cssi/SciSciGPT-SciSciNet huggingface dataset:
PDF2LaTeX: A Deep Learning System to Convert Mathematical Documents from PDF to LaTeX

The mathematical contents of scientific publications in PDF format cannot be easily analyzed by regular PDF parsers and OCR tools. In this paper, we propose a novel OCR system called PDF2LaTeX, which extracts math expressions and text in both postscript and image-based PDF files and translates them into LaTeX markup. As a preprocessing step, PDF2LaTeX first renders a PDF file into its image format, and then uses projection profile cutting (PPC) to analyze the page layout. The analysis of math expressions and text is based on a series of deep learning algorithms. First, it uses a convolutional neural network (CNN) as a binary classifier to detect math image blocks based on visual features. Next, it uses a conditional random field (CRF) to detect math-text boundaries by incorporating semantics and context information. In the end, the system uses two different models based on a CNN-LSTM neural network architecture to translate image blocks of math expressions and plaintext into the LaTeX representations. For testing, we created a new dataset composed of 102 PDF pages collected from publications on arXiv.org and compared the performance between PDF2LaTeX and the state-of-the-art commercial software InftyReader. The experiment results showed that the proposed system achieved a better recognition accuracy (81.1%) measured by the string edit distance between the predicted LaTeX and the ground truth.
The T3SS Effector Protease NleC Is Active within Citrobacter rodentium

Whether type III secretion system (T3SS) effector proteins encoded by Gram-negative bacterial pathogens have intra-bacterial activities is an important and emerging area of investigation. Gram-negative bacteria interact with their mammalian hosts by using secretion systems to inject virulence proteins directly into infected host cells. Many of these injected protein effectors are enzymes that modify the structure and inhibit the function of mammalian proteins. The underlying dogma is that T3SS effectors are inactive until they are injected into host cells, where they then fold into their active conformations. We previously observed that the T3SS effectors NleB and SseK1 glycosylate Citrobacter rodentium and Salmonella enterica proteins, respectively, leading to enhanced resistance to environmental stress. Here, we sought to extend these studies to determine whether the T3SS effector protease NleC is also active within C. rodentium. To do this, we expressed the best-characterized mammalian substrate of NleC, the NF-κB p65 subunit in C. rodentium and monitored its proteolytic cleavage as a function of NleC activity. Intra-bacterial p65 cleavage was strictly dependent upon NleC. A p65 mutant lacking the known CE cleavage motif was resistant to NleC. Thus, we conclude that, in addition to NleB, NleC is also enzymatically active within C. rodentium.
Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1 (NR4A2)

ABSTRACT The nuclear receptor-related 1 protein, Nurr1, is a transcription factor critical for the development and maintenance of dopamine-producing neurons in the substantia nigra pars compacta, a cell population that progressively loses the ability to make dopamine and degenerates in Parkinson’s disease. Recently, we demonstrated that Nurr1 binds directly to and is regulated by the endogenous dopamine metabolite 5,6-dihydroxyindole (DHI). Unfortunately, DHI is an unstable compound, and thus a poor tool for studying Nurr1 function. Here we report that 5-chloroindole, an unreactive analog of DHI, binds directly to the Nurr1 ligand binding domain with micromolar affinity and stimulates the activity of Nurr1, including the transcription of genes governing the synthesis and packaging of dopamine.
Socrates and Thrasymachus on Perfect and Imperfect Injustice

It is argued that the true definition of justice in Plato’s Republic appears not in Book IV but in Book I, where it is clear that justice is other-oriented or external rather than internal as per Book IV. Indeed, on Book IV’s definition, there is virtually no difference between justice and moderation. Considered here is a single argument between Socrates and Thrasymachus (351b-352d), in which Socrates contends that imperfect injustice is “stronger” than perfect. Rather than producing a just group, the justice between members of a group strengthens the injustice of a group whose external project is already unjust.
Radiocarbon Dates: Eastern Colorado

Neuman (1967) lists seven radiocarbon dates from archaeological sites in eastern Colorado. However, due to publication delays, his compila tion includes only those dates generally available through the first half of 1965. At the present time (fall 1968) there are at least 56 radiocarbon dates from some 36 localities in eastern Colorado (Fig. 1). Prior to the compilation of the present list, a preliminary listing of radiocarbon dates from eastern Colorado was assembled and distributed to some 15 individuals. Their comments and additions, in some cases pertaining to material not yet published, are sincerely appreciated. However, any errors or misrepresentations in the present listing are my sole responsibility. Due to terminological inconsistencies and the fact that some of the radiocarbon determinations are not yet described in published media, I will present the available dates under the following headings: Paleo-Indian, Archaic, Early Ceramic, Middle Ceramic, and Late Ceramic. As appro priate, specific dates will receive comment.
Novel approaches to improving disease resistance in plants

