cssi/SciSciGPT-SciSciNet huggingface dataset:
The proliferative capacity and DNA synthesis of osteoblasts during fracture repair in normal and hypophysectomized rats

P recursor cells preparing for mitosis may be radioactively labeled so that the subsequently differentiated cells can be identified. Tritiated thymidine specifically labels deoxyribonucleic acid during the synthesis period. Tonna,l in a study primarily concerned with aging, fractured the right femurs of albino Swiss mice of varying ages and killed the animals at intervals of 24 hours, 1 week, and 2 weeks. One hour prior to sacrifice, “flash” labeling of the cells was obtained by subcutaneous injection of tritiated thymidine. Tonna observed that osteogenic cells of the periosteum were most frequently labeled, although the number of labeled cells decreased with age. However, by 24 hours after fracture there was an increase in the population of labeled cells, even in mice 52 weeks old. Also, labeled cells were most numerous when osteogenic or chrondrogenic cells from the periosteum were actively converting the fracture callus into cartilage, Tonna concluded that the potential for fracture repair resides essentially in the proliferative capacity of the cells of the periosteum, which diminishes with age. This reduced capacity accounts for the reduction in the rate of fracture repair in older animals. According to Enoch and Coventry, 2 the periosteum consists of an outer layer of collagenous fibers, in which most of the cells are fibroblasts, and an inner layer composed of single fusiform cells in the resting state. The latter becomes a multicellular layer of plump osteoblasts when bone fracture occurs.
Lymphoepithelial cyst in the lung: A case report

An unusual endobronchial presentation of lymphoepithelial cysts (LECs) is described in a HIV-seropositive patient. The bilateral infrahilar cysts had followed an apparently benign course for 2 years. Bronchoscopy revealed an endobronchial mass occluding the anterior basilar segment of the left lower lobe. Biopsy resulted in emptying of the cyst and showed the typical pseudostratified columnar epithelium with intraepithelial lymphocytes of an LEC. This diagnosis should be considered in patients with HIV infection and pulmonary cysts on CT.
Technology brokering in action: revolutionizing the skiing and tennis industries

Purpose – This paper aims to explore the true sources of innovation that revolutionized two sports industries – skiing and tennis, tracking the flow of ideas and power of technology brokering through the eyes of the innovator, Howard Head. Design/methodology/approach – Using a focal innovation action-set framework, the authors unite heretofore-disparate pieces of information to paint a more complete picture of the innovation and technology brokering process. Primary source material from Head’s patents, personal memoirs and journals and documented correspondence between him, his brother and his colleagues are augmented with secondary source material from periodicals, media excerpts and the academic literature. Findings – Head stands as an exemplar example of a technology broker, both through his serial practice of recombinant innovation and his savvy exploitation of resources. Results discredit the Great Man Theory of Innovation, while emphasizing the importance of exploiting social capital to realize oppo...
Regulation of bacterial physiological processes by three types of protein phosphorylating systems

A single type of protein-phosphorylating system, the ATP-dependent protein kinases, is employed in the regulation of a variety of cellular physiological processes in eukaryotes. By contrast, recent work with bacteria has revealed that three types of protein-phosphorylating systems are involved in regulation: (1) the classical protein kinases, (2) the newly discovered sensor-kinase/response-regulator systems, and (3) the multifaceted phosphoenolpyruvate-dependent phosphotransferase system. Physiological and mechanistic aspects of these three evolutionarily distinct systems are discussed.
Search for Radio Pulses from the Galactic Centre

THERE have been several searches for pulsed electromagnetic radiation from the direction of the galactic centre1–5 and one report of their detection6. Here we present the results of another search, at 430 MHz, conducted as part of a deep pulsar search using the 140-foot telescope of the National Radio Astronomy Observatory, in Green Bank, West Virginia. There was no evidence for pulses of extraterrestrial origin within the limits and assumptions we discuss.
Wittgenstein on Meaning and Life

This is a paper about the way language meshes with life. It focuses on Ludwig Wittgenstein’s later work, and compares it with Leo Tolstoy and Saint Augustine’s confessions. My aim is to better understand in this way what it means to have meaning in language, as well as meaning in life.
Modeling Agglomeration and Dispersion in City and Country: Gunnar Myrdal, François Perroux, and the New Economic Geography

The new economic geography is a recent body of literature that seeks to explain how resources and production come to be concentrated spatially for reasons other than the standard geographic ones. Some authors outside the new economic geography have criticized it a simplistic, irrelevant, or passe. They claim it employs overly abstract analysis, prioritizes mathematical technique over realistic explanation, and is reminiscent of the much earlier worlds of Gunnar Myrdal and Francois Perroux - in comparison to which, however, it falls short. This paper investigates the similarities and differences between the new economic geography and the work of Myrdal and Perroux. It examines how the techniques of analysis and intuitive explanations of agglomeration compare between these economic sociologists and the new economic geographers. The paper highlights what has been gained and what has been lost by the new economic geographers, who generally eschew interdisciplinary study.
Magnetic resonance imaging and magnetic resonance angiography before postchemotherapy retroperitoneal lymph node dissection

