A Survey on the Impact of Intelligent Surfaces in the Terahertz Communication Channel Models.

Terahertz (THz) band will play an important role in enabling sixth generation (6G) envisioned applications. Compared with lower frequency signals, THz waves are severely attenuated by the atmosphere temperature, pressure, and humidity. Thus, designing a THz communication system must take into account how to circumvent or diminish those issues to achieve a sufficient quality of service. Different solutions are being analyzed: intelligent communication environments, ubiquitous artificial intelligence, extensive network automation, and dynamic spectrum access, among others. This survey focuses on the benefits of integrating intelligent surfaces (ISs) and THz communication systems by providing an overview of IS in wireless communications with the scanning of the recent developments, a description of the architecture, and an explanation of the operation. The survey also covers THz channel models, differentiating them based on deterministic and statistical channel modeling. The IS-aided THz channels are elucidated at the end of the survey. Finally, discussions and research directions are given to help enrich the IS field of research and guide the reader through open issues.

Adaptive focusing for transcranial ultrasound imaging using dual arrays.

Ultrasonic brain imaging remains difficult and limited because of the strong aberrating effects of the skull (absorption, diffusion and refraction of ultrasounds): high resolution transcranial imaging would require adaptive focusing techniques in order to correct the defocusing effect of the skull. In this paper, a noninvasive brain imaging device is presented. It is made of two identical linear arrays of 128 transducers located on each side of the skull. It is possible to separate the respective influence of the two bone windows on the path of an ultrasonic wave propagating from one array to the other, and thus estimate at each frequency the attenuation and phase shift locally induced by each bone window. The information obtained on attenuation and phase is used to correct the wave fronts that have to be sent through the skull in order to obtain a good focusing inside the skull. Compared to uncorrected wave fronts, the spatial shift of the focal spot is corrected, the width of the focal spot is reduced, and the sidelobes level is decreased up to 17 dB. Transcranial images of a phantom are presented and exhibit the improvement in image quality provided by this new noninvasive adaptive focusing method.

Anti-growth factor activities of benzothiophenes in human breast cancer cells.

We have tested the effects of two Eli-Lilly compounds, LY 117, 018 and raloxifene, on E2-regulated and IGF-I-induced proliferation or AP-1 activity in human breast cancer cells. We now demonstrate that both molecules have strong antiestrogenic and anti-growth factor inhibitory effects in MCF7 cells. They were as potent as ICI 182, 780 and more efficient than OH-Tam to prevent estradiol action whereas their inhibition on IGF-I stimulation was less than with ICI 182, 780 and equivalent to that of OH-Tam. Moreover, raloxifene was the most efficient molecule to prevent IGF-I-induced AP-1 activity, with a significant effect observed with a concentration as low as 5 x 10(-11)M in the presence of IGF-I alone. Similar dose-response curves were obtained with a combined treatment of IGF-I and E2 with a 2log shift. Their action on IGF-I-induced proliferation was completely abrogated in MCF7 transfectants in which the expression of an antiestrogen-regulated protein tyrosine phosphatase, PTPL1, was abolished by antisense RNA transfection. Accordingly, they were both able to dose-dependently regulate the expression of PTPL1 and to interfere with the PI3-K/Akt pathway by drastically decreasing Akt phosphorylation exclusively in wild-type PTPL1 expressing cells. Our data altogether demonstrate that raloxifene has a potent inhibitory effect on IGF-I action, with a drastic effect on AP-1 triggered responses as well as on Akt phosphorylation, suggesting that it might be a useful therapeutic agent in tumors in which these signalling pathways become constitutively active.

Loss of ERbeta expression as a common step in estrogen-dependent tumor progression.

The characterization of estrogen receptor beta (ERbeta) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and the mitogenic effects of estrogen in these tissues (such as breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERbeta expression in cancer as compared with benign tumors or normal tissues, whereas ERalpha expression persists. The loss of ERbeta expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERalpha target genes by ERbeta or ERbeta-specific gene induction could explain that ERbeta has a differential effect on proliferation as compared with ERalpha. ERbeta may exert a protective effect and thus constitute a new target for hormone therapy, such as ligand specific activation. The potential distinct roles of ERalpha and ERbeta expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review.

Histone deacetylase inhibition and estrogen receptor alpha levels modulate the transcriptional activity of partial antiestrogens.

