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International audience; Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

This paper presents the first silicon-based parabolic Sub-THz reflector antenna with corresponding fabrication processes. The antenna is side fed with an on-chip 340 GHz patch antenna on a reflector made of stacked micromachined silicon substrates with a parabolic-shaped Kapton film coated with aluminum on top. The antenna with a size of 18 ×18 ×4 mm3 and an aperture of ∼10mm can be easily integrated with monolithic microwave integrated circuit sources, i.e. 40 nm CMOS triple-push oscillator in this case, and exhibit not only ∼12.4 dB directive gain enhancement and 4.34° HPBW (Half Power Beam Width) for far field radiation but also an excellent near field focus characteristic with a 28.5 mm depth of field (DOF).

PCOS is one of the most common endocrine disorders affecting women and it is characterized by a combination of hyper-androgenism, chronic anovulation, and insulin resistance. While a significant progress has recently been made in the diagnosis for PCOS, the optimal infertility treatment remains to be determined. Two inositol isomers, myo-inositol (MI) and D-chiro-inositol (DCI) have been proven to be effective in PCOS treatment, by improving insulin resistance, serum androgen levels and many features of the metabolic syndrome. However, DCI alone, mostly when it is administered at high dosage, negatively affects oocyte quality, whereas the association MI/DCI, in a combination reproducing the plasma physiological ratio (40:1), represents a promising alternative in achieving better clinical results, by counteracting PCOS at both systemic and ovary level.

The electrofiltration performance of non-circular ceramic membranes using whey suspensions is investigated and appraised with reference to permeate flux and whey removals. Poor filtration performances were observed in the absence of an applied electric field. Increasing the applied voltages increases the permeate flux when the cathode was on the retentate side. The opposite trend is observed when the applied polarity of voltage is reversed. Chemical oxygen demand (COD) removals, used primarily to evaluate whey removal efficiencies, of up to 95% are achieved which increase with increasing voltages. The use of an electric field to enhance filtration is accompanied by substantial increase in energy consumption.

International audience; In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).

A substantial body of research on mammalian gametogenesis and human reproduction has recently investigated the effect of myo-inositol (MyoIns) on oocyte and sperm cell quality, due to its possible application to medically assisted reproduction. With a growing number of both clinical and basic research papers, the meaning of several observations now needs to be interpreted under a solid and rigorous physiological framework. The 2013 Florence International Consensus Conference on Myo- and D-chiro-inositol in obstetrics and gynecology has answered a number of research questions concerning the use of the two stereoisomers in assisted reproductive technologies. Available clinical trials and studies on the physiological and pharmacological effects of these molecules have been surveyed. Specifically, the physiological involvement of MyoIns in oocyte maturation and sperm cell functions has been discussed, providing an answer to the following questions: (1) Are inositols physiologically involved in oocyte maturation? (2) Are inositols involved in the physiology of spermatozoa function? (3) Is treatment with inositols helpful within assisted reproduction technology cycles? (4) Are there any differences in clinical efficacy between MyoIns and D-chiro-inositol? The conclusions of this Conference, drawn depending on expert panel opinions and shared with all the participants, are summarized in this review paper.

The use of non-circular-channelled membranes and their performance in microfiltration as a pretreatment for desalination for wastewater reuse has been investigated. The membrane performance is appraised with reference to (i) fouling propensity, i.e. critical flux and (ii) removal of organics in terms of solid retention efficiency. Critical flux determinations were carried out, employing the step by step technique, under various operating conditions (Reynolds number, pore sizes and pH). The effluent from a synthetic activated sludge production process was used. Increasing the pore size appears to increase the critical flux as does increased pH. It is shown that the non-circular geometry gives rise to a very high critical flux under turbulent flow conditions whilst the opposite effect is observed under laminar flow conditions. Solid retention efficiencies of up to 92% are achieved which decrease with increment in pore size. It seems that a larger pore size allows the transmission of smaller particles accounting for the lower rejection seen. All observations are explained in terms of the hydrodynamics and particle interactions involved within the membrane filtration system.

