. Design, Setting, and Participants This retrospective cohort study used deidentified claims data from Blue Cross Blue Shield beneficiaries aged 40 to 89 years from January 1, 2013, through December 31, 2019. Exposures Publication of the USPSTF’s draft (April 2017) and final (May 2018) recommendation on prostate cancer screening. Main Outcomes and Measures Age-adjusted rates of PSA testing in bimonthly periods were calculated, and PSA testing rates from calendar years before (January 1 to December 31, 2016) and after (January 1 to December 31, 2019) the guideline change were compared. Interrupted time series analyses were used to evaluate the association of the draft (April 2017) and published (May 2018) USPSTF guideline with rates of PSA testing. Changes in rates of PSA testing were further evaluated among beneficiaries within the age categories reflected in the guideline: 40 to 54 years, 55 to 69 years, and 70 to 89 years. Results The median number of eligible beneficiaries for each bimonthly period was 8 087 565 (range, 6 407 602-8 747 308), and the median age of all included eligible beneficiaries was 53 years (IQR, 47-59 years). Between 2016 and 2019, the mean (SD) rate of PSA testing increased from 32.5 (1.1) to 36.5 (1.1) tests per 100 person-years, a relative increase of 12.5% (95% CI, 1.1%-24.4%). During the same period, mean (SD) rates of PSA testing increased from 20.6 (0.8) to 22.7 (0.9) tests per 100 person-years among men aged 40 to 54 years (relative increase, 10.1%; 95% CI, −2.8% to 23.7%), from 49.8 (1.9) to 55.8 (1.8) tests per 100 person-years among men aged 55 to 69 years (relative increase, 12.1%; 95% CI, −0.2% to 25.2%), and from 38.0 (1.4) to 44.2 (1.4) tests per 100 person-years among men aged 70 to 89 years (relative increase, 16.2%; 95% CI, 4.2%-29.0%). Interrupted time series analysis revealed a significantly increasing trend of PSA testing after April 2017 among all beneficiaries (0.30 tests per 100 person-years for each bimonthly period;P Conclusions and Relevance This large national cohort study found that rates of PSA testing increased after the USPSTF’s draft statement in 2017, reversing trends seen after earlier guidance against PSA testing for all patients. Increased testing was also observed among older men, who may be less likely to benefit from prostate cancer screening.
Deflection of Circular Plate wiht Built-In Edges

The theory of elasticity is used to approximate the boundary conditions for a built-in edge for the problem of the bending of a clamped circular plate. The top and bottom surfaces are held in such a manner as to prevent vertical displacement, but they are smooth with respect to tangential shears. Loading is applied to the plate so as to insure antisymmetrical bending stresses. Results from the elasticity solution are compared with analogous solutions obtained from elementary plate theory and from a plate theory modified to include shear deformations.
Gaseous hydrogen embrittlement of aerospace materials

With the increasing use of hydrogen in the aerospace industries, there has been an increasing concern with the problem of gaseous hydrogen embrittlement. The problems have led to a rather large amount of research on the phenomenon. This paper reviews some of the results of this research and discusses possible mechanisms for the phenomenon.
Generation of synthetic structural magnetic resonance images for deep learning pre-training

Deep learning methods have significantly improved classification accuracy in different areas such as speech, object and text recognition. However, this field has only began to be explored in the brain imaging field, which differs from other fields in terms of the amount of data available, its data dimensionality and other factors. This paper proposes a methodology to generate an extensive synthetic structural magnetic resonance imaging (sMRI) dataset to be used at the pre-training stage of a shallow network model to address the issue of having a limited amount of data available. Our results show that by extending our dataset using 5,000 synthetic sMRI volumes for pretraining, which accounts to approximately 10 times the size of the original dataset, we can obtain a 5% average improvement on classification results compared to the regular approach on a schizophrenia dataset. While the use of synthetic sMRI data for pre-training has only been tested on a shallow network, this can be readily applied to deeper networks.
Modulatory and Command Interneurons for Behaviour

Modulatory neurons change the properties of synapses and neurons, and thereby change the excitability or performance of neural circuits. Command neurons activate specific neural circuits that mediate discrete behaviour patterns. By operating on command neurons, on the inputs that excite them and on the circuits that they excite, modulatory neurons can transform individual patterns of behaviour and ensembles of behaviour in an adaptive manner. Keywords: neuromodulation; stomatogastric nervous system; crustacea; spinal pattern generator; rhythmic motor pattern; reconfiguration; command neuron; mauthner neuron; lamprey; sensorimotor integration
Finite Deflections of Circular Membranes

