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Failed fertilization and the appearance of immature oocytes are common in IVF practice; rescue intracytoplasmic sperm injection can be used as a therapy. However, this study indicates that embryos created after in vitro maturation and delayed intracytoplasmic sperm injection contain an increase in aneuploidy (79.7%) over control embryos (60.5%). Therefore, patients should be informed of the possible risk when presented with delayed intracytoplasmic sperm injection.

Purpose : To compare maturation rates of mouse preantral follicles cultured using two previously reported follicle in vitro follicle culture protocols, and to compare the aneuploidy of oocytes derived from the two protocols with in vivo-matured control oocytes. Methods : Mouse preantral follicles were either mechanically isolated then cultured in individual microdroplets, or enzymatically isolated and cultured in groups in a modified culture medium. Maturation of the follicles/oocytes and resulting oocyte aneuploidy rates were evaluated and compared. Results : The mechanical isolation and individual culture protocol (M/I) resulted in higher follicle survival than the enzymatic isolation and group culture protocol (E/G) (89.1% versus 79.1%, p < 0.01), and better maturation to the metaphase 2 stage (61.5% versus 39.5%, p = 0.01) The rate of aneuploidy of oocytes not significantly higher in oocytes from the E/G group than the M/I group (15.4% versus 9.9%), but hypoploidy was significantly increased (4.7% versus 0.9%, p < 0.05). Both groups had a higher rate of aneuploidy than the control oocytes (2.9%, p < 0.02). Conclusions : These results indicate an increased survival and competency of oocytes derived from the M/I protocol, compared to the E/G protocol. The data highlight an increased susceptibility to meiotic errors in early stage follicles undergoing in vitro culture, compared to in vivo-matured oocytes.

Our studies document a unique and unexpected advantage of the combination of HPMA copolymer bound doxorubicin with mesochlorin e6/photodynamic therapy in the treatment of ovarian cancer. Each drug's activity is individually enhanced when compared with free (low molecular weight) drugs, furthermore, in combination these HPMA copolymer bound agents act synergistically to create an unexpected biological effect. Figure 8 depicts the known activities of each agent which may play synergistic roles. HPMA copolymer-doxorubicin has been widely evaluated in preclinical and clinical studies. It demonstrates marked advantages over free doxorubicin: control of biodistribution and accumulation via molecular weight restrictions, biodegradability, minimal immunogenicity, subcellular localization, anticancer activity, enhanced permeability and retention, increased apoptosis, lipid peroxidation, DNA damage, and reduced nonspecific toxicity. Recent clinical trials in the UK provide "proof of principle" of the "enhanced permeability and retention effect" for solid tumors and the unique advantages of this novel drug delivery system for the treatment of ovarian cancer. With regards to photodynamic therapy using the photosensitizer mesochlorin e6, the preclinical evaluations thus far document: control of biodistribution and accumulation via molecular weight restrictions, biodegradability, subcellular localization, anticancer activity, enhanced permeability and retention, and reduced nonspecific toxicity. Ongoing microarray studies document unique cellular pathways and new pharmaceutical properties which are initiated by the HPMA copolymer delivery delivery of these agents, and predict an exciting future for this novel drug delivery system.

Previous studies have indicated that sperm quality may be related to unexplained recurrent pregnancy loss. This study evaluated the degree of sperm DNA fragmentation using the TUNEL assay on sperm from 24 couples with unexplained recurrent pregnancy loss (RPL) compared to sperm from 2 control groups: donors of known fertility and unscreened men from the general population. The percentage of sperm staining positive for DNA fragmentation was increased (p < .001) in the RPL group (38 +/- 4.2) compared to the donor (11.9 +/- 1.0) or general population (22 +/- 2.0) control groups. In the RPL group, no correlation was observed between semen quality parameters and the TUNEL data. These data indicate that some RPL patients have a significant increase of sperm DNA fragmentation, which may be causative of pregnancy loss in some patients.

To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP.Before and after intervention study.Two IVF programs using the same embryology laboratory and IVF protocols.All IVF patients undergoing fresh embryo transfers.Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent.HMP and pregnancy outcomes.In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE35 andor=35 years (donor age), and non-DE cycles35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE35 years withor=3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates.The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

[1] We have utilized telescopic near-infrared spectra and multispectral images of the Moon provided by the Galileo and Clementine missions to determine the distribution and modes of occurrence of pure anorthosite. Anorthosites have now been identified in all portions of the nearside, including the site of the putative Procellarum basin. Anorthosite is associated with the rings of Orientale, Grimaldi, Humorum, Nectaris, Nubium, Mutus-Vlaq, and Balmer basins. Major portions of the inner rings of Grimaldi, Humorum, Crisium, Orientale, and Nectaris are composed of pure anorthosite. The large spatial extent of these anorthosites appears to rule out an origin in the upper portions of discrete differentiated Mg-suite plutons. In every instance, the anorthosites were exposed from beneath a shallower near-surface layer of more pyroxene-rich material. More mafic material also occurs beneath the pure anorthosite unit. Large expanses of the northern farside exhibit very low FeO values. This region contains abundant anorthosite and stands in stark contrast to the mafic composition exhibited by the interior of the South Pole-Aitken basin (SPA). The distribution of compositional units on large portions of the lunar farside as well as the southern portion of the lunar nearside appears to be largely attributable to the SPA impact event. The distribution and modes of occurrence of anorthosites clearly indicate that a thick, global layer of anorthosite is present at various depths beneath most portions of the lunar surface. This anorthosite layer dominated the upper portion of the primordial crust and was produced by plagioclase flotation in the global magma ocean.