Peroxide cured PP/metallocene polyethylene (mPE) to form a novel thermoplastic vulcanizate has been prepared. Metallocene polyethylenes with two different levels of comonomer contents were chosen for the investigation. The mixing of mPE (40 wt%) and PP (60 wt%) containing various dosages of peroxide was performed to activate dynamic cure using an internal mixer. Thermal behaviors remain largely unchanged for PP, indicating the dominant effect of cured mPE domains on mechanical properties for the vulcanizates. Tensile strength decreases at first with increasing the levels of peroxide concentrations yet increases again at higher level of peroxide concentrations at all test temperatures. Tear strength generally decreases with reduced energy dissipation and tends to level off at higher degree of cure. The values of cutting strength are comparable with the results for different types of materials and are generally two orders of magnitude smaller than the results from tear measurements. Strength of materials was clearly dominated by the crystalline yielding effect than viscoelastic effect, even in this nano-fracture zone of deformation in the cutting measurement. Morphological observations were also elucidated as well.

Superconducting onset temperatures T c up to 23-44 K are reported for the new RuCa 2 RCu 2 O 8+δ ( R = Pr , Nd , Sm , Eu , Gd ) system with a Ru -1212 RuCa 2 PrCu 2 O 8+δ-type structure. Preliminary study indicates that the crystal structure is an orthorhombic distortion of the tetragonal RuSr 2 GdCu 2 O 8+δ-type structure ,which has space group P4/mmm, T m~136 K , and T c( max )~65 K . With similar RuO 6 octahedral and CuO 5 pyramidal units, superconductivity from the Cu - O bi-layers apparently coexists with the weak ferromagnetic (WFM) order with magnetic ordering temperature T m~49 K . Low temperature anomalous in magnetic properties observed in both field-cooled (FC) and zero-field-cooled (ZFC) modes are closely related to the complex interplay and coexistence between weak ferromagnetic order and superconductivity as well as from structural distortion and sensitive sample oxygen concentration variation. No superconductivity or Ru -1212 structure can be detected for larger rare earth compounds R = La and Ce .

The observed initial gain degradation of AlGaAs/GaAs heterojunction bipolar transistors under current stress was investigated. The change in device characteristics is attributed to a dissociation of passivating hydrogen in the base layer during stress. The hydrogen passivation occurs during the implant isolation process. An activation energy of 0.75 eV was measured for the junction temperature dependence of the dissociation process.

BACKGROUND: The follicular microenvironment is an important determinant of oocyte development. The aim of this study was to examine whether the myo-inositol (MI) content in human follicular fluid (FF) was associated with better oocyte quality. METHODS: A total of 53 patients treated with IVF was recruited to a prospective observational study. FF and serum samples collected were divided into two groups: group A consisted of FF associated with matured and fertilized oocytes, whilst group B was from follicles with immature and unfertilized oocytes. RESULTS: Patient’s age, total ampoules of HMG used, days of stimulation, basal levels of FSH, estradiol (E 2) levels on the day of HCG, and serum MI content were not significantly different between the two groups. FF volume and its MI content were significantly higher in group A compared with group B (P < 0.05). The levels of MI in FF were positively correlated with the amount of E 2 in their corresponding FF samples and also correlated with embryo quality. CONCLUSIONS: We propose that higher concentrations of MI and E2 in human FF appear to play a role in follicular maturity and provide a marker of good quality oocytes.

Objective: To determine whether oviduct mucosal cell culture supports the continued production of oviductin, a putative embryotrophic protein. Design: Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of oviductin messenger RNA (mRNA) expression after oviduct mucosal cell culture. Setting: University-based obstetrics and gynecology department. Patient(s): Ten women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids.. Intervention(s): The mucosal layer was isolated from the oviduct tissue and subjected to routine culture conditions; semiquantitative RT-PCR was performed. Main Outcome Measure(s): The relationship between duration of cell culture and expression of oviductin mRNA. Result(s): There was a significant reduction in oviductin mRNA expression after 3 days in culture, with a complete loss after 6 days in 70% of the samples and after 12 days in the remaining 30%. Conclusion(s): This is the first study to investigate whether oviductin mRNA continues to be expressed in cultured human oviduct mucosal cells. Our results suggest that oviduct mucosal cells lose their ability to produce oviductin after short-term culture. This method of culture does not appear to be appropriate for a coculture system reliant upon oviductal secretion of oviductin.