The behavior of membrane-like structures is of interest in conjunction with problems concerning slack diaphragms, inflatable structures, explosive forming of metals, interpretation of hydrostatic bulge tests, and continuous analysis of cable nets. For rotationally symmetric loadings of initially flat elastic circular membranes (the subject of this note), the Foppl-Von Karman equations are usually used to carry out the stress and deformation analysis. These equations are valid for moderate rotations and deformations and small strains. The membrane form of the equations given by Reissner represents a generalization of the Foppl-Von Karman theory to the case of arbitrarily large rotations and deformations, while retaining the small strain assumption. The purpose of the present work is to obtain some solutions to the Reissner membrane equations and compare these results to those previously found from the Foppl-Von Karman equations.
On the Reaction between the Extracellular Ribonuclease of Bacillus amyloliquefaciens (Barnase) and Its Intracellular Inhibitor (Barstar)

Abstract It is shown that the interaction between barnase and its inhibitor barstar involves the formation of a one-to-one complex which dissociates only in the presence of strongly dissociating solvents.
GridTorrent framework: A High-performance data transfer and data sharing framework for scientific computing

Large amount of data that is often stored in many thousands of files is created as part of today’s geographically distributed scientific computation and collaboration environments. Managing and transferring large volumes of data sets present a significant challenge and are often a bottleneck in the scientific computing community. In this paper, we introduce an architecture to manage data distributions in a collaborative fashion through a GridTorrent Framework (GTF) whose data transfer mechanism inspired by Bittorrent. We present performance experiment data that compares our framework to parallel TCP (PTCP) and Bittorrent. Experimental results conducted suggest that using GridTorrent for large data set has significant advantages over parallel TCP in LAN and WAN type of computer networks.
The inhibition of glucosylceramide β-glucosidase and other acid hydrolases by nucleic acids

During the isolation of the activator protein for glucosylceramide beta-glucosidase, we found that certain column fractions contained an inhibitor of the enzyme. After separation from the activator protein by a DEAE-Sephacel column, the inhibitor was purified further with a Spehadex G-75 column. The u.v. absorption spectrum of the purified material was similar to that of nucleic acids and the protein content of the purified material was negligible. Furthermore the purified inhibitor reacted with orcinol but not with diphenylamine, and its inhibitory activity was completely destroyed by treatment with RNAases. It seems likely that the purified inhibitor was tRNA. Authentic RNA, tRNA and DNA had similar inhibitory effects on beta-glucosidase (Ki 17 micrograms/ml for tRNA, noncompetitive toward the substrate). The inhibitory effect of nucleic acids was not fully overcome by an excess amount of the activator protein, but phosphatidylserine could restore the activity to normal. Tests with several other hydrolases revealed that the inhibitory effect of nucleic acids was fairly general.
``Weak links'' in polysaccharide chains as related to modified groups

Celluloses of different origin are hydrolyzed at different rates in acid medium both in fiber form (heterogeneous process) and in solution (homogeneous process). On the basis of measurements for well purified samples of commercial wood and cotton celluloses, molecularly dissolved in concentrated phosphoric acid, it was recently proposed that the fact that initial rates of hydrolysis are higher for wood cellulose than for cotton cellulose is largely related to inductive effects from modified (electrophilic) groups, e.g., carboxyls and carbonyls. Some of these groups are no doubt introduced during purification processes involving oxidative bleaching. It is possible that some of the modified groups are of native origin, but they are few (less than one modified group for 400 glucose units). The probable mechanisms for the influence on the rate of hydrolysis of modified groups, e.g., inductive and steric effects, rearrangements of the ring structure, are discussed in relation to the present knowledge of polysaccharide reactions. The concepts of inductive effects are supported by evidence from the hydrolysis of hemicelluloses and other polysaccharides containing uronic acid groups.
Investigating the techno‐economic trade‐offs of hydrogen source using a response surface model of drop‐in biofuel production via bio‐oil upgrading

This study presents a parametric fitting of the economics of bio-oil stabilization and hydroprocessing to naphtha and diesel range blend fuel. The data is fit with a response surface model (RSM). Technical variables evaluated in this study are rate of bio-oil upgrading and natural gas input rate. Economic variables considered include bio-oil, natural gas, hydrogen, catalyst, capital, and fossil carbon costs. Our base case consists of a 1440 tonnes per day bio-oil upgrading biorefinery concept design for the production of naphtha and diesel range blend stock fuels. The RSM represents variation around this base case. The process model includes reforming, stabilization, and hydroprocessing sections. Total project investment for this concept is $171.5 million or $2.34 per gallon of bio-oil input capacity. This base case biorefinery generates 71.8 million gallons of fuel (5182 barrels per day) at a minimum fuel selling price (MFSP) of $2.48 per gallon. We investigated the techno-economic impacts of different hydrogen sources on the bio-oil upgrading process. Hydrogen from bio-oil reforming results in the lowest biofuel emissions but is not always economical. A portion of available bio-oil should be converted to hydrogen under two main conditions: the cost of hydrogen from bio-oil is lower than procuring hydrogen from other sources and the lost income due to a lower biofuel output; and/or when there is a market or policy constraint limiting fossil fuel use. Results indicate that to minimize fuel costs, the amount of bio-oil upgraded should decrease from ≥90% to 80% as bio-oil prices decline from $1.37 to $0.70 per gallon depending on market conditions. Carbon emission constrains such as those mandated by the Renewable Fuels Standard (RFS) could force bio-oil upgrading rates to less than 90%.
Oocyte-specific expression of mouse Zp-2: developmental regulation of the zona pellucida genes.