Abstract Objectives. Retroperitoneal lymph node dissection (RPLND) after primary chemotherapy is an accepted therapeutic approach for metastatic nonseminomatous germ cell testicular cancer. Because of the intense desmoplastic reaction and adherence to venous and arterial walls, accurate imaging of the retroperitoneal vasculature and its relation to residual tumor is essential. We report our experience with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), including the recently developed technique of bolus-contrast MRA, in patients undergoing postchemotherapy RPLND. Methods. Eighteen patients underwent MRI of the retroperitoneal region before RPLND. In addition to routine sequences, MRA was performed in 10 patients, including 8 with a three-dimensional technique using bolus intravenous MR contrast. Results were compared with intraoperative and pathologic findings. Results. MRI and MRA provided detailed information on retroperitoneal vasculature and its relation to tumor, including multiple renal vessels (n = 5), duplex inferior vena cava (n = 1), left retroaortic renal vein (n = 2), and common iliac vein thrombus (n = 1). In all cases, bolus-contrast MRA provided unique information on the location and number of renal and lumbar arteries, in addition to information on the aorta and the mesenteric and iliac vessels. The origin and number of renal arteries were accurately identified in all patients by bolus-contrast MRA; 2 patients had supernumerary renal arteries discovered at RPLND that had not been identified on non-bolus-contrast MRI. Conclusions. Bolus-contrast three-dimensional MRA provides unique information on renal and lumbar vessels. The potential benefit of avoiding vascular injury during dissection should be prospectively evaluated.
Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction.

Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury.
Chemopreventive Properties of trans-Resveratrol Are Associated with Inhibition of Activation of the IκB Kinase

trans-Resveratrol (Res), a phytoalexin found at high levels in grapes and in grape products such as red wine, has been shown to have anti-inflammatory and antioncogenic properties. Because the transcription factor nuclear factor kappaB (NF-kappaB) is involved in inflammatory diseases and oncogenesis, we tested whether Res could modulate NF-kappaB activity. Res was shown to be a potent inhibitor of both NF-kappaB activation and NF-kappaB-dependent gene expression through its ability to inhibit IkappaB kinase activity, the key regulator in NF-kappaB activation, likely by inhibiting an upstream signaling component. In addition, Res blocked the expression of mRNA-encoding monocyte chemoattractant protein-1, a NF-kappaB-regulated gene. Relative to cancer chemopreventive properties, Res induced apoptosis in fibroblasts after the induced expression of oncogenic H-Ras. Thus, Res is likely to function by inhibiting inflammatory and oncogenic diseases, at least in part, through the inhibition of NF-kappaB activation by blocking IkappaB kinase activity. These data may also explain aspects of the so-called "French paradox" that is associated with reduced mortality from coronary heart disease and certain cancers and provide a molecular rationale for the role of a potent chemopreventive compound in blocking the initiation of inflammation and oncogenesis.
Using clausal graphs to determine the computational complexity of k-bounded positive one-in-three SAT

The one-in-three SAT problem is known to be NP-complete even in the absence of negated variables [T.J. Schaefer, The complexity of satisfiability problems, in: Proceedings of the 10th Annual ACM Symposium on Theory of Computing, ACM, New York, 1978, pp. 216-226], a variant known as positive (or monotone) one-in-three SAT. In this note, we use clausal graphs to investigate a further restriction: k-bounded positive one-in-three SAT (kBP one-in-three SAT), in which each variable occurs in no more than k clauses. We show that for k=2, k BP one-in-three SAT is in the polynomial complexity class P, while for all k>2, it is NP-complete, providing another way of exploring the boundary between classes P and NP.
Phrase structure and intonational phrases: comments on the chapters by Marcus and Steedman

This paper is a commentary on two papers presented at the Workshop on Cognitive Models of Language, Sperlonga (Italy), May 1988. These two papers are: "Description Theory and Intonation Boundaries" by Mitch Marcus, and "Syntax and Intonation Structure in Combinatory Grammar" by Mark Steedman. Their approaches to the interface between syntax and metrical phonology are compared and certain problems with their approaches have been pointed out. A phrase structure-like approach, which is able to support some flexible phrasing and permit a set of analyses to hold simultaneously has been discussed also. This approach is based on structured objects as syntactic types rather than on curried functional syntactic types as in Steedman's work. Comments University of Pennsylvania Department of Computer and Information Science Technical Report No. MSCIS-89-56. This technical report is available at ScholarlyCommons: http://repository.upenn.edu/cis_reports/849 PHRASE STRUCTURE AND INTONATIONAL PHRASES: COMMENTS ON THE PAPERS BY MARCUS AND STEEDMAN Aravind K. Joshi MS-CIS-89-56 LING LAB 160 Department of Computer and Information Science School of Engineering and Applied Science University of Pennsylvania Philadelphia, PA 19 104
Intonational convergence in language contact: Utterance-final F0 contours in Catalan–Spanish early bilinguals