Since homozygosity of the α-thalassemia-1 of Southeast Asian (SEA) type deletion results in hydrops fetalis, a novel protocol based on the real-time quantitating polymerase chain reaction (PCR) technique has been developed to quantify the intact and aberrant α-globin genes in adults. The ratio of the normal/SEA-bearing α-globin genes was expressed in cycle threshold (CT) values. Theoretically, a relative ratio of one to one was anticipated in individuals carrying the SEA type deletion. Twenty-five heterozygous and 20 normal cases were analyzed retrospectively with this protocol. Data showed that the CT values for the intact α-globin gene allele and the allele bearing the SEA type deletion in carriers were 28.74±1.49 and 26.46±2.05, respectively. Therefore, the ratio of normal/SEA type deletion-bearing α-globin genes in the carriers was 1.09±0.043. No ambiguous results were observed from other less common genotypes associated with α-thalassemia, such as the Philippine type deletion. Based on the results, we concluded that this protocol could provide a rapid method to mass screen carriers with α-thalassemia-1 of SEA type deletion in this region.

Objective: To examine changes in oviductin mRNA expression in oviductal mucosal tissue from fertile women throughout an ovulatory cycle. Design: Semiquantitative reverse-transcriptase–polymerase chain reaction (RT-PCR) analysis of oviductin mRNA. Setting: University-based obstetrics and gynecology department. Subject(s): Twenty women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. Intervention(s): The mucosal layer was isolated from the oviduct tissue, and semiquantitative RT-PCR was performed. Main Outcome Measure(s): The relationship between serum estradiol, luteinizing hormone, and progesterone concentrations and the expression of oviductin mRNA. Result(s): There was a significant positive correlation between serum estradiol and luteinizing hormone concentrations and oviductin mRNA expression. There was a significant inverse correlation between serum progesterone concentrations and oviductin mRNA expression. Conclusion(s): Little is known about the regulation of human oviductin. This study was the first to examine the relationship between oviductin mRNA expression and serum estradiol and luteinizing hormone and progesterone concentrations in fertile women. Estradiol and luteinizing hormone both have a stimulatory effect on oviductin mRNA in humans, however, it is difficult to determine whether the effects are independent of one another, as the luteinizing hormone surge is dependent on the estradiol increase. Progesterone shows a clear inhibitory effect on oviductin mRNA.

Purpose: To evaluate the effects of follicular fluid and platelet-activating factor on sperm motion characteristics of cryopreserved oligospermic and normospermic samples. Methods: Sperm motion characteristics were evaluated prior to cryopreservation, immediately after thawing and following incubation in human tubal fluid, follicular fluid, or 1-μM platelet-activating factor cultures. Sixteen oligospermic samples and 20 normospermic samples were examined. Sperm motion characteristics were analyzed manually according to WHO criteria (1999) and also with an automated videomicrography system. Result(s): Incubation in follicular fluid increased overall motility and the percentage of sperm with fast progressive motility in normospermic but not oligospermic samples. Incubation with platelet-activating factor increased overall motility and the percentage of sperm showing nonprogressive motility in both oligospermic and normospermic samples. Conclusion(s): The stimulatory effects of culture in follicular fluid as seen in normospermic samples do not show a significant benefit in oligospermic cryopreserved samples. Platelet-activating factor and follicular fluid increase motility via different mechanisms. Incubation of oligospermic cryopreserved sperm with PAF increases the number of motile sperm, thereby enabling easier identification of viable sperm for intracytoplasmic sperm injection in samples with severe asthenozoospermia.

α-Thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in α-thalassemia-1 cases in Taiwan is deletion of a large segment of the α-globin gene cluster, termed the Southeast Asian-type deletion (−SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion. Am. J. Med. Genet. 95:332–335, 2000. © 2000 Wiley-Liss, Inc.

Scaled bipolar transistors for bipolar complementary metal oxide semiconductor (BiCMOS) integrated circuits require low collector-substrate capacitance in order to minimize power consumption. The unintentional incorporation of dopant into a growing epitaxial layer, known as autodoping, can affect the ultimate lower limit of the collector-substrate capacitance. In this work, we studied the effects of epitaxial layer growth rate, arsenic-buried layer implant dose, and pre-epitaxial bake temperature on autodoping using rapid thermal epitaxy (RTE). To begin, we experimented with the buried layer implant dose to check its affect on lateral autodoping. The amount of autodoping increased when the buried layer implant dose increased, confirming the source of the arsenic autodoping as the buried layer. Also, in contrast to data from conventional reactors, we found the peak interface concentration and integrated dose in regions adjacent to the buried layer to be linearly dependent on the growth rate (i.e., low growth rates trap less arsenic at the substrate/epi layer interface) for all growth rates studied. Next, by adjusting the prebake temperature over a range from 800 to 1050°C without changing the growth conditions, we first observed a rise in autodoping with temperature to 950°C, at which point the incorporated autodoping dose and peak concentration began to fall. Through simulation of the evaporated arsenic from the buried layer and data for arsenic desorption from the silicon surface, we explain this behavior. Finally, using the data gathered on the autodoping characteristics of RTE, we show a process using two growth rate steps and a low temperature prebake step which completely eliminates the lateral autodoping peak. Using this new growth process, epitaxial silicon films over arsenic-doped buried layers for low power BiCMOS are possible.

