Endometrial cancer

Carcinoma of the uterine corpus (endometrial cancer) remains the gynecologic malignant disease with the highest annual prevalence in the United States. The most common histologic type is adenocarcinoma, although more aggressive variants (e.g., papillary serous carcinoma and clear cell carcinoma) have been identified. Risk factors that are strongly associated with the development of endometrial cancer include tamoxifen therapy, obesity, and stimulation from unopposed estrogen (from exogenous sources or endogenously secreting ovarian tumors). The current staging system of the International Federation of Gynecology and Obstetrics is based on surgical-pathologic findings. Survival has been directly correlated with tumor stage in this staging system. The cornerstone of therapy is total abdominal hysterectomy with bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy may provide additional prognostic information but probably does not confer a therapeutic advantage. Moreover, such nodal dissections predispose to the development of complications, especially in women who subsequently receive pelvic irradiation. Other than surgical treatment, irradiation is the single most active therapy for endometrial carcinoma. In fact, some women who are not candidates for hysterectomy because of medical contra-indications can be cured with radiation alone. Adjuvant therapy following hysterectomy is based on patient- and tumor-related features that provided prognostic information for incidence and pattern of recurrence. Adjuvant treatment usually includes pelvic irradiation for selected patients. Current investigational strategies are directed at the role of whole-abdomen irradiation, extended-field irradiation, and systemic chemotherapy. The most active systemic agents include cisplatin, doxorubicin, paclitaxel, and progestins.     

A stimulation-retreat special care unit for elders with dementing illness

Pigeons discriminated the serial position of a target duration among a sequence of 3 stimulus durations; the specific duration sequences changed across trials. In different conditions, the target duration was the shortest, intermediate, or longest duration in the sequence. Conditions involved a series of transitions in which new duration sequences were added to the stimulus set, providing an assessment of transfer. Pigeons learned and transferred the discrimination when the target was the shortest or longest duration. When, however, the target was the intermediate duration, the birds had great difficulty learning the task and exhibited little transfer to novel sequences. These findings are similar to those observed with nontemporal stimuli in a classic discrimination task, the intermediate stimulus problem. They provide an extension of work on relational timing to a more complex situation.     

Chronobioengineering toward a cost-effective quality health care

The current disease-cure-oriented health care system does too little too late for too few. Engineering for concomitantly resolving the external conditions and the internal schedules, chronoengineering in the broad sense, could change this status quo into a system that recognizes environmental and organismic risk early, blows a whistle as a minimum and acts automatically, as an optimum. The chronobioengineering feature (of the broader chronoengineering for external as well as internal monitoring and decision helping) would gain new individualized information from the resolution of predictable variations that occur within the physiologic range, the chronomes, genetically anchored multifrequency rhythms and trends. Their resolution by chronobiometry provides a more precise and more accurate mean value (than the arithmetic mean) along with new dynamic endpoints for improved screening, diagnosis, prognosis, and timely and timed treatment. Trends are those with growth, development, maturation and aging, and also those with risk elevation or disease and treatment. Risk elevation may change amplitude or timing, but not necessarily the mean. The implementation of engineering for concomitantly resolving the external and internal schedules depends on telecommunications and telehygiene as well as telemedicine for (i) universal chronobiologic education (to assume self-responsibility and self-help in health care), (ii) physiologic monitoring (complemented as a sine qua non by chronobiologic data analysis and interpretation of the results) and (iii) the monitoring of pertinent environmental conditions. Thus, the number of cases of catastrophic diseases could be reduced and quality (since preventive) health care made available to all.     

Surface plasmon resonance phase imaging measurements of patterned monolayers and DNA adsorption onto microarrays

