Phase behaviour and dynamics of three-dimensional active dumbbell systems.

We present a comprehensive numerical study of the phase behavior and dynamics of a three-dimensional active dumbbell system with attractive interactions. We demonstrate that attraction is essential for the system to exhibit nontrivial phases. We construct a detailed phase diagram by exploring the effects of the system's activity, density, and attraction strength. We identify several distinct phases, including a disordered, a gel, and a completely phase-separated phase. Additionally, we discover a novel dynamical phase, that we name percolating network, which is characterized by the presence of a spanning network of connected dumbbells. In the phase-separated phase we characterize numerically and describe analytically the helical motion of the dense cluster.

Topological phases and curvature-driven pattern formation in cholesteric shells.

We study the phase behaviour of cholesteric liquid crystal shells with different geometries. We compare the cases of tangential anchoring and no anchoring at the surface, focussing on the former case, which leads to a competition between the intrinsic tendency of the cholesteric to twist and the anchoring free energy which suppresses it. We then characterise the topological phases arising close to the isotropic-cholesteric transition. These typically consist of quasi-crystalline or amorphous tessellations of the surface by half-skyrmions, which are stable at lower and larger shell sizes, respectively. For ellipsoidal shells, defects in the tessellation couple to a local curvature, and according to the shell size, they either migrate to the poles or distribute uniformly on the surface. For toroidal shells, the variations in the local curvature of the surface stabilise heterogeneous phases where cholesteric or isotropic patterns coexist with hexagonal lattices of half-skyrmions.

Cholesteric Shells: Two-Dimensional Blue Fog and Finite Quasicrystals.

We study the phase behavior of a quasi-two-dimensional cholesteric liquid crystal shell. We characterize the topological phases arising close to the isotropic-cholesteric transition and show that they differ in a fundamental way from those observed on a flat geometry. For spherical shells, we discover two types of quasi-two-dimensional topological phases: finite quasicrystals and amorphous structures, both made up of mixtures of polygonal tessellations of half-skyrmions. These structures generically emerge instead of regular double twist lattices because of geometric frustration, which disallows a regular hexagonal tiling of curved space. For toroidal shells, the variations in the local curvature of the surface stabilizes heterogeneous phases where cholesteric patterns coexist with hexagonal lattices of half-skyrmions. Quasicrystals and amorphous and heterogeneous structures could be sought experimentally by self-assembling cholesteric shells on the surface of emulsion droplets.

Soft channel formation and symmetry breaking in exotic active emulsions.

We use computer simulations to study the morphology and rheological properties of a bidimensional emulsion resulting from a mixture of a passive isotropic fluid and an active contractile polar gel, in the presence of a surfactant that favours the emulsification of the two phases. By varying the intensity of the contractile activity and of an externally imposed shear flow, we find three possible morphologies. For low shear rates, a simple lamellar state is obtained. For intermediate activity and shear rate, an asymmetric state emerges, which is characterized by shear and concentration banding at the polar/isotropic interface. A further increment in the active forcing leads to the self-assembly of a soft channel where an isotropic fluid flows between two layers of active material. We characterize the stability of this state by performing a dynamical test varying the intensity of the active forcing and shear rate. Finally, we address the rheological properties of the system by measuring the effective shear viscosity, finding that this increases as active forcing is increased-so that the fluid thickens with activity.

Rheology of active polar emulsions: from linear to unidirectional and inviscid flow, and intermittent viscosity.

The rheological behaviour of an emulsion made of an active polar component and an isotropic passive fluid is studied by lattice Boltzmann methods. Different flow regimes are found by varying the values of the shear rate and extensile activity (occurring, e.g., in microtubule-motor suspensions). By increasing the activity, a first transition occurs from the linear flow regime to spontaneous persistent unidirectional macro-scale flow, followed by another transition either to a (low shear) intermittent flow regime with the coexistence of states with positive, negative, and vanishing apparent viscosity, or to a (high shear) symmetric shear thinning regime. The different behaviours can be explained in terms of the dynamics of the polarization field close to the walls. A maximum entropy production principle selects the most likely states in the intermittent regime.

Lamellar ordering, droplet formation and phase inversion in exotic active emulsions.

We study numerically the behaviour of a two-dimensional mixture of a passive isotropic fluid and an active polar gel, in the presence of a surfactant favouring emulsification. Focussing on parameters for which the underlying free energy favours the lamellar phase in the passive limit, we show that the interplay between nonequilibrium and thermodynamic forces creates a range of multifarious exotic emulsions. When the active component is contractile (e.g., an actomyosin solution), moderate activity enhances the efficiency of lamellar ordering, whereas strong activity favours the creation of passive droplets within an active matrix. For extensile activity (occurring, e.g., in microtubule-motor suspensions), instead, we observe an emulsion of spontaneously rotating droplets of different size. By tuning the overall composition, we can create high internal phase emulsions, which undergo sudden phase inversion when activity is switched off. Therefore, we find that activity provides a single control parameter to design composite materials with a strikingly rich range of morphologies.

