T Cell Antigen Receptor Vaccines for Active Therapy of T Cell Malignancies

T cell lymphoproliferative disorders continue to be serious management problems, and so alternative therapeutic modalities are continuously being explored. One such strategy involves immunotherapy using the T cell receptor (TCR) as a target. Specifically we are attempting to develop a T cell receptor idiotype (TCR-Id) vaccine because the TCR-Id can serve as a tumor-specific antigen. In this article we will briefly review the rationale for TCR-Id vaccines, the preclinical models as developed in our laboratory, and a discussion of our current plans for a vaccine trial in mycosis fungoides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72794/1/j.1749-6632.2001.tb03714.x.pd

Economic Impacts of Farm Program Payment Limits

The high levels of government payments to farmers resulting from the 1985 farm bill have once again led the Congress to examine the payment limit issue. Payment limits were initially established in 1970 and have since been revised several times. In this report, policy and farm management economists analyze the consequences of alternative payment limits on economic efficiency, economic viability of family-size farms, international competitiveness, and consumer food costs. Effective payment limits encourage reduced farm size and in the presence of economies of size, tend to increase production costs for program crops. The Agricultural and Food Policy Center is charged with evaluating economic impacts of policy alternatives -- not recommending, advocating, or opposing particular policies. The Center's orientation is toward Texas agriculture -- evaluating policy impacts on its producers and consumers. Farm prices and income, however, are determined in world markets that are influenced by national economic policy and farm programs. Texas impacts, therefore, must be evaluated in a much broader national and international market and policy context.Agricultural and Food Policy,

Improved persistence and adherence to diuretic fixed-dose combination therapy compared to diuretic monotherapy

<p>Abstract</p> <p>Background</p> <p>Diuretics are recommended as initial treatment for hypertension. Several studies have suggested suboptimal persistence and adherence to thiazide diuretic monotherapy; this study compared patient persistence and adherence with hydrochlorothiazide (HCTZ) monotherapy to fixed-dose combinations containing HCTZ.</p> <p>Methods</p> <p>Patients with at least one prescription claim during 2001 to 2003 for either HCTZ or one of the following fixed-dose combinations: angiotensin-receptor blockers/HCTZ (ARB/HCTZ), angiotensin-converting enzyme inhibitor/HCTZ (ACEI/HCTZ), or beta blockers/HCTZ (BB/HCTZ) were identified. Patients were required to be continuously benefit-eligible six months pre- and one year post-index date, and to have no prescription claims for any antihypertensive therapy six months prior to the index date. Patients were followed for one year to assess persistence, medication possession ratio (MPR), adherence (MPR >80%), and proportion of days covered (PDC) with initial antihypertensive therapy. Logistic regression was used to calculate adjusted odds ratios for persistence, adherence and PDC, adjusted for age, gender, business segment, RxRisk disease categories, average co-pay and concurrent cardiovascular-related medication utilization.</p> <p>Results</p> <p>The study cohort consisted of 48,212 patients; 72.5% used HCTZ, 13.2% ACEI/HCTZ, 9.3% ARB/HCTZ, and 5.0% BB/HCTZ. Mean age was 53.7 years and 66.5% were female. A significantly lower proportion of patients using HCTZ (29.9%) remained persistent with therapy at 12 months compared with ARB/HCTZ (52.6%; OR = 0.37, CI = 0.36, 0.38), ACEI/HCTZ (51.4%; OR = 0.38, CI = 0.37, 0.39), and BB/HCTZ (51.9%; OR = 0.38, 0.37, 0.40). Similarly, PDC was lower for HCTZ patients (32.5%) as compared to ARB/HCTZ (53.7%; OR = 0.39, CI = 0.37, 0.40), ACEI/HCTZ (50.9%; OR = 0.42, CI = 0.40, 0.43), and BB/HCTZ (51.3%; OR = 0.44, CI 0.42, 0.45). MPR was also significantly lower for HCTZ patients as compared to those using fixed-dose combination therapies.</p> <p>Conclusion</p> <p>Initiating HCTZ fixed-dose combination therapy with an ACEI, ARB, or BB was associated with greater persistence and adherence as compared to HCTZ monotherapy. Further research is needed to determine the relationship between improved persistence and adherence with blood pressure control.</p