Abstract The zona pellucida surrounds all mammalian oocytes and plays a vital role at fertilization and in early development. The genes that code for two of the mouse zona proteins (ZP2 and ZP3) represent a developmentally regulated set of genes whose expression serves as markers of mouse oocyte growth and differentiation. We previously characterized the single-copy Zp-3 gene and showed that its expression is oocyte specific and restricted to a narrow window of oocyte development. We now define the Zp-2 gene transcript and show that it is coordinately expressed with Zp-3 only during the 2-week growth phase of oogenesis that occurs prior to ovulation. Like Zp-3, the expression of Zp-2 is restricted to oocytes, and, although not detectable in resting oocytes, both ZP2 and ZP3 transcripts accumulate to become very abundant messengers in 50-microns-diameter oocytes. Ovulated eggs contain ZP2 and ZP3 transcripts which are 200 nucleotides shorter than those found in growing oocytes and have an abundance of less than 5% of the peak levels. In an attempt to understand the molecular details associated with the developmentally regulated, tissue-specific gene expression of the zona genes, the Zp-2 genetic locus has been characterized and its 5' flanking sequences have been compared with those of Zp-3. Both genes contain three short (8- to 12-base-pair) DNA sequences of 80 to 88% identity located within 250 base pairs of their transcription start sites.
Scarcity and the Future of Politics

Assuming that political system is a resource-distribution mechanism, the author examines the possible effects of the predicted new age of scarcity on the system built on the assumption of continuing abundance of both energy and resource stocks. He does this by examining generally the relationship between the carrying-capacity (along a scarcity and abundance continuum) and the value-system (along a steady-state and growth-oriented continuum), and showing the possible outcomes of the interaction between the two.
Decreased transforming growth factor-(β) response and binding in insulin-independent teratoma-derived cell lines with increased tumorigenic properties

The mouse C3H teratoma-derived cell line 1246 is an adipogenic cell line which stringently requires insulin to proliferate and differentiate in defined medium. From this cell line an insulin-independent cell line called 1246-3A was isolated. It was found that, in contrast to 1246 cells, 1246-3A cells had lost the ability to differentiate and became tumorigenic when injected at a density of 10(6) cells/mouse into syngeneic host C3H mice. In addition, they produce in their culture medium transforming growth factor alpha- and beta-like polypeptides which stimulate their proliferation. Highly tumorigenic insulin-independent cell lines able to give rise to tumor when injected at a density of 10(4) cells/mouse were isolated by using an in vitro-in vivo shuttle technique. The highly tumorigenic cell lines have lost the response to TGF-beta 1. The binding of TGF-beta 1 to the nontumorigenic parent cell line or to cells displaying increased tumorigenic properties was investigated. The data presented here indicate that the increased tumorigenicity is accompanied by a progressive decrease of specific binding of TGF-beta 1 to the cells. However, the decreased number of cell surface TGF-beta 1 binding sites in the highly tumorigenic cells did not correlate with an increase in the secretion of TGF-beta protein by the tumorigenic cells, as all of TGF-beta produced by the cells was in a latent form. Affinity cross-linking experiments indicated that the 1246 cell line displayed several TGF-beta cross-linked molecular species (MW 140, 92, and 70 kDa). Increase of tumorigenicity was accompanied by a marked decrease in the intensity of the cross-linked bands, particularly of the 92 and 70 kDa species.
The effects of fractionated thermally oxidized corn oil on drug-metabolizing enzyme systems in the rat.