Exposure to microgravity and/or spaceflight causes dramatic losses in both muscle and bone mass. In normal gravity, resistance exercise has been effectively used to increase muscle and bone mass. We tested a novel form of resistance exercise training using flywheel technology as a countermeasure to offset the loss of musculoskeletal mass during 4 weeks of adult rat hindlimb suspension (HS), an unloading model of microgravity. Male, Sprague-Dawley rats (6-month old) were operantly conditioned to perform resistance exercise, and then randomly assigned to groups of sedentary control (CON), HS, and HS with resistance exercise training (HSRT; 2 sets of approximately 21 repetitions, 3 days week(-1) for 4 weeks during suspension). In soleus, HS resulted in lower (P0.05) muscle mass to body mass ratio (approximately 50% of controls) and rates of protein synthesis. HSRT significantly attenuated the loss of muscle mass in soleus muscle, and rates of protein synthesis for soleus were similar for HSRT and controls. There were no differences among groups for mass or rates of protein synthesis in extensor digitorum longus. In cancellous regions of the distal femur, HS resulted in significant reductions of bone mineral density (BMD), but this was restored to control levels with HSRT. Cortical regions of the femur were not different among HS, HSRT or control groups. Together, these data suggest that resistance training using flywheel technology may be a promising tool to attenuate losses of the musculoskeletal system during periods of hindlimb unloading.

Objective: To evaluate variability in donor semen quality between seven commercial donor sperm banks, within sperm banks, and between intracervical insemination and intrauterine insemination. Design: Prospective, randomized, blind evaluation of commercially available donor semen samples. Setting: An academic andrology laboratory. Patient(s): Seventy-five cryopreserved donor semen samples were evaluated. Intervention(s): Samples were coded, then blindly evaluated for semen quality. Main Outcome Measure(s): Standard semen quality parameters, including concentration, motility parameters, World Health Organization criteria morphology, and strict criteria morphology. Result(s): Significant differences were observed between donor semen banks for most semen quality parameters analyzed in intracervical insemination samples. In general, the greatest variability observed between banks was in percentage progressive sperm motility (range, 8.8 ± 5.8 to 42.4 ± 5.5) and normal sperm morphology (strict criteria; range, 10.1 ± 3.3 to 26.6 ± 4.7). Coefficients of variation within sperm banks were generally high. Conclusion(s): These data demonstrate the variability of donor semen quality provided by commercial sperm banks, both between banks and within a given bank. No relationship was observed between the size or type of sperm bank and the degree of variability. The data demonstrate the lack of uniformity in the criteria used to screen potential semen donors and emphasize the need for more stringent screening criteria and strict quality control in processing samples.

Free-space quantum key distribution (QKD), more popularly know as quantum cryptography, uses single-photon free-space optical communications to distribute the secret keys required for secure communications. At Los Alamos National Laboratory we have demonstrated a fully automated system that is capable of operations at any time of day over a horizontal range of several kilometers. This has proven the technology is capable of operation from a spacecraft to the ground, opening up the possibility of QKD between any group of users anywhere on Earth. This system, the prototyping of a new system for use on a spacecraft, and the techniques required for world-wide quantum key distribution will be described. The operational parameters and performance of a system designed to operate between low earth orbit (LEO) and the ground will also be discussed.

Background Catamenial pneumothorax, a rare complication of systemic endometriosis, has been difficult to treat successfully. Successful medical therapy is associated with amenorrhea. Case A 44-year-old white woman with recurring catamenial pneumothorax underwent thoracotomy and abrasive pleurodesis. Following the procedures, pneumothorax occurred again and she was treated with the GnRH analogue leuprolide acetate, 3.75 mg monthly intramuscularly. After 6 months, her therapy was changed to continuous hormonal suppression with norethindrone, 0.7 mg/day. After 6 months of this therapy and into the third episode of vaginal bleeding, the patient had another recurrent pneumothorax. Conclusion Leuprolide acetate followed by continuous hormonal suppression with norethindrone was successful for 1 year in resolving recurring postsurgical catamenial pneumothorax, but the problem recurred with the resumption of vaginal bleeding during progestin therapy. Successful medical therapy requires amenorrhea.

tion of miR-122 underexpression with steatohepatitis. To our knowledge, this is the first report of underexpression of miR-370 in steatohepatitis. This result is mechanistically consistent with a previous study that showed upregulation of miR-122 by miR-370. Our findings suggest that miR-122 and miR-370 in particular may have a role in the progression of NAFLD and could be useful as diagnostic markers to differentiate different stages of NAFLD.

Over the past few years we have seen enormous progress in uncovering the critical roles that chromatin structure has on the control of gene expression, the regulation of developmental processes, and the control of cell cycle checkpoints. No longer is chromatin research the "last bastion of scoundrels." The recent intensity of chromatin research, however, might lead a young scientist to conclude that the field is saturated or that all the big mysteries have been solved. This view could not be further from the truth! Here I briefly outline four areas of chromatin research where new paradigms and mysteries are still waiting to be discovered.

