Hypertension, kardiotoxicitet och njursvikt i samband med tyrosinkinashämmaren sunitinib

Nybildning av blodkärl från tidigare existerande kärl, angiogenes, är ett väsentligt skede vid tumörtillväxt. Denna process regleras av bland annat tillväxtfaktorer, var av den vaskulära endoteliala tillväxtfaktorn har en central roll. Hämning av angiogenes kan ske antingen extracellulärt med hjälp av humaniserade monoklonala antikroppar eller intracellulärt med hjälp av småmolekylära hämmaren. Sunitinib är en småmolekylär multikinashämmare och inhiberar flera tyrosinkinasreceptorer som påverkar tumörtillväxten och metastasutvecklingen vid cancer. Sunitinibs främsta indikationer är gastrointestinala stromacellstumörer, metastaserad njurcellscancer och neuroendokrina tumörer i bukspottskörteln. Behandling med tyrosinkinashämmare orsakar biverkningar som hypertension, kardiotoxicitet och njursvikt, vilka antas bero på de hämmande effekterna på mål som inte är väsentliga för anti-cancer-aktiviteten (”off-target” biverkningar). Bland annat AMP-aktiverat proteinkinas (AMPK), ett kinas som upprätthåller metabolisk homeostas i hjärtat, inhiberas av sunitinib och antas framkalla kardiovaskulära biverkningar. För att reducera ”off-target” biverkningar strävar man till att hitta alternativ som minskar de skadliga effekterna utan att den terapeutiska aktiviteten försvagas. Bland annat ett begränsat kaloriintag har uppvisat skyddande effekt på hjärtat via mekanismer sammankopplade till ökad resistens mot oxidativ stress, inflammation och mitokondriell dysfunktion, samt avtagande apoptos och autofagi. Detta sker delvis genom aktivering av enzymet Sirt1. Syftet med den här studien var att undersöka ifall kaloribegränsning skyddar mot kardiovaskulära och renala biverkningar inducerade av sunitinib hos råttor. Dessutom studerades vilka signalkedjor i cellen som medverkar. I studien användes 40 spontant hypertensiva råttor samt 10 normotensiva Wistar-Kyoto råttor. Försöksdjuren delades in i fem grupper beroende på behandling; I WKY kontroll, II SHR kontroll, III SHR + kaloribegränsning 70 %, IV SHR + sunitinib 3 mg/kg och V SHR + sunitinib 3 mg/kg + kaloribegränsning 70 %. Behandlingsperioden var åtta veckor. Blodtrycket mättes varje vecka med svansmanchett, urinutsöndringen undersöktes vecka 4 och vecka 8 med metabolismburar, ultraljudsundersökning av hjärtat utfördes sista veckan och blodkärlens respons till acetylkolin och natriumnitroprussid studerades i samband med avlivning. Proteinerna Sirt1 och AMPK analyserades i hjärtat med Western blotting samt förekomsten av makrofagmarkören ED1 i njurarna med immunhistokemi. Studien visade att sunitinibdosen 3 mg/kg är mycket väl tolererbar hos råttor eftersom sunitinib inte orsakade högre blodtryck, kraftigare hypertrofi eller mer omfattande njurskada jämfört med obehandlade SHR- grupper. Utgående från resultaten kan man också konstatera att kaloribegränsningen har positiva kardiovaskulära effekter.

De "de" : Estudio histórico-comparativo de los usos y la semántica de la preposición "de" en español

