Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.     

Long-term results of total penile reconstruction with a prefabricated lateral arm free flap

Trifluoroethanol (TFE) is often used to increase the helicity of peptides to make them usable as models of helices in proteins. We have measured helix propensities for all 20 amino acids in water and two concentrations of trifluoroethanol, 15 and 40% (v/v) using, as a model system, a peptide derived from the sequence of the alpha-helix of ribonuclease T1. There are three main conclusions from our studies. (1) TFE alters electrostatic interactions in the ribonuclease T1 helical peptide such that the dependence of the helical content on pH is lost in 40% TFE. (2) Helix propensities measured in 15% TFE correlate well with propensities measured in water, however, the correlation with propensities measured in 40% TFE is significantly worse. (3) Propensities measured in alanine-based peptides and the ribonuclease T1 peptide in TFE show very poor agreement, revealing that TFE greatly increases the effect of sequence context.     

Leakage power analysis and reduction during behavioral synthesis

This paper presents a high-level leakage power analysis and reduction algorithm. The algorithm uses device-level models for leakage to precharacterize a given register-transfer level module library. This is used to estimate the power consumption of a circuit due to leakage. The algorithm can also identify and extract the frequently idle modules in the datapath, which may be targeted for low-leakage optimization. Leakage optimization is based on the use of dual threshold voltage (V/sub T/) technology. The algorithm prioritizes modules giving a high-level synthesis system an indication of where most gains for leakage reduction may be found. We tested our algorithm using a number of benchmarks from various sources. We ran a series of experiments by integrating our algorithm into a low-power high-level synthesis system. In addition to reducing the power consumption due to switching activity, our algorithm provides the high-level synthesis system with the ability to detect and reduce leakage power consumption, hence, further reducing total power consumption. This is shown over a number of technology generations. The trend in these generations indicates that leakage becomes the dominant component of power at smaller feature size and lower supply voltages. Results show that using a dual-V/sub T/ library during high-level synthesis can reduce leakage power by an average of 58% for the different technology generations. Total power can be reduced by an average of 15.0%-45.0% for 0.18-0.07 /spl mu/m technologies, respectively. The contribution of leakage power to overall power consumption ranges from 22.6% to 56.2%. Our approach reduced these values to 11.7%-26.9%.     

The bendistal pliers: a solution for distal end bending of superelastic wires

These new pliers were designed specifically to work with the currently and widely used superelastic arch wires and bondable molar tubes. They place an effective distal end bend without the need for wire annealing or overtwisting that frequently results in fracture of bondable molar tubes.     

High-voltage management in single-supply CHE NOR-type flash memories

In a flash memory, a number of voltage levels different from V/sub DD/ are needed to perform the required operations (read, program, and erase) on the array cells. In the case of single-supply memory devices, voltages higher than V/sub DD/ as well as negative voltages, which are referred to as high voltages (HVs), must be produced on-chip. This paper aims at giving the reader an overview of how HVs are generated and managed in single-supply NOR-type flash memories programmed by channel hot-electron injection. Both schemes used for conventional (i.e., bilevel) memory devices and schemes designed to meet multilevel memory requirements are addressed.     

The self-fulfilling prophecy in close relationships: rejection sensitivity and rejection by romantic partners

The authors hypothesized a self-fulfilling prophecy wherein rejection expectancies lead people to behave in ways that elicit rejection from their dating partners. The hypothesis was tested in 2 studies of conflict in couples: (a) a longitudinal field study where couples provided daily-diary reports and (b) a lab study involving behavioral observations. Results from the field study showed that high rejection-sensitive (HRS) people's relationships were more likely to break up than those of low rejection-sensitive (LRS) people. Conflict processes that contribute to relationship erosion were revealed for HRS women but not for HRS men. Following naturally occurring relationship conflicts, HRS women's partners were more rejecting than were LRS women's partners. The lab study showed that HRS women's negative behavior during conflictual discussions helped explain their partners' more rejecting postconflict responses.     

System identification using a standard finite element program

Frequently, experimental results for scale models or for prototypes of structural systems do not produce mode shapes and natural frequencies which concur with analytical results for the same structure. An algorithm for an iterative identification process for improving structural models is described, which relates structural parameters to changes in system response by application of the Bayesian technique of probability and statistics. Revision of the structural parameters is made using expansions of differences between experimental and analytical mode shapes and frequencies. Since the revision is based on modification of partial stiffness and mass matrices of beam, membrane, and shell elements in the element library of a commonly available finite element program, a method is developed to calculate those partial matrices with the matrix generating subprograms of the finite element program itself.