Improved disease and pest resistance in plants is one of the more lucrative possibilities for utilization of recombinant DNA technology. This optimism results from recent increases in our knowledge of how naturally occurring disease resistance functions and to the fact that modulation of resistance expression is often controlled by single dominant alleles in plants. Historically these disease resistance genes could only be transferred between plants that can be intercrossed. Recently, however, technologies have been developed which permit gene transfer between taxonomically diverse plants by (i) protoplast fusion and selection of somatic recombinants or (ii) introduction of specific DNA sequence into plants via Ti plasmid vectors. Disease resistance genes have not yet been isolated to permit full utilization of these technologies, but several rationales are being pursued in attempts to molecularly clone them. These include the use of transposable elements to tag resistance gene sequences, the screening of c-DNA libraries from inoculated plants and the use of specific pathogen metabolites called elicitors as probes to detect the protein products of plant disease resistance genes.
Discrimination issues affecting the selection of salespeople in the United States

Traditionally, European firms have opted for hiring Americans to sell their products in the USA. However, the recent enactment of the Americans with Disabilities Act (ADA) highlights the growing complexity of discrimination regulation in the USA. Even before enactment of this landmark legislation the number of federal suits alleging workplace discrimination in the USA was staggering. Claims that in this litigious environment, European companies that choose to hire Americans to sell their products in the USA must be aware of the legal implications of all selection practices. Aims to provide the sales manager with the basic information needed for a comprehensive orientation to non‐discriminatory selection practices in the USA.
A High-Performance Neutron Time Correlation Counter

A new, high-performance neutron time correlation, or coincidence, counter has been developed for the measurement of nuclear materials. This detector is an improvement over the high-level neutron coincidence counter that was used previously in that it has better counting rate capability, electronic stability, noise resistance, uniform counting zone, and portability. The system uses /sup 3/He gas tubes coupled to the shift register coincidence electronics through a new hybrid charge-sensitive preamplifier/discriminator. Counting rates of 1.3 MHz have been obtained and a counting stability of 0.002% has been measured. The system has been applied to the assay of plutonium content in metal, PuO/sub 2/, and PuF/sub 4/, as well as in uraniumplutonium mixtures.
Political Contingencies of Witchcraft in Colonial Central Africa: Culture and the State in Marxist Theory

RESUMEL'article est une analyse critique de la notion de “legitimite” de Max Weber et des concepts marxistes apparentes, ideologie, hegemonie et fausse conscience, qui servent a expliquer le maintien d'un ordre politique. L'auteur attire l'attention sur la place qu'y tiennent les facteurs culturels et surtout les routines de pensee et d'action.Appliquee aux attitudes face a la magie et a la sorcellerie, l'etude montre que la colonisation britannique, tout en etant consciente de sa “mission civilisatrice”, fut contrainte de s'appuyer sur les systemes politiques locaux et de se rapprocher des cultures autochtones.
Stoichiometric Foundation of Large-Scale Biochemical System Analysis

The traditional approach to unraveling functions of a biochemical system is to study isolated enzymes and/or complexes, and to determine their kinetic mechanisms for catalyzing given biochemical reactions along with estimates of the associated parameter values [41,47]. While this reductionist approach has been fruitful, the buzzwords of the present are integration and systems. One of the important tasks in current computational biology is to assimilate and integrate the behaviour of interacting systems of many enzymes and reactants. Understanding of such systems lays the foundation for modelling and simulation of whole-cell systems, a defining goal of the current era of biomedical science.
Performance characteristics of a second generation micro crystal element (MiCE2) detector

This work reports on performance characteristics of a second generation micro crystal element (MiCE2) detector for a dedicated PET system to image mice. Our MiCE2 detector consists of a 22/spl times/22, array of 0.8/spl times/0.8/spl times/6 mm mixed lutetium silicate (MLS) crystals. Five sides of the crystals are polished with one 0.80.8 mm face left unpolished. The crystals are placed within a grid made of a highly reflective polymer film material. The grid optically isolates the crystals and also functions as a reflective wrap. The detector unit is directly coupled to a 6+6 cross-anode position sensitive PMT. The crystal of interaction is determined using simple Anger style logic. Crystal maps have been created for a 22/spl times/22 crystal array. All 484 crystals are visualized in the full detector module's crystal map. The average peak to valley ratio between neighboring crystals was 6.4. There was greater than a factor of two difference between the photopeak energy channel for high versus low light collection efficiency crystals. The energy resolution for individual crystals varied between 14% and 23%. Partial detector arrays (e.g., 22/spl times/4) using 0.8/spl times/0.8/spl times/10 mm crystals with an etched surface finish have also been built and decoded. A miniature line source phantom consisting of five 1 mm diameter lines with 2 mm center-to-center spacing has been imaged using two partial MiCE2 detectors. All lines are distinguished and. the average peak to valley ratio between lines is 2.7.
Nonlinear planning: a rigorous reconstruction

