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Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.

Superconducting QUantum Interference Devices (SQUIDs) are extremely sensitive detectors for the measurement of magnetic flux. In particular the high critical temperature SQUIDs, which can be operated at liquid nitrogen temperature with easy cryogenic requirement, are well suited for nondestructive evaluation (NDE) of cracks and corrosion which result from the machining process or aging of electrically conductive structures. The main characteristics of SQUIDs as eddy-cunent NDE sensors are : high sensitivity even in unshielded environments, a large frequency range of operation which allows the detection of surface and subsurface flaws and high spatial resolution. We performed magnetic field measurements on the eddy-current double-D inducing coil, used in many NDE experimental systems, and on 200x100x4m m3Al plates with a 6mm surface-breaking hole using high critical temperature SQUIDs in unshielded environments. The sensitivity to the anomalous magnetic field related to the defect along the three spatial directions is discussed in terms of unperturbed magnetic field distributions due to the eddy-current source.

Tunnel quasi-particle injection into a superconducting film provides useful information on the non-equilibrium state inside the perturbed superconductor as well as on the potential application to electronic devices. Three terminal injector-detector superconducting devices have a long history in non-equilibrium superconductivity. In the recent past non-equilibrium phenomena have attracted again considerable attention because of many superconducting based detectors involve processes substantially non-equilibrium in nature. The possibility of using a stacked double tunnel junction to study the influence of non-equilibrium superconductivity on the Josephson critical current is now considered. An experimental study of the effect of quasi-particle injection on the Josephson current both in steady-state and pulsed experiments down to T=1.2K is presented using 3 terminal Nb-based stacked double tunnel devices. The feasibility of a new class of particle detectors based on the direct measurement of the change in the Josephson current following the absorption of a X-ray quantum is also discussed in terms of non-equilibrium theories.

Josephson tunnel junctions are well known as low temperature electronics devices. However, they are also important as very powerful sensors. A novel class of sensors is constituted by radiation detectors based on superconducting tunnel junctions, which could lead in next future to an advanced instrumentation with an interesting applicative future. So far this area is restricted to low-temperature superconductors. Several superconducting materials have been considered. Among them, Niobium is very attractive because of its highest critical temperature Tc. We have measured detailed X-ray detection characteristics for Nb-based tunnel junction made with different fabrication processes. We will discuss the difference in the X-ray response in terms of the relevant junction's parameters, underlying the problems of the niobium as suitable material for this kind of device.

Superconductors are highly suitable materials for radiation detection. Several detector types have been proposed, with properties of fast detection or high wavelength resolution over a wide range of optical frequencies. Their performances depend on the relaxation processes involving phonons, quasiparticles and Cooper pairs occurring during the energy cascade following the absorption of the radiation in the superconductor. The energy down-conversion processes are related to the electron–phonon scattering strength λe−ph which is usually expressed in terms of the electron–phonon coupling time, τ0, which is characteristic for each material. In this paper we estimate the value of τ0 for several classes of superconducting materials not yet investigated. It is calculated in the framework of the McMillan model for the superconducting critical temperature Tc within the Debye approximation. The values obtained for τ0 are discussed as regards new possibilities for unexplored materials in the field of superconducting detectors. In particular, we focus our attention on materials with τ0 values that could play a significant role in both hot electron photodetectors and superconducting tunnel junction devices.

After about 10 years of experience, laparoscopic adrenalectomy has become the gold standard for the treatment of adrenal lesions. Here, we describe the presenting features, imaging methods, and current surgical approaches to diseases of the adrenal gland. There is general agreement on the suitability of the laparoscopic approach for benign adrenal lesions, but controversy exists about using laparoscopy for suspected adrenal malignancy, metastasis, and partial adrenalectomy. This article reviews the literature on laparoscopic adrenalectomy. In particular, we focus our attention on the new surgical approaches to the gland. We evaluate the indications, operative techniques, and tools for partial adrenalectomy, and we discuss new surgical strategies such as cryosurgery and radiofrequency ablation.