A high performance BiCMOS technology, BEST2 (Bipolar Enhanced super Self-aligned Technology) designed for supporting low-power multiGHz mixed-signal applications is presented. Process modules to produce low parasitic device structures are described. The developed BiCMOS process implemented with 1 /spl mu/m design rules (0.5 /spl mu/m as one nesting tolerance) has achieved f/sub l/ and f/sub max/ for npn bipolar (A/sub e/=1/spl times/2 /spl mu/m/sup 2/) of 23 GHz and 24 GHz at V/sub ce/=3 V, respectively, with BV/sub ceospl ges/5.5 volts, and /spl beta/V/sub A/ product of 2400. Typical measured ECL gate delay is 48 ps/37 ps per stage (A/sub e/=1/spl times/2 /spl mu/m/sup 2/; 500 mV swing) at 0.6 mA/2.1 mA switching currents, and CMOS gate delay (gate oxide=125 /spl Aring/, L/sub eff/=0.6 /spl mu/m; V/sub th,nch/=0.45 V; V/sub th,pch/=-0.45 V) 70 ps/stage. A BiCMOS phase-locked-loop (emitter width=1 /spl mu/m; gate L/sub eff/=0.7 /spl mu/m) has achieved 6 GHz operation at 2 V power supply with total power consumption of 60 mW. >

We have developed a half-micron super self-aligned BiCMOS technology for high speed application. A new SIlicon Fillet self-aligned conTact (SIFT) process is integrated in this BiCMOS technology enabling high speed performances for both CMOS and ECL bipolar circuits. In this paper, we describe the process design, device characteristics and circuit performance of this BiCMOS technology. The minimum CMOS gate delay is 38 ps on 0.5 /spl mu/m gate and 50 ps on 0.6 /spl mu/m gate ring oscillators at 5 V. Bipolar ECL gate delay is 24 ps on 0.6 /spl mu/m emitter ring oscillators with collector current density of 40 kA/cm/sup 2/. A single phase decision circuit operating error free over 8 Gb/s and a static frequency divider operating at 13.5 GHz is demonstrated in our BiCMOS technology. >

Diet is a critical factor for the development of both embryo and fetus, as well as maternal health. In particular, two natural molecules have been shown to exert beneficial effects on fertility, pregnancy wellness and embryo development: myo-inositol and melatonin, whose requirements increase during pregnancy. In the present review, we summarize the most important functions of melatonin and myo-inositol on male and female reproductive systems (oocyte quality and development, sperm quality), on the maintenance of a physiological pregnancy and on embryo development.

The authors have modeled the base current change with different percentages of broken interface-oxide area (interface void). A pseudo-two-dimensional structure of dual channels of minority-carrier transport at the interface between the polysilicon and the silicon emitter, is constructed in analogy with an electrically equivalent conductance network. Using the conductance network, an analytical expression of base current is easily derived. For typical polysilicon emitter devices of approximately 10-15 AA interface oxide, the experimental results show that the strong dependence of base current on the fraction of interface void can be modeled. The simulation predicts that the base current will be insensitive to the fraction of interface oxide breakup for very thin interface-oxide polysilicon emitter devices. Recent reports on finding a process window between current gain and emitter resistance optimization in a certain range of interface breakup ratios are confirmed by the model. >

Myo-inositol is involved in several aspects of human reproduction. Elevated concentrations of myo-inositol in human follicular fluids appear to play a positive function in follicular maturity and provide a marker of good quality oocytes. Nevertheless its positive role in PCOS women is a consequence of a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) that seems to be primarily implicated in the pathogenesis of insulin resistance. This article will review the involvement of inositol in female reproduction. After describing the biologic function of inositol and its derivatives, studies are quoted in which the role of inositol in fertility, oogenesis, and polycystic ovary syndrome are examined.