The problem of achieving several goals simultaneously lias been central to domain-independent planning research, the nonlinear constraint-posting approach has been most successful Previous planners of this type ''. 4, 5. f> have been complicated, heuristic, and ill-defined. 1 have combined and distilled the state of the art into a simple, precise, implemented algorithm (TWEAK) which I have proved correct and complete The simplicity and rigor of this algorithm illuminate the workings of previous planners, the range of applicability of current planning technology, and suggest future directions for research. This paper presents the mathematical foundations for non-linear planning; due to space limitations, I have omitted proofs, some detail, and much discussion These appear in 1
Overview: Gastrointestinal Manifestations and Management

Systemic sclerosis (SSc, scleroderma) is a chronic, connective tissue disease characterized by vascular damage and fibrosis of the skin and internal organs including the gastrointestinal (GI) tract. After skin involvement, the GI tract is the second most commonly involved organ system with the esophagus being the most frequent segment involved. Involvement of the stomach, small intestine, colon, and anorectum is less common but may lead to severe complications and debility. Ultimately, over 80% of individuals with scleroderma will experience a change in normal GI function (Szamosi S, Szekanecz Z, Szucs G. Gastrointestinal manifestations in Hungarian scleroderma patients. Rheumatol Int. 2006;26:1120–4; Weston S, Thumshirn M, Wiste J, et al. Clinical and upper gastrointestinal motility features in systemic sclerosis and related disorders. Am J Gastroenterol. 1998;93:1085–9).
"Flipped" patterns of lactate dehydrogenase isoenzymes in serum of elite college basketball players.

We kinetically measured total lactate dehydrogenase (LD, EC 1.1.1.27), total creatine kinase (CK, EC 2.7.3.2), and aspartate aminotransferase (AST, EC 2.6.1.1.) in 16 elite college basketball players, before the competition season and not in close temporal relation to near-maximal exercise, and in 17 healthy non-athlete controls. LD isoenzymes were determined by both electrophoretic and immunoprecipitation methods. CK-MB isoenzyme was measured electrophoretically. We found significantly higher mean LD-1 values and LD-1/LD-2 ratios in the players than the controls: 31.6 (SD 3.7)% vs 25.8 (SD 3.2)% (P less than 0.005) and 1.1 (SD 0.13) vs 0.87 (SD 0.16) (P less than 0.001), respectively. A "flipped" LD pattern (LD-1 greater than LD-2) was found in half the players and in six of the eight black athletes, but in only two of the control group and in none of the black controls. Mean CK activity in serum exceeded normal values in the serum of the athletes and was higher in comparison with the control group [274 (SD 156) vs 103 (SD 82) U/L]. Mean CK was significantly higher in the eight athletes with the flipped LD pattern than in those with LD-1 less than LD-2 [322 (SD 163) vs 180 (SD 98) U/L; P = 0.05], and also in comparison with CK in the two controls with flipped LD pattern. We saw no significant difference in mean CK between the nine players with normal immunochemical LD-1/LD ratios and the seven players with above-normal ratios. CK-MB was not detected in either athletes or controls. None of the players had any clinical or electrocardiographic evidence for myocardial ischemia or infarction. Evidently the flipped LD pattern usually found in patients with acute myocardial infarction and reported in some athletes after extreme exercise such as ultra-marathon running may also be found in athletes who are in their "basal fitness shape" but who are not involved in competitive physical activity.
The effects of α-cellulose extraction and blue-stain fungus on retrospective studies of carbon and oxygen isotope variation in live and dead trees

Tree-ring carbon and oxygen isotope ratios from live and recently dead trees may reveal important mechanisms of tree mortality. However, wood decay in dead trees may alter the δ13C and δ18O values of whole wood obscuring the isotopic signal associated with factors leading up to and including physiological death. We examined whole sapwood and α-cellulose from live and dead specimens of ponderosa pine (Pinus ponderosa), one-seed juniper (Juniperous monosperma), pinon pine (Pinus edulis) and white fir (Abies concolor), including those with fungal growth and beetle frass in the wood, to determine if α-cellulose extraction is necessary for the accurate interpretation of isotopic compositions in the dead trees. We found that the offset between the δ13C or δ18O values of α-cellulose and whole wood was the same for both live and dead trees across a large range of inter-annual and regional climate differences. The method of α-cellulose extraction, whether Leavitt-Danzer or Standard Brendel modified for small samples, imparts significant differences in the δ13C (up to 0.4‰) and δ18O (up to 1.2‰) of α-cellulose, as reported by other studies. There was no effect of beetle frass or blue-stain fungus (Ophiostoma) on the δ13C and δ18O of whole wood or α-cellulose. The relationships between whole wood and α-cellulose δ13C for ponderosa, pinon and juniper yielded slopes of ~1, while the relationship between δ18O of whole wood and α-cellulose was less clear. We conclude that there are few analytical or sampling obstacles to retrospective studies of isotopic patterns of tree mortality in forests of the western United States.
Material characterization uncertainty analysis for Rectangular to Square Waveguide