Three-terminal superconducting devices which operate on the basis of the non-equilibrium state produced in the intermediate electrode by quasi-particle injection are very promising for their transistor-like properties at T &equal; 4.2 K. Nb-based stacked double-tunnel junction structures with Nb/Al as an intermediate electrode can produce large current amplification at T &equal; 4.2 K when the Al film is in the normal metal state. Experimental results are discussed in the framework of the QUAsiparticle TRApping TRANsistor. The possibility of using a stacked double junction structure to study the proximity effect in thin superconducting bilayers is also discussed. In particular, the stacked devices are particularly useful for determining both the effective interface coupling parameters, the quasi-particle density of states and the Cooper pair potential at both sides of the bilayer. The knowledge of the Nb/Al interface parameters can be very useful for determining non-equilibrium behaviour of proximized structures. Measurements concerning the steady-state and pulsed characterizations of the stacked double Josephson devices are also presented. The possibility of a flip-flop state for these devices has been demonstrated. Experimental results are compared with numerical simulations based on the perturbed sine–Gordon model of the stack in the presence of pulsed electronic pumping.

Abstract:: A new fabrication process for three-terminal superconducting devices consisting of two Josephson junctions in a stacked configuration is reported. The process is based on the deposition of the whole Nb/AlxOy/Nb-Al/AlxOy/Nb multilayer on a Si crystalline wafer without any vacuum breaking. Lift-off techniques, anodization processes and a SiO film deposition have been adopted for patterning and insulating the two tunnel stacked junctions. Devices have been characterized in terms of current-voltage (I-V) curves and Josephson critical current vs. the externally applied magnetic field. They show high quality factors (V m values up to 65 mV at 4.2 K), and good current uniformity.

Bioactive macromolecules resulting from chemical modification of hyaluronic acid (Hyal) have been designed to improve the compatibility of biomaterials used for cardiovascular prostheses. Hyal has been sulphated to obtain derivatives (HyalS) with a number of sulphate groups ranging from 1 to 4 per disaccharide unit. Hydrogels of Hyal have been obtained by cross‐linking the free polysaccharide. An appropriate Hyal/cross‐linking agent ratio has produced a hydrogel with a degree of crosslinking of 50%.

There are many data on the activity of the RBgene in neural differentiation and apoptosis, but the role of pRb2/p130 in neuronal and glial maturation has been far less investigated. To elucidate the role of pRb2/p130 in astrocyte development we overexpressed this protein in astrocytoma and normal astrocyte cultures by adenoviral-mediated gene transfer. In astrocytoma cells, p130/RB2 overexpression resulted in a significant reduction of cell growth and in an increased G0/G1cell population. We did not observe any induction of programmed cell death as determined by TUNEL reaction. Interestingly, pRb2/p130 overexpression induced astrocyte differentiation. Astrocyte cell cycle arrest and differentiation seemed to proceed through a way distinct from the p53 pathway.

The understanding of substrate dependence of cellular differentiation is important in the surface design of biocompatible artificial devices as well as cell-incorporated tissue engineered devices. In an attempt to understand some of the genetic and epigenetic aspects of the control of cell differentiation in the presence of two different materials, Chronoflex (CH) and plasma treated Chronoflex coated with Hyaluronan (CH-HA), we used primary cultures of human myogenic cells, a model that encompasses cell proliferation, migration, fusion, and differentiation dependent gene activation. By testing both the material samples on the growth of human myoblasts in primary cultures, we demonstrated that both CH and CH-HA substrates were able to support the cell growth since they did not affect cell count and DNA synthesis. On the contrary, the degree of myoblast differentiation, assessed as a function of creatine phosphokinase (CPK) activity on living cells, was completely different on the two biomaterials. Indeed, the amount of CPK increased on CH-HA cultured cells as a result of myotube formation, while CH grown myoblasts remained unfused and displayed no increase on the CPK activity even after 12 days culture. Moreover, the expression level of MyoD and myogenin mRNA, both related to myogenic cell differentiation, appeared extremely low in CH-grown cells, while they were rapidly induced in CH-HA cultured myoblasts. © 1999 Kluwer Academic Publishers