Thisstudyinvestigatesutterance-finalpitchaccentsindeclarativesintwocontactlanguages (Catalan and Spanish) as produced by two groups of Catalan‐Spanish bilinguals (Catalandominant and Spanish-dominant). It contributes to a growing body of research showing that bilinguals transfer the intonational patterns of their native language to their non-native language, and it provides a sociolinguistic profile of an intonational variable in a language contact situation. We also examine the interaction of native and non-native patterns within the performance of the bilinguals. Evidence is presented for the existence of a process of phonetic category assimilation of non-native pitch contrasts to native pitch contours, as well as for phonetic new-category formation in second language learning.
Comparison of the Morphological and Optical Characteristics of InP Islands on GalnP/GaAs (311)A and (100)

We have studied the effect of surface orientation on the optical and morphological characteristics of coherently-strained InP islands grown on GaInP/GaAs. The differences between islands grown on the (100) orientation and the (311)A orientation are studied. Islands grown on the (311)A orientation are more dense than the islands grown on the (100) orientation. For the (100) orientation, the island height distribution is bimodal peaked at 20 A and 220 A. For the (311)A orientation, the island height distribution is also bimodal peaked at 15 A and 60 A. Photoluminescence measurements for the (311)A orientation show a peak at 1.9 eV attributed to small islands. This peak is shifted to higher energies in comparison to the corresponding peak for the (100) orientation which is at 1.77 eV. This peak shift is due to the fact that the small islands on the (311)A orientation are smaller than the corresponding islands on the (100) orientation.
Replicative stress, stem cells and aging

DNA synthesis is a remarkably vulnerable phase in the cell cycle. In addition to introduction of errors during semi-conservative replication, the inherently labile structure of the replication fork, as well as numerous pitfalls encountered in the course of fork progression, make the normally stable double stranded molecule susceptible to collapse and recombination. As described in this issue, maintenance of genome integrity in the face of such events is essential to prevent the premature onset of age-related diseases. At the organismal level, the roles for such maintenance are numerous; however, the preservation of stem and progenitor cell pools may be particularly important as indicated by several genetically engineered mouse models. Stresses on stem and progenitor cell pools, in the form of telomere shortening (Terc(-/-)) or other genome maintenance failures (ATR(mKO), Ku86(-/-), LIG4(Y288C), XPD(R722W/R722W), etc.), have been shown to degrade tissue renewal capacity and accelerate the appearance of age-related phenotypes. In the case of telomere shortening, exhaustion of replicative potential appears to be at least partially dependent on the cell cycle regulatory component of the DNA damage response. Therefore, both the genome maintenance mechanisms that counter DNA damage and the cell cycle checkpoint responses to damage strongly influence the onset of age-related diseases and do so, at least in part, by affecting long-term stem and progenitor cell potential.
Subchronic Hepatotoxicity Evaluation of Hydrazobenzene in Fischer 344 Rats

Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or 13 weeks duration. End points evaluated included clinical observations, body weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver histopathology. There were no HZB exposure-related clinical signs of toxicity. During study weeks 8 through 13, body weight means in rats of the 300 ppm group were 6% lower compared to control rat means. Serum alkaline phosphatase concentrations were decreased in rats of the 300 ppm group at all time points. Relative (to body weight) liver weight increases were observed in rats of the 200 and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13 weeks of exposure. Following 13 weeks of exposure, microscopic findings in the liver were observed only in rats of the 200 and 300 ppm groups and consisted of hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct duplication. Blood HZB concentrations ranged from 0.002 to 0.006 µg/mL in rats of the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per d) was selected based on the observation of microscopic hepatocyte alterations at ≥200 ppm HZB.
Fast numerical method for the solution of the quasigeostrophic vorticity equation

Particle methods are typically O(N2), where N is the number of computational elements. We present an O(N) particle method for the equations for the conservation of potential vorticity. This method is based on the idea of grouping the particles. The necessary expansions and truncation errors are given. The accuracy and speed of the method are presented for both scalar and vector machines. © 1993 John Wiley & Sons, Inc.
On the interannual variability of poleward transport and storage of heat in the ocean-atmosphere system