The advent of physically realizable bi-isotropic, anisotropic and bi-anisotropic media poses new challenges to material characterization techniques and requires better measurement uncertainty understanding to accurately quantify complex media performance. A Waveguide Rectangular to Waveguide Square (WRWS) biaxial anisotropic material measurement capability has been developed to evaluate 3-D printed anisotropic samples. The X-band WRWS system has tapered waveguide transitions that mount to a cubic sample holder for 2-port network analyzer measurements. The WRWS transitions adapt WR-90 rectangular waveguides to the square aperture of a cubic sample holder without exciting higher order modes. A closed form, analytic biaxial anisotropic material parameter extraction methodology has been developed to evaluate a 3-D printed cubic biaxial anisotropic sample about its six orientations.
Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. “Khella”) are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of A. visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of CaOx deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.
MyLifeBits: a personal database for everything

MyLifeBits is a system that began in 2001 to explore the use of SQL to store all personal information found in PCs. The system initially focused on capturing and storing scanned and encoded archival material e.g. articles, books, music, photos, and video as well as everything born digital e.g. office documents, email, digital photos. It evolved to have a goal of storing everything that could be captured. The later included web pages, phone calls, meetings, room conversations, keystrokes and mouse clicks for every active screen or document, and all the 1-2 thousand photos that SenseCam captures every day. In 2006 the software platform is used for research including real time data collection, advanced SenseCams, and particular applications e.g. health and wellness. This article expands on the January 2006, CACM publication of the same name. MyLifeBits features, functions, and use experience are given in the main body, followed by an appendix of future research and product needs that the research has identified.
Role of attached polymer chains on the vibrational relaxation of a C 60 fullerene in aqueous solution

We have investigated the vibrational relaxation of a bare ${\mathrm{C}}_{60}$ fullerene and ${\mathrm{C}}_{60}$ fullerenes with covalently attached poly (ethylene oxide) (PEO) chains in aqueous solution using classical molecular dynamics simulations. The rate of transfer of vibrational energy from the excited fullerene to the surrounding water was found to be slow for the bare fullerene, with a vibrational relaxation time of approaching $200\phantom{\rule{0.3em}{0ex}}\mathrm{ps}$. Attachment of a single short PEO chain $({M}_{W}=250)$, yielding ${\mathrm{C}}_{60}$-PEO, was found to decrease the vibrational relaxation time by about a factor 5, while the vibrational relaxation time for a fullerene with six attached PEO chains, or ${\mathrm{C}}_{60}\text{\ensuremath{-}}{(\mathrm{PEO})}_{6}$, exhibited approximately 25 times faster vibrational relaxation than the bare fullerene. The temperature of the attached PEO chain(s) was found to increase during the vibrational relaxation of the fullerene, but remained well below that of the fullerene, indicating that the rate limiting step in vibrational relaxation of ${\mathrm{C}}_{60}$-PEO is energy transfer from the fullerene to the attached PEO.
Properties of the cysteine residues and iron-sulfur cluster of the assimilatory 5'-adenylyl sulfate reductase from Pseudomonas aeruginosa.

APS reductase from Pseudomonas aeruginosa has been shown to contain a [4Fe-4S] cluster. Thiol determinations and site-directed mutagenesis studies indicate that the single [4Fe-4S] cluster contains only three cysteine ligands, instead of the more typical arrangement in which clusters are bound to the protein by four cysteines. Resonance Raman studies in the Fe-S stretching region are also consistent with the presence of a redox-inert [4Fe-45] 2 + cluster with three cysteinate ligands and indicate that the fourth ligand is likely to be an oxygen-containing species. This conclusion is supported by resonance Raman and electron paramagnetic resonance (EPR) evidence for near stoichiometric conversion of the cluster to a [3Fe-4S] + form by treatment with a 3-fold excess of ferricyanide. Site-directed mutagenesis experiments have identified Cysl39, Cys228, and Cys231 as ligands to the cluster. The remaining two cysteines present in the enzyme, Cys140 and Cys256, form a redox-active disulfide/dithiol couple (E m = -300 mV at pH 7.0) that appears to play a role in the catalytic mechanism of the enzyme.
Prognostic factors in node-negative male breast cancer.