During the last few years, on the basis of their physico-chemical characteristics, thermoplastic materials, already used in several advanced industries, have become very attractive candidates for biomedical applications as matrix for composite femoral stems and bone plates. In the present study, the biocompatibility of a thermoplastic material, polyetherimide (PEI), was investigated both in vivo, and in vitro. Our results show that PEI did not elicit any toxic response in cell culture testing. It was possible to grow on PEI surfaces not only 3T3 fibroblasts but also human endothelial cells (HEC) from human umbelical cord, with no apparent deleterious effects on the cell viability. The attachment, spreading, and growth of cells on PEI material was followed with respect to time. Both the number of adhering HEC, and the spreading area of individual cells, increased as a function of time. The hydrogen peroxide-sensitive dye DCFH-DA was used to examine the functional activity of cells adherent to PEI or control material implants. PEI material did not induce significant DCFH oxidation until day 14, when levels of DCFH oxidation were significantly higher than observed with PDMS negative control, but lower than those observed on Pellethane positive control.

In this work the proliferation of mitogen-activated human T lymphocytes, and human endothelial cells (HEC) adhesion and growth have been evaluated in vitro with two segmented polyurethanes (SPUs) having different chemical structure: Pellethane 2363-80A, a poly-ether-urethane, and Corethane 55D, a polycarbonate-urethane. The effect of the two SPUs on phytohemoagglutinin (PHA)-induced T-cells proliferation was analysed by evaluating both morphological changes of the lympho-monocyte system with scanning electron microscopy (SEM), and the perturbation of cell cycle progression with a cytofluorimetric technique. Results showed that, although the PHA stimulation of T-cells cultured on Corethane was sufficient to induce entry into the cell cycle, as evidenced by an increase in RNA content, the DNA synthesis appeared similar to that of unstimulated cultures. On the other hand, there was a significant increase of the DNA and RNA content in the culture performed in the presence of Pellethane, as in the case of PHA-stimulated control cultures. Moreover, in comparison with Pellethane, a strong decrease in monocyte attachment and spreading was observed on Corethane; with lymphocytes scattered around the monocytes, and not attached to them as in the case of Pellethane. In the experiment with HEC, the cells were directly seeded on the materials, and the number of cells attached after 4 and 72 h culture was then evaluated, the former reading being a measure for cell adhesion, the latter indicating the capacity of the cells to proliferate. Although both SPUs allowed a HEC adhesion lower than the positive control, it was possible to confirm that Pellethane well supports cell proliferation, whereas Corethane is less prone to promote cell growth

The pretreatment of epididymal spermatozoa with SV-IV, one of the major secretory protein produced by the epithelium of adult rat seminal vesicles, was found to markedly decrease their ability to induce in vivo peritoneal macrophage activation, measured as class II major histocompatibility complex surface antigen expression, superoxide anion production, phagocytic activity, and antigen presentation. In addition, the treatment of spermatozoa with SV-IV produced a significant decrease of their immunogenicity evaluated in vitro by [3H]thymidine incorporation in splenocyte/spermatozoon co-culture. The concurrent presence of SV-IV and transglutaminase, an enzyme secreted in large amounts from the rat anterior prostate, amplified these phenomena. The suppression of the epididymal sperm immunogenicity is suggested to be of crucial importance for the prevention of the immune response to the sperm introduced in the immunocompetent female genital tract during coitus.

Carnitine is present in the eye tissues of the rabbit and the highest concentration is found in the lens.

Measurements of the temperature dependence of the maximum dc Josephson current in V-VxOy-Pb tunnel structures have been performed. Junctions exhibiting a vanadium critical temperature close to the bulk value and a uniform supercurrent density have been considered. In spite of the high quality of the samples, the results still differ markedly from the BCS calculation of Ambegaokar and Baratoff.