El presente estudio supone un intento de describir y analizar el uso de la preposición "de" sobre la base de un corpus diacrónico, con énfasis en las diferentes relaciones semánticas que establece. Partiendo de un total de más de 16.000 casos de "de" hemos establecido 48 categorías de uso, que corresponden a cuatro tipos de construcción sintáctica, a saber, el uso de "de" como complemento de nombres (CN), verbos (CV), adjetivos (CA) y, finalmente, su uso como núcleo de expresiones adverbiales independientes (CI). El estudio consta de tres partes fundamentales. En la parte I, se introduce la Lingüística Cognitiva, que constituye la base teórica esencial del trabajo. Más exactamente, se introducen conceptos como la teoría del prototipo, la teoría de las metáforas conceptuales y la gramática cognitiva, especialmente las ideas de "punto de referencia" y "relación intrínseca" (Langacker 1995, 1999). La parte II incluye el análisis de las 48 categorías. En esta parte se presentan y comentan casi 2.000 ejemplos del uso contextual de "de" extraídos del corpus diacrónico. Los resultados más importantes del análisis pueden resumirse en los siguientes puntos: El uso de "de" sigue siendo esencialmente el mismo en la actualidad que hace 800 años, en el sentido de que todas las 48 categorías se identifican en todas las épocas del corpus. El uso de "de" como complemento nominal va aumentando, al contrario de lo que ocurre con su uso como complemento verbal. En el contexto nominal son especialmente las relaciones posesivas más abstractas las que se hacen más frecuentes, mientras que en el contexto verbal las relaciones que se hacen menos frecuentes son las de separación/alejamiento, causa, agente y partitivo indefinido. Destaca la importancia del siglo XVIII como época de transición entre un primer estado de las cosas y otro posterior, en especial en relación con el carácter cada vez más abstracto de las relaciones posesivas así como con la disminución de las categorías adverbales de causa, agente y partitivo. Pese a la variación en el contexto inmediato de uso, el núcleo semántico de "de" se mantiene inalterado. La parte III toma como punto de partida los resultados del análisis de la parte II, tratando de deslindar el aporte semántico de la preposición "de" a su contexto de uso del valor de la relación en conjunto. Así, recurriendo a la metodología para determinar el significado básico y la metodología para determinar lo que constituyen significados distintos de una preposición (Tyler , Evans 2003a, 2003b), se llega a la hipótesis de que "de" posee cuatro significados básicos, a saber, 'punto de partida', 'tema/asunto', 'parte/todo' y 'posesión'. Esta hipótesis, basada en las metodologías de Tyler y Evans y en los resultados del análisis de corpus, se intenta verificar empíricamente mediante el uso de dos cuestionarios destinados a averiguar hasta qué punto las distinciones semánticas a las que se llega por vía teórica son reconocidas por los hablantes nativos de la lengua (cf. Raukko 2003). El resultado conjunto de los dos acercamientos tanto refuerza como especifica la hipótesis. Los datos que arroja el análisis de los cuestionarios parecen reforzar la idea de que el núcleo semántico de "de" es complejo, constando de los cuatro valores mencionados. Sin embargo, cada uno de estos valores básicos constituye un prototipo local, en torno al cual se construye un complejo de matices semánticos derivados del prototipo. La idea final es que los hablantes son conscientes de los cuatro postulados valores básicos, pero que también distinguen matices más detallados, como son las ideas de 'causa', 'agente', 'instrumento', 'finalidad', 'cualidad', etc. Es decir, "de" constituye un elemento polisémico complejo cuya estructura semántica puede describirse como una semejanza de familia centrada en cuatro valores básicos en torno a los cuales se encuentra una serie de matices más específicos, que también constituyen valores propios de la preposición. Creemos, además, que esta caracterización semántica es válida para todas las épocas de la historia del español, con unas pequeñas modificaciones en el peso relativo de los distintos matices, lo cual está relacionado con la observada variación diacrónica en el uso de "de".