To provide further understanding of how oxidative damage affects red cell membrane function, the effects of low levels of two different types of oxidants on selected red cell properties have been studied. Hydrogen peroxide (H 2 O 2 ), an example of a water soluble oxidant, and t -butylhydroperoxide (tBHP), a hydrophobic hydroperoxide, were compared with respect to their effects on membrane permeability, membrane mechanical properties and binding of autologous serum antibodies to the cell surface. Whereas H 2 O 2 treatment resulted in a dose-dependent increase in membrane permeability to potassium that was evident after one hour of oxidant exposure, cells treated with tBHP at doses up to 5 μmol/ ml cells showed no immediate change in cation permeability. H 2 O 2 also caused a marked decrease in membrane deformability, whereas tBHP-treated cells showed minimal loss of deformability. However, tBHP treatment did result in a dose-dependent increase in the susceptibility of the membrane to fragmentation under high shear stress. With exclusion of treated samples that bound excess rabbit anti-spectrin antibody, indicating exposure of intracellular components, neither agent promoted the binding of autologous serum antibody in amounts comparable to that found in vivo on high density or some pathologic red cells. Taken together, the results suggest that tBHP and H 2 O 2 cause damage to human red cells by distinct oxidative mechanisms which do not lead directly to substantive generation of binding sites for autologous serum antibodies.

The design and experimental measurements on a clocked decision circuit for optical communication applications are reviewed. The circuit, fabricated in a 1.5- mu m super-self-aligned silicon bipolar technology, yields a bit-error rate (BER) >

Using an algorithm to calculate the base current increase due to local thermal effects, the authors show that one can accurately measure the impact ionization current over the full range of collector current. From the measured impact ionization ratio, it was possible to quantitatively describe the characteristics of the space-charge modulation and base push-out effect over a wide range of collector current. Computer simulation results support the measured data. It is also shown that one can use the measured impact ionization ratio to distinguish small collector concentration variations and thickness differences. The characterization was performed for self-aligned polysilicon-emitter transistors in an advanced BiCMOS technology. >

An optimal device structure for integrating bipolar and CMOS is described. Process design and device performance are discussed. Both the vertical n-p-n and MOS devices have non-overlapping super self-aligned (NOVA) structures. The base-collector and source/drain junction capacitances are significantly reduced. This structure allows complete silicidation of active polysilicon electrodes, cutting down the parasitic resistances of source, drain, and extrinsic base. The critical gate and emitter regions are protected from direct reactive ion etching exposure and damage. All shallow junctions are contacted by polysilicon electrodes which suppress silicide-induced leakage. An arsenic buried layer minimizes collector resistance and collector-substrate capacitance. A novel selective epitaxy capping technique suppresses lateral autodoping from the arsenic buried layer. Fully recessed oxide with polysilicon buffer layer is used to achieve a low defect density device isolation. CMOS with L/sub eff/=1.1 mu m and W/sub n//W/sub p/=10 mu m/10 mu m exhibits averaged ring oscillator delay of 128 ps/stage. An n-p-n transistor with f/sub T/, of 14 GHz and low-power emitter-coupled logic ring oscillator with a delay of 97 ps/stage have been fabricated. >

Purpose : To examine changes in the ratio of Bax and Bcl-2 mRNA expression throughout the ovulatory cycle in the ampullary region of the human oviduct. Methods : The mucosal layer was isolated from the human oviduct tissue and semiquantitative reverse-transcriptase polymerase chain-reaction (RT-PCR) analysis of mRNA of Bax and Bcl-2 was performed. Immunohistochemistry provided the cellular localization of the Bax and Bcl-2 proteins. The ratio of expression of Bax and Bcl-2 mRNA was examined in the ampullary region of the oviduct in samples obtained in the follicular, periovulatory, and luteal phases of the ovulatory cycle. Results : Bax expression was constant in the follicular and periovulatory phase but showed a significant increase in the luteal phase. The Bax protein was present in all oviduct mucosal epithelial cells and the intensity of staining increased in luteal phase samples. Bcl-2 was expressed at a relatively constant level throughout the ovulatory cycle. The Bcl-2 protein was present in some but not all mucosal epithelial cells and the proportion of positive cells remained constant throughout the ovulatory cycle. Conclusion : The proapoptotic gene Bax shows a significant increase in mRNA expression in the luteal phase of the ovulatory cycle while the expression level of the antiapoptotic gene Bcl-2 remains constant throughout the ovulatory cycle. The ratio of Bax:Bcl-2 increases significantly in the luteal phase consistent with cells undergoing apoptosis.