To examine associations between puberty and disordered eating, body image, and other psychological variables.Females were grouped into three categories of age at puberty onset (Study 1; N = 267) as well as three categories of self-perception of prepubertal weight (Study 2; N = 222). Participants in both studies were matched on current body mass index (BMI) across categories.Females who perceived themselves to be overweight prior to puberty scored significantly higher on measures of disordered eating, body dissatisfaction, asceticism, drive for thinness, impulse regulation, interoceptive awareness, and perfectionism. They also perceived their current body figure to be larger when compared with those who believed they were average or underweight prior to puberty. Age at puberty onset was not significantly associated with disordered eating, body dissatisfaction, depression, or self-esteem. However, females who entered puberty at an earlier age scored higher on measures of asceticism, drive for thinness, impulse regulation, and social insecurity. They also chose a more slender ideal body figure than those who entered at an older age.Females who believe they are overweight prior to puberty may be at risk for the development of disordered eating, body image dissatisfaction, and related problems. Age at puberty onset is not a consistent risk factor of pathological eating.

This article summarizes the proceedings of a workshop presented at the 2000 RSA Meeting in Denver, Colorado. The aim of this workshop was to discuss the basic methodologies, diagnostic performance, and clinical utility of three technologies: carbohydrate-deficient transferrin, the "Early Detection of Alcohol Consumption" score, and whole blood associated acetaldehyde. Each method adopts a different strategy to identify heavy alcohol consumption and offers a unique approach to determine alcohol abstinence and relapses. Appropriate application of these technologies can lead to early intervention for alcohol problems before significant tissue damage occurs. To date these methodologies have yet to be formally contrasted and compared. Sensitivity, specificity, predictive value, availability, ease of use, and interpretation of tests results are important aspects to consider when selecting the most appropriate and cost-effective system. Critical evaluation of these methodologies can enable research and clinical laboratories to choose the system that best meets their particular needs in terms of assay feasibility, budget, and goals.

The article examines the issue of nursing workforce planning within the present health system environment and addresses ethical issues related to the shortage. Numerous factors are influencing both the supply of registered nurses as well as the demand for nursing services. Of particular concern is the negative impact that the current nursing practice environment is having on the retention of registered nurses as well as the ability of the profession to recruit students. Other factors driving this present nursing shortage include the increasing age of working nurses and the potential for retirement; the aging of nursing faculty impacting the capacity of nursing schools; and poor wage compensation. The continual swing in the supply of and demand for nursing services will always be present; however, it is time that nursing sat at the policy-making table with the other decision makers to better anticipate the nature of these changes and how to address them.

Using polarization-entangled photons, we have implemented the “six-state” quantum cryptography protocol, whereby each photon is measured in one of three bases. The resulting eavesdropper-induced error rate, experimentally investigated for several attacks, is enhanced to 33%.

Variability in grain color of hard white wheat was investigated incultivars grown over two years in Nebraska and Kansas and related tovariation observed in grain hardness, kernel weight, kernel size, and proteincontent and to color of ground meal and flour. Grain color was scoredsubjectively, through visual evaluation, and objectively through use of acolorimeter. Of the 543 hard white wheat samples examined byUSDA-GIPSA grain inspectors, 15.5% were scored as visually darker thanthe 1990 grain color standard established as a minimum for hard whitewheat classification. The remaining samples were scored as having graincolor essentially equal (28.2%), or visually `whiter' (56.4%), than thecolor standard. Distributions of colorimeter L, a, and b values suggest thatthe colorimeter had difficulty in capturing the subtleties of visual ratings.There were significant decreases in kernel hardness and grain proteincontent among samples that scored visually `whiter' than the colorstandard. Grain color, measured either visually or by colorimeter, was nota reliable indicator of either ground meal color or flour color. As such, itmay provide little indication of grain quality, end-product color, orprocessing value to the milling and baking industries.

To evaluate the relationship between women's body image, self-image, and sexual behaviors; to determine the effect of body image on personal and sex variables; and to identify factors that contribute to more frequent and greater comfort with sex.A magazine survey that included items about body image, self-image, and sexual behaviors was completed by 3,627 women.Women more satisfied with body image reported more sexual activity, orgasm, and initiating sex, greater comfort undressing in front of their partner, having sex with the lights on, trying new sexual behaviors, and pleasing their partner sexually than those dissatisfied. Positive body image was inversely related to self-consciousness and importance of physical attractiveness, and positively related to relationships with others and overall satisfaction. Body image was predictive only of one's comfort undressing in front of partner and having sex with lights on. Overall satisfaction was predictive of frequency of sex, orgasm, and initiating sex, trying new sexual behaviors, and confidence in giving partner sexual pleasure.Results indicate that overall self-image and body image are significant predictors of sexual activity. Directions for future research are discussed.

Adventitious roots of marsh-grown Pontederia cordata were examined to determine cortical development and structure. The innermost layer of the ground meristem forms the endodermis and aerenchymatous cortex. The outermost layer of the early ground meristem undergoes a precise pattern of oblique and periclinal cell divisions to produce a single or double layer of prohypodermis with an anchor cell for each radial file of aerenchyma cells. At maturity, endodermal cell walls are modified only by narrow Casparian bands. The central regions of the ground meristem become proaerenchyma and exhibit asymmetric cell division and expansion. They produce an aerenchymatous zone with barrel-shaped large cells and irregularly shaped small cells traversing the aerenchyma horizontally along radii; some crystalliferous cells with raphides are present in the aerenchyma. The walls of the hypodermis are modified early by polyphenols. The outermost layer of the hypodermis later matures into an exodermis with Casparian bands that are impermeable to berberine, an apoplastic tracer dye. The nonexodermal layer(s) of the hypodermis has suberin-modified walls. Radial files of aerenchyma are usually connected by narrow protuberances near their midpoints, the aerenchyma lacunae having been produced by expansion of cells along walls lining intercellular spaces. We are terming this type of aerenchyma development, which is neither schizogenous nor lysigenous, "differential expansion."