Abstract Background Male breast cancer has traditionally been compared with female breast cancer, using the same staging system and prognostic indicators. A variety of histochemical and pathologic factors commonly used in node-negative female breast cancer were applied to 18 node-negative male breast cancers to assess their relevance to survival. Patients and Methods A slide review was performed for nuclear grade, lymphocytic infiltration, and lymphatic and vascular invasion. Flow cytometry was available on all the specimens. Immunohistochemistry was used to assess p53, estrogen receptors (ERs), cathepsin D, Ki-67, and c-erbB-2 (HER2/ neu ). A clinical correlation was performed based on chart reviews and phone interviews, recording demographics, treatment, and long-term survival. Results The average age at diagnosis was 64 years (range, 34-85 years). There were 15 T1 lesions, 2 T2 lesions, and 1 T3 lesion. All patients had a modified radical mastectomy. None received radiation therapy. The mean follow-up was 73 months. Three patients died of their disease (17.6%), 2 patients died from unrelated reasons, 1 patient was lost to follow-up, and the other 12 patients are alive with no evidence of disease. The actuarial 5-year survival was 83%. Estrogen receptor and HER2/ neu overexpression were significantly more predominant in male breast cancer than in female breast cancer. Estrogen receptor positivity was present in 17 of 18 patients and HER2/ neu overexpression in 10 of 18. A positive ER status and overexpression of cathepsin or p53 were correlated with a better survival, but only ER ( P = 0.026) and p53 ( P = 0.023) reached statistical significance. Conclusion In this study, ER status was the only commonly used prognostic marker for female breast cancer found to be applicable in node-negative male breast cancer.
Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding.

Heme oxygenase (HO) catalyzes the O2- and NADPH-dependent conversion of heme to biliverdin, CO, and iron. The two forms of HO (HO-1 and HO-2) share similar physical properties but are differentially regulated and exhibit dissimilar physiological roles and tissue distributions. Unlike HO-1, HO-2 contains heme regulatory motifs (HRMs) (McCoubrey, W. K., Jr., Huang, T. J., and Maines, M. D. (1997) J. Biol. Chem. 272, 12568–12574). Here we describe UV-visible, EPR, and differential scanning calorimetry experiments on human HO-2 variants containing single, double, and triple mutations in the HRMs. Oxidized HO-2, which contains an intramolecular disulfide bond linking Cys265 of HRM1 and Cys282 of HRM2, binds heme tightly. Reduction of the disulfide bond increases the Kd for ferric heme from 0.03 to 0.3 μm, which is much higher than the concentration of the free heme pool in cells. Although the HRMs markedly affect the Kd for heme, they do not alter the kcat for heme degradation and do not bind additional hemes. Because HO-2 plays a key role in CO generation and heme homeostasis, reduction of the disulfide bond would be expected to increase intracellular free heme and decrease CO concentrations. Thus, we propose that the HRMs in HO-2 constitute a thiol/disulfide redox switch that regulates the myriad physiological functions of HO-2, including its involvement in the hypoxic response in the carotid body, which involves interactions with a Ca2+-activated potassium channel.
Multiteam, Multiproject Research and Development Planning with GERT

This paper reports on a simulation study of multiple research and development projects that are worked on concurrently and sequentially by more than one research team. The technique employed in the modeling and simulation effort was GERT, which was used because of its capability to incorporate the probabilistic outcomes and feedback loops common to R&D projects. The GERT Graphical Evaluation and Review Technique includes the modeling of systems in network form and analysis through simulation. It is an important example of technological spin-off from space science research. GERT provides the capability to model and analyze networks of a very general form. Some of the features included in GERT networking are probabilistic branching stochastic models, network looping feedback loops, multiple sink nodes multiple outcomes, multiple node realizations repeat events, and multiple probability distributions assigned to activity times. GERT networks are typically analyzed using the GERTS IIIZ simulation package, which provides statistics on project times and cost. Results of the simulation included statistical data on individual project duration and cost as well as overall network time and cost. These results were employed to provide management with an evaluation of different model configurations, prepare overall time and cost estimates as inputs to contract negotiations and to plan and schedule manpower, equipment and capital. Sensitivity analysts was employed to determine key stages in the R&D process where changes in success-failing probabilities might reduce network time and cost. Implementation experiences validated the model as satisfactory with the exception of several minor problems.
The role of genomics in the management of advanced bladder cancer.