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

[Viral and/or intraepithelial lesions of the lower female genital tract: diagnostic and prognostic value of in situ molecular hybridization]. / Lesioni virali e/o intraepiteliali del basso tratto genitale femminile: valore diagnostico e prognostico dell'ibridizzazione molecolare in situ.

Fourteen patients (mean age 37 years) suffering from viral and/or intraepithelial cervico-vagino-vulvar pathologies underwent colposcopic and cyto-histological tests and molecular hybridization. The following types of HPV were assayed: 6/11-16/18-31/35/51 in cytological tissues (exocervical scraping) and biopsy material immersed in paraffin and fixed in formalin buffered with 10% PBS. The aim of the study was to identify different types of HPV using molecular hybridisation in situ. The paper reports the results and correlations with colposcopic, cytological and histological diagnosis, and then discuss the clinico-biological and prognostic aspects of this method.

C-MYB activation and the pathogenesis of ovarian cancer.

We have detected the expression of the MYB proto-oncogene in ovarian cancer. This oncogene was thought to be expressed in a tissue-specific manner in cells of hematopoietic lineage. Total RNA from three established cell lines and four human primary ovary cancers was examined by Northern and Southern blot, RNAse protection, in situ hybridization and cytogenetic analysis. A 3.8 kb RNA transcript was present in one human primary cell culture which is the same size as that found in the immature myeloid HL60 cell line. No expression was detected in normal ovary tissue. Southern blot analysis of DNA from five ovarian tumors indicated that this gene is not rearranged. Chromosomal analysis of three samples show many abnormalities in two cases and a normal karyotype in another one. The presence of MYB transcript in ovarian cancer suggests that MYB may play a specific role in the pathogenesis of this disease.

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes.

During a six-month randomized study involving 460 post-menopausal women, transdermal estradiol has proved to be as effective as oral conjugated equine estrogens in the control of menopausal symptoms and to produce similar estrogenic effects on the endometrium. The group of patients treated with transdermal estradiol showed better compliance and had fewer drop-outs. Moreover, the quality and duration of menstrual bleeding were considered more physiological in the transdermal estradiol group than in the orally treated patients. The trial was carried out with the co-operation of 17 Italian University Centres, under the supervision of Ciba-Geigy Italy S.p.A. Medical Department.

Chemosensitivity and DNA content as prognostic factors in ovarian cancer: preliminary results.

Fourteen samples of epithelial ovarian cancer were studied; chemosensitivity in vitro was examined by clonogenic assay, and DNA content was measured by static cytometry. Seven cases were aneuploid. The average survival of the diploid cases was almost twice that of the aneuploid cases (21 vs 11 months). Five of the 7 diploid, and 4 of the aneuploid cases were chemosensitive in vitro; 4 diploid and 3 aneuploid tumors were sensitive in vivo. The vitro/vivo correlation was positive for 6 out of 7 aneuploid tumors, and for 4 out of 7 diploid cases. Patients sensitive in vitro to at least one of the two drugs tested responded more often to chemotherapy, whatever drugs were used in vitro. The patients whose 5 C exceeding rate was 10% survived 12 months at most, with an average survival of 8 months; patients with a low aneuploidy index survived an average of 20 months. The behavior of the diploid tumors in vitro was more varied. Ploidy would seem to be an additional factor to other parameters of prognosis, while no correlation is evident between chemosensitivity in vitro, D.I., and 5 C exceeding rate.

Ovarian cancer: relationship between in vitro chemosensitivity and clinical response.

Thirty-nine samples from 30 patients with epithelial ovarian cancer were collected. Using the method described by A. Hamburger (J. Natl. Cancer Inst. 66, 981 (1981] and P. Salmon et al. (N. Engl. J. Med. 308, 129 (1983], tumor cells were exposed to antineoplastic agents (Adriamycin and cis-platinum) and then cultured in double-layer agar. There were 23 evaluable patients. The percentage of complete and partial responses for patients whose cells were sensitive in vitro, whether or not treated with the same drugs, was 68, vs 44% compared to patients whose cells were resistant in vitro and treated in vivo with therapeutic regimens which may or may not have included drugs used in the test. More patients with residual tumor greater than 2 cm were resistant to chemotherapy.