Deutschland, Deutschland über alles : Tysk föreningsverksamhet i Finland och Sverige 1910-1950

The voluntary associations dealt with in this dissertation were ethnic clubs and societies promoting the interests of German immigrants in Finland and Sweden. The associations were founded at the end of the 19th century as well as at the beginning of the 20th century during a time in which migration was high, the civil society grew rapidly and nationalism flourished. The work includes over 70 different associations in Finland and Sweden with a number of members ranging from ten to at most 2, 500. The largest and most important associations were situated in Helsinki and Stockholm where also most of the German immigrants lived. The main aim of this work is to explore to what extent and how the changes in government in Germany during 1910 to 1950 were reflected in the structures and participants, financial resources and meeting places, networks and activities of the German associations in Finland and Sweden. The study also deals with how a collective German national identity was created within the German associations. The period between 1910 and 1950 has been described by Hobsbawm as the apogee of nationalism. Nationalism and transnationalism are therefore key elements in the work. Additionally the research deals with theories about associations, networking and identity. The analysis is mostly based on minutes of meetings, descriptions of festivities, annual reports and historical outlines about the associations. Archival sources from the German legations, the German Foreign Office, and Finnish and Swedish officials such as the police and the Foreign Offices are also used. The study shows that the collective national identity in the associations during the Weimar Republic mostly went back to the time of the Wilhelmine Empire. It is argued that this fact, the cultural propaganda and the aims of the Weimar Republic to strengthen the contacts between Germany and the German associations abroad, and the role of the German legations and envoys finally helped the small groups of NSDAP to infiltrate, systematically coordinate and finally centralize the German associational life in Finland and Sweden. The Gleichschaltung did not go as smoothly as the party wanted, though. There was a small but consistent opposition that continued to exist in Finland until 1941 and in Sweden until 1945. The collective national identity was displayed much more in Sweden than in Finland, where the associations kept a lower profile. The reasons for the profile differences can be found in the smaller number of German immigrants in Finland and the greater German propaganda in Sweden, but also in the Finnish association act from 1919 and the changes in it during the 1920s and 1930s. Finally, the research shows how the loss of two world wars influenced the associations. It argues that 1918 made the German associations more vulnerable to influence from Germany, whereas 1945 brought the associational life back to where it once started as welfare, recreational and school associations.

Dokumentation och beskrivning som språkplanering : perspektiv från arbete med tre tecknade minoritetsspråk

Language Documentation and Description as Language Planning Working with Three Signed Minority Languages Sign languages are minority languages that typically have a low status in society. Language planning has traditionally been controlled from outside the sign-language community. Even though signed languages lack a written form, dictionaries have played an important role in language description and as tools in foreign language learning. The background to the present study on sign language documentation and description as language planning is empirical research in three dictionary projects in Finland-Swedish Sign Language, Albanian Sign Language, and Kosovar Sign Language. The study consists of an introductory article and five detailed studies which address language planning from different perspectives. The theoretical basis of the study is sociocultural linguistics. The research methods used were participant observation, interviews, focus group discussions, and document analysis. The primary research questions are the following: (1) What is the role of dictionary and lexicographic work in language planning, in research on undocumented signed language, and in relation to the language community as such? (2) What factors are particular challenges in the documentation of a sign language and should therefore be given special attention during lexicographic work? (3) Is a conventional dictionary a valid tool for describing an undocumented sign language? The results indicate that lexicographic work has a central part to play in language documentation, both as part of basic research on undocumented sign languages and for status planning. Existing dictionary work has contributed new knowledge about the languages and the language communities. The lexicographic work adds to the linguistic advocacy work done by the community itself with the aim of vitalizing the language, empowering the community, receiving governmental recognition for the language, and improving the linguistic (human) rights of the language users. The history of signed languages as low status languages has consequences for language planning and lexicography. One challenge that the study discusses is the relationship between the sign-language community and the hearing sign linguist. In order to make it possible for the community itself to take the lead in a language planning process, raising linguistic awareness within the community is crucial. The results give rise to questions of whether lexicographic work is of more importance for status planning than for corpus planning. A conventional dictionary as a tool for describing an undocumented sign language is criticised. The study discusses differences between signed and spoken/written languages that are challenging for lexicographic presentations. Alternative electronic lexicographic approaches including both lexicon and grammar are also discussed. Keywords: sign language, Finland-Swedish Sign Language, Albanian Sign Language, Kosovar Sign Language, language documentation and description, language planning, lexicography