Advanced bladder cancer (ABC) is an aggressive malignancy with a poor prognosis. For the last 30 years, the standard of care for this disease has consisted of combination chemotherapy with a platinum-containing regimen as first-line therapy. Cisplatin is the most active cytotoxic agent against bladder cancer, but because of competing comorbidities, many patients are ineligible for this agent and instead receive carboplatin. The two-drug regimen of cisplatin and gemcitabine was found to be better tolerated and have comparable efficacy as the four-drug regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in a randomized study of patients with advanced disease. Therefore, cisplatin (or carboplatin) and gemcitabine is the most commonly used first-line regimen in this setting. No agents have been approved by the Food and Drug Administration (FDA) for second-line therapy in ABC. If patients are eligible for additional systemic treatment at the time of progression, options include single-agent therapy such as a taxane or pemetrexed, though given the lack of standard approaches participation in a clinical trial should be strongly encouraged. Recent molecular characterization of ABC reveals significant genetic heterogeneity and actionable genomic alterations in the majority of tumors. Emerging therapies may effectively target known molecular drivers of ABC, including the FGFR2, EGFR/HER2, VEGF, MET, and PI3/AKT/mTOR pathways. Reports of dramatic and prolonged responses to targeted therapy provide additional support for the use of genome sequencing in the rationale selection of treatment for subsets of patients. The current focus of clinical trial development is to design molecularly driven studies that “match” tumors with driver mutations and appropriate targeted therapies rather than a “one-size-fits-all” approach based on clinical and pathologic parameters of disease. The hope of patients and clinicians alike is that this therapeutic approach combined with novel agents may usher in a new era of effective treatments for patients with ABC.
Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation.

Purpose To present the clinical data of 35 patients with T3 unresectable hepatocellular carcinoma (HCC) that were treated with 90Y with the specific intent of downstaging to resection, radiofrequency ablation (RFA) candidate, United Network for Organ Sharing (UNOS) stage T2 or liver transplantation. Materials and Methods One hundred fifty patients with unresectable HCC were treated with 90Y microspheres. Of these, 35 patients were UNOS stage T3 at the time of treatment. Patients were followed for clinical toxicities, alterations in model for end-stage-liver disease (MELD) score, tumor response, downstaging to RFA, resection, transplantation, and survival. Results Nineteen of 34 patients (56%) were successfully downstaged from T3 to T2 following treatment. 11 of 34 (32%) patients treated were downstaged to target lesions measuring 3.0 cm or less. Twenty-three of 35 (66%) were downstaged to either T2 status, lesion < 3.0 cm (RFA candidate), or resection. Seventeen of 34 (50%) had an objective tumor response by WHO criteria. Eight patients (23%) were successfully downstaged and underwent OLT following treatment. 1, 2, and 3-year survival was 84%, 54%, and 27%, respectively. Median survival by Kaplan–Meier analysis for the entire cohort was 800 days. Conclusion These data suggest that intra-arterial 90Y microspheres can be used as a bridge to transplantation, surgical resection, or RFA. J. Surg. Oncol. 2006;94:572–586. © 2006 Wiley-Liss, Inc.
Chronic pain in individuals with previously undiagnosed autistic spectrum disorders.

Abstract The aim of this article is to heighten clinician awareness by describing 2 patients with signs and symptoms of a possible autistic disorder. Autistic spectrum disorders are neurodevelopmental disorders characterized by impairment in reciprocal social interaction skills or communication skills and/or by the presence of stereotyped behavior, interests, and activities. Pain can be the initial presenting symptom for individuals with a previously undiagnosed autistic spectrum disorder. Two case presentations show indicators, such as reported sensory abnormalities, impaired social behaviors, and unusual interests, that should lead the physician to consider a referral for further evaluation. An accurate diagnosis of autism or related disorder can lead to a greater understanding of the nature of the patient's pain, as well as to more appropriate and effective treatment strategies. In addition, such patients might benefit from therapeutic interventions to improve overall functioning and decrease distress and, consequently, to decrease pain and other symptoms. Finally, autism research might inform pain researchers on topics such as neurobiology, development, and treatment of chronic pain disorders. Perspective Pain experts might be underrecognizing signs and symptoms of autistic spectrum disorders (ASDs) in their patients. Clinical evaluation for ASDs should be considered in patients with specific unusual characteristics. Research on the topic of ASDs and pain is encouraged.
Invasive Pathogens At Alpine Treeline: Consequences for Treeline Dynamics

The potential impact of invasive forest pathogens on alpine treeline dynamics has not previously been considered. Whitebark pine (Pinus albicaulis), a foundation and keystone species of subalpine forests and major component of alpine treeline in the northern Rocky Mountains of the United States and southern Canada, is infected nearly range-wide by the exotic pathogen Cronartium ribicola, which causes white pine blister rust. A major component of treeline in the northern Rocky Mountains, whitebark pine initiates tree islands on the eastern slope in northwestern Montana more than any other conifer species. Blister rust infects whitebark pine throughout the region, and both infection and mortality are already evident at treeline. We discuss the cascading ecological effects of the loss of treeline whitebark pine and expected changes in landscape vegetation patterns. Potential implications of the loss of whitebark pine for northwestern Montana treelines are examined in the context of climate change within a co...
Myotonic dystrophy type 1 coexisting with myasthenia gravis and thymoma