In this study, we have analysed the effects of histone deacetylase (HDAC) inhibition on estrogen receptor (ER) expression and on its transcriptional activity in response to antiestrogens. In several breast cancer cell lines, trichostatin A (TSA), a potent HDAC inhibitor, strongly decreases ERalpha expression in a dose-dependent manner. This repression is observed independently of the presence of ligand and also occurs in ovarian and endometrial cell lines. In addition, we show that in MCF7 cells bearing a stably transfected reporter plasmid (MELN cells), partial antiestrogens such as 4-OH-tamoxifen (OHTam), raloxifen or LY117018, switch to an agonist activity upon HDAC inhibition. This effect is blocked by the pure antiestrogen ICI182780 and exhibits a half-maximal concentration of OHTam equivalent to its affinity for ERalpha. The TSA-dependent decrease of ERalpha expression is required to induce the agonist switch of OHTam properties as it is lost in cells constitutively expressing exogenous receptors (MELN-ERalpha or ERbeta). By contrast, the transrepression activity of OHTam is abolished by TSA independently of the decrease of ERalpha expression. Interestingly, in MELN-ERalpha, ICI182780 remains inhibitory suggesting the involvement of HDAC-independent mechanisms. Finally, in the absence of TSA, transcriptional activity in response to OHTam is significantly raised in MELN cells expressing low levels of ERalpha after transfection of antisense oligonucleotides. In conclusion, inhibition of HDAC enzymatic activity and modulation of ERalpha levels tightly control the relative agonist activity of partial antiestrogens on a stably integrated reporter transgene.

[Clinical assessment of the risk of Human Immunodeficiency virus (HIV) infection in the population consulting an anonymous and free screening center]. / Evaluation clinique du risque d'infection par le virus de l'immunodéficience humaine (VIH) de la population consultant dans un centre de dépistage anonyme et gratuit (CDAG).

INTRODUCTION: The anonymous and free AIDS screening centers were developed in France in 1987 to incite the general population to undergo screening for HIV infection. The aim of this paper was to conduct a prospective study describing the principle characteristics and level of risk of those consulting a center in the Year 1999. POPULATION AND METHODS: A face to face physician-consultant questionnaire was proposed to all the consultants that Year. It included 20 questions regrouped in general characteristics of the subject, number of previous screenings, reason for screening, type of risk taken, date of last risk taken, and number of sexual partners during the past 12 Months and throughout their life without the use of a condom. RESULTS: Two thousand six hundred seventy-eight persons consulted (sex ratio=1) aged a mean of 25.8 Years. The men were older than the women (respectively 27 versus 24.6; p<0.05). The reason for screening was a decision made by the couple in 44.6 p. 100, an unprotected sexual relationship in 47.6 p. 100 another reason in 7.6 p. 100 and drug abuse in 0.2 p. 100 of cases. The sex mode declared was heterosexual in 94.5 p. 100 and homo or bisexual in 5.4 p. 100. The majority of those consulting (66.2 p. 100) had had between 0 and 2 partners during the past 12 Months; 66 p. 100 had had more than 10 during their life without using a condom. The assessment of the global risk by the physician was: very high in 1 p. 100, high in 2.5 p. 100, moderate in 13.3 p. 100, low in 70.7 p. 100 and nil in 12.5 p. cent. Five HIV infections were diagnosed, all in persons at high or very high risk. DISCUSSION: These results should stimulate the radical differentiation of the management of persons consulting according to the level of risk identified by the medical questionnaire.

Oestrogen receptor alpha increases p21(WAF1/CIP1) gene expression and the antiproliferative activity of histone deacetylase inhibitors in human breast cancer cells.

We analysed the antiproliferative activity of various histone deacetylase (HDAC) inhibitors such as trichostatin A (TSA) on human breast cancer cells. We observed a lower sensitivity to HDAC inhibition for oestrogen receptor negative (ER-) versus positive (ER+) cell lines. This differential response was associated neither with a modification of drug efflux via the multidrug resistance system nor with a global modification of histone acetyltransferase (HAT)/HDAC activities. In contrast, we demonstrated that in ER+ breast cancer cells the p21(WAF1/CIP1) gene was more sensitive to TSA regulation and was expressed at higher levels. These differences were observed both in transient transfection experiments and on the endogenous p21(WAF1/CIP1) gene. The Sp1 transcription factor, which was shown to interact in vitro with both class I and class II HDACs, is sufficient to confer the differential sensitivity to TSA and participated in the control of p21(WAF1/CIP1) basal expression. Finally, re-expression of ERalpha following adenoviral infection of ER- breast cancer cells increased both p21(WAF1/CIP1) protein accumulation and the growth inhibitory activity of TSA. Altogether, our results highlight the key role of ERalpha and p21(WAF1/CIP1) gene expression in the sensitivity of breast cancer cells to hyperacetylating agents.

Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells.