Evaluation of tumor and trophoblastic marker concentration in breast cyst fluid.

In our study we have examined 314 samples of cyst fluid taken from women suffering from fibrocystic breast disease (gross cystic disease). We have subdivided the cyst fluid with respect to epithelial coating and we have related trophoblastic protein content of the cyst fluid with age, seriousness of illness, and cytology of epithelial lining. We have performed RIA analysis of the trophoblastic proteins betahCG, beta1-SP-1, and alphahCG and in a smaller (n=84) group of specimens we have also tested for CEA, TPA, and ferritin. Trophoblastic proteins were positive in cystic fluids but the biological meaning of this is not known and the values are not related to clinical manifestations, except in a group of patients with apocrine metaplasia in which we tried to find a relationship between fertile age and increased betahCG. This finding presumably has a prognostic meaning that can be further understood by epidemiologic studies (of dietary intake and evaluation of lipid metabolites) and by information about inflammatory state of cystic fluid.

[Therapy and iron supplements with ferritin iron during pregnancy. Randomized prospective study of 458 cases]. / Terapia e supplemento marziale con ferro ferritinico durante la gravidanza. Studio prospettico randomizzato di 458 casi.

A randomized polycentric study was programmed to establish the effects of daily administration of ferritin iron from early pregnancy to puerperium. 254 women with normal iron balance at the beginning of their pregnancy were randomized receiving no supplements or 40 mg iron daily. At the end of pregnancy iron balance was still normal only in one third of the pregnant women of the first group versus two third of the second group. 204 women who were iron-deficient received daily 40 or 120 mg of iron; in this group anemia developed less frequently (13% versus 29%) and iron balance normalized in one subject on four; the great majority of these women remained iron-deficient. Unwanted effects of minimal or mild relevance, and almost always sporadic were observed in 6.5% of cases and with the reduction or withdraw of the treatment in only 1.4% of cases. These results showed that daily administration of ferritin iron during pregnancy is effective and well tolerated; furthermore they suggest that the treatment must be done with at least 60 mg daily in women with normal iron balance and protracted also after the puerperium in iron deficient subjects.

The rationale for treatment of cervical lesions (HPV +/- CIN).

In the laser surgery service of the 2nd Department of the Obstetric and Gynecologic Clinic of the University of Rome "La Sapienza", from October 1984 to March 1987, we have treated with CO2 laser surgery (vaporization and conization) 228 patients affected with cervical lesions (HPV +/- CIN). The choice of the treatment must be based on two parameters: site and extension of the lesion. The results we have obtained with CO2 laser vaporization (201 cases) are most satisfactory (92%); patients have been followed-up from two to twenty-six months. As far as the CO2 laser conization is concerned (27 cases), patients were followed-up from two to twenty-two months and the percentage of success was 96.1%. The Authors evaluated also the side effects of the CO2 laser surgery.

Immunochemical and biological characteristics of a human autoantibody to human chorionic gonadotropin and luteinizing hormone.

Anti-hCG/LH autoantibodies were found in the serum of an infertile woman a few days after an abortion which occurred after 46 days of amenorrhea. The antibody titer increased for approximately 4 more weeks, and then declined to low levels during a 14-month anovulatory period, after which regular menses resumed. Immunoglobulins isolated from a pool of serum obtained during the postabortion period neutralized the activity of both hCG and LH in an in vivo bioassay, and the binding affinity of the antibodies toward both hormones was high. When menses were resumed, there was a considerable reduction of the affinity toward LH. The variations in antibody titers and/or affinities can explain the sequence of fertilization, abortion, anovulatory period, and normalization of menses.

Parametrial involvement and therapeutic programming in stage Ib cervical cancer.

The philosophical basis of oncological surgery has always been the removal of not only the primary lesion but also of a considerable amount of healthy tissue. In the surgical treatment of cervical cancer, the extensive dissection of the ureter, bladder and rectum facilitates a more complete removal of the parametrium and of the paracervical tissue, but gives rise to a series of bladder and rectal dysfunctions. Complications are certainly taken into account, but more consideration could be given to the cost to the patient in terms of severe disturbances in life-style and to the dysfunctions caused by radical surgery. Unfortunately, we do not know exactly the incidence of this damage since the data available from the literature are not always uniform. In order to overcome this discrepancy we suggest that Rutledge's classification is still the most valid point of reference. We also consider that accurate urodynamic follow-up methodology is necessary to evaluate bladder dysfunctions and to compare data from the different centres. Finally, we propose moderately radical hysterectomy--Rutledge's Class II--with adjuvant therapy in the presence of adverse prognostic factors as the most effective method for controlling the disease and reducing treatment-related side-effects.