Institutional Response to Crisis

The Institutional Response to Crisis panel focuses on analyzing and understanding institutions and the crises they might face, more specifically the limits and opportunities for preparing for a crisis, responding to crises, and the long-term consequences of crises. The panelists provide both theoretical analyses and specific, personal experiences to discuss these points. As panel moderator Noah Pickus, the director of the Kenan Institute for Ethics at Duke University stated in his opening: Crises are no rare thing in human history and it seems as if of late we turn around everyday and there\u27s another one that stares us in the face. Questions/themes/discussion topics Should institutions respond to crises? How do institutions respond to crises? Response to crisis as a springboard for long term change within an institution Leadership opportunities within a crisi

Backward And Simultaneous Masking Measured In Children With Language-Learning Impairments Who Received Intervention With Fast Forword Or Laureate Learning Systems Software

The developers of a computer-assisted language intervention program called Fast ForWord (FFW) have claimed that their software changes temporal processing abilities as a result of specialized modifications to the acoustic and temporal properties of the speech signal within the program. This pilot study compared changes in auditory temporal processing in children who received FFW training and in children who received training with computer-assisted language intervention programs that were not designed to improve auditory perceptual skills. Four boys with Language-Learning Impairments (LLI) and 3 boys with typical language participated. Two of the boys with LLI received the FFW program, and the other 2 received a bundle of computer-assisted instruction (CAI) programs published by Laureate Language Systems (LLS). The FFW and LLS programs were presented on the same schedule. To assess temporal processing, signal thresholds in backward and simultaneous masking conditions were evaluated just before, during, and immediately after language training. The boys with typically developing language received no training. Children with typical language produced signal thresholds in the backward masking condition that were markedly lower than those in the simultaneous masking condition. This disparity is indicative of normal temporal processing. Conversely, 3 of 4 children with LLI failed to demonstrate a simultaneous-backward difference during baseline. The lack of a difference implies that temporal processing was not normal in these children. The fourth child with LLI had signal thresholds that paralleled those of the children with normal language development. This child also had the mildest form of LLI. Of the 3 children whose temporal processing was abnormal, 2 boys showed decreased signal thresholds in the backward masking condition. However, the improvement was sudden, occurring relatively early in the training sequence, and observed with both treatment programs. The third child with abnormal temporal processing failed to show a change in backward masking at any time during treatment. Over the course of the experiment, signal thresholds for all listeners decreased by similar amounts in both backward and simultaneous masking. Taken together, these results do not support the presence of a program-specific improvement in temporal processing. In addition to the temporal processing deficits revealed by backward masking, group differences in response patterns implicate auditory memory involvement or differences in maintaining attention.Communication Sciences and Disorder

Orientation and structure of the Ndc80 complex on the microtubule lattice

The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential α/β-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends

Methods and systems for advanced spaceport information management

Advanced spaceport information management methods and systems are disclosed. In one embodiment, a method includes coupling a test system to the payload and transmitting one or more test signals that emulate an anticipated condition from the test system to the payload. One or more responsive signals are received from the payload into the test system and are analyzed to determine whether one or more of the responsive signals comprises an anomalous signal. At least one of the steps of transmitting, receiving, analyzing and determining includes transmitting at least one of the test signals and the responsive signals via a communications link from a payload processing facility to a remotely located facility. In one particular embodiment, the communications link is an Internet link from a payload processing facility to a remotely located facility (e.g. a launch facility, university, etc.)

RDE-2 interacts with MUT-7 to mediate RNA interference in Caenorhabditis elegans

In Caenorhabditis elegans, the activity of transposable elements is repressed in the germline. One of the mechanisms involved in this repression is RNA interference (RNAi), a process in which dsRNA targets cleavage of mRNAs in a sequence-specific manner. The first gene found to be involved in RNAi and transposon silencing in C.elegans is mut-7, a gene encoding a putative exoribonuclease. Here, we show that the MUT-7 protein resides in complexes of ∼250 kDa in the nucleus and in the cytosol. In addition, we find that upon triggering of RNAi the cytosolic MUT-7 complex increases in size. This increase is independent of the presence of target RNA, but does depend on the presence of RDE-1 and RDE-4, two proteins involved in small interfering RNA (siRNA) production. Finally, using a yeast two-hybrid screen, we identified RDE-2/MUT-8 as one of the other components of this complex. This protein is encoded by the rde-2/mut-8 locus, previously implicated in RNAi and transposon silencing. Using genetic complementation analysis, we show that the interaction between these two proteins is required for efficient RNAi in vivo. Together these data support a role for the MUT-7/RDE-2 complex downstream of siRNA formation, but upstream of siRNA mediated target RNA recognition, possibly indicating a role in the siRNA amplification step