Published satellite measurements of net radiation at the top of the atmosphere show anapparent imbalance of the global annual mean of the order of ± 10 W m−2, while for the required poleward heat transport at the latitudes of largest transport 30–40 °N and S, a range of about 200 and 100 × 1013 W, respectively, is indicated. It is suggested that (i) part of theapparent interannual variability of global-mean net radiation at the top of the atmosphere may bereal, while part is due to deficiencies in sampling, sensing, and processing; (ii) year-to-year variations of temperature in the top layer of the World oceanmay be large enough to account for a substantial portion of the apparent interannual variability of global-mean net radiation at the top of the atmosphere; (iii) the interannual variability of meridional heat transport in the combined hydrosphere-atmosphere system may in large part result from processes in the ocean. The currently available oceanic observations and satellite data are insufficient to weigh even the relative importance of interannual variability in (a) meridional heat transport in the combined atmosphere-ocean system, (b) meridional heat transport in the global ocean, and (c) heat storage in the global ocean, so that none of these three components can be considered negligible.
Hot-Embossed Piezoelectric Polymer Micro-Diaphragm Arrays Integrated with Lab-on-a-Chip for Protein Analysis

Piezoelectric copolymer, PVDF-TrFE, diaphragm arrays with integrated microfluidic chip for high performance protein immunosensors were developed and characterized in this work. Mold-transfer and hot-embossing techniques provide a high throughput and repeatable way to fabricate piezoelectric polymer diaphragms and PVDF-TrFE's hydrophobic surface acts as a natural bioreceptor to capture proteins of interest. In addition, integrated microfluidic devices enhance reaction efficiency and reduce the assay time.
Output regulation of linear systems subject to input constraints

This paper studies the output regulation problem for linear systems subject to input constraints. It presents a new controller that uses a conditional servocompensator. Previous work introduced the conditional servocompensator, which acts as a traditional servocompensator only in a neighborhood of the zero-error manifold, while acting as a stable system outside a boundary layer, leading to improvement in the transient response while achieving zero steady-state regulation error. Starting with a low-gain stabilizing state feedback controller, based on the solution of an algebraic Riccati equation, Lyapunov redesign is used to implement the state feedback control in a saturated high-gain feedback form that includes the conditional servocompensator. The design is extended to output feedback via a full-order high-gain observer.
Context-aware scanning for parsing extensible languages

This paper introduces new parsing and context-aware scanning algorithms in which the scanner uses contextual information to disambiguate lexical syntax. The parser uses a slightly modified LR-style algorithm that passes to the scanner the set of valid symbols that the scanner may return at that point in parsing. This set is those terminals whose entries in the parse table for the current parse state are shift, reduce, or accept, but not error. The scanner then only returns tokens in this set. An analysis is given that can statically verify that the scanner will never return more than one token for a single input. Context-aware scanning is especially useful when parsing and scanning extensible languages in which domain specific languages can be embedded. It has been used in extensible versions of Java 1.4 and ANSI C. We illustrate this approach with a declarative specification of a subset of Java and extensions that embed SQL queries and Boolean expression tables into Java.
The role of endothelial activation in the pathogenesis of transfusion-related acute lung injury

ALI = acute lung injury; ARDS = acute respiratory distress syndrome; EBS = Earl’s buffered saline; FP = fresh plasma; ICAM-1 = intracellular adhesion molecule-1; NBF = National Blood Foundation; PMN(s) = polymorphonuclear leukocyte(s).From the Bonﬁls Blood Center and the Departments of Pediatrics and Surgery, University of Colorado School of Medicine, Denver, Colorado.
Odorant tuning of olfactory crypt cells from juvenile and adult rainbow trout.

SUMMARY Teleost fish lack independent olfactory organs for odorant and pheromone detection. Instead, they have a single sensory epithelium with two populations of receptor neurons, ciliated and microvillous, that are conserved among vertebrates, and a unique receptor cell type named the olfactory crypt cell. Crypt cells were shown to be chemosensory neurons that project to specific areas in the olfactory bulb, but their odorant tuning and overall function remain unclear. Reproduction in fish is generally synchronized by sex pheromonal signaling between males and females, but the sensors responsible for pheromone detection remain unknown. In crucian carp, a seasonal variation in the population of olfactory crypt cells and their brain projections pathways, involved in reproduction, led to the hypothesis of a role as sex pheromone detectors. In the present study, morphology and localization of olfactory crypt cells were compared between juvenile and mature rainbow trout of both sexes, and calcium imaging was used to visualize responses of crypt cells from the three groups to common social and food-related odorants, sex hormones and conspecific tissue extracts. Crypt cells from mature trout were found to be larger than those of juvenile specimens, and preferentially localized to the apical surface of the olfactory epithelium. Although a fraction of crypt cells of all groups responded to common odorants such as amino acids and bile salts, cells from mature trout showed a characteristic preference for gonadal extracts and hormones from the opposite sex. These results support an involvement of olfactory crypt cells in reproduction-related olfactory signaling in fishes.
Keeping faith, losing faith: religious belief and political economy

Bradley Bateman and H. Spencer Banzhaf (eds.), Keeping Faith, Losing Faith: Religious Belief and Political Economy. Durham, NC and London: Duke University Press, 2008. viii + 369 pp. ISBN 978-0-822...
A Chinese Zodiac Mathematical Structure.