The ratio of the active progesterone receptor B isoform is higher in the ampullary region of the oviduct. Purpose: To examine mRNA expression of progesterone receptor isoforms AB and B in oviduct mucosal tissue during the ovulatory cycle and in the different functional regions of the human oviduct. Methods: The mucosal layer was isolated from human oviduct tissue and semi-quantitative RT-PCR for progesterone isoforms AB and B was performed. The RT-PCR results were verified by immunohistochemistry. Results: The isthmic region showed no mRNA expression of either progesterone receptor isoform while the relative ratio of the B isoform was significantly higher in the ampullary region compared to the fimbrial region. There was a significant increase in the ratio of PRB to PRAB in the ampullary region compared to the fimbrial region in all samples. Conclusions: We found an increase in the relative abundance of the progesterone receptor B isoform in the ampullary region which is the site of fertilization and early embryo cleavage. Our results indicate that progesterone responsive genes are more likely to be activated in the ampullary region of the oviduct due to the difference in PRAB to PRB ratio. Providing support for the hypothesis that progesterone may play a specific role in providing an appropriate environment for sperm capacitation, fertilization and early embryo cleavage.

BACKGROUND. This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF. METHODS. Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600mg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation. RESULTS. There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 6 0.58 versus 1.50 6 0.83; P 5 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant. CONCLUSION. A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.

Trisomy 21 is the most common chromosomal aberration in live births. In this study we employed human chromosome 21-specific short tandem repeat (STR) DNA markers to determine the numbers of chromosome 21 present in fetal cells. Forty amniotic fluid samples from pregnancies complicated with fetal Down syndrome and 98 samples from euploid pregnancies were analyzed for D21S11 and interferon-alpha receptor (IFNAR) gene intervening sequence. Fluorescent dye-labeled primers were used in PCR amplification of these 2 markers. The PCR amplicon was analyzed with an automatic DNA sequence analyzer. The results showed that 35 of 40 fetal Down syndrome samples analyzed for IFNAR showed 3 distinct peaks, while 24 of 30 cases analyzed for D21S11 showed 3 distinct peaks. Two Down syndrome samples showed two uneven peaks. By analyzing 98 euploid pregnancies as controls, the ratios of area under the peaks were determined to be 1.31 +/- 0.22 and 1.96 +/- 0.18 (mean +/- SD) for the euploid pregnancies and pregnancies complicated by fetal Down syndrome with 2 peaks, respectively. Our data showed that altogether 39 of 40 (97.5%) Down syndrome cases were correctly identified based on either the 3-peak pattern in one or more of the DNA markers or the relative peak area ratio calculation. In conclusion, polymorphic STR DNA markers are useful for determining the numbers of chromosome 21 in fetal cells. The high sensitivity and automation of the procedures suggest a good prospect for use of this method in prenatal detection of fetal Down syndrome. However, this is a preliminary investigation and a large-scale study is necessary to validate the clinical application of this protocol.

Purpose: To investigate whether commonly used test tube warming devices maintain a constant temperature in follicular fluid aspirates. Methods: By using a digital thermocouple, temperature was measured and comparisons were made between an analog dry block heater, a digital dry block heater, and a thermostatic test tube heater. Results: For small fluid volumes, temperature in the block heaters increased above 37°C after being in the block for over 2 min. The thermostatic heater maintained a constant temperature, but this was below the factory setting of 36.9°C. Temperature maintenance was influenced by fluid volume in each tube. Conclusions: One of the key factors in the handling of gametes and embryos is the maintenance of constant temperature. Test tube warming devices require verification of their ability to maintain fluid at the desired temperature. Temperature may vary with fluid volume and the type of test tube warming device used.

Objective To report the birth of a healthy baby after transfer of blastocysts derived from frozen eggs and frozen spermatozoa. Design Case report. Setting University-based assisted reproduction center. Patient(s) A 37-year-old woman with secondary infertility of 4 years' duration. Intervention(s) Retrieved oocytes were cryopreserved in 1.5 M 1,2-propanediol (PROH) and 0.3 M sucrose by a slow freezing–rapid thawing protocol, semen cryopreservation, and insemination by intracytoplasmic sperm injection (ICSI) at 4 hours after thawing. Main Outcome Measure(s) Fertilization and embryo development to blastocyst stage, pregnancy, and outcome. Result(s) Ten of 14 frozen oocytes survived after thawing. Eight of them were fertilized by performing ICSI and three developed into 7- to 8-cell embryos on day 3. Two of these embryos developed into blastocysts on day 5 and were transferred. This resulted in a successful pregnancy and the delivery of a healthy baby boy. Conclusion(s) This case demonstrates the feasibility of inseminating the frozen-thawed human oocytes after 4 hours of in vitro culture and the zygotes derived from frozen oocytes and frozen spermatozoa can be cultured to blastocysts resulting in the live birth of a healthy baby boy.