Measurements on the temperature dependence of the magnetic field penetration in Nb-NbxOy-Pb and V-VxOy-Pb Josephson junctions have been performed. Results on the zero-temperature penetration depth in niobium films are far above the bulk values although consistent with other measurements on junctions reported in the literature. For vanadium junctions anomalously large penetration depth values are obtained at low temperatures. Nevertheless, the temperature dependence is in reasonable agreement with the local dirty limit model.

The thermodynamic Lagrangian formulation of nonequilibrium statistical mechanics is extended to include linear interacting processes that are weakly coupled with wide separation of time scales. The kernel, which is the probability for a transition from one nonequilibrium state to another, is an exponential function of the time integral of the sum of dissipation functions (the thermodynamic Lagrangian). The equilibrium time correlation function is the expectation value of this kernel. In the presence of interactions, the kernel contains a thermodynamic Lagrangian of interaction. Provided that there is a wide separation of time scales between the primary process, having the largest relaxation time, and the weakly coupled set of irreversible processes that make up the environment, the configuration space variables of the processes comprising the environment can be integrated out by the correlation function as the expectation value of the influence functional which is evaluated by means of the unperturbed thermodynamic action. Since energy can be temporarily stored in the environment, which is equivalent to a set of oscillators that are independently coupled to the primary process, noninstantaneous interactions occur in which the primary process at one time can affect itself at a later time. Noninstantaneous interactions are the cause of memory effects that are observed in the transport properties of the primary process. The operator and path integral formulations are shown to be equivalent. Si estende la formulazione della meccanica statistica del nonequilibrio in termini di lagrangiana termodinamica a processi lineari interagenti che si accoppiano debolmente con scale dei tempi molto diverse. Il kernel, cioè la probabilità di transizione tra due stati di nonequilibrio, è l’esponenziale dell’integrale rispetto al tempo della somma delle funzioni di dissipazione (la lagrangiana termodinamica). In presenza di interazione, il kernel contiene una lagrangiana termodinamica di interazione. Se il processo primario, che ha un tempo di rilassamento più lungo, e i processi irreversibili debolmente accoppiati che costituiscono l’ambiente si manifestano su scale dei tempi molto diverse, le variabili dello spazio delle configurazioni dei processi che costituiscono l’ambiente possono essere integrate. Si ottiene in questo modo la funzione di correlazione come il valore di aspettativa del funzionale influenza valutato usando l’azione termodinamica imperturbata. Poiché l’ambiente, descritto come un insieme di oscillatori accoppiati indipendentemente con il processo primario, può immagazzinare temporaneamente energia, si hanno interazioni non istantanee in cui il processo primario in un certo istante può modificare se stesso ad un istante successivo. Queste interazioni non istantanee causano gli effetti di memoria osservati nella proprietà di trasporto del processo primario. Si mostra che le formulazioni in termini di operatori ed in termini di integrale di cammino sono equivalenti. Формулировка термод инамического Лагранжиана неравно весиой статистической меха ники обобщается для т ого, чтобы включить линейные пр оцессы взаимодействия, кото рые слабо связаны из-з а широкого временного интер вала. Ядро, которое пре дставляет вероятнос ть перехода из одного неравновес ного состояния в друг ое, является экспонен циальной функцией ин теграла по времени экспоненциальной фу нкцией интеграла по в ремени от суммы диссиипатив ных функций (термодин амический Лагранжиан). Равновес ная временная корреляци онная функция предст авляет величину ожидания для этого ядра. При нал ичии взаимодействий ядро содержит термодинам ический Лагранжиан в заимодействия. При ус ловии, что имеется шир оки взаимодействия. При у словии, что имеется ши рокий временной инте рвал между первичным процессом, который им еет наибольшее время релаксац временной интервал м ежду первичным проце ссом, который имеет на ибольшее время релак сации, и слабо связанн ой системой необрати мых процессов, которы е происходят в окружа ющей среде; пер который имеет наибол ьшее время релаксаци и, и слабо связанной си стемой необратимых п роцессов, которые про исходят в окружающей среде; переменные, опи сывающие эти процесс ы в конфигурационном пространстве, включа я окружающую среду, мо г связанной системой н еобратимых процессо в, которые происходят в окружающей среде; пе ременные, описывающи е эти процессы в конфи гурационном простра нстве, включая окружа ющую среду, могут быть проинтегрированы, в происходят в окружаю щей среде; переменные, описывающие эти проц ессы в конфигурацион ном пространстве, вкл ючая окружающую сред у, могут быть проинтег рированы, в описывающие эти проц ессы в конфигурацион ном пространстве, вкл ючая окружающую сред у, могут быть проинтег рированы, в пространстве, включа я окружающую среду, мо гут быть проинтегрир ованы, в проинтегрированы, в результате чего полу чается корреляционн ая функция, как величина ожидани я для функционала влия ния, который оценивае тся с помощью невозмущенн ого термодинамическ ого действия. Так как э нергия может временн о запасаться в Так как энергия может временно запасаться в окружающей среде, кот орая эквивалентна си стеме осцилляторов, связан ных независимым образом с первичным процессо м, то могут иметь место немгнове нные взаимодействия, в которых первичный п роцесс в один момент в ремени может возде первичный процесс в о дин момент времени мо жет воздействовать н а себя в последующий м омент времени. Немгно венные взаимодейств ия являются причиной эф воздействовать на се бя в последующий моме нт времени. Немгновен ные взаимодействия я вляются причиной эфф ектов памяти, которые наблюдаются в трансп ортных Немгновенные взаимо действия являются пр ичиной эффектов памя ти, которые наблюдают ся в транспортных эффектов памяти, кото рые наблюдаются в тра нспортных свойствах первичног о процесса. Показывае тся, что операторная формули ровка эквивалентна формул ировке с помощью инте гралов по траекториям.