EFFEKTUTVÄRDERING INOM FÖRETAGANDEUTBILDNING

Effektutvärdering inom företagandeutbildning är ett forskningsfält som karakteriseras av brist på modeller ifråga om utvärdering. De få och hittills existerande utvärderingsmodellerna verkar ha förbisett de pedagogiska variablerna såsom utbildningens innehåll och metoder. Därför har det varit problematiskt att beskriva företagandeutbildningen i högskolor och analysera hur företagandeutbildningen bidrar till studerandes inlärning och deras förmåga att utnyttja kunskapen i näringslivet. Avhandlingen som är en deduktiv studie granskar den tidigare forskningen på området och förespråkar en tvärvetenskaplig ansats vid mätning och presentation aveffekter inom företagandeutbildning. Den nya modellen, ROEE-modellen, bidrar till teoribildningen om lärandets ”vad” och lärandets ”hur” inom företagandeutbildningen. En av de första teorierna om inlärning (Herbart 1776-1841) och Kirkpatricks (1998) fyra-stegs modell för kursutvärdering byggs ut med en ny referensram baserad på examensutbildning inom företagande. En intressant aspekt metodmässigt utgör att försöksplanering och diagnostik inom medicinens område tillämpas på företagandeutbildningen. Avhandlingen visar att variabeln innehåll i företagandeutbildningen inom examensutbildning har en klar koppling till beteendet. Ett välavvägt innehåll kan utnyttjas i arbetslivet såväl av entreprenören som av intraprenören. Vid metodval i undervisningen visar den empiriska undersökningen att variation i metoder ger de positivaste upplevelserna.

Role of CIP2A in carcinogenesis

Worldwide and notably in the developed countries, cancer is an increasing cause of morbidity and mortality, being the second most common cause of death after ischemic heart disease. Now and in the future new cancer cases need to be diagnosed earlier. Prognostic factors may be helpful in recognizing and handling those patients who need more aggressive therapy, and it is also desirable to predict treatment response accurately. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein predominantly expressed in malignant tissues and inhibiting protein phosphatase 2A (PP2A) activity; it is a promising target for cancer therapy. The aim of this thesis was to evaluate the prognostic role of CIP2A in solid cancers, and for this purpose to explore expression of CIP2A, and investigating regulation of CIP2A in order to gain insight into signalling pathways leading to alteration in prognosis. Patients diagnosed with gastric, serous ovarian, tongue, or colorectal cancer at Helsinki University Central Hospital were included. Tumour tissue microarrays assembled from specimens from these patients were prepared and stained immunohistochemically for CIP2A protein expression. Associations with clinicopathologic parameters and other biomarkers were explored, and survival analyses were done according to the Kaplan-Meier method. Study of the role of CIP2A in intracellular signalling in vitro involved gastric, ovarian, and tongue cancer cell lines. We found CIP2A to be highly expressed in gastric, ovarian, tongue, and colorectal cancer specimens. CIP2A was associated with clinicopathologic parameters characterizing an aggressive disease, namely advanced stage, high grade, p53 immunopositivity, and high proliferation index. CIP2A led to recognition of gastric, ovarian, and tongue cancer patients with poor prognosis, however, with a cancer type-specific cut-off level for prognostic significance. In tongue cancer, it served as an independent prognostic marker. In contrast, in colorectal cancer, CIP2A provided no prognostic value. In cancer cell lines, CIP2A was highly expressed at both protein and mRNA levels, and promoted cell proliferation and anchorage-independent growth. In gastric cancer, we demonstrated with a MYCER construct in mouse embryo fibroblasts that activation of MYC led to increased CIP2A mRNA expression, and hence we suggested that a positive feedback mechanism between CIP2A and MYC may potentiate and prolong the oncogenic activity of these proteins. We demonstrated in ovarian cancer an association between CIP2A and EGFR protein overexpression and EGFR gene amplification. In ovarian and tongue cancer cells we showed that depletion of EGFR downregulates CIP2A expression. In conclusion, high CIP2A expression occurred frequently among patients with aggressive disease. CIP2A may serve as a prognostic marker in gastric, ovarian, and tongue cancer and thus may help in tailoring therapy for cancer patients. The positive feedback mechanism between CIP2A and MYC, as well as the positive regulation of CIP2A by EGFR, are a few signalling pathways regulating and regulated by CIP2A. These and other mechanisms need to be studied further, however. CIP2A is a potential target for therapy, and its potential role as predictive marker and as a tumour marker in serum requires exploration.