Objective To determine whether oviduct mucosal cell culture with exogenous hCG or 17-β estradiol (E2) supports the continued production of oviductin, a putative embryotrophic protein. Design Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin mRNA expression after oviduct mucosal cell culture in the presence of hCG or 17-β E2. Setting University-based Obstetrics and Gynecology Department. Subject(s) Ten women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. Intervention(s) The mucosal layer was isolated from the oviduct tissue, subjected to routine culture conditions with the addition of various concentrations of hCG or 17-β E2 or the equivalent vehicle-only control and semiquantitative RT-PCR performed. Main outcome measure(s) The relationship between exposure to hCG or 17-β E2 and expression of oviductin mRNA by cultured oviduct mucosal cells. Result(s) There was a significant increase in oviductin mRNA expression after the addition of hCG to the culture medium but only in samples that had maintained a baseline level of oviductin expression. Addition of 17-β E2 to the culture medium had no significant effect on oviductin mRNA expression. Conclusion(s) Under standard cell culture conditions, baseline human oviductin mRNA expression is increased by the addition of hCG. This effect is likely to be a secondary or synergistic effect as exogenous hCG failed to restore oviductin mRNA expression in samples where expression was lost after culture. E2 failed to alter oviductin mRNA expression in oviduct mucosal cells cultured under these conditions.

Objective To determine whether oviduct mucosal cell culture with exogenous 17β E 2 supports the continued production of oviductin, a putative embryotrophic protein. Design Semiquantitative reverse-transcriptase polymerase chain reaction analysis of oviductin mRNA expression after oviduct mucosal cell culture in the presence of 17β E 2 . Three different culture systems were studied to investigate the response to E 2 . Setting University-based obstetrics and gynecology department. Subjects Oviduct tissue was obtained from 18 women undergoing laparoscopy for benign gynecologic conditions. Intervention(s) The mucosal layer was isolated from the oviduct tissue and exposed to three different culture systems, which contained various concentrations of 17β E 2 , or vehicle-only control. Main outcome measure(s) The relationship between exposure to 17β E 2 and expression of oviductin messenger (m)RNA by cultured oviduct mucosal cells. Result(s) There was a significant increase in oviductin mRNA expression after the addition of 17β E 2 to the culture system in which the in vivo cell-to-cell and cell-to-basement-membrane contacts of the oviduct had been maintained. Conclusion(s) Estradiol failed to alter oviductin mRNA expression in oviduct mucosal cells cultured under conditions in which the ciliated mucosal cell phenotype plus the cell-to-cell and cell-to-basement-membrane contacts of the oviduct were lost. However, with a culture system that maintained the cell architecture, E 2 initiated and significantly increased oviductin mRNA expression.

The study aim was to assess whether the incorporation of myo-inositol (MI) into culture medium could improve oocyte maturation in vitro.We performed a controlled prospective study using female ICR strain mice superovulated with pregnant mare's serum gonadotrophins. Cumulus-enclosed germinal vesicle (GV) oocytes were randomly cultured in medium with or without MI supplementation. The kinetics of GV breakdown after 4 h of incubation was significantly higher in oocytes incubated with 30 mmol/l of MI than in controls (P0.001). Accordingly, this concentration of MI was used for subsequent experiments. The proportion of metaphase II oocytes achieved after 24 h of culture, their fertilization and cleavage rates were significantly higher in the MI-treated group (P0.01, P0.05, P0.05 respectively). This group also demonstrated significant improvement in postimplantation development after transferring the 2-cell embryos to pseudopregnant mice. Confocal microscopy revealed spontaneous intracellular Ca(2+) oscillations within competent GV oocytes and treatment with MI caused an earlier onset of these Ca(2+) signals.Our results suggest that MI may affect meiotic progression of mouse GV oocytes possibly by enhancing the intracellular Ca(2+) oscillations. Supplementation of MI in culture medium may be useful for human oocyte maturation.