Urine proteins in the molecular weight range of 9–137 kDa deposit to an equal extent from pooled human urine onto glass (12.7 ± 1.9 µg/cm) and polystyrene (11.8 ± 1.8 µg/cm). Selective desorption of the proteins was achieved by washing with water or water/isopropanol mixtures. Irrespective of the washing process, proteins of molecular weight greater than 90 kDa remained associated with both surfaces while water washings alone removed most low molecular weight material. A 29 kDa protein, a-1-microglobulin, was removed from glass by water washing but required a 30% (v/v) isopropanol wash to desorb from polystyrene, implying attachment via hydrophobic bonding. The adhesion to polystyrene surfaces of Pseudomonas aeruginosaB4, a clinical isolate from a urinary tract infection (UTI), was strongly associated with the presence of a-1-microglobulin, which may be acting as a mediator of bacterial adhesion. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 365–370, 1998.

Because of its chemical versatility and demonstrated biocompatibility, poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used as a polymer for biomedical applications. Since this hydrophilic material shows a poor interface with cells, blendings with other polymers were done to improve cytocompatibility. In our polymer, the presence of hydrophobic dominions on the material surface, due to the interpenetrating polymerization of pHEMA with poly(caprolactone) (PCL), seems to ameliorate the cytocompatibility in terms of cell adhesion and metabolism. For our experiments, we used IMR-90 human fibroblasts, as these cells strongly regulate DNA, RNA, and protein synthesis as anchorage-dependent variables. Cell attachment on a pHEMA/PCL interpenetrating polymer network was optimal, suggesting a strong adhesion between the cells and the polymer surface. Cell adhesion was weaker on pHEMA, as a significant fraction of the fibroblasts revealed a lack of spreading, with most cells remaining spherical. Moreover, only fibroblasts seeded on pHEMA significantly decreased mRNA synthesis; collagen production and cell shapes ranged from fully flat and proliferating, to minimally spread and nonproliferating. Finally, DNA synthesis, as a measure of cell proliferation, was markedly inhibited in cells cultured on pHEMA but not on pHEMA/PCL. In conclusion, our results suggest that control of cell growth and metabolism by biomedical polymers is based on physicochemical mechanism(s) in which the hydrophilicity/hydrophobicity ratio of the material surfaces may play an important role. © 1997 John Wiley & Sons, Inc.