Corn oil samples were heated, with aeration, to 210°C for a total of 5 hr. Both fresh and oxidized samples were urea-fractionated and the individual fractions were administered to male Sprague-Dawley rats by gastric intubation. The effects of urea adducts, adduct-free fractions, non-saponifiable fractions and unfractioned fresh and thermally oxidized oil samples on hepatic, intestinal and colonic drug-metabolizing enzymes were determined. The treatments had no significant effects on hepatic or intestinal drug-metabolizing or mixed-function oxidase activities. There was a significant (P < 0.05) increase in colonic UDP-glucuronyltransferase activity in rats treated with thermally oxidized corn oil, while the non-saponifiable fraction of the same sample decrease (P < 0.1) the activity of this enzyme. There was also a significant increase in the activity of colonic benzo[a]pyrene hydroxylase in rats treated with the non-adduct fraction or with urea adducts of the thermally oxidized corn oil. These data suggest the colon as a possible specific site for the alteration of mixed-function oxidase activities by products of thermally oxidized oils.
Rab1 Recruitment of p115 into a cis-SNARE Complex: Programming Budding COPII Vesicles for Fusion

The guanosine triphosphatase Rab1 regulates the transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus through interaction with effector molecules, but the molecular mechanisms by which this occurs are unknown. Here, the tethering factor p115 was shown to be a Rab1 effector that binds directly to activated Rab1. Rab1 recruited p115 to coat protein complex II (COPII) vesicles during budding from the endoplasmic reticulum, where it interacted with a select set of COPII vesicle-associated SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. We propose that Rab1-regulated assembly of functional effector-SNARE complexes defines a conserved molecular mechanism to coordinate recognition between subcellular compartments.
Study of metal adhesion on porous low-k dielectric using telephone cord buckling

Abstract The interfacial adhesion energy between metal and porous low-k dielectrics is an important parameter for the reliability study of back-end of line integration. In this work, we have observed the spontaneous film delamination with telephone cord morphology after 130 nm thick Ta was sputtered onto methyl silsesquioxane (MSQ) low-k dielectric. The highly compressive stress inside the Ta film is the driving force for the spontaneous buckling. The adhesion failure was identified to be at Ta/MSQ interface by using focused ion beam and scanning electron microscopy. Pinned circular blister model was applied to fit the buckling morphology. The interfacial adhesion energy was extracted to be 7.90 J/m2 at 87° phase angle. The Cu/MSQ interface was evaluated in a similar fashion by using a stressed overlayer Ta/Cu. The fracture energy was calculated to be 3.34 J/m2 with the similar phase angle. The results suggest that an adhesion promoter between Cu and low-k dielectrics is essential for a mechanically stable structure.
Krylov Iterative Methods and the Degraded Effectiveness of Diffusion Synthetic Acceleration for Multidimensional SN Calculations in Problems with Material Discontinuities

A loss in the effectiveness of diffusion synthetic acceleration (DSA) schemes has been observed with certain SN discretizations on two-dimensional Cartesian grids in the presence of material discon...
Differential gene expression in primary and recurrent carotid stenosis.

Abstract Apoptosis of the cellular components of complex atherosclerotic plaque may lead to plaque instability and rupture. In this study, five primary plaques and one recurrent fibrointimal lesion obtained from patients undergoing carotid endarterectomy for symptomatic carotid stenosis ⩾70% were analyzed by immunohistochemistry and cDNA microarray to identify gene expression patterns that may determine plaque susceptibility or resistance to apoptosis. Immunohistochemistry showed expression of active caspase 3, an effector of apoptosis, in macrophages and lymphocytes surrounding the lipid core, in smooth muscle cells in the fibrous cap, and media of primary plaques as well as in occasional smooth muscle cells in the recurrent lesion. Among the genes demonstrating increased expression in primary plaques were IGFR2, DR4, DAPK1, Bak, and ERK 1 and 2 and those showing decreased expression included the TNF receptors 1 and 2, akt1, and IGFBP3. When comparing the recurrent lesion to the normal tissue, the expression of 13 genes was decreased by 3-fold, including IGFBP2 and IGFBP3, and none were increased by more than 1.5-fold. The analysis of gene expression patterns in primary and recurrent stenotic lesions provides a powerful approach to identify the signaling pathways that alter cellular apoptotic patterns in such lesions.
The mechanism(s) of superoxide reduction by superoxide reductases in vitro and in vivo.

Exposure of obligately anaerobic bacteria and archaea to transiently aerobic or micro-aerobic growth habitats requires that these microorganisms protect against oxidative stress resulting from adventitious dioxygen reduction. Superoxide reductases (SORs), which catalyze reduction of superoxide to hydrogen peroxide, have been identified as one component of a novel oxidative stress protection system in anaerobic bacteria and archaea. SORs contain a unique non-heme [Fe(His)4(Cys)] active site. This Commentary addresses the mechanism of superoxide reduction catalyzed by this unique active site in SORs both in vitro and in vivo.
Applicability of photothermal radiometry for temperature measurement of semiconductors

This work explores the applicability of photothermal radiometry for the temperature measurement of semiconductors. Although this technique has been used to measure the surface temperature of metals, additional considerations must be given for temperature measurement of semiconductors due to electron-hole pair generation by the laser. Criteria for the applicability of photothermal radiometry to temperature measurement of semiconductors are established in this work and experimental results are presented for temperature measurement of a silicon sample in a radiation environment. This study demonstrates that photothermal radiometry can be applied to the temperature measurement of heavily-doped samples, but care must be taken to minimize the effect of electron-hole pair generation by choosing appropriate experimental conditions.
Respiratory deposition of hair spray aerosol and acute lung function changes