BiCMOS technology which merges optimal CMOS and bipolar device structure is reported. Based on a nonoverlapping super-self-aligned structure (NOVA), the latest 1.5- mu m CMOS and ECL (emitter-coupled logic) ring oscillators have minimum delays of 110 ps/stage and 87 ps/stage, respectively. A frequency divider operating up to 4.6 GHz has been fabricated. A multiplexer and demultiplexer function up to 5.1 Gb/s. In addition to double self-alignments, a unique epi/isolation scheme combining lateral autodoping free epi deposition with a new fully recessed oxide process have been developed. This approach significantly simplifies the isolation process and is an important factor in achieving high speed with a conservative 1.5- mu m design rule. >

It is demonstrated that high-speed bipolar and CMOS processes can be merged without compromise on either device. A NOVA (nonoverlapping super self-aligned) structure with an advanced epi/isolation process that reduces parasitic capacitances and resistances is reported. The scheme combines lateral autodoping free epi deposition with a novel fully recessed oxide process. This approach significantly simplifies the isolation process and is an important factor in achieving high speed with a conservative 1.5- mu m design rule. A high-speed frequency divider, a multiplexer, and a demultiplexer operating up to 4.1 GHz, 5.5 Gb/s, and 6.2 Gb/s, respectively, have been fabricated. The results show that NOVA BiCMOS is suitable for Gb/s digital VLSI application. >

A technique for directly measuring the base drift field in bipolar transistors has been developed and used to study the effects of various base-formation and emitter drive-in conditions on the effective base drift field, a major factor determining the unity-current-gain cutoff frequency f/sub T/, has been studied. Measurements of base drift fields created with these drive-in conditions revealed that insufficient thermal treatment leaves a large portion of the base region with a retarding field, producing low base drift fields and low f/sub T/'s. An appropriate thermal treatment creates a monotonically varying base profile with large drift fields and therefore high f/sub T/'s. >

An ultra-high-speed half-micron non-overlapped super self-aligned BiCMOS technology that uses a silicon fillet self-aligned contact technology (SIFT) for both bipolar and MOS transistors is discussed. The SIFT process reduces the device capacitances and series resistances by minimizing the diffusion region area as well as the polysilicon electrode area. Deep trench isolation for bipolar transistors allows the device area to be much reduced for VLSI applications. The ECL gate delay is demonstrated to be 31 ps for devices with emitter polysilicon widths of 0.6 mu m. The CMOS ring oscillator gate delays are 58 ps for 0.5- mu m gate length and 67 ps for 0.6- mu m gate length at 5 V. >

The authors examine the considerations for choosing among the various types of BiCMOS technology. They examine several BiCMOS approaches with increasing levels of sophistication. The many approaches to BiCMOS process integration are described. No fundamental incompatibility in process or device structure stands in the way of bipolar-CMOS integration. Significant performance enhancement over pure CMOS has been demonstrated. >

The authors describe the process integration issues of high-performance BiCMOS technologies intended to be used not only in high-density digital applications but also in high speed ECL (emitter coupled logic) and mixed analog/digital signal applications. In particular, they describe a half-micron super-self-aligned BiCMOS technology with bipolar f/sub max/ of 34 GHz and a CMOS gate delay of 50 psec. Circuit applications for multi-gigahertz communication are presented to show the potential of high-performance BiCMOS technology.

This paper reports in detail the process and electrical results of a novel approach to optimize collector-substrate capacitance (C/sub cs/). Shallow arsenic buried layer combined with fully recessed LOCOS isolation have been developed for ATT gate L/sub eff/=0.7 /spl mu/m) has achieved a world record of 6 GHz operation at 2 V power supply with total power consumption of 60 mW. >

A method for experimentally determining the base and emitter delay time is described. It is based on direct monitoring of excess charge in the base and f/sub T/ measurement as a function of collector current and base-collector voltage. The sum of the excess carrier mobilities is extracted directly from these measurements. >

We report a new Si/SiGe HBT device structure using selective and non-selective rapid thermal epitaxy. The structure has the potential to simultaneously provide for high level integration and a high Ge fraction strained alloy base which allows high base doping. We used an in-situ As doped polysilicon emitter contact to provide low R/sub E/ (9 to 12 /spl Omega/ for A/sub E/=0.5/spl times/10 /spl mu/m/sup 2/) without the enhanced diffusion effects associated with direct implantation or phosphorous doped poly emitters. In addition, we studied the effects of the extrinsic base implant position on the device I-V characteristics, junction capacitances, and high frequency performance. The collector current increased by over 3 decades as the extrinsic base implant position moved from the single crystal region to an adjacent poly region due to the containment of damage. S-parameter measurements of a 0.5/spl times/10 /spl mu/m/sup 2/ device yielded a cutoff frequency of 54 GHz for V/sub CE/=1.5 V and I/sub C/=14.8 mA.