Effect of hydrogen on fracture of U-notched bend specimens of quenched and tempered AISI 4340 steel

U-notched bend specimens of quenched and tempered AISI 4340 steel were deformed in the uncharged condition and after either precharging or dynamically charging with hydrogen. In the uncharged condition fracture initiated at the notch surface and progressed in mode II along a characteristic slip trace. For precharged specimens, strain to fracture was markedly reduced, cracks nucleated internally in a mode I manner and the crack progressed to the surface in mode II. Dynamic charging reduced plastic strain to essentially zero at crack nucleation, which occurred when the notch root stress reached the yield stress, and the crack grew by mode I. The results are compared to those on lower strength steels and are discussed in view of theories for hydrogen degradation of mechanical properties. Formerly with the Ohio State University Formerly with the Ohio State University     

Development of a streptavidin-anti-carcinoembryonic antigen antibody, radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal cancer. Reagent development

With pretargeting, radioisotope delivery to tumor is decoupled from the long antibody localization process, and this can increase tumor:blood ratios dramatically. Several reagents were prepared for each step of a "two-step" pretargeting method, and their properties were investigated. For pretargeting tumor, streptavidin-monoclonal antibody (StAv-mab) conjugates were prepared by cross-linking sulfo-SMCC-derivatized streptavidin to a free thiol (SH) group on MN-14 [a high-affinity anti-carcinoembryonic antigen (CEA) mab]. Thiolated mabs were generated either by reaction of 2-iminothiolane (2-IT) with mab lysine residues or by reduction of mab disulfide bonds with (2-mercaptoethyl)amine (MEA). Both procedures gave protein-protein conjugates isolated in relatively low yields (20-25%) after preparative size-exclusion (SE) chromatography purification with conservative peak collection. Both StAv-MN-14 conjugates retained their ability to bind to CEA, to an anti-idiotypic antibody to MN-14 (WI2), and to biotin, as demonstrated by SE-HPLC. Two clearing agents, WI2 mab and a biotin-human serum albumin (biotin-HSA) conjugate, were developed to remove excess circulating StAv-MN-14 conjugates in animals. Both clearing proteins were also modified with galactose residues, introduced using an activated thioimidate derivative, to produce clearing agents which would clear rapidly and clear primary mab rapidly. At least 14 galactose residues on WI2 were required to reduce blood levels to 5.9 +/- 0.7% ID/g in 1 h. Faster blood clearance (0.7 +/- 0.2% ID/g) was observed in 1 h using 44 galactose units per WI2. For the delivery of radioisotope to tumor, several biotinylated conjugates consisting of biotin, a linker, and a chelate were prepared. Conjugates showed good in vitro and in vivo stability when D-amino acid peptides were used as linkers, biotin-peptide-DOTA-indium-111 had a slightly longer blood circulation time (0.09 +/- 0.02% ID/g in 1 h) than biotin-peptide-DTPA-indium-111 (0.05 +/- 0.03% ID/g in 1 h) in nude mice. A longer circulation time with the neutral DOTA complex might allow higher tumor uptake.     

Prostate cancer: 6. Surgical treatment of localized disease

A 65-year-old man undergoes a routine checkup before retiring. His wife has urged him to have his prostate examined, because she has read about testing for prostate cancer and a friend has just died of this disease. During the rectal examination, the man's physician discovers some firmness in the right lobe of the prostate gland. The patient has had no urinary symptoms and is in excellent general health. Sexual function is normal. There is no history of prostate cancer; his father died of a stroke at age 86 years. Testing shows that the patient's prostate-specific antigen level is 9.3 ng/mL, and he is referred to a urologist. Transrectal ultrasound-guided needle biopsy reveals adenocarcinoma with a Gleason score of 7 (intermediate grade). At a follow-up meeting with his physician, the patient says, "I have been doing some research, and it appears that I should have treatment. However, what is less clear to me is what form of therapy is best--surgery or radiation treatment. Please tell me what you can about the state of the art with respect to surgery."     

Local dynamics and synchronization in a granular glass

We follow over a long time sequence, the motion of individual particles in an experimental model of “glassy” granular material. In spite of the weak level of vibration applied to the packing, the particles display individual motion in the form of a sub-diffusive random walk followed by a standard diffusive motion. The statistical features of the random walk is examined in detail. Though the motion is tiny at the local granular level, we demonstrate collective synchronizations of the jump dynamics involving several tens of particles. This collective motion is directly related to the caging effect observed in other glassy systems. Through an analysis of the motion kinematics, we relate the granular motion to a collective “solid-like” dynamics keeping its coherence over the whole sub-diffusive domain.     