The purpose of this investigation was to determine the test-retest reliability of the Eating Disorder Examination (EDE).This study examined the test-retest and interrater reliability of the EDE in 20 adult women with a range of eating disorder symptoms. Trained assessors administered the EDE to participants on two separate occasions, ranging from 2 to 7 days apart.Test-retest correlations were.7 or greater for all subscales and measures of eating disorder behaviors except for subjective bulimic episodes and subjective bulimic days. Interrater reliability was uniformly high with correlations above.9.Results provide further support for the reliability of the EDE, but suggest that smaller binge episodes may not be reliable indicators of eating pathology.

The purpose of this study was to identify predictors of short-term treatment outcome for individuals with binge eating disorder (BED).Fifty women who met DSM-IV criteria for BED were enrolled in a manual-based group cognitive-behavioral therapy that consisted of fourteen 1-hr sessions over an 8-week period. Baseline measures included the frequency of self-reported binge eating from the Eating Behaviors-IV (EB-IV), severity of binge eating and dietary restraint using the Binge Eating Scale (BES) and Three-Factor Eating Questionnaire (TFEQ), depressive symptoms as assessed by the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and self-esteem as measured by the Rosenberg Self-Esteem Questionnaire (RSEQ).Logistic regression analyses indicated that the baseline frequency of self-reported episodes of binge eating that were objectively large predicted the likelihood of such episodes at the end of treatment. No variables predicted the likelihood of binge eating episodes that were objectively and subjectively large at the conclusion of treatment.This study indicates that the frequency of binge eating episodes at baseline is predictive of outcome status at the end of treatment, suggesting that meaningful prognostic factors in BED are identifiable.

The actin superfamily of ATPases includes cytoskeletal actins, the stress 70 proteins (e.g. hsc70), sugar kinases, glycerol kinase, and several prokaryotic cell cycle proteins. Although these proteins share limited sequence identity, they all appear to maintain a similar tertiary structure, the "actin fold", which may serve to couple ATP hydrolysis to protein conformational changes. Recently, an actin-related protein (Arp) subfamily has been identified based on sequence homology to conventional actin. Although some Arps are clearly involved in cytoskeletal functions, both actin and/or Arps have been found as stoichiometric subunits of several nuclear chromatin-remodeling enzymes. Here we present two related models in which actin and/or Arps function as conformational switches that control either the activity or the assembly of chromatin-remodeling machines.

The assembly of eukaryotic DNA into folded nucleosomal arrays has drastic consequences for many nuclear processes that require access to the DNA sequence, including RNA transcription, DNA replication, recombination, and repair. Two types of highly conserved chromatin remodeling enzymes have been implicated as regulators of the repressive nature of chromatin structure: ATP-dependent remodeling complexes and nuclear histone acetyltransferases (HATs). Recent studies indicate that both types of enzymes can be recruited to chromosomal loci through either physical interactions with transcriptional activators or via the global accessibility of chromatin during S phase of the cell cycle. Here we review these recent observations and discuss the implications for gene-specific regulation by chromatin remodeling machines.

Serum measurement of ECP (eosinophil cationic protein) is used as an indication of eosinophil activation in diseases such as asthma. The levels are dependent on sample handling, since a certain amount of ECP is released during storage. The mechanisms that induce this in vitro release are not known, but are supposed to be related to the coagulation process. The aim of this study was to investigate this further. ECP was measured in EDTA plasma and serum at 22 and 37 degrees C from healthy individuals and patients with asthma and allergy. The serum levels of ECP increased with temperature. Recalcification of citrated plasma in the presence of granulocytes with increasing concentrations of Ca(2+) showed a dissociation between the levels of ECP and the occurrence of coagulation. Further experiments indicated that plasma coagulation is not of any importance for the degranulation of eosinophils, nor did the addition of platelets or mononuclear cells affect the ECP levels. Incubations of granulocytes with fresh or frozen plasma and Ca(2+) suggested the existence of a freezing labile factor in plasma, necessary for the degranulation of healthy eosinophils, but not for allergic/asthmatic eosinophils. Further experiments with pure eosinophils indicated the existence of factors in serum and plasma which facilitate ECP secretion of an active, temperature-dependent nature. We conclude that the raised ECP levels in serum, as compared to EDTA plasma, are unrelated to the coagulation process, but are due to the continuous secretion ex vivo of ECP from active eosinophils. This process is time and temperature dependent and may be facilitated by eosinophil-activating components in the extracellular environment.

Fetal pancreatic tissue has been suggested to be less immunogenic than adult islets. Thus, transplantation of human fetal pancreatic tissue as treatment for type 1 diabetes has been gaining interest. To investigate this question, we tested the peripheral blood mononuclear cell (PBMC) responses from different subject populations to human adult islet proteins (AIP) versus human fetal pancreatic proteins (FPP).PBMC responses to FPP and AIP from normal controls (n=14), newly diagnosed type 1 diabetes patients (n=5), long-term type 1 diabetes patients (n=9), and subjects at-risk for development of type 1 diabetes (n=3) were studied.We observed that normal controls demonstrated PBMC reactivity to 0-3 molecular weight regions (mwr) for both the AIP (mean+/-SD, 0.8+/-1.1) and the FPP (0.6+/-0.7). In contrast, newly diagnosed type 1 diabetic patients (1 year) demonstrated PBMC responses to 9-16 mwr for the AIP (12.8+/-2.5) and 0-14 mwr for the FPP (6.8+/-5.0). The PBMCs from long-term type 1 diabetes patients (3 years) were responsive to 2-11 mwr for AIP (6.0+/-2.8) and 0-11 mwr for FPP (4.9+/-4.0). Three nondiabetic ICA positive subjects at-risk for development of type 1 diabetes demonstrated positive PBMC reactivity to 9-18 mwr for the AIP (12.7+/-3.9) and 4-18 mwr for the FPP (10.0+/-5.9).We conclude that human fetal pancreatic proteins are not significantly less stimulatory than human adult islet proteins to PBMCs of subjects with or at risk for type 1 diabetes.