Molecular diagnosis of developmental disorders

ABSTRACT Idiopathic developmental disorders (DDs) affect ~1% of the population worldwide. This being a considerable amount, efforts are being made to elucidate the disease mechanisms. One or several genetic factors cause 30-40% of DDs, and only 10% are caused by environmental factors. The remaining 50% of DD patients go undiagnosed, mostly due to a lack of diagnostic techniques. The cause in most undiagnosed cases is though to be a genetic factor or a combination of genetic and environmental factors. Despite the surge of new technologies entering the market, their implementation into diagnostic laboratories is hampered by costs, lack of information about the expected diagnostic yield, and the wide range of selection. This study evaluates new microarray methods in diagnosing idiopathic DDs, providing information about their added diagnostic value. Study I analysed 150 patients by array comparative genomic hybridization (array CGH, 44K and 244K), with a subsequent 18% diagnostic yield. These results are supported by other studies, indicating an enourmous added diagnostic value of array CGH, compared with conventional cytogenetic analysis. Nevertheless, 80% of the patients remained undiagnosed in Study I. In an effort to diagnose more patients, in Study IV the resolution was increased from 8.9 Kb of the 244K CGH array to 0.7 Kb, by using a single-nucleotide polymorphism (SNP) array. However, no additional pathogenic changes were detected in the 35 patients assessed, and thus, for diagnostic purposes, an array platform with ca 9 Kb resolution appears adequate. The recent vast increase in reports of detected aberrations and associated phenotypes has enabled characterization of several new syndromes first based on a common aberration and thereafter by delineation of common clinical characteristics. In Study II, a familial deletion at 9q22.2q22.32 with variable penetrance was described. Despite several reports of aberrations in the adjacent area at 9q associated with Gorlin syndrome, the patients in this family had a unique phenotype and did not present with the syndrome. In Study III, a familial duplication of chromosome 6p22.2 was described. The duplication caused increased expression of an important enzyme of the γ-aminobutyric acid (GABA) degradation pathway, causing oxidative stress of the brain, and thus, very likely, the mild mental retardation of these patients. These two case studies attempted to pinpoint candidate genes and to resolve the pathogenic mechanism causing the clinical characteristics of the patients. Presenting rare genetic and clinical findings to the international science and medical community enables interpretation of similar findings in other patients. The added value of molecular karyotyping in patients with idiopathic DD is evident. As a first line of testing, arrays with a median resolution of at least 9 Kb should be considered and further characterization of detected aberrations undertaken when possible. Diagnostic whole-exome sequencing may be the best option for patients who remain undiagnosed after high-resolution array analysis.

Ring Resonators and Micro Fluidics: Novel Design for Drug/Disease Detection

MEMS systems are technologically developed from integrated circuit industry to create miniature sensors and actuators. Originally these semiconductor processes and materials were used to build electrical and mechanical systems, but expanded to include biological, optical fluidic magnetic and other systems 12]. Here a novel approach is suggested where in two different fields are integrated via moems, micro fluidics and ring resonators. It is well known at any preliminary stage of disease onset, many physiological changes occur in the body fluids like saliva, blood, urine etc. The drawback till now was that current calibrations are not sensitive enough to detect the minor physiological changes. This is overcome using optical detector techniques 1]. The basic concepts of ring resonators, with slight variations can be used for optical detection of these minute disease markers. A well known fact of ring resonators is that a change in refractive index will trigger a shift in the resonant wavelength 5]. The trigger for the wavelength shift in the case discussed will be the presence of disease agents. To trap the disease agents specific antibody has to be used (e. g. BSA).

