Dīvān-i farīd ʾal-ʾaqṭār va vaḥīd ʾal-ʾasrār ḥakīm-i māhir va suk︠h︡an sanj-i sāḥir ... Ḥakīm Qāʾānī Mīrzā Ḥabīb S︠h︡īrāzī.

Lithographed.

Istoricheskīi︠a︡ statʹi M.D. Khmyrova.

1. General-Anshef Avraam Petrovich Gannibal (arap Petra Velikago) -- 5. Posli︠e︡dnee chetyrekhli︠e︡tīe zhizni Suvorova.

Evaluation of the chapter 30 program for the Department of Veterans Affairs : final report.

"Contract no. V101(93)P-1203; Task order no. 2."

For the record : fiscal year 1967 highlights, Title I Elementary & Secondary Education Act of 1965.

"OE-37017."

I funghi d'Italia e principalmente le loro specie mangefeccie, velenose, o sospelle descritte ed illustrate con tavole diseguate,

Title vignette.

Vista de la bahía de Alicante [Material gráfico] = Vue de la rade d'Alicante = View of the harbour of Alicant

Resumen: Descrición: vista de la bahía de la ciudad de Alicante, en segundo término varios barcos

A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors

Purpose: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits heparanase, an extracellular matrix endoglycosidase, and the binding of angiogenic growth factors to heparan sulfate. This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part 2). Results: Forty-two patients [median age, 53 years (range, 19-78 years); median performance status, 1] with a range of advanced solid tumors received a total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was generally mild and included prolongation of the activated partial thromboplastin time and injection site echymosis. The pharmacokinetics were linear with dose. Intrapatient variability was low and interpatient variability was moderate. Both AUC and C-max correlated with the percent increase in activated partial thromboplastin time, showing that this pharmacodynamic end point can be used as a surrogate for drug exposure, No association between PI-88 administration and vascular endothelial growth factor or basic fibroblast growth factor levels was observed. One patient with melanoma had a partial response, which was maintained for >50 months, and 9 patients had stable disease for >= 6 months. Conclusion: The recommended dose of PI-88 administered for 4 consecutive days bimonthly or weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in melanoma supports further evaluation of PI-88 in phase II trials.

Internal versus external R&D:a study of R&D choice with sample selection

This paper extends previous analyses of the choice between internal and external R&D to consider the costs of internal R&D. The Heckman two-stage estimator is used to estimate the determinants of internal R&D unit cost (i.e. cost per product innovation) allowing for sample selection effects. Theory indicates that R&D unit cost will be influenced by scale issues and by the technological opportunities faced by the firm. Transaction costs encountered in research activities are allowed for and, in addition, consideration is given to issues of market structure which influence the choice of R&D mode without affecting the unit cost of internal or external R&D. The model is tested on data from a sample of over 500 UK manufacturing plants which have engaged in product innovation. The key determinants of R&D mode are the scale of plant and R&D input, and market structure conditions. In terms of the R&D cost equation, scale factors are again important and have a non-linear relationship with R&D unit cost. Specificities in physical and human capital also affect unit cost, but have no clear impact on the choice of R&D mode. There is no evidence of technological opportunity affecting either R&D cost or the internal/external decision.

Research activities arising from the University of Kent

In this paper I describe research activities in the field of optical fiber sensing undertaken by me after leaving the Applied Optics Group at the University of Kent. The main topics covered are long period gratings, neural network based signal processing, plasmonic sensors, and polymer fiber gratings. I also give a summary of my two periods of research at the University of Kent, covering 1985–1988 and 1991–2001.

“I had a different way of governing”: The evangelical presidential style of Jimmy Carter and his mission for Middle East peace