The respiratory deposition patterns of hair spray aerosol inhaled via oral and nasal passages were measured in nine nonsmoking human subjects. For the first hour following inhalation, small airway resistance changes were determined using the flow rate at 40% vital capacity during an expiratory flow effort following partial inspiration. Oral aerosol deposition averaged 52% of the total respiratory tract deposition, while the nasal deposition average was 97%. Decreases in the expiratory flow rate at 40% vital capacity averaged 16% for mouth breathing and 10% for nasal breathing. A majority of the subjects experienced cough, phlegm, a burning sensation in the throat, and chest tightness up to 2 h after mouth breathing; the symptoms occurred much less frequently following nasal breathing and persisted for a shorter time. The inhaled aerosol size distribution has a mass median diameter of 7.8 µm and a geometric standard deviation of 2.0.
Adhesions ring: a structural comparison between podosomes and the immune synapse

Podosomes and the immune synapse are integrin-mediated adhesive structures that share a common ring-like morphology. Both podosomes and immune synapses have a central core surrounded by a peripheral ring containing talin, vinculin and paxillin. Recent progress suggests significant parallels between the regulatory mechanisms that contribute to the formation of these adhesive structures. In this review, we compare the structures, functions and regulation of podosomes and the immune synapse.
Left lateralized white matter microstructure accounts for individual differences in reading ability and disability

Diffusion tensor imaging (DTI) was used to investigate the association between variation in white matter microstructure and individual differences in reading skill within children. Unlike previous DTI studies of reading, our sample examined children in both the average reading range as well as several children in the performance range of reading disability (RD). Results replicate previous findings of a strong correlation between fractional anisotropy (FA) values in a left temporo-parietal white matter region and standardized reading scores of typically developing children. Furthermore, FA values in this same region accounted for differences between children scoring in the average range and children scoring in the RD range, suggesting that the role of white matter tract microstructure is best characterized as an extreme range on a continuum of typical variation. Furthermore, significant correlations between working memory and frontal white matter tract regions were present in this same population, yet were demonstrated to be independent of the relationships found between reading and more posterior regions. Results form a “correlational double dissociation” that demonstrates domain specificity in the influence of white matter tract structures to individual differences in cognitive performance.
New chemotherapy agents in veterinary medicine

Several anticancer drugs have been added to the therapeutic armamentarium in recent years. Some of these agents are traditional drugs with a long history of use in human oncology. Increased sophistication in clinical trial design in veterinary oncology has allowed the incorporation of agents previously viewed as excessively toxic. Other agents have been developed more recently. This article summarizes the veterinary experience with two older alkylating agents, lomustine and streptozocin, and newer compounds ifosfamide and gemcitabine. The published literature regarding veterinary use of these agents is limited, and the reader is advised to contact a veterinary oncologist for current guidelines when contemplating use of these agents.
Testing Rodent Chemosterilants1

This paper presents some recommended procedures and test methods for evaluating rodent chemosterilants, including laboratory test procedures to determine acceptance and efficacy of such compounds, the kind of test animals to use, safety measures to adhere to, and methods of evaluating the efficacy of potential rodent chemosterilants in pen and field stations. Emphasis is on the Norway rat, Rattus norvegicus (Berkenhout).
Effects of Xenopus laevis Mitochondrial Single-stranded DNA-binding Protein on Primer-Template Binding and 3′→5′ Exonuclease Activity of DNA Polymerase γ

Mitochondrial DNA (mtDNA) is replicated by DNA polymerase gamma by a strand displacement mechanism involving mitochondrial single-stranded DNA-binding protein (mtSSB). mtSSB stimulates the overall rate of DNA synthesis on singly-primed M13 DNA mainly by stimulating the processivity of DNA synthesis rather than by stimulating primer recognition. We used electrophoretic mobility shift methods to study the effects of mtSSB on primer-template recognition by DNA pol gamma. Preliminary experiments showed that single mtSSB tetramers bind tightly to oligo(dT) single strands containing 32 to 48 residues. An oligonucleotide primer-template was designed with an 18-mer primer annealed to the 3'-portion of a 71-mer template containing 40 dT residues at its 5'-end as a binding site for mtSSB. DNA pol gamma bound to this primer-template either in the absence or presence of mtSSB in complexes that remained intact and enzymatically active following native gel electrophoresis. Association of mtSSB with the 5'-dT40-tail in the 18:71-mer primer-template reduced the binding of DNA polymerase gamma and the efficiency of primer extension. Binding of mtSSB to single-stranded DNA was also observed to block the action of the 3'-->5' exonuclease of DNA polymerase gamma. The size of fragments protected from 3'-->5' exonuclease trimming increases with increasing ionic strength in a manner consistent with the known salt dependence of the binding site size of Escherichia coli SSB.
MEMS Shear Stress Sensors: Promise and Progress