1H NMR study of molecular dynamics and phase transition in (NH4)2ZnBr4

The proton second moment (M2) and spin-lattice relaxation time (T1) have been measured in (NH4)2ZnBr4 in the range 77-300 K. The room-temperature spectrum shows a structure which disappears around 243 K. The signal is strong and narrow even at 77 K. Proton T1 shows a maximum at 263 K, caused by spin rotation interaction and decreases with decreasing temperature till 235 K, where it shows a sudden increase. Below 235 K, again it decreases and shows a slope change around 216.5 K (reported Tc). From 216.5 K, T1 decreases continuously without exhibiting any minimum down to 77 K. The narrow line at 77 K, and absence of a T1 minimum down to 77 K indicate the possibility of quantum mechanical tunnelling in this system. Motional parameters such as activation energy and pre-exponential factor have been evaluated for the reorientational motion of the NH+4 ion.

Expression of microinjected foreign DNA in silkworm,bombyx mori

As a prelude to achieving transgenesis in Bombyx mori, conditions have been established for successful microinjection of cloned foreign genes into the silk worm eggs. A sharpened metallic needle is used to pierce the thick chorion layer of the eggsheil, approaching through a droplet of DNA solution deposited on its surface. The microinjection is carried out within 2-2.5 h after oviposition and the injected eggs show 3-5% hatchability and 80-90% survival. Such larvae continuously expressed the microinjected cloned reporter gene, beta-galactosidase, placed under the control of a constitutively expressed cytoplasmic actin A3 gene promoter from B. mori. The expression is seen in different tissues, viz. the fat body, tracheae and the silk glands, till the late larval instars. The microinjected DNA sequences are retained in the adult G(o) moths.

Kinetic evolution studies of silver nanoparticles in a bio-based green synthesis process

Silver nanoparticles are being extensively studied due to their widespread applications and unique properties. In the present study, the growth kinetics of silver nanoparticles as synthesized on reduction of silver nitrate solution by aqueous extract of Azadirachta indica leaves was investigated. The formation of silver nanoparticles was preliminarily monitored by measuring the absorption maxima at different time intervals after adding the reducing agent to the silver salt solution (0.5, 1, 1.5, 2, 2.5, 3, 3.5 and 4 h). At different time points characterization studies were conducted using X-ray diffraction studies, FT-IR techniques, zeta potential studies and transmission electron microscopy. The total available silver in the reaction medium was determined at different durations using ICP-OES. The changes in reduction potential in the medium were also monitored using potentiometric analysis. The results confirm a definite change in the medium pertaining to formation of the stable nanoparticles after 2 h, and a significant increase in the agglomeration tendency after 4 h of interaction. The growth kinetic data of the nanoparticles till 3.5 h was found to fit the LSW model confirming diffusion limited growth. (C) 2011 Elsevier B.V. All rights reserved.

Surface barrier effects in non-resonant microwave absorption by superconducting thin films of YBa2Cu3O7??

We present an unusual temperature dependence of hysteresis in the Lion resonant microwave absorption (NRMA) signals from superconducting thin films of YBa2Cu3O7-delta. We observe that the hysteresis increases with increase in temperature till T-c which we interpret as evidence for the presence of Bean-Livingston surface barriers (BLSB) in the single crystalline films.

The dynamics of the Ramdas layer

A little more than sixty years ago, the late L. A. Ramdas discovered a curious atmospheric phenomenon which had not been satisfactorily explained till recently. The phenomenon is the observation of a temperature minimum some 20-50 cm above bare soil on calm, clear nights. The first reports of these observations were treated with much scepticism, as the prevailing view was that the nocturnal temperature minimum always occurs at ground. In the present address the history of work on the lifted temperature minimum is traced and a new explanation is offered. It is emphasized that in this as well as many other phenomena, it is important to account for surfaces that are not perfectly black radiatively, i.e. those whose emissivity is not unity.