People enjoy finding the year of their birth and reading about themselves Many Chinese restaurants use place mats that depict the Chinese zodiac-a twelve year cycle of years named after animals. Legend has it that long ago, one Chinese New Year, the Buddha invited all the animals in his kingdom to come before him. Unfortunately, only twelve turned up. The first to arrive was the rat, followed by the ox, tiger, rabbit, dragon, snake, horse, sheep, monkey, rooster, dog, and finally the boar. In grati tude, the Buddha decided to name a year after each of the animals. The mats usually describe the traits and talents of each animal, list the animals that are compatible with it, and indicate its opposite. People enjoy passing the time while waiting for a meal by finding the year of their birth on the mat and reading about themselves. The reader soon begins to notice some patterns in those animals that are compatible and those that are not. One purpose of this article is to help readers identify the animal that corresponds to the year of their birth. Another is to define a structure on the Chinese zodiac so that the subsets of compatibles and opposites form closed substructures with inter esting mathematical properties.
Transitional Property Rights and Local Developmental History in China

Among the societies that are moving from a centrally planned economy with weak property rights towards a market-oriented economy with stronger and more privatised property rights, China is undergoi...
Shareholder Remuneration Votes and CEO Compensation Design

Using a sample of large UK firms from 2002 - 2006, we examine the role that shareholder remuneration votes play in executive compensation design. In particular, we investigate what aspects of CEO compensation shareholders vote against and whether corporate boards, in turn, respond to negative votes by making changes in those CEO pay elements. Prior research investigates US firms that voluntarily seek shareholder ratification of equity compensation plans and thus may suffer from self-selection bias. Conversely, the UK provides an ideal setting because remuneration votes have been required for all listed firms since 2002. Results indicate that shareholders disapprove of higher salaries, weak pay-for-performance sensitivity in bonus pay and greater potential dilution in stock-based compensation, particularly stock option pay. We find some evidence that boards respond to past remuneration votes by decreasing grants of stock option compensation but not by changing salary or the pay-for-performance link in bonus pay accordingly.
Synthesis and characterization of (BaxSr1−x)Ti1+yO3+z thin films and integration into microwave varactors and phase shifters

Abstract Precise control of composition and microstructure is critical for the production of (BaxSr1−x)Ti1+yO3+z (BST) dielectric thin films with the large dependence of permittivity on electric field, low losses, and high electrical breakdown fields that are required for successful integration of BST into tunable high frequency devices. Here we review recent results on composition-microstructure-electrical property relationships of polycrystalline BST films produced by magnetron sputter deposition, that are appropriate for microwave devices such as phase shifters. Films with controlled compositions were grown from a stoichiometric Ba0.5Sr0.5TiO3 target by control of the background processing gas pressure. It was determined that the (Ba+Sr)/Ti ratios of these BST films could be adjusted from 0.73 to 0.98 by changing the total (Ar+O2) process pressure, while the O2/Ar ratio did not strongly affect the metal ion composition. Film crystalline structure and dielectric properties as a function of the (Ba+Sr)/T...
THE MEDIEVAL AFFECTIVE DIONYSIAN TRADITION

Thomas Gallus is often credited with introducing an affective innovation in medieval reception of Dionysius. While desire is not absent from the CD, no form of human affectivity plays an explicit role in Moses’ ascent to union with God in the darkness of unknowing, as described in the MT. With Gallus, however, after all knowledge fails, union occurs through love. This innovation was influential, shaping subsequent interpretations of the CD, such as The Cloud of Unknowing. Yet, the subtle interplay of love and knowledge and the complex conception of love's own cognition of God in Gallus’ theology were not generally retained by those whom he influenced.
Telco 2015: Re-envision the future of mobile communications

Telco 2015 is IBM's analysis of four plausible scenarios that might emerge over the next 5–10 years, based on the trajectory and interplay of two uncertainties: future addressable market growth and industry competition/integration structure.
IS5-4CHECKPOINT INHIBITORS AS A FOUNDATION FOR ANTI-CANCER IMMUNE THERAPY