Two phenomena have long been observed to correlate with transcriptionally active chromatin: increased histone acetylation and increased sensitivity to nucleases, including specific patterns of nuclease hypersensitivity in the promoters of active or inducible genes. Work in recent years has at last identified protein complexes required to form these hallmarks of active chromatin: histone acetyltransferases (HATs) and ATP-dependent chromatin remodeling complexes. This review traces the history of these discoveries, including the development of essential tools that allowed the major advances in the field, and describes the current understanding of the interactions between HATs and ATP-dependent remodelers.

Quantum cryptography is an emerging technology in which two parties may simultaneously generate shared, secret cryptographic key material using the transmission of quantum states of light. The security of these transmissions is based on the inviolability of the laws of quantum mechanics and information-theoretically secure post-processing methods. An adversary can neither successfully tap the quantum transmissions, nor evade detection, owing to Heisenberg's uncertainty principle. In this paper we describe the theory of quantum cryptography, and the most recent results from our experimental free-space system with which we have demonstrated for the first time the feasibility of quantum key generation over a point-to-point outdoor atmospheric path in daylight. We achieved a transmission distance of 0.5 km, which was limited only by the length of the test range. Our results provide strong evidence that cryptographic key material could be generated on demand between a ground station and a satellite (or between two satellites), allowing a satellite to be securely re-keyed on orbit. We present a feasibility analysis of surface-to-satellite quantum key generation.

This study demonstrates the selective tumor targeting and the antitumor efficacy of the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound mesochlorin e6 monoethylenediamine (Mce6) and HPMA copolymer-bound Adriamycin (ADR) in combination photodynamic therapy (PDT) and chemotherapy against human ovarian OVCAR-3 carcinoma xenografted in female athynmic mice. The concentrations of Mce6 and ADR in blood and tissues, in free or HPMA copolymer-bound form, were determined by fluorescence and high-performance liquid chromatography fluorescence assays, respectively. Xenograft responses to single and combination therapies were recorded. The peak concentration of HPMA copolymer-Mce6 conjugate in tumor was achieved 18 h after administration. For HPMA copolymer-bound drugs, the concentration ratios of liver and spleen versus muscle were significantly higher than those of free drugs. The HPMA copolymer-bound drugs demonstrated selective targeting and accumulation in the tumor, probably attributed to the enhanced permeability and retention effect. In vivo studies revealed that all tumors in the treatment groups showed significant responses after receiving any of the various types of therapy as compared with controls (P0.001). PDT with HPMA copolymer-Mce6 conjugate (PDTMC) at a dose of 13.4 mg/kg (1.5 mg/kg of Mce6 equivalent) and light doses of 110 J/cm2 at 12 and 18 h, respectively, resulted in significant suppression of the growth of OVCAR-3 tumors. Three courses of chemotherapy using 35 mg/kg (2.2 mg/kg of ADR equivalent) of HPMA copolymer-ADR conjugate (CHEMO) were effective in suppressing the growth of tumors. Single PDTMC plus multiple CHEMO exhibited significantly greater therapeutic efficacy than multiple CHEMO. In the group of mice receiving multiple PDTMC, tumor recurrence became obvious after day 20. However, 10 of 12 tumors exhibited complete responses in the group of mice receiving multiple PDTMC plus multiple CHEMO. The least to most effective treatments were ranked as follows: multiple CHEMOsingle PDTMC plus multiple CHEMOmultiple PDTMCmultiple PDTMC plus multiple CHEMO. The results clearly demonstrate that: (a) HPMA copolymer-bound drugs exhibited selective tumor accumulation contrary to free drugs; (b) PDT using HPMA copolymer-Mce6 conjugate with multiple light irradiations was a better therapy than that with single light irradiation; and (c) combination chemotherapy and photodynamic therapy with HPMA copolymer-ADR and HPMA copolymer-Mce6 conjugates was the most effective regimen.

Insulin-dependent (type 1) diabetes is a cell-mediated autoimmune disease. Successful transplantation of human fetal pancreatic tissue into type 1 diabetic patients must address both autoimmunity and allograft rejection. We investigated whether humoral and cellular responses to islet antigens could be demonstrated in the peripheral blood of type 1 diabetic subjects receiving human fetal pancreatic tissue transplants.We investigated peripheral blood mononuclear cell (PBMC) responses, using cellular immunoblotting, and autoantibody responses to islet proteins, before transplantation and at 3-month intervals after transplantation. Our study population included nine long-term type 1 diabetes patients (mean disease duration of 21 years) receiving human fetal pancreatic tissue subcutaneously into the abdominal wall without immunosuppression.Before transplantation, all nine subjects tested negative for islet cell autoantibody (ICA), and seven of nine subjects tested positive for glutamic acid decarboxylase autoantibody (GADAb). After transplantation, all subjects became ICA(+), and the two patients who were GADAb(-) before transplantation, became GADAb(+) after transplantation. Maximum PBMC reactivity to separated human fetal pancreatic proteins was observed in four patients at 3 months, in one patient at 6 months, in two patients at 9 months, and in one patient at 12 months after transplantation. One subject, who had PBMC reactivity to multiple islet proteins before transplantation, continued to respond to multiple islet proteins throughout the study.We conclude that the development in the peripheral blood of ICA, GADAb, and PBMC reactivity to human fetal pancreatic proteins in the transplant recipients is most consistent with reactivation of the type 1 diabetes disease process.