Abstract : This paper reviews existing microelectromechanical systems (MEMS)-based shear stress sensors. The promise and progress of MEMS scaling advantages to improve the spatial and temporal resolution and accuracy of shear stress measurement is critically reviewed. The advantages and limitations of existing devices are discussed. Finally, unresolved technical issues are summarized for future sensor development.
Product Family Concept Generation and Validation Through Predictive Decision Tree Data Mining and Multi-Level Optimization

The formulation of a product family requires extensive knowledge about the product market space and also the technical limitations of a company’s engineering design and manufacturing processes. We present a methodology to significantly reduce the computational time required to achieve an optimal product portfolio by eliminating the need for an exhaustive search of all possible product concepts. This is achieved through a data mining decision tree technique that generates a set of product concepts that are subsequently validated in the engineering design level using multi-level optimization techniques. The final optimal product portfolio evaluates products based on the following three criteria: 1) The ability to satisfy customer’s price and performance expectations (based on predictive model) defined here as the feasibility criterion. 2) The feasible set of products/variants validated at the engineering level must generate positive profit that we define as the optimality criterion. 3) The optimal set of products/variants should be a manageable size as defined by the enterprise decisions makers and should therefore not exceed the product portfolio limit. The strength of our work is to reveal the tremendous savings in time and resources that exist when data mining predictive techniques are applied to the formulation of an optimal product portfolio. Using data mining tree generation techniques, a customer response data set of 40,000 individual product preferences is narrowed down to 46 product family concepts and then validated through the multilevel engineering design response of feasible architectures. A cell phone example is presented and an optimal product portfolio solution is achieved that maximizes company profit, while concurrently satisfying customer product performance expectations.Copyright © 2007 by ASME
Scaling floating-body DRAM: Rationale for a refined 2T Cell

SOI floating-body (1T) DRAM cells (FBCs) are of much interest today mainly because of integration problems associated with the storage capacitor of conventional 1T/1C DRAM in sub-50nm CMOS technology. Two fully depleted (FD) FBCs appear to have the best scaling potential: the planar thin-BOX FD/SOI MOSFET [1], and the quasi-planar double-gate (DG) FinFET [2]. We first examine, via 2-D and 3-D numerical simulations, the scalability of these 1T DRAM cells as implied by the memory margin and its dependence on the transistor body (UTB) thickness (t Si ). Then, after showing and explaining significant margin losses in both devices as they are scaled to nanoscale gate lengths (L g ), we argue that better scalability is achievable in a 2T FBC, or floating-body/gate cell (FBGC), that we have previously presented [3], and we describe a novel refinement of the FBGC that yields very long charge/data retention times without undermining the good DRAM performance.
Selective induction of apoptosis by the cytotoxic analog AN-207 in cells expressing recombinant receptor for luteinizing hormone-releasing hormone

The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells. Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubicin (AN-201) conjugated to [d-Lys6] luteinizing hormone-releasing hormone (LH-RH) (AN-207), was demonstrated to be less toxic than the nonconjugated chemotherapeutic radical and significantly more active in slowing neoplastic cellular growth. In this study we investigate the molecular mechanisms underlying the cytotoxic action of AN-207. We stably transfected COS cells with a LH-RH receptor (LH-RH-Rc) mammalian expression vector and examined the effect of AN-207 on known markers of cellular apoptosis. Apoptotic induction by AN-207, as measured by Bax and Bcl-2 protein levels, was increased in stable cells that express LH-RH-Rc compared with parental cells. DNA fragmentation also was increased by AN-207 treatment when compared with AN-201. Clinically used LH-RH antagonists partially inhibited apoptotic Bax expression and DNA fragmentation induced by AN-207, and blocked AN-207 induced down-regulation of Bcl-2 steady-state protein levels. In cell proliferation studies, after 72 h AN-207 exhibited greater cytotoxicity than AN-201 at equivalent concentrations, in COS cells expressing LH-RH-Rc but not in parental COS cells. In addition, survival of LH-RH-Rc positive cells treated with AN-207 was partially restored by LH-RH antagonist. This study demonstrates the receptor-specific cytotoxic effect of 2-pyrrolinodoxorubicin conjugated to [d-Lys6] LH-RH, exerted through induction of apoptosis and modulation of Bax, Bcl-2, and DNA fragmentation.
An Occupational Therapy Approach to Persons with Chronic Fatigue Syndrome: Part Two, Assessment and Intervention