Intranasal administration of hormone replacement therapy presents an original plasma kinetic profile with transient estrogen levels giving rise to the concept of pulsed therapy. To further understand the molecular effects of this new therapy, we have compared the effects of pulsed and continuous estradiol treatments on two critical aspects of estradiol action: gene expression and cell proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h continuous treatments at concentrations such that the 24-h exposure (concentration x time) was identical in both conditions. In MCF7 cells, the transcriptional activity of estrogen receptors (ER) on a transiently transfected responsive estrogen response element-luciferase reporter construct was shown to be drastically (approximately 10-fold) and similarly stimulated after both treatments. Moreover, the increased mRNA expression of three representative estradiol-sensitive genes (pS2, cathepsin D, progesterone receptor), evaluated by Northern blot, was identical after 1-h pulse with 7 nM estradiol or continuous treatment with 0.29 nM estradiol with the same kinetic profile over 48 h. Proliferation was quantified by a histomorphometric method on primary cultures of human normal breast cells from reduction mammoplasties and using a fluorescence DNA assay in six human breast cancer cell lines which were ER positive or negative. After a 7-day treatment period, estradiol had no effect on the proliferation of the three ER negative cell lines (BT20, MDA MB231, SK BR3) but significantly stimulated the proliferation of the normal cells and of the three tumoral hormone-sensitive cell lines (MCF7, T47D, ZR 75-1); both hormone treatments producing the same increases in cell growth. In conclusion, we have shown that the genomic or proliferative effects of estradiol were identical with pulsed or continuous treatments, thus indicating that estrogenic effects are not strictly related to concentrations but rather to total hormone exposure.

[Hungry bone syndrome after surgical treatment of severe primary hyperparathyroidism: about 3 cases]. / Hungry bone syndrome après traitement de l'hyperparathyroïdie primaire sévère.

Persistant hypocalcemia occurring after surgical treatment of severe primary hyperparathyroidism may be due to transient or permanent hypoparathyroidism but also to a bone disease. We report three cases of hypocalcemia after surgery of large parathyroid adenoma or hyperplasia in women. Plasma calcium, phosphate and PTH levels are in accordance with Hungry Bone Syndrome (HBS). HBS is related to both excessive bone demineralization and turn over. It is a major importance to distinguish HBS from surgical hypoparathyroidism in order to start early the appropriate treatment given for a long period.

ER beta inhibits proliferation and invasion of breast cancer cells.

Recent studies indicate that the expression of ER beta in breast cancer is lower than in the normal breast, suggesting that ER beta could play an important role in carcinogenesis. To investigate this hypothesis, we engineered ER-negative MDA-MB-231 (human breast cancer cells) to reintroduce either ER alpha or ER beta protein with an adenoviral vector. In these cells, ER beta (as ER alpha) expression was monitored using RT-PCR and Western blot. ER beta protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of E2. ER beta and ER alpha induced the expression of several endogenous genes such as pS2, TGF alpha, or the cyclin kinase inhibitor p21 but, in contrast to ER alpha, ER beta was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ER alpha and ER beta estrogen-induced activities. ER beta inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ER alpha inhibition of proliferation is hormone dependent. Moreover, ER beta and ER alpha decreased cell motility and invasion. Our data bring the first evidence that ER beta is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ER beta expression could be one of the events leading to the development of breast cancer.

[Non-genomic steroid effects: estrogen action revisited]. / Les effets non-transcriptionnels des oestrogènes refont surface.

Estrogen receptors (ERs) are members of the nuclear receptor superfamily and act classically as transcription factors. However, it has been noted that estrogens could have early cell effects (within a few minutes) that cannot be explained by transcription activation and protein synthesis. There is now an emerging body of evidence that estrogens, like many other steroids, may cause rapid activation of signal transduction pathways. These non-genomic effects involve common second messengers, such as increased intracellular calcium levels phosphoinositide turnover or cAMP accumulation. Recent studies have also shown that estrogens can stimulate the MAP kinase signaling pathway through ERs. These effects have been observed in various estrogen target cells, including endothelial cells, osteoblasts, neurons and breast cancer cells. The ER membrane signaling pathway is thus a new component that could be taken into account to understand the complex modulation of estrogen effects in specific tissues. It could also be a new therapeutic target for the treatment of neurodegenerative, cardiovascular or breast cancer diseases.

Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines.

We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormone-dependent MCF7 cell line, within the pS2 gene 5'-flanking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located -10.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor alpha, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor alpha, there was only one hormone-independent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-flanking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions -2.3 Kb and -3.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormone-independent DNase I hypersensitive site, catD-HS4, located at position -4.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.

Extinction of insulin-like growth factor-I mitogenic signaling by antiestrogen-stimulated Fas-associated protein tyrosine phosphatase-1 in human breast cancer cells.