Gas-liquid nucleation at large metastability: unusual features and a new formalism

Nucleation at large metastability is still largely an unsolved problem, even though it is a problem of tremendous current interest, with wide-ranging practical value, from atmospheric research to materials science. It is now well accepted that the classical nucleation theory (CNT) fails to provide a qualitative picture and gives incorrect quantitative values for such quantities as activation-free energy barrier and supersaturation dependence of nucleation rate, especially at large metastability. In this paper, we present an alternative formalism to treat nucleation at large supersaturation by introducing an extended set of order parameters in terms of the kth largest liquid-like clusters, where k = 1 is the largest cluster in the system, k = 2 is the second largest cluster and so on. At low supersaturation, the size of the largest liquid-like cluster acts as a suitable order parameter. At large supersaturation, the free energy barrier for the largest liquid-like cluster disappears. We identify this supersaturation as the one at the onset of kinetic spinodal. The kinetic spinodal is system-size-dependent. Beyond kinetic spinodal many clusters grow simultaneously and competitively and hence the nucleation and growth become collective. In order to describe collective growth, we need to consider the full set of order parameters. We derive an analytic expression for the free energy of formation of the kth largest cluster. The expression predicts that, at large metastability (beyond kinetic spinodal), the barrier of growth for several largest liquid-like clusters disappears, and all these clusters grow simultaneously. The approach to the critical size occurs by barrierless diffusion in the cluster size space. The expression for the rate of barrier crossing predicts weaker supersaturation dependence than what is predicted by CNT at large metastability. Such a crossover behavior has indeed been observed in recent experiments (but eluded an explanation till now). In order to understand the large numerical discrepancy between simulation predictions and experimental results, we carried out a study of the dependence on the range of intermolecular interactions of both the surface tension of an equilibrium planar gas-liquid interface and the free energy barrier of nucleation. Both are found to depend significantly on the range of interaction for the Lennard-Jones potential, both in two and three dimensions. The value of surface tension and also the free energy difference between the gas and the liquid phase increase significantly and converge only when the range of interaction is extended beyond 6-7 molecular diameters. We find, with the full range of interaction potential, that the surface tension shows only a weak dependence on supersaturation, so the reason for the breakdown of CNT (with simulated values of surface tension and free energy gap) cannot be attributed to the supersaturation dependence of surface tension. This remains an unsettled issue at present because of the use of the value of surface tension obtained at coexistence.

Is there a role for estrogen in follicular maturation in the primate

The present study focusses attention on the effects of blocking estrogen synthesis, during follicular phase, on follicular maturation in the adult female bonnet monkey (Macaca radiata). Administration of cycling females (n = 4) with an aromatase inhibitor CGS 16949A (AI) by Alzet mini-pump (2.5 mg/day) from day 3 of cycle resulted in significant reduction in basal (by 53%) and surge levels of estrogen (by 70%) but this had no effect on follicular maturation, ovulation and luteal function as assessed by serum hormone profiles as well as laparotomy. This lack of need for estrogen for completion of follicular maturation process was confirmed by administering cycling monkeys hFSH (25 IU/day) from day 3 till day 8 of the cycle along with (5 mg AI/day) or without Al (n = 3/group). Administration of Al resulted in suppression of FSH induced increase in serum estrogen (by 100%) and elevation in circulating androstenedione. Aromatase inhibitor treatment had no effect on either the number of follicles developed or their size relative to control. Testing the ability of both granulosa and thecal cells, removed on day 9 of treatment cycle, to respond to gonadotropins in vitro showed no change indicating that cellular development and maturation of follicular cells had occurred normally. It is concluded that follicular maturation in the primate can occur even when increase in estrogen synthesis is blocked.