In 1898, Tiegerstadt and Bergman noted that the crude saline extracts of the kidney had a powerful pressor activity, which they named renin (1). This discovery eventually lead to the understanding of the circulating renin angiotensin system (RAS) as a unique endocrine appendage with a clear role in blood pressure control. In the classical circulating RAS system, the JG cells secrete prorenin that is subsequently converted by endopeptidases to renin, a 347 amino acid (Fig. 12.1). Prorenin is secreted from the renal juxtaglomerular cells at 10 times the concentration of renin. Prorenin, which was originally considered a unique product of the kidney, has now been located in chorion, tumor cells, and blood vessels, as well as the adrenal gland, brain, testis, and ovary. In fact, these extrarenal sources, or tissue-based renin angiotensin systems, may account for up to 10% of the total plasma prorenin concentration.

The purpose of this study was to examine the biodistribution of the photosensitizing drug, mesochlorin e(6) monoethylenediamine (Mce(6)), and the antineoplastic agent, adriamycin (ADR), as well as their N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates in female nu/nu athymic mice bearing human ovarian carcinoma OVCAR-3 xenografts. The levels of Mce(6) and HPMA copolymer-bound Mce(6) in tissues were assayed spectrophotometrically, while the levels of ADR and HPMA copolymer-bound ADR were determined using high-performance liquid chromatography. It appeared that the circulation lifetimes of HPMA copolymer-bound Mce(6) and ADR were three times more than those of the drugs in the free form. The concentrations of the HPMA copolymer-conjugated drugs in tumor reached maximum levels 18 h post injection. Intravenous injection routinely gave higher tissue levels of the drugs than intraperitoneal administration at time intervals less than 24 h. The biodistribution of the HPMA copolymer-bound drugs in tumor-bearing mice was significantly different from that of the free drugs, which is important in optimizing the treatment protocols. In particular, the HPMA copolymer-conjugated drugs accumulated at significantly higher levels in tumor tissues. This effect is attributed to the increased vascular permeability and reduced lymphatic drainage characteristic of tumor tissues [enhanced permeability and retention (EPR) effect].

Potential differences in the hedonics of binge eating between female subjects with bulimia nervosa (BN) and female subjects with binge eating disorder (BED) were examined.Women seeking treatment for BN (N = 29) and BED (N = 49) completed the Eating Hedonics Questionnaire.Subjects in both groups reported similar precipitants and levels of distress associated with binge eating. Of interest, BED subjects were more likely to report that they enjoyed the food, the taste of the food, the smell and the texture of the food while binge eating. In addition, the BED group reported more relaxation and less physical discomfort and anxiety as a consequence of binge eating compared to the BN group.There are interesting and potentially important differences between individuals with BN and BED in the cognitions and behaviors associated with binge eating.

We have demonstrated point-to-point single-photon quantum key distribution (QKD) over a free-space optical path of {approximately}475 m under daylight conditions. This represents an increase of >1,000 times farther than any reported point-to-point demonstration, and >6 times farther than the previous folded path daylight demonstration. We expect to extend the daylight range to 2 km or more within the next few months. A brief description of the system is given here. The QKD transmitter, a.k.a. ''Alice'' (Fig. 1), consists of three thermoelectrically cooled diode lasers, a single interference filter (IF), two optical attenuators, two linear polarizers, two non-polarization beam-splitters (BSs), and a 27x beam expander. The two data-lasers' (dim-lasers') wavelengths are temperature controlled and constrained by the IF to {approximately}773 {+-} 0.5 nm, while the transmitted wavelength of the bright-laser (timing-laser) is {approximately}768 nm; the data-lasers are configured to emit a weak pulse of approximately 1 ns duration. The transmitter incorporates no active polarization switching--a first in QKD.

Studies were carried out to determine if an intraspinal transplant (Trpl) of fetal spinal cord tissue or hind limb exercise (Ex) affected the changes in myosin heavy chain (MyHC) composition or myofiber size that occur following a complete transection (Tx) of the lower thoracic spinal cord of the adult rat. In one group of animals, transplants were made acutely, whereas in a second group, daily cycling exercise was initiated 5 days after injury, with animals in both groups being sacrificed 90 days after injury. The soleus muscle is normally composed of myofibers expressing either type I (90%) or type IIa (10%) MyHC. Following a spinal transection, expression of type I MyHC isoform decreased (18% of myofibers), type IIa MyHC expression increased (65% of myofibers), and the majority of myofibers (80%) expressed type IIx MyHC. Most myofibers coexpressed multiple MyHC isoforms. Compared with Tx only, with Ex or with Trpl, there was a decrease in the number of myofibers expressing type I or IIa isoforms but little change in expression of IIx MyHC. Myofibers expressing the IIb isoform appeared in several transplant recipients but not after exercise. Transection resulted in atrophy of type I myofibers to approximately 50% of normal size, whereas myofibers were significantly larger after exercise (74% of control) and in Trpl recipients (77% of control). Type IIa myofibers also were significantly larger in Trpl recipients compared with the Tx only group. Overall, the mean myofiber size was significantly greater after exercise and in Trpl recipients compared with myofibers in Tx only animals. Thus, although neither strategy shifted the MyHC profile towards the control, both interventions influenced the extent of atrophy observed after spinalization. These data suggest that palliative strategies can be developed to modulate some of the changes in hind limb muscles that occur following a spinal cord injury.