The optical technique of surface plasmon resonance phase imaging (SPR-PI) is implemented in a linear microarray format for real-time measurements of surface bioaffinity adsorption processes. SPR-PI measures the phase shift of p-polarized light incident at the SPR angle reflected from a gold thin film in an ATR Kretschmann geometry by creating an interference fringe image on the interface with a polarizer-quartz wedge depolarizer combination. The position of the fringe pattern in this image changes upon the adsorption of biomolecules to the gold thin film. By using a linear array of 500 μm biosensor element lines that are perpendicular to the interference fringe image, multiple bioaffinity adsorption measurements can be performed in real time. Two experiments were performed to characterize the sensitivity of the SPR-PI measurement technique: First, a ten line pattern of a self-assembled monolayer of 11-mercaptoundecamine (MUAM) was created via photopatterning to verify that multiple phase shifts could be measured simultaneously. A phase shift difference (Δφ) of Δφ = 182.08 ± 0.03° was observed for the 1.8 nm MUAM monolayer; this value agrees with the phase shift difference calculated from a combination of Fresnel equations and Jones matrices for the depolarizer. In a second demonstration experiment, the feasibility of SPR-PI for in situ bioaffinity adsorption measurements was confirmed by detecting the hybridization and adsorption of single stranded DNA (ssDNA) onto a six-component DNA line microarray patterned monolayer. Adsorption of a full DNA monolayer produced a phase shift difference of Δφ = 28.80 ± 0.03° at the SPR angle of incidence and the adsorption of the ssDNA was monitored in real time with the SPR-PI. These initial results suggest that SPR-PI should have a detection limit roughly 100 times lower than traditional intensity-based SPR imaging measurements.     

<Emphasis Type="Italic">An evaluation of</Emphasis> maraging steel sheet

Results of investigations into the metallurgical and mechanical behavior of 18Ni-9Co-5Mo maraging steel—one of a series of tough, high-strength alloys in a period of rapid development.     

Surface plasmon resonance imaging measurements of DNA and RNA hybridization adsorption onto DNA microarrays

Surface plasmon resonance (SPR) imaging is a surface-sensitive spectroscopic technique for measuring interactions between unlabeled biological molecules with arrays of surface-bound species. In this paper, SPR imaging is used to quantitatively detect the hybridization adsorption of short (18-base) unlabeled DNA oligonucleotides at low concentration, as well as, for the first time, the hybridization adsorption of unlabeled RNA oligonucleotides and larger 16S ribosomal RNA (rRNA) isolated from the microbe Escherichia coli onto a DNA array. For the hybridization adsorption of both DNA and RNA oligonucleotides, a detection limit of 10 nM is reported; for large (1,500-base) 16S rRNA molecules, concentrations as low as 2 nM are detected. The covalent attachment of thiol-DNA probes to the gold surface leads to high surface probe density (10(12) molecules/cm2) and excellent probe stability that enables more than 25 cycles of hybridization and denaturing without loss in signal or specificity. Fresnel calculations are used to show that changes in percent reflectivity as measured by SPR imaging are linear with respect to surface coverage of adsorbed DNA oligonucleotides. Data from SPR imaging is used to construct a quantitative adsorption isotherm of the hybridization adsorption on a surface. DNA and RNA 18-mer oligonucleotide hybridization adsorption is found to follow a Langmuir isotherm with an adsorption coefficient of 1.8 x 10(7) M(-1).     

Fabrication of histidine-tagged fusion protein arrays for surface plasmon resonance imaging studies of protein-protein and protein-DNA interactions

The creation and characterization of histidine-tagged fusion protein arrays using nitrilotriacetic acid (NTA) capture probes on gold thin films for the study of protein-protein and protein-DNA interactions is described. Self-assembled monolayers of 11-mercaptoundecylamine were reacted with the heterobifunctional linker N-succinimidyl S-acetylthiopropionate (SATP) to create reactive sulfhydryl-terminated surfaces. NTA capture agents were immobilized by reacting maleimide-NTA molecules with the sulfhydryl surface. The SATP and NTA attachment chemistry was confirmed with Fourier transform infrared reflection absorption spectroscopy. Oriented protein arrays were fabricated using a two-step process: (i) patterned NTA monolayers were first formed through a single serpentine poly(dimethylsiloxane) microchannel; (ii) a second set of parallel microchannels was then used to immobilize multiple His-tagged proteins onto this pattern at discrete locations. SPR imaging measurements were employed to characterize the immobilization and specificity of His-tagged fusion proteins to the NTA surface. SPR imaging measurements were also used with the His-tagged fusion protein arrays to study multiple antibody-antigen binding interactions and to monitor the sequence-specific interaction of double-stranded DNA with TATA box-binding protein. In addition, His-tagged fusion protein arrays created on gold surfaces were also used to monitor antibody binding with fluorescence microscopy in a sandwich assay format.