We have designed and tested a 5×5 mm2 chip which includes 24 “island” Josephson tunnel junctions (STJs) with square, circular and diamond geometries, two arrays of 100 “island” junctions and other detection devices. The junctions were based on Nb-AlOx-Nb trilayers, obtained on Si substrate by a process consisting of underlayer Nb deposition, self-aligned insulation and anodization steps. The junction quality was extensively tested by measurements of the I–V characteristics down to T=1.2 K. IcRn values up to 2.16 mV have been obtained. Preliminary results concerning the response of these samples to 6 keV X-ray radiation are discussed. Effects of the substrate on the detector response have also been observed and reported. A rough estimation of the energy resolution gives about 700 eV. The quality of the junctions is such that the electronic noise is the predominant limitation to the ultimate resolution.

The effect of a nonhomogeneous base electrode on point contact spectroscopy is discussed in the framework of the proximity effect, and a phenomenological model is proposed. The appearance of zero-bias anomalies and bumps in thedI/dV vs.V characteristics is explained through our model, in agreement with experimental evidence on high- and low-critical-temperature superconductors.

In this paper the influence of proximity effects on the transport properties of high-Tc superconductors is considered. On the basis of the experimental results on tunneling spectroscopy reported in the current literature, we discuss some of the main features ofdI/dV vs.V characteristics. More particularly, attention is focused on the depression of gap structure, the presence of conductance peaks due to the counterelectrode gap, and “zero-bias anomalies.” A possible explanation of those features in terms of the McMillan proximity model is given along with some examples of application of the model to experimental data.

superconducting thin films by Mo75Re25 single-target magnetron sputtering at various temperatures on sapphire substrates were prepared. Sharp superconductive transitions andTcvalues above 10 K were achieved, and the deposited films showed a good metallic behavior. According to structural analyses (EDS and X-rays), all the samples have the same stoichiometry as the target and, even at low deposition temperatures, they exhibit theA15 phase. From measured residual resistivities and superconducting critical temperatures the theoretical BCS surface resistances were estimated and compared to those o Mo60Re40 films, presented in a previous work. Both these alloys, in fact, being characterized by low surface resistances and high critical fields, are good candidates as coating films in r.f. cavities.

Cell interaction(s) with biomaterial undergo a multistep-step paradigm of adhesion, contact, attachment, and spreading. However, the molecular mechanism(s) underlying the cell anchorage on a material surface is not yet well understood. Transglutaminases, a family of calcium-dependent enzymes, has been implicated in the interactions between cells and extracellular matrix. To investigate the functions of this enzyme in cell-material interactions, Balb-C 3T3 fibroblasts were cultured, stably expressing high levels of tissue transglutaminase (TGase), on dishes precoated with thin layers of the hydrophilic hydrogel poly (2-hydroxyethyl methacrylate) (polyHEMA). Results suggest that in the presence of a relatively high poly (HEMA) dilution, the transfected cells showed a more complex morphologic pattern, characterized by many spread and flattened cells, in comparison with a control culture. These studies support the hypothesis that the overexpression of tissue transglutaminase may contribute both to changes in cellular morphology and adhesiveness.

Biodegradable aliphatic polyamides have been prepared from CIO and C14 dicarboxylic acids and amide-diamines containing one or two preformed amide linkages susceptible to enzymatic cleavage in their molecules. L-phenylalanine, either by itself or together with L-valine, was used to generate amide bonds which are cleavable by chimotrypsine. Improved chain flexibility and hydrophilicity of the polyamides was obtained using a triethyleneoxy based amide-diamine. Characterization of the novel monomers and polymers by FTIR and 1H-NMR spectroscopy confirms the expected structures. Thermal data and solubility tests indicate that both Tmand solubility depend on the length and nature of the aliphatic segment present in the amide-diamine as well as on the “density” of interchain hydrogen bonds. Finally the polymers tested are capable of supporting fibroblast adherence and proliferation, and proved to be non cytotoxic.