The purpose of this study was to determine the interaction between free (unbound) and N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer bound adriamycin and meso-chlorin e6 monoethylene diamine (Mce6) induced photodynamic therapy in combination in their cytotoxic activities against human ovarian epithelial carcinoma (OVCAR-3) in vitro. The effects of each agent (free drugs and HPMA copolymer bound) alone and in combination were measured simultaneously utilizing two measures of cell viability: a) mitochondrial respiration via the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide reduction (MTT) assay; and b) thymidine incorporation via the tritiated thymidine incorporation (TI) assay. These were performed at 72 and 144 h after drug exposure. Forty-eight hours from time zero (24 h after drug addition), the cells treated with Mce6 (free and HPMA copolymer bound) and controls were exposed to 650 nm light (13 min at 15 mW/cm2, 11.7 J/cm2). The calculated ED50 values by the MTT 72 h assay for adriamycin (A) and Mce6/light (C) were 1.5 microg/ml and 209 ng/ml, respectively. Adriamycin demonstrated progressive cellular toxicity over time in both assays. Mce6/light demonstrated initial damage at 72 h by MTT and TI which recovered by 144 h. Adriamycin and Mce6/light acted cooperatively to increase the percentage of cells inhibited. In combination, 21.3+/-1.5% MTT reduction activity was observed by free adriamycin and Mce6/light compared to the expected 27+/-5% (p

Placental proteins, such as inhibin A and hCG and its subunits, as well as the placental steroid progesterone, are elevated in second-trimester maternal serum from cases of fetal Down syndrome. Since different cellular mechanisms are required for protein versus steroid synthesis and secretion, these data suggest that a generalized placental hypersecretory phenomenon is associated with Down syndrome. Inhibin A and hCG are also elevated in cases of Turner syndrome with hydrops, and are reduced in cases of Turner syndrome without hydrops and in trisomy 18. The objective of the present study was to determine maternal serum levels of the placental steroid progesterone in cases of Turner syndrome and trisomy 18. Twenty-one cases of trisomy 18, 10 cases of Turner syndrome without hydrops and 12 cases of Turner syndrome with hydrops were identified and each matched to five control samples. Maternal serum progesterone levels were significantly elevated in Turner syndrome with hydrops (2.11 MoM), slightly reduced in Turner syndrome without hydrops (0.90 MoM) and modestly, though significantly, reduced in trisomy 18 (0.73 MoM). These data are similar to the patterns seen for inhibin A and hCG, suggesting that the overall synthetic and/or secretory activity of the placenta is increased in Turner syndrome with hydrops and decreased in Turner syndrome without hydrops and in trisomy 18. These data may be helpful in understanding the pathophysiological basis of serum marker patterns in these aneuploidies.

Attachment of the sheep metallothionein la promoter to the sheep growth hormone gene (oMT1a-oGH) has resulted in a closely regulated transgene in mice that can respond to elevated levels of zinc ions provided in the drinking water. The objective of this study was to explore the effects of zinc ion concentration on postweaning growth, fat content, organ size, and female reproduction. At weaning (3 weeks of age), hemizygous oMT1a-oGH mice were assigned randomly to receive 0, 12.5, 25, 37.5, or 50 mM ZnSO4 in distilled drinking water for 5 weeks. Males were killed at 8 weeks and selected organs and fat pads were weighed. Females received tap water from 8 to 10 weeks and then were mated to unrelated non-transgenic fertile males to obtain ovulation rate and embryo survival. Mortality rate was increased (P0.05) at 37.5 mM (15.2%) and 50 mM (33.3%) ZnSO4 compared with lower levels. Postweaning growth was highest at 12.5 mM ZnSO4 followed by 25 and 37.5 mM, respectively. At 50 mM ZnSO4, 8 week-old males were 20% smaller than males not receiving a supplement while females did not differ from females not receiving a supplement. Epididymal (EFP) and subcutaneous (SFP) fat pad weights of males decreased linearly (P0.01) with increased dosage of ZnSO4, while on a percentage of body weight basis, EFP and SFP decreased quadratically (P0.01). Males receiving 12.5 mM ZnSO4 had their EFP and SFP as a percentage of body weight reduced (P0.01) to 54.1% and 65.9% of controls (0 mM), respectively. As a percentage of body weight, liver spleen and kidney weights increased with doses of 12.5, 25 and 37.5 mM ZnSO4 compared with no supplemental zinc, while testis weight as a percentage of body weight was reduced (P0.05); percentage heart weight was only reduced at 12.5 mM (P0.05). No significant differences in female fertility were associated with ZnSO4 treatment. Females receiving ZnSO4 supplement had higher ovulation rates than those that received no supplement, but there were no differences (P0.05) in ovulation rates among the zinc levels. A decrease (P0.05) in pre- and post-implantation embryo survival was detected at 37.5 mM ZnSO4. These results indicate that zinc dosage affects phenotypic expression of the oMT1a-regulated oGH transgenic mice, and the dose responses are trait-dependent.