Chronic Fatigue Syndrome (CFS) is a highly disabling condition that significantly interferes with occupational life. Occupational therapy services are very relevant for this population. Yet, information about the assessment and treatment of CFS is almost absent from occupational therapy literature. As a result, few occupational therapists possess expertise in evaluating and providing therapy for this complex condition. This paper describes an approach to evaluating and providing services for individuals with CFS according to the Model of Human Occupation. This model offers an integrative means of understanding the synergistic and evolving relationships between motivation, values, roles, habits, functional capabilities, and the environment as they influence individuals with CFS, and it provides a framework for the types of changes required in these different domains during the rehabilitation process. A case study illustrates recommended assessment and intervention approaches.
Physical enhancement of dermatologic drug delivery: Iontophoresis and phonophoresis

Iontophoresis and phonophoresis are emerging technologies capable of enhancing drug penetration through the stratum corneum, the principal barrier to percutaneous absorption. With utilization of applied electric current or ultrasonic waves, respectively, iontophoresis and phonophoresis have shown efficacy in an increasing number of clinical applications. This article reviews the underlying principles, current status, and potential of iontophoresis and phonophoresis in dermatologic therapy.
Cellulose digestion in primitive hexapods: Effect of ingested antibiotics on gut microbial populations and gut cellulase levels in the firebrat, Thermobia domestica (Zygentoma, Lepismatidae)

Antibiotic feeding studies were conducted on the firebrat,Thermobia domestica (Zygentoma, Lepismatidae) to determine if the insect's gut cellulases were of insect or microbial origin. Firebrats were fed diets containing either nystatin, metronidazole, streptomycin, tetracycline, or an antibiotic cocktail consisting of all four antibiotics, and then their gut microbial populations and gut cellulase levels were monitored and compared with the gut microbial populations and gut cellulase levels in firebrats feeding on antibiotic-free diets. Each antibiotic significantly reduced the firebrat's gut micro-flora. Nystatin reduced the firebrat's viable gut fungi by 89%. Tetracycline and the antibiotic cocktail reduced the firebrat's viable gut bacteria by 81% and 67%, respectively, and metronidazole, streptomycin, tetracycline, and the antibiotic cocktail reduced the firebrat's total gut flora by 35%, 32%, 55%, and 64%, respectively. Although antibiotics significantly reduced the firebrat's viable and total gut flora, gut cellulase levels in firebrats fed antibiotics were not significantly different from those in firebrats on an antibiotic-free diet. Furthermore, microbial populations in the firebrat's gut decreased significantly over time, even in firebrats feeding on the antibiotic-free diet, without corresponding decreases in gut cellulase levels. Based on this evidence, we conclude that the gut cellulases of firebrats are of insect origin. This conclusion implies that symbiont-independent cellulose digestion is a primitive trait in insects and that symbiont-mediated cellulose digestion is a derived condition.
Background motion silences awareness of foreground change

When a set of objects changing in brightness, color, size, or shape moves across the visual field, the objects appear to stop changing [Suchow & Alvarez, 2011]. In previous work introducing this effect ("silencing"), we showed that its strength depends on speed: the faster the objects move, the less noticeable the change. (See the demos at http://bit.ly/cW0YCB.) In order to explain it, we had proposed the brief window hypothesis, which supposes that change detection relies on the success of local detectors---i.e., ones that monitor a fixed location in the visual field. Then, since a fast-moving object spends little time at any one location, each detector is afforded only a brief window in which to assess the changing object; this brevity may preclude the detection of change. Here, we show that the brief window hypothesis is wrong via a demonstration of silencing by background motion.
Coordination and decentralized cooperation of multiple mobile manipulators

Mobile manipulation capabilities are key to many new applications of robotics in space, underwater, construction, and service environments. This article discusses the ongoing effort at Stanford University for the development of multiple mobile manipulation systems and presents the basic models and methodologies for their analysis and control. This work builds on four methodologies we have previously developed for fixed-base manipulation: the Operational Space Formulation for task-oriented robot motion and force control; the Dextrous Dynamic Coordination of Macro/Mini structures for increased mechanical bandwidth of robot systems; the Augmented Object Model for the manipulation of objects in a robot system with multiple arms; and the Virtual Linkage Model for the characterization and control of internal forces in a multi-arm system. We present the extension of these methodologies to mobile manipulation systems and propose a new decentralized control structure for cooperative tasks. The article also discusses experimental results obtained with two holonomic mobile manipulation platforms we have designed and constructed at Stanford University. © 1996 John Wiley & Sons, Inc.
Lack of effect of DL-α-aminoadipate, an excitatory amino acid antagonist, on cat auditory nerve responses to sound

Abstract DL-α-aminoadipate, locally applied to the cat cochlea at concentrations of 1 mM and 10 mM, has no effect on the amplitude, latency or shape of click evoked auditory nerve compound action potentials at 5, 10 and 40 dB above threshold. It is concluded that the postsynaptic receptor of the hair cell — auditory nerve synapse is not of the N-methyl-D-aspartate, aspartate-prefering type. The possibility remains that the responses produced by exogenously applied glutamate and aspartate reported by others are the result of an interaction with a non-N-methyl-D-aspartate receptor at the hair cell-auditory nerve synapse or an extrasynaptic receptor.
A novel paradigm for assessing efficacies of potential antidotes against neurotoxins in mice.

Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD50 for cyanide elicited by the antidotes. This required the use of high doses of cyanide following pretreatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD50 determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately one h with minimal deaths was then selected. Using this paradigm, the current cyanide antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel antidotes against cyanide and should be equally applicable for evaluating putative antidotes for other neurotoxins.
The use of Medical Manpower in a Seventh Grade Drug Education Program

The use of medical and nursing students in an ongoing drug education program for the seventh grade is described. The results of a questionnaire given to the pupils are shown to demonstrate the effectiveness of this program with respect to both information transmission and the influencing of predicted future use. With the methods used, the program is shown to be objective and effective in stimulating rational drug “use-nonuse” decisions.
Intravitreal bevacizumab (AVASTIN®) in the treatment of diabetic macular oedema

Purpose To report visual acuity and anatomic response to intravitreal bevacizumab(IVB) injection in patients with persistent diabetic macular oedma(DMO). Methods Clinic notes of 19 patients (20eyes)were retrospectively evaluated. VA in ETDRS, central retinal thickness (CRT) and number of IVB (1.25mg/0.05mi)injections required was recorded. All patients underwent at least one FFA prior to IVB therapy. Re-treatment was PRN based on persistent or increase in fluid with drop of VA.Previous treatments included triamcinolone (IVTA),grid (micropulse and green) lasers.Follow up was every 6weeks. Results The mean age was 69.5±6.9 (range 59-81) years. All eyes had previous lasers. Seven eyes had both laser and IVTA. Mean number of bevacizuamab injection was 1.15. Three eyes received 2nd injection at mean of 13.3weeks (range 4-24) and 1 eye a 3rd injection at 9weeks. The average interval between the grid lasers and avastin therapy was 18.9weeks (SD=10.35). Mean follow up was 6.45±1.1 (6-9) months. The mean baseline VA was 42.51±16.24 and mean baseline CRT was 471±95.23. The mean change in vision at 1st 3rd and 6th month was +10.8, +11.8 and +13.2(p=0.0867) The mean reduction in CRT from baseline was -101.36µm,-167.7µm and-149.25µm at month 1, 3 and 6 respectively. (p= 0.00912). Three patients completed 9months follow up with a mean change in VA of +10.83 and CRT of-105µm. Twenty- five percent gained >15letters, 75% maintained stable vision and none lost more than 15 letters. No complications recorded. Conclusion Intravitreal bevacizumab 1.25mg was followed by improvement of vision and a significant reduction in persistent DMO. Further, larger studies are needed to evaluate the long term efficacy and safety of IVB on persistent diabetic macular oedema.
Monolithic nanoporous gold disks with large surface area and high-density plasmonic hot-spots

Plasmonic metal nanostructures have shown great potential in sensing, photovoltaics, imaging and biomedicine, principally due to enhancement of the local electric field by light-excited surface plasmons, the collective oscillation of conduction band electrons. Thin films of nanoporous gold have received a great deal of interest due to the unique 3- dimensional bicontinuous nanostructures with high specific surface area. However, in the form of semi-infinite thin films, nanoporous gold exhibits weak plasmonic extinction and little tunability in the plasmon resonance, because the pore size is much smaller than the wavelength of light. Here we show that by making nanoporous gold in the form of disks of sub-wavelength diameter and sub-100 nm thickness, these limitations can be overcome. Nanoporous gold disks (NPGDs) not only possess large specific surface area but also high-density, internal plasmonic “hot-spots” with impressive electric field enhancement, which greatly promotes plasmon-matter interaction as evidenced by spectral shifts in the surface plasmon resonance. In addition, the plasmonic resonance of NPGD can be easily tuned from 900 to 1850 nm by changing the disk diameter from 300 to 700 nm. The coupling between external and internal nanoarchitecture provides a potential design dimension for plasmonic engineering. The synergy of large specific surface area, high-density hot spots, and tunable plasmonics would profoundly impact applications where plasmonic nanoparticles and non-plasmonic mesoporous nanoparticles are currently employed, e.g., in in-vitro and in-vivo biosensing, molecular imaging, photothermal contrast agents, and molecular cargos.