Abstract. T-lymphocyte subpopulations, anti-thyroid microsomal antibody titres, and free triiodothyronine and free thyroxine levels were investigated in 10 patients with Graves' disease before, during and after pregnancy. Twenty pregnant subjects and 100 normal age-matched, non-pregnant female volunteers served as controls.Pregnant patients with Graves' disease showed decrease levels of free triiodothyronine and free thyroxine, and decreased titres of anti-thyroid microsomal antibodies, with clinical remission during the second and third trimesters of pregnancy. Post partum, 9 patients showed clinical relapse, and all showed a return of enhanced levels of free triiodothyronine, free thyroxine and anti-thyroid microsomal antibodies.The percentage and absolute number of total T-lymphocytes (OKT3+) and OKT4+cells significantly decreased during pregnancy in patients with Graves' disease and in normal women. Post partum, OKT3+and OKT4+cells returned to pre-pregnancy levels in both groups. In Graves patients and in controls, the percentage and absolute number of OKT8+cells during pregnancy and post partum were not significantly different from pre-pregnancy levels. Lastly, the OKT4+/OKT8+ratio, which decreased in normal subjects at the three sampling times during pregnancy, decreased only in the last two trimesters of pregnancy in patients with Graves' disease.

Following the characterization of polyoxypregnane esters and esterified glycosides from the less polar extracts of Leptadenia hastata, 34 new congeners have been isolated from the more polar extracts. They possess sarcostin or deacetylmetaplexigenin as the aglycons and acetyl, benzoyl, cinnamoyl, nicotinoyl, and m-hydroxybenzoyl residues as the ester moieties linked at C-12 and/or C-20 of the aglycons. The oligosaccharide moiety linked to C-3 of the aglycons was made up of three to five 2,6-dideoxy-3-O-methylpyranoses, 6-deoxy-3-O-methylpyranoses, or glucose. Their structures have been elucidated on the basis of spectral evidence. Glycosides with more complex oligosaccharidic chains were tested for their antitumor activity on Raji cells.

A comparison of both amino acid composition and sequence of the rabbit uteroglobin (UG) subunit and the rat seminal vesicle sperm-binding protein (rSBP) by computer analysis indicates homology between the two polypeptide chains. These findings are supported by immunological studies showing the occurrence of similar antigenic determinants. In addition, our data indicate the glutamine-9 of the rat seminal vesicle sperm-binding protein and glutamine-40 of UG as the possible glutamine residues involved when the proteins act as transglutaminase (TGase) substrates. The latter results represent an interesting approach to determining the general structural features of the acyl donor site in the TGase-catalyzed reaction.

Abstract: Nb−Al−AlOx−Al−Nb−Al−AlOx−Nb Josephson Tunnel structures have been fabricated and investigated. The configuration of such structures allows to measure separately top and bottom junctions, i.e. injection and detection junctions respectively. Current-voltage characteristics have been measured at temperatures down to 1.2 K for different values of the injection current. The detection efficiency of the device has been also investigated in order to get information about the non-equilibrium relaxation processes which take pace into a steady-state non-equilibrium Nb layer.

Whitham's averaged Lagrangian approach to the asymptotic analysis of non-linear dispersive wave trains is generalized to include non-linear dissipation. The averaged thermodynamic Lagrangian analysis is applied to wave equation analogues of the classic Van der Pol equation. In the case of linear dispersion, the amplitude tends asymptotically to a specific, finite value that is independent of arbitrary initial or boundary conditions. The phenomenon can be considered to be the wave analogue of limit cycles in non-linear mechanics. In the case of non-linear dispersion, the previous analysis does not provide information regarding the asymptotic development of the non-linear dissipative and dispersive wave train. A different averaging method is employed which utilizes the properties of the unknown solution of the non-linear equation. A limit wave phenomenon is found in the case where the system is hyperbolic.