Abstract Substantial experimental data demonstrate that patients with advanced cancer can generate T lymphocyte immune responses to tumor specific mutations, re-expressed developmental proteins and tissue differentiation antigens. In normal immune function, T lymphocyte responses are tightly regulated by inhibitory checkpoints to prevent both self-reactivity and excessive tissue damage in response to infection. Similar regulatory checkpoints act to limit tumor-specific immune responses. Antagonist antibodies targeting CTLA-4, PD-1 or PD-1 ligand (B7-H1/PD-L1) were brought into clinical development to test the hypothesis that blockade of T-cell inhibitory ligand-receptor interactions and/or inhibition of T-regulatory cells could activate/expand/restore anti-tumor T-lymphocyte responses and produce meaningful clinical benefit in advanced cancer. Indeed, anti-CTLA-4 (ipilimumab) prolonged survival in 2 randomized trials conducted in metastatic melanoma, and demonstrated clinical activity in a small subset of patients with other malignancies through limited phase 2 evaluation. Several antibody PD1/PD-L1 pathway antagonists are now in clinical trials and overall demonstrated objective response rates of 17-41% in metastatic melanoma, 10-22% in NSCLC, and 12- 29% in metastatic renal carcinoma. Responses were also observed in colon (2/37), gastric, ovarian (1/20), and head and neck cancer. Phase 2 studies in additional tumor types are indicated based on the association between tumor PD-L1 expression and response to PD1/PD-L1 pathway antagonists. A substantial proportion of responders to PD-1/PD-L1 blockade remained progression-free for long periods without maintenance therapy. Autoimmune type toxicity can be observed with both ipilimumab and the PD1/PD-L1 pathway antagonists; treatment algorithms for toxicity management to include steroids and other immune suppressants as necessary have been instituted successfully. The first combination of an anti-CTLA- 4 plus an anti-PD-1 produced greater toxicity than expected for either single agent, but toxicity was manageable, and activity in melanoma appeared to surpass reported data for either single agent. Multiple other immune checkpoints are known, and based on current data, it is reasonable to predict that inhibition of one or more checkpoints will likely become the foundation on which successful and broadly active combination immunotherapies are built.
Extracellular matrix-based biomaterial scaffolds and the host response

Extracellular matrix (ECM) collectively represents a class of naturally derived proteinaceous biomaterials purified from harvested organs and tissues with increasing scientific focus and utility in tissue engineering and repair. This interest stems predominantly from the largely unproven concept that processed ECM biomaterials as natural tissue-derived matrices better integrate with host tissue than purely synthetic biomaterials. Nearly every tissue type has been decellularized and processed for re-use as tissue-derived ECM protein implants and scaffolds. To date, however, little consensus exists for defining ECM compositions or sources that best constitute decellularized biomaterials that might better heal, integrate with host tissues and avoid the foreign body response (FBR). Metrics used to assess ECM performance in biomaterial implants are arbitrary and contextually specific by convention. Few comparisons for in vivo host responses to ECM implants from different sources are published. This review discusses current ECM-derived biomaterials characterization methods including relationships between ECM material compositions from different sources, properties and host tissue response as implants. Relevant preclinical in vivo models are compared along with their associated advantages and limitations, and the current state of various metrics used to define material integration and biocompatibility are discussed. Commonly applied applications of these ECM-derived biomaterials as stand-alone implanted matrices and devices are compared with respect to host tissue responses.
Shell-Shocked! PTSD in Fitzgerald's Tender is the Night

This paper focuses on the characters in TITN and the impact World War I had on them throughout the novel.
Illusory vowels in perceptual epenthesis: the role of phonological alternations*

Listeners often perceive illusory vowels when presented with consonant sequences that violate phonotactic constraints in their language. Previous research suggests that the phenomenon motivates speech-perception models that incorporate surface phonotactic information and the acoustics of the speech tokens. In this article, inspired by Bayesian models of speech perception, we claim that the listener attempts to identify target phonemic representations during perception. This predicts that the phenomenon of perceptual illusions will be modulated not only by surface phonotactics and the acoustics of the speech tokens, but also by the phonological alternations of a language. We present the results of three experiments (an AX task, an ABX task and an identification task) with native Korean listeners, and native English listeners as a control group, showing that Korean listeners perceive different sets of illusory vowels in different phonological contexts, in accordance with the phonological processes of vowel deletion and palatalisation in the language.
Hypercalcemia of Malignancy and Colorectal Cancer

Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.
Real-Time Imaging of Platinum−Sulfur Ligand Exchange Reactions at the Single-Molecule Level via a General Chemical Technique