President Jimmy Carter once said, "I had a different way of governing." In attempting to explain what he meant by this, Carter has been variously described as a political amateur, a trustee, a non-political politician, an "active-positive" president, and a forerunner of the 1990s' New Democrats. It is argued here, however, that mere secular descriptions and categories such as these do not adequately capture the essence of Carter's brand of politics and his understanding of the presidency. Rejecting Richard Neustadt's prescriptions for effective presidential leadership, Carter thought political bargaining and compromise were "dirty" and "sinful." He deemed the ways of Washington as "evil," and considered many, if not most, career politicians immoral. While he fully supported the institutional separation of church and state, politics for Carter was about "doing right," telling the truth, and making the United States and the world "a better demonstration of what Christ is." Like two earlier Democrats, William Jennings Bryan and Woodrow Wilson, Carter understood politics as an alternative form of Christian ministry and service. In this regard, Carter was a presidential exception. Carter's evangelical faith gave his politics meaning, skill, vision, and a framework for communication. Using Fred Greenstein's categories of presidential leadership, Carter's faith provided him with "emotional intelligence", too. However, Carter's evangelical style provoked many of his contemporaries, including many of his fellow Democrats. To his critics at home and abroad, Carter was often accused of being arrogant, stubborn, naive, and ultimately a political failure. But as evinced by his indispensable role in negotiating peace between Israel and Egypt, his leadership style also provided him some remarkable achievements. The research here is based on a thorough examination of President Carter's many writings, his public papers, interviews, and opinion pieces. Written accounts from former Carter administration officials and from Israeli and Egyptian participants at Camp David are also used. This project is largely descriptive, qualitative in approach, but quantitative data are used when appropriate and as supplements.

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.
Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.
Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.
Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.

Scavo 2015 della necropoli romana di Porta Nocera a Pompei: nascita e sviluppo di un paesaggio funerario romano (I sec. a.C. - I sec. d.C.)

The Porta Nocera 2 program aims to study the process of establishing and developing a Roman urban necropolis from a road network, which is an essential setting in the expression of death in the Roman time. As such, the necropolis of Porta Nocera essentially excavated between 1952 and 1958 and then in 1983 offers a privileged field study. Indeed, monuments and funerary enclosures with burial structures (graves, cremation areas) built along the road to Nocera are well preserved and allow to observe funerary practices on a relatively short time, about 160 years, since we can assume that the necropolis has been founded with the colony in 80 BC. It is then the necessity to organize a burial area according to Roman customs, which is at the origin a new landscape development until then essentially marked by the presence of the urban wall.

Theod. I. F. Graswinckeli, I.C. Delphensis. Stricturae ad censuram Ioannis à Felden I.U.D. ad libros Hugonis Grotii De iure belli ac pacis.

Signatures: A-K¹² L¹⁰.

Studies of MHC class I antigen presentation & the origins of the immunopeptidome

La présentation d'antigène par les molécules d'histocompatibilité majeure de classe I (CMHI) permet au système immunitaire adaptatif de détecter et éliminer les agents pathogènes intracellulaires et des cellules anormales. La surveillance immunitaire est effectuée par les lymphocytes T CD8 qui interagissent avec le répertoire de peptides associés au CMHI présentés à la surface de toutes cellules nucléées. Les principaux gènes humains de CMHI, HLA-A et HLA-B, sont très polymorphes et par conséquent montrent des différences dans la présentation des antigènes. Nous avons étudié les différences qualitatives et quantitatives dans l'expression et la liaison peptidique de plusieurs allotypes HLA. Utilisant la technique de cytométrie de flux quantitative nous avons établi une hiérarchie d'expression pour les quatre HLA-A, B allotypes enquête. Nos résultats sont compatibles avec une corrélation inverse entre l'expression allotypique et la diversité des peptides bien que d'autres études soient nécessaires pour consolider cette hypothèse. Les origines mondiales du répertoire de peptides associés au CMHI restent une question centrale à la fois fondamentalement et dans la recherche de cibles immunothérapeutiques. Utilisant des techniques protéogénomiques, nous avons identifié et analysé 25,172 peptides CMHI isolées à partir des lymphocytes B de 18 personnes qui exprime collectivement 27 allotypes HLA-A,B. Alors que 58% des gènes ont été la source de 1-64 peptides CMHI par gène, 42% des gènes ne sont pas représentés dans l'immunopeptidome. Dans l'ensemble, l’immunopeptidome présenté par 27 allotypes HLA-A,B ne couvrent que 17% des séquences exomiques exprimées dans les cellules des sujets. Nous avons identifié plusieurs caractéristiques des transcrits et des protéines qui améliorent la production des peptides CMHI. Avec ces données, nous avons construit un modèle de régression logistique qui prédit avec une grande précision si un gène de notre ensemble de données ou à partir d'ensembles de données indépendants génèrerait des peptides CMHI. Nos résultats montrent la sélection préférentielle des peptides CMHI à partir d'un répertoire limité de produits de gènes avec des caractéristiques distinctes. L'idée que le système immunitaire peut surveiller des peptides CMHI couvrant seulement une fraction du génome codant des protéines a des implications profondes dans l'auto-immunité et l'immunologie du cancer.