Steroidal (ICI 182, 780) and nonsteroidal hydroxytamoxifen (OH-Tam) antiestrogens inhibit growth factor-mitogenic activity in MCF 7 estrogen receptor-positive human breast cancer cells. Cell inhibition is correlated with an increase in membrane protein tyrosine phosphatase (PTP) activity, and the addition of orthovanadate prevents OH-Tam inhibition. After RT-PCR cloning of PTPs expressed in MCF 7 cells with primers to their catalytic domains, we have shown, by differential screening, that the expression of two enzymes, leukocyte common antigen-related PTP (LAR) and Fas-associated PTP-1 (FAP-1), was modulated by antiestrogens. By comparative RT-PCR, in situ hybridization, and Northern blot, LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently increased by antiestrogens. To further demonstrate that PTPs were key mediators of antiestrogen-inhibitory action on the growth factor pathway, a panel of stable FAP-1 transfectants expressing low to high levels of antisense mRNAs was established. In these clones, the level of antisense RNA expression was correlated with a reduction in basal levels and a complete inhibition of antiestrogen-stimulated values of PTP activity. When FAP-1 expression was abolished, OH-Tam was no longer able to block insulin-like growth factor I mitogenic activity even though it remained strongly antiestrogenic. However, ICI 182,780 was still inhibitory, indicating that its effect was not exclusively mediated by PTP. Our data first demonstrate that a specifically regulated phosphatase (FAP-1) is implicated in the triggering of negative proliferation signals in breast cancer cells.

Sertoli cell barrier dysfunction and spermatogenetic cycle breakdown in the human testis: a lanthanum tracer investigation.

The introduction of nitrate of lanthanum in fixative solutions for testicular biopsies improves ultrastructural observations of the blood-testis barrier. In complete (normal) spermatogenesis, junctional specializations impede the diffusion of lanthanum into the adluminal compartment. They clearly exhibit a three-storied disposition in orthogonal sections. In maturation arrest, lanthanum passes easily through the junctional specializations surrounding the germ cells and up to the lumen. In irregular hypospermatogenesis, the Sertoli cell barrier is permeable, but diffusion of the tracer is less significant and variable. Unexpectedly, in germ cell aplasia, the barrier remains efficient

Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion.

Antiestrogens increase protein tyrosine phosphatase activity in human breast cancer cells.

Growth of human breast cancer cells is controlled by multiple interacting factors that trigger different intracellular signaling pathways. The nonsteroidal antagonist 4-hydroxytamoxifen (OH-Tam), which acts as an antiestrogen, is also able to inhibit the mitogenic activity of epidermal growth factor (EGF) on hormone-responsive MCF7 cells. To further characterize the mechanism of this antigrowth factor activity, which is accompanied by an increase of high-affinity EGF binding and a drastic decrease in EGF receptor autophosphorylation, we studied the effect of OH-Tam on protein tyrosine phosphatase (PTPase) activity with specific in vitro assays using two different substrates. OH-Tam increased membrane PTPase activity in a time- and dose-dependent fashion whereas cytoplasmic enzyme activity remained unchanged. The increase in PTPase activity was mediated by the estrogen receptor (ER) since it was restricted to ER-positive cells, and the optimal OH-Tam concentration (ED50 = 1 nM) was correlated with the ligand affinity for ER. The increase in enzyme activity was selectively obtained with nuclear receptor ligands (OH-Tam, ICI 164,384) that inhibited growth factor-induced proliferation, whereas other inhibitors of estrogenic responses such as synthetic progestins and antiprogestins had no effect. The time course of stimulation (maximal stimulation at day 4) was concomitant to the loss of EGF mitogenic response. Moreover, addition of a specific PTPase inhibitor (5 microM sodium orthovanadate) to intact cells in culture prevented OH-Tam inhibition of cell proliferation, suggesting that these two events are closely associated.(ABSTRACT TRUNCATED AT 250 WORDS)

Supernumerary chromosomes and spermatogenesis in a human male carrier.

A 57-year-old patient was referred because of primary sterility. Spermogram and testicular histology showed moderate oligospermia and irregular hypospermatogenesis. Karyotypic analysis revealed the presence of a metacentric supernumerary chromosome. Synaptonemal complex analysis using the surface-spreading technique was undertaken to study the meiotic behaviour of the extra chromosome during the pachytene stages. The relationship of the extra chromosome to the infertility of the carrier is discussed.

William L. McGuire Memorial Symposium. Control of breast cancer cell growth by steroids and growth factors: interactions and mechanisms.

Over the past two decades, the simple model for control of breast cancer growth involving one or two factors acting directly or indirectly via endocrine pathways has turned into a complex model implicating numerous interacting factors and the diverse cell populations constituting breast tumors. Current approaches to breast cancer therapy now require integration of these multiple parameters and enhanced understanding of the different levels of their intricate interactions.