A powerful fluorescence technique for imaging individual covalent-bond-forming events in diverse chemical reactions is reported. The generality originates from employing the fluorophore as a spectator rather than a chemical reaction partner. This spectator technique was used to image individual ligand exchange reactions between platinum complexes and sulfur in real time. The chemical reactions were imaged on a key industrial catalyst support, a siloxy-modified surface, providing insight about reactivity distribution on these surfaces. Such reactivity distribution information is not available via traditional solution ensemble techniques, which average the properties of billions of molecules, or via AFM measurements, which provide information about the topology of the surface. Using superlocalization techniques, the positions of individual chemical reactions on the surface were localized below the diffraction limit, with a positional accuracy of up to ±11 nm.
Effects of diabetes on the carnitine palmitoyltransferase of isolated hepatic mitochondrial outer membranes

cold, prolonged cold exposure does lead to unmasking. Since insulin resistance has been implicated in the defective coldinduced activation of the mitochondrial proton conductance pathway in ob/ob mice (Mercer & Trayhurn, 1984, 1986), we suggest that the unmasking of GDP binding sites in the obese animals following 3 days of exposure to 13°C may result from a cold-induced restoration of insulin sensitivity in brown adipose tissue.
Integration of geriatric assessment into the community.

The integration of geriatric assessment into the community calls for more than effective communication. There should be a defined approach to comprehensive care, of which the assessment service is a regular part, and the assessment process should have a predictable influence on further care decisions. Three types of integrating approaches are described: the “recognized specialty" approach, which is typical of several other developed countries; the “consolidated model," such as the On Lok program in San Francisco; and the “brokerage" model, such as the ACCESS program in Rochester, New York. Each approach has strengths and limitations. We may expect further evolution toward fully integrated programs.
Caliban’s Burden: Applicability of the Convention on the International Sale of Goods (CISG) to St. Vincent and the Grenadines: A Step Towards Uniformity, Synthesis, or Interpretive Injustice in International Contracts

This paper will explore the multifaceted legal, social and political cultures that exist in the Commonwealth Caribbean. This paper supports adoption of the U.N. Convention on the International Sale of Goods (CISG) by countries in the region based on the premise that the goal should not be to promote uniformity in a normative sense, but to arrive at a synthesis of a legal tradition that is often bogged down in a simmering vat of indigenous, Afro-Caribbean, colonial, and post-colonial ideologies. The final question this paper seeks to answer is whether international treaties like the CISG can operate within the confines of Caribbean legal traditions in a practical way to move the former Commonwealth nations towards equity in the area of international trade. International treaties spring from a desire to unify the world – to establish a sort of universal “common sense.” This desire is based on the assumption that the global economy operates within a particular social formation, constructed from specific ideological discourses. But, at the intersubjective juncture of law, politics, and culture, well-meaning discourses become ensnared by different winds of doctrine. Historically, the junction of commerce has been the legal space for the battles of legal interpretation. The United Nation Convention on Contracts for the International Sale of Goods (hereinafter CISG) is one of these legal instruments that is on an idealized quest to remove linguistic, and cultural nuances from the space of international trade. The CISG provides that the adoption of uniform rules, which govern contracts for the international sale of goods should take into account the different social, economic and legal culture as a means of ending injustice in the area of international trade. But this push for international uniformity is a double-edged sword because while the countries in the developed world upholds the CISG as the salve to soothe the wounds of global trade barriers, some countries in the developing world are wary that the Treaty is another agent of imperialist ideology.
[Detection of enterohemorrhagic Escherichia coli O157:H7 by loop-mediated isothermal amplification].

Objective To develop a loop-mediated isothermal amplification (LAMP) method for rapidly diagnosing of Escherichia coli (EHEC) O157:H7 in pathogen detection department or small-scale laboratories. Methods Primers for LAMP test were designed by targeting the antigen coding rfhE of EHEC O157:H7, the Shiga-like toxin stx2 and the fliC encoding gene of H7 flagella antigen, respectively. The reaction condition and reaction system of LAMP were optimized. 2 EHEC O157:H7 type strains, 17 local strains and 33 other enterobacteria were analyzed to evaluate the LAMP's specificity and sensitivity. The results of the LAMP reaction were also compared with routine PCR method. Results The amplification products of O157 which had the corresponding target genes turned green by visual inspection and had ladder-like pattern on the gel, but products of other enterobacteria remained orange by visual examination and had no band on the gel. The detection results of LAMP were the same as of routine PCR method. The reaction time of the LAMP method was only 1.5 hours and the detection limit of LAMP assay was 26 CFU/reaction. In addition,the LAMP results could be determined only by visual inspection. Conclusion LAMP assay is rapid,specific,and sensitive for the detection of EHEC O157: H7. This method might not only reduce the dependence of complicated equipments but also be a potential method for wider use in pathogen detection department, small-scale laboratory, emergency motor vehicle or field survey. Key words: Escherichia coli O157; Nucleic acid amplification techniques; Environmental monitoring
Effects of Days Open Days Dry, and Season of Freshening on Income over Feed Cost and 305-Day Mature Equivalent Milk Yield, for Three Different Production Levels1