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multisystemic disorder that may rarely be associated with benign and malignant neoplasms. Cases of both thymoma and myasthenia gravis in association with DM1 are extremely rare. A literature review revealed only three prior reports. We present a 51-year-old man with a family history of DM1 and fluctuating diplopia and ptosis, who was found to have acetylcholine receptor-binding antibodies, thymoma, and a clinical presentation compatible with ocular myasthenia gravis as well as positive genetic testing for DM1. Needle electromyographic (EMG) study demonstrated diffuse runs of myotonic discharges in multiple muscles, consistent with the diagnosis of DM1. Single-fiber EMG showed both increased jitter and blocking. Due to somatic instability, which has been shown previously in DM1, the myotonin protein kinase (DMPK) gene appears to act as a tumor suppressor. Therefore, abnormal CTG repeat expansions in the gene could lead to the development of thymoma and myasthenia gravis.
The Size-Dependence of 1,5-Diphenyl-3-naphthyl-2-pyrazoline Nanocrystals.

1,5-Diphenyl-3-naphthyl-2-pyrazoline nanocrystals with different sizes from 400 to 20 nm were prepared by the reprecipitation method. As the nanocrystal size decreased, the nanocrystal absorption peak was observed to shift to high-energy side due to size effect, and in the same period the peak shape changed from asymmetric to symmetric due to the gradual disappearance of the aggregate absorption.
Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance

The increasing incidence and prevalence of multidrug resistance (MDR) among contemporary Gram-negative bacteria represents a significant threat to human health. Since their discovery, β-lactam antibiotics are a major component of the armamentarium against these serious pathogens. Unfortunately, a wide range of β-lactamase enzymes have emerged that are capable of inactivating these powerful drugs. In the past 30 years, a major advancement in the battle against microbes has been the development of β-lactamase inhibitors, which restore the efficacy of β-lactam antibiotics (e.g., ampicillin/sulbactam, amoxicillin/clavulanate, ticarcillin/clavulanate, and piperacillin/tazobactam). Unfortunately, many newly discovered β-lactamases are not inactivated by currently available inhibitors. Is there hope? For the first time in many years, we can anticipate the development and introduction into clinical practice of novel inhibitors. Although these inhibitors may still not be effective for all β-lactamases, their introduction is still welcome. This review focuses on the novel β-lactamase inhibitors that are closest to being introduced in the clinic.
Lean Enablers for Systems Engineering

Systems Engineering (SE) is regarded as a sound practice but not always delivered effectively, as documented in recent NASA, GAO, and DoD studies. Lean Thinking is the holistic work system credited for the extraordinary rise of Toyota to the most profitable and the largest auto company in the world. Lean Thinking has been successfully applied in other work fields such as general manufacturing, aerospace, healthcare, and service industries. The emerging field of Lean Systems Engineering (LSE) is the application of Lean principles, practices, and tools to SE and to the related aspects of enterprise management (EM) in order to enhance the delivery of value (which is defined as flawless delivery of product or mission with satisfaction of all stakeholders) while reducing waste. This paper contains four parts: (1) historical background of the new field of LSE and a review of the fundamental concepts of Lean Thinking; (2) the development process of a new product called “Lean Enablers for Systems Engineering”; (3) a list of the Enablers organized into six Lean principles; (4) summary and conclusions. The Lean Enablers for Systems Engineering is a comprehensive checklist of nonmandatory practices and recommendations formulated as “do's” and “don't's” of SE, and containing tacit knowledge (collective wisdom) on how to prepare for, plan, execute, and practice SE and EM using Lean Thinking. Each enabler has the potential to enhance program value and reduce waste. The Enablers are formulated as a web-based addendum to the current SE Handbook published by the International Council for Systems Engineering (INCOSE), and do not repeat the practices made therein, which are regarded as sound. They should be an equally valuable addendum to other SE handbooks such as NASA, DoD, or company manuals. The enablers' development followed a classical process: Concept, Alpha, Beta, Prototype, and Version 1.0. This paper reports on Version 1.0 of the enablers, which are regarded as mature enough for dissemination, but which are intended to be a living online document to be continuously improved by interested practitioners as new knowledge and experience are acquired. The enablers were evaluated by surveys in the Beta and Prototype phases. The Prototype version has also been benchmarked with recent NASA and GAO studies. This project has been carried out by two core teams involving 14 volunteers from the LSE Working Group of INCOSE. The teams included representatives from industry, academia, and governments from United States, Israel, and the United Kingdom, with cooperation from the LSE Working Group membership at large. © 2010 Wiley Periodicals, Inc. Syst Eng 14: 29–55, 2011
Hexosephosphate formation and the regulation of glycolysis in muscle