MEMS optical switches

Leveraging MEMS's inherent advantages such as the batch fabrication technique, small size, integrability, and scalability, MEMS is positioned to become the dominant technology in optical crossconnect switches. MEMS optical switches with complex movable 3D mechanical structures, micro-actuators, and micro-optics can be monolithically integrated on the same substrate by using the matured fabrication process of the integrated circuit industry. In this article we report various popular actuating mechanisms and switch architectures of MEMS optical switches. The basics of surface and bulk micromachining techniques used to fabricate MEMS devices are reviewed. Examples of 2D and 3D approaches to MEMS optical switches are described. The pros and cons of the two approaches are analyzed. In the short term, MEMS-based optical switches seem to have captivated the attention of both the industry and academia. However, there are challenges that threaten the long-term survival of this technology. The problems that remain to be fully addressed are discussed     

Inhibition of thrombin and SFLLR-peptide stimulation of platelet aggregation, phospholipase A2 and Na+/H+ exchange by a thrombin receptor antagonist

A thrombin receptor has been described that is activated by thrombin cleavage generating a new N-terminus. The newly exposed SFLLR-containing "tethered-ligand" then activates the receptor. In these studies, we used 3-mercapto-propionyl-Phe-Cha-Cha-Arg-Lys-Pro-Asn- Asp-Lys-amide (Mpapeptide) as a thrombin receptor antagonist. This compound was capable of preventing both thrombin- and SFLLR-peptide-induced platelet aggregation with little effect on collagen-induced platelet aggregation. It also prevented thrombin- and SFLLRNP-induced calcium mobilization with little effect on thromboxane receptor-activated platelet Ca2+ mobilization. Platelet membrane GTPase could be activated by peptides that activated the thrombin receptor, and the thrombin receptor antagonist also prevented receptor-stimulated GTPase activity. Platelet phospholipase A2 (PLA2) activity (measured as the release of radiolabeled arachidonic acid) and Na+/H+ exchange activation were stimulated by alpha-thrombin and by SFLLR-containing peptides. Activation of both processes with low concentrations of thrombin required thrombin's anion-binding exosite, as they were not activated by similar concentrations of gamma-thrombin, and the alpha- and zeta-thrombin activation was blocked by peptides mimicking the C-terminal region of hirudin. Stimulation of PLA2 and Na+/H+ exchange by both thrombin and SFLLR-containing peptides was inhibited by the thrombin receptor antagonist Mpa-peptide. These results support the hypothesis that thrombin stimulation of PLA2 activity and Na+/H+ exchange occurs via activation of the thrombin tethered-ligand receptor. Moreover, these data are consistent with the tethered-ligand receptor mediating most actions elicited by low concentrations of alpha-thrombin involved in human platelet activation.     

Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. Canadian Urologic Oncology Group

PURPOSE: A prospective, multicenter, randomized study was done to test the hypothesis that neoadjuvant androgen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Observations were made of 213 patients randomized to undergo radical prostatectomy alone (101) or to receive a 12-week course of 300 mg. cyproterone acetate daily followed by surgery (112). Groups were similar at baseline in terms of clinical stage, serum prostate specific antigen and Gleason score. Of 192 patients available for efficacy analysis 9 had stage T1b, 8 stage T1c, 63 stage T2a, 36 stage T2b and 76 stage T2c disease. RESULTS: One or more positive surgical margins were found in 59 of 91 patients (64.8%) in the surgery only group compared to 28 of 101 (27.7%) in the cyproterone acetate group (p = 0.001). Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not (17.8 versus 47.8%, respectively, p < 0.0001). There was no statistically significant difference in surgical (p = 0.8645) or postoperative (p = 0.173) complications between the 2 groups. CONCLUSIONS: Neoadjuvant androgen withdrawal with a 12-week course of 300 mg. cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery. The impact on patient survival will be determined by long-term followup.     

Negotiating Norms of Discussion in the Public Arena: The Use of Irony in Israeli Political Radio Phone‐In Programs

Phone‐in radio programs are part of the public sphere and thus require open access, rationality, and practicality. Simultaneously, they are a media product, which requires entertaining content. We demonstrate these demands through the analysis of interactional irony in Israeli political radio phone‐ins. From an emic perspective, callers see irony as detrimental to the discussions, yet hosts and regular callers use it to make entertaining interactions. Irony is a critical tool that points to violations of norms: the norm of a clear 2‐sided interaction; norms akin to the Habermasian public sphere; and at the content level, irony is used to reject racist positions. Being indirect, irony can be used to create an entertaining yet critical discussion in the public sphere.     

Path Planning for Autonomous Mobile Robots Using the Boundary Integral Equation Method

Path planning is a fundamental problem in mobile robotics. The objective of path planning is to find a sequence of states that carries a robot from some start state to the goal while avoiding obstacles. This paper focuses on point-to-point path planning, ie., developing a path between given points in a known environment with obstacles. A novel environment representation method is introduced which utilizes the Boundary Integral Equation (BIE) method to map the environment into continuous Harmonic potential fields. Different mappings and mechanisms for utilizing these mappings for path planning are developed, and a collection of path planning algorithms are described which exploit the properties of Harmonic fields and the computational efficiency of the BIE method.