ABSTRACT Days open, days dry, and season of calving were examined to maximize Income Over Feed Cost (IOFC) and 305-d mature equivalent milk production for three different production levels. Models with all fixed effects were analyzed using SAS® PROC GLM for 50,743 Holstein cows from 4687 herds calving in yr 1990 and 1991. Production level of cow was not important to determine optimum days open to maximize 305-d milk yield, but was important for days open to maximize IOFC. For 305-d milk yield, days open of 91 to 105 d, 76 to 90 d, and 61 to 75 d were optimum for cows calving in season 2 (February through April), season 3 (May through July), and season 4 (August through October) respectively. For IOFC, optimum days open was 15 d higher for average and above average production levels for seasons 2 and 3 than for below average production level. Optimum days open to maximize IOFC for calving season 4 was 15 d higher for above average production level than for below average and average levels. Cows calving in season 2 had highest optimum days open. Conclusive results could not be obtained for season 1 as less than 10% of records in the data set belonged to that season and of those only 10% had an open period shorter than 150 d. On average, cows calving in season 3 yielded highest IOFC, which was $667, $482, and $276 more than cows calving in season 1 (November to January), season 2, and season 4 respectively. The 305-d milk yield was not different for the four seasons of calving.
Asian, Black, and Hispanic Anatomy

While a complete anatomical/ethnographical nasal study of all the different races with every possible variation within the groups might be interesting, I have limited myself to three non-Caucasian groups who commonly request rhinoplasty: Asians, blacks, and Hispanics, with a special emphasis on the black nose. Again, understanding black nasal anatomy is the key to attaining facile comprehension and good surgical technique for most ethnic rhinoplasties.
Technical Note: A minimally invasive experimental system for p CO 2 manipulation in plankton cultures using passive gas exchange (atmospheric carbon control simulator)

Abstract. As research into the biotic effects of ocean acidification has increased, the methods for simulating these environmental changes in the laboratory have multiplied. Here we describe the atmospheric carbon control simulator (ACCS) for the maintenance of plankton under controlled pCO2 conditions, designed for species sensitive to the physical disturbance introduced by the bubbling of cultures and for studies involving trophic interaction. The system consists of gas mixing and equilibration components coupled with large-volume atmospheric simulation chambers. These chambers allow gas exchange to counteract the changes in carbonate chemistry induced by the metabolic activity of the organisms. The system is relatively low cost, very flexible, and when used in conjunction with semi-continuous culture methods, it increases the density of organisms kept under realistic conditions, increases the allowable time interval between dilutions, and/or decreases the metabolically driven change in carbonate chemistry during these intervals. It accommodates a large number of culture vessels, which facilitate multi-trophic level studies and allow the tracking of variable responses within and across plankton populations to ocean acidification. It also includes components that increase the reliability of gas mixing systems using mass flow controllers.
Monosubstituted Phenylboronic Acids, R–B(OH) 2 (R = C 6 H 5 , C 6 H 4 CH 3 , C 6 H 4 NH 2 , C 6 H 4 OH, and C 6 H 4 F): A Computational Investigation

Phenylboronic acids (PBAs) are an important class of compounds with diverse applications in synthetic, biological, medicinal, and materials chemistry. In this investigation we report structural and thermochemical parameters for several monosubstituted ortho, meta, and para PBAs, R-B(OH)2 (R = C6H5, C6H4CH3, C6H4NH2, C6H4OH, and C6H4F). Equilibrium geometries of all the PBAs discussed in this article were obtained using second-order Moller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVDZ basis set; heats of formation (HOF) were calculated at the Gaussian-3 (G3) level of theory. The endo-exo conformers of all the positional isomers of these PBAs were lowest in energy. Using HOF for the monosubstituted PBAs calculated at the G3 level of theory, in conjunction with the experimental HOF for benzene, toluene, aniline, phenol, and fluorobenzene, the values of [Formula: see text] for the transfer processes C6H6 + C6H4X-B(OH)2 → C6H5X + C6H5-B(OH)2 (X = CH3, NH2, OH, and F) are found to be in good agreement with values of [Formula: see text] calculated at the MP2(FC)/aug-cc-pVTZ//MP2(FC)/aug-cc-pVTZ computational level; the bonding in the reactants and products for these transfer reactions are well-matched and thermochemical calculations at this level are expected to be very accurate, providing checks on the G3 HOF calculations.
Spontaneous remission of acute myeloid leukemia after discontinuation of lenalidomide.

Multiple reports over the past several years have suggested an association of secondary myeloid malignancies with lenalidomide maintenance therapy in multiple myeloma (MM) [1–3]. To date, however, ...