Abstract The steady state concentrations of the hexosephosphates, and tracer data with 32Pi suggest that the formation of glucose-6-phosphate in resting muscle takes place predominantly from the glucose and Pi present in the extracellular phase, and that the phosphorylase system is essentially inactive under these conditions. The rate of glycogenolysis in tetanic contraction is such that it is adequate to support the very high rate of lactic acid formation under these extreme conditions. The apparent primary rate-limiting step in glycolysis is the phosphohexose isomerase reaction, both in resting muscle and in contraction. The activity of phosphofructokinase in resting muscle is sufficient so that this reaction is not rate-limiting; however, the activation of this enzyme in tetanic contraction is not necessarily adequate to the situation, and this reaction may then become rate-limiting. The tracer data indicate that the formation of fructose-1,6-diphosphate in contraction may take place by some mechanism other than the phosphofructokinase reaction.
Ancient neurilemmoma of the oral cavity.

Abstract A case of ancient neurilemmoma arising in oral soft tissues displays features in common with a similar, if not identical, tumor encountered in the thorax. It is suggested that the histologic features typifying this tumor are degenerative changes occurring as a manifestation of longevity in what was at one time a neurilemmoma in the classic sense.
CALIBRATION OF THE 1-MHZ SONITRON ULTRASOUND SYSTEM

Successful drug and gene delivery across cellular membranes can lead to improved therapeutic outcomes. Recent studies have suggested that sonoporation may enhance drug and gene delivery across cellular membranes. The enhancement may be a result of transient permeation of the membrane from cavitation or micro- streaming effects of microbubbles exposed to ultrasound. Given limited acoustic pressure calibration and beam profile characterization of the Sonitron ultrasound systems in cellular bioeffects studies previously published, the objective of this work was to calibrate the acoustic output and explore the potential for standing waves in a cell-well plate. In this study, three 1-MHz transducers driven by Sonitron ultrasound systems, which have been used in a number of sonoporation studies, were calibrated. Transducers with 10-mm, 6-mm and 20-mm- diameter apertures (Sonitron 1000 and 2000, Rich-Mar, Inola, OK, USA) were calibrated using polyvinylidene fluoride (PVDF) needle hydrophones. Axial and transverse beam profiles were obtained, and the pressures were measured as a function of Sonitron intensity dial setting and duty cycle. The acoustic intensity was calculated and compared with the Sonitron intensity dial setting for duty cycles from 10-100%. Standing waves caused by reflections from the hydrophone holder were detected for each transducer. This observation may also have impli- cations for invitro sonoporation studies. Acoustic field characterization is an important first step in understanding the mechanisms of sonoporation and drug delivery across biomembranes. (E-mail: kopechja@uc.edu) 2010 World Federation for Ultrasound in Medicine & Biology.
Magnetic resonance imaging of trabecular bone structure in the distal radius: relationship with X-ray tomographic microscopy and biomechanics.

The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 µm isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156×156×300 µm). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (∼3 times), trabecular width (∼3 times), fractal dimension (∼1.4 times) and first Betti number/ volume (∼10 times), and an underestimation of trabecular spacing (∼1.6 times) in the MR images compared with the 18-µm XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.
Blunting airway eosinophilic inflammation results in a decreased airway neutrophil response to inhaled LPS in patients with atopic asthma: a role for CD14.

Abstract Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expression and the subsequent airway polymorphonuclear neutrophil (PMN) response to inhaled LPS in subjects with atopic asthma. Twelve such subjects underwent a 2-week, placebo-controlled trial of inhaled steroid (440 μg fluticasone propionate [FP] twice per day); this was followed 48 hours later by an inhaled LPS (5 μg) challenge. A comparison of LPS-induced inflammatory cells in sputum, CD14 expression, and methacholine responsiveness with FP or placebo was conducted. Flow cytometry was used to analyze membrane-bound CD14 expression (mean fluorescence intensity) on sputum macrophages. We report that 48 hours before inhaled LPS challenge (baseline), FP significantly blunted airway eosinophils (cells per milligram; P = .04) and mCD14 expression (mean fluorescence intensity; P = .03) but did not decrease the number of PMNs (cells per milligram). Six hours after LPS challenge, airway PMNs and mCD14 expression were significantly decreased for FP in comparison with placebo ( P = .04). Our data suggest that decreasing airway allergic inflammation with corticosteroids results in both decreased expression of CD14 on airway monocytic cells and a decreased PMN response to inhaled LPS. (J Allergy Clin Immunol 2001;108:577-80.)