Quantum cryptography is an emerging technology in which two parties may simultaneously generate shared, secret cryptographic key material using the transmission of quantum states of light. The security of these transmissions is based on the inviolability of the laws of quantum mechanics and information-theoretically secure post-processing methods. An adversary can neither successfully tap the quantum transmissions, nor evade detection, owing to Heisenberg's uncertainty principle. In this paper we describe the theory of quantum cryptography, and the most recent results from our experimental free-space system with which we have demonstrated for the first time the feasibility of quantum key generation over a point-to-point outdoor atmospheric path in daylight. We achieved a transmission distance of 0.5 km, which was limited only by the length of the test range. Our results provide strong evidence that cryptographic key material could be generated on demand between a ground station and a satellite (or between two satellites), allowing a satellite to be securely re-keyed on orbit. We present a feasibility analysis of surface-to-satellite quantum key generation.

A primary heparin-binding site in vitronectin has been localized to a cluster of cationic residues near the C terminus of the protein. More recently, secondary binding sites have been proposed. In order to investigate whether the binding site originally identified on vitronectin functions as an exclusive and independent heparin-binding domain, solution binding methods have been used in combination with NMR and recombinant approaches to evaluate ligand binding to the primary site. Evaluation of the ionic strength dependence of heparin binding to vitronectin according to classical linkage theory indicates that a single ionic bond is prominent. It had been previously shown that chemical modification of vitronectin using an arginine-reactive probe results in a significant reduction in heparin binding (Gibson, A., Baburaj, K., Day, D. E., Verhamme, I. , Shore, J. D., and Peterson, C. B. (1997) J. Biol. Chem. 272, 5112-5121). The label has now been localized to arginine residues within the cyanogen bromide fragment-(341-380) that contains the primary heparin-binding site on vitronectin. One- and two-dimensional NMR on model peptides based on this primary heparin-binding site indicate that an arginine residue participates in the ionic interaction and that other nonionic interactions may be involved in forming a complex with heparin. A recombinant polypeptide corresponding to the C-terminal 129 amino acids of vitronectin exhibits heparin-binding affinity that is comparable to that of full-length vitronectin and is equally effective at neutralizing heparin anticoagulant activity. Results from this broad experimental approach argue that the behavior of the primary site is sufficient to account for the heparin binding activity of vitronectin and support an exposed orientation for the site in the structure of the native protein.

This study examined the validity of trait anger as a predictor of aggressive behavior among juvenile offenders. Two standard self-report anger scales were administered to 65 recently incarcerated male adolescents. These youths were followed prospectively for physical and verbal aggression during 3 months of subsequent incarceration. Anger scores were not correlated with participant history of violent offending or staff ratings of anger. However, anger scores from both instruments were predictive of subsequent physical and verbal aggression. For example, the Trait Anger scale successfully classified 66% of juvenile offenders into high and low aggressive groups; receiver operating characteristic analysis obtained an effect size of .72. These results support the predictive validity of self-reported anger in identifying juvenile offenders at risk for institutional aggression.

We briefly review the development and theory of an experiment to investigate quantum computation with trapped calcium ions. The ion trap, laser and ion requirements are determined, and the parameters required for simple quantum logic operations are described. (LAUR 98-314)

An experimental free-space quantum key distribution (QKD) system has been tested over an outdoor optical path of ~ 1 km under nighttime conditions at Los Alamos National Laboratory. This system employs the Bennett 92 protocol; here we give a brief overview of this protocol, and describe our experimental implementation of it. An analysis of the system efficiency is presented, as well as a description of our error detection protocol, which employs a two-dimensional parity check scheme. Finally, the susceptibility of this system to eavesdropping by various techniques is determined, and the effectiveness of privacy amplification procedures is discussed. Our conclusions are that free-space QKD is both effective and secure; possible applications include the rekeying of satellites in low earth orbit.

Hormone replacement of hypogonadal women is a highly effective preventive health care measure. Estrogen replacement results in a nearly a 50% reduction in the risks of cardiovascular disease, vertebral and hip fractures, and Alzheimer’ s disease. Hypogonadal symptomatology such as hot flushes, irritability, anxiety, mood disturbances, loss of libido and genitourinary atrophy are reduced and often alleviated by estrogen replacement. Numerous estrogen formulations and delivery systems are available and reviewed. Progestogens are utilized in women with a uterus to reduce the risk of endometrial hyperplasia and endometrial cancer. Available progestogen formulations are discussed. The role of androgens, phytoestrogens, and DHEA in hormone replacement therapy (HRT) are noted. Risks and complications of HRT are outlined, including the potential risk of breast cancer, reduced cardiovascular benefits after long-term use, and nuisance side effects. The future role of selective estrogen receptor modulators (SERM’s) is highlighted.

The objective was to investigate whether cases of fetal trisomy 18 and Turner syndrome with and without hydrops were associated with alterations in the second-trimester levels of maternal serum inhibin A. Twenty-one cases of trisomy 18, 10 cases of Turner syndrome without hydrops and 12 cases of Turner syndrome with hydrops were identified. Five control samples were matched to each case for date of sample collection and completed week of gestation. Inhibin A levels were modestly, but significantly reduced in cases of trisomy 18 (median = 0.88 MoM) and Turner syndrome without hydrops (median = 0.64 MoM). In contrast, inhibin A levels were markedly increased in cases of Turner syndrome with hydrops (median = 3.91 MoM). These data for Turner syndrome are similar to those for human chorionic gonadotropin (hCG). The addition of inhibin A to multiple marker screening (alpha-fetoprotein, unconjugated oestriol and hCG) resulted in a median increase in the Down syndrome risk of 2.6-fold in cases of Turner syndrome with hydrops. The addition of inhibin A to multiple marker Down syndrome screening programmes will be likely to enhance the detection of fetal Turner syndrome with hydrops, but will not contribute substantially to the detection of fetal trisomy 18.