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Two-dimensional (2D) layered SnP2S6has been synthesized in experiments, which has attracted much attention for application in optoelectronic devices. However, the influence of common adsorbates (i.e., H2O and O2) and vacancy defects may play a key role in optoelectronic devices. Herein, we systematically investigate the optoelectronic properties of the SnP2S6monolayer in the presence of H2O, O2, and vacancies by first principles. The results show that the O2and H2O molecules behave qualitatively differently on the SnP2S6surface. The presence of S atom vacancies significantly enhanced the adsorption of H2O and O2molecules. Furthermore, H2O reduces the dissociation potential of O2on the surface of pristine SnP2S6, while S vacancies significantly facilitate the dissociation of O2, indicating that SnP2S6will readily be oxidized under ambient conditions in the presence of S vacancies. Importantly, it is confirmed that the H2O adsorption slightly influenced the electronic properties of monolayer SnP2S6. In sharp contrast, O2adsorption and vacancies enable significant changes in the properties of monolayer SnP2S6. Furthermore, an indirect-to-direct band gap transition was observed when the S atom vacancy concentration of monolayer SnP2S6was 6.25%.

In this article, the horizontal hinged heavy duty servo cylinder is taken as the research object. In the actual working process, while the servo hydraulic cylinder outputs the curve force, the cylinder body will also rotate with the hinge point to a certain extent. Because the position of the center of gravity is constantly changing, and the weight of the cylinder body is too large, the friction causes damage to the sealing structure and seriously affects the working efficiency of the equipment. In order to improve the sealing performance of the servo hydraulic cylinder, a corresponding study is carried out. Firstly, the working angle interval of servo cylinder is optimized to ensure that the friction is the least in this range. Based on this, a new supporting structure is proposed, in which a small hydraulic cylinder is installed at the bottom of the servo hydraulic cylinder body. By controlling the output force of the small hydraulic cylinder, the cylinder body and piston rod are aligned all the time. The servo cylinder body is flexibly processed to more realistically see the adverse effect of the friction, and the co-simulation method using MSC.ADAMS and MATLAB/Simulink verifies the new support structure to improve the sealing performance. According to the simulation results and experiment results, and combined with the deformation curve of the hydraulic cylinder, when the maximum displacement is 336 mm, the maximum rotation angle is 15.6°, the friction is the smallest, about 5801.9 N. It is known from the experiment results that after adding the new support structure, the frictional force is reduced to 1365.9 N, which reduces the friction of nearly 76.5%.

When an output curve force is applied to a horizontal servo cylinder with a heavy load, the piston rod bears a dynamic partial load based on the installation and load characteristics, which significantly affects the frequency response and control accuracy of the servo cylinder. Based on this partial load, increased friction can lead to cylinder bore scuffing, leakage, lack of output power, or even system failure. In this paper, a novel asymmetric static-pressure support structure is proposed based on the principle of hydrostatic support. The radial component force of a dynamic partial load is balanced by cooperation between the support oil cushion of the variable hydraulic pressure support structure, oil cushion of the supportive force, and the damper. Adaptive control of the servo cylinder piston rod, guide sleeve, and piston, as well as the cylinder oil film friction between lubricated surfaces is achieved. In this paper, theoretical design and analysis of the traditional hydrostatic bearing structure and novel structure are presented. A hydraulic dynamic shear scissor is used as a research target to derive a structural dynamic model. Comparative simulations are performed using Matlab Simulink. Additionally, flow field analysis of the novel structure is performed, which verifies the rationality and feasibility of the proposed structure and system.

Here we report stable gene transfer in cord blood-derived CD34+ hematopoietic stem cells using a hyperactive nonviral Sleeping Beauty (SB) transposase (SB100X). In colony-forming assays, SB100X mediated the highest efficiency (24%) of stable Discosoma sp red fluorescent protein (DsRed) reporter gene transfer in committed hematopoietic progenitors compared with both the early-generation hyperactive SB11 transposase and the piggyBac transposon system (1.23% and 3.8%, respectively). In vitro differentiation assays further demonstrated that SB100X-transfected CD34+ cells can develop into DsRed+ CD4+CD8+ T (3.17%-21.84%; median, 7.97%), CD19+ B (3.83%-18.66%; median, 7.84%), CD56+CD3− NK (3.53%-79.98%; median, 7.88%), and CD33+ myeloid (7.59%-15.63%; median, 9.48%) cells. SB100X-transfected CD34+ cells achieved approximately 46% engraftment in NOD-scid IL2γcnull (NOG) mice. Twelve weeks after transplantation, 0.57% to 28.96% (median, 2.79%) and 0.49% to 34.50% (median, 5.59%) of total human CD45+ cells in the bone marrow and spleen expressed DsRed, including CD19+ B, CD14+ monocytoid, and CD33+ myeloid cell lineages. Integration site analysis revealed SB transposon sequences in the human chromosomes of in vitro differentiated T, B, NK, and myeloid cells, as well as in human CD45+ cells isolated from bone marrow and spleen of transplanted NOG mice. Our results support the continuing development of SB-based gene transfer into human hematopoietic stem cells as a modality for gene therapy.

Here we report stable gene transfer in cord blood-derived CD34+hematopoietic stem cells using a hyperactive nonviral Sleeping Beauty(SB) transposase (SB100X). In colony-forming assays, SB100X mediated the highest efficiency (24%) of stable Discosoma spred fluorescent protein (DsRed) reporter gene transfer in committed hematopoietic progenitors compared with both the early-generation hyperactive SB11 transposase and the piggyBactransposon system (1.23% and 3.8%, respectively). In vitro differentiation assays further demonstrated that SB100X-transfected CD34+cells can develop into DsRed+CD4+CD8+T (3.17%-21.84%; median, 7.97%), CD19+B (3.83%-18.66%; median, 7.84%), CD56+CD3−NK (3.53%-79.98%; median, 7.88%), and CD33+myeloid (7.59%-15.63%; median, 9.48%) cells. SB100X-transfected CD34+cells achieved approximately 46% engraftment in NOD-scid IL2γcnull(NOG) mice. Twelve weeks after transplantation, 0.57% to 28.96% (median, 2.79%) and 0.49% to 34.50% (median, 5.59%) of total human CD45+cells in the bone marrow and spleen expressed DsRed, including CD19+B, CD14+monocytoid, and CD33+myeloid cell lineages. Integration site analysis revealed SB transposon sequences in the human chromosomes of in vitro differentiated T, B, NK, and myeloid cells, as well as in human CD45+cells isolated from bone marrow and spleen of transplanted NOG mice. Our results support the continuing development of SB-based gene transfer into human hematopoietic stem cells as a modality for gene therapy.

Few studies have examined the functional limitations, physical health, mental health, and general quality of life in cancer survivors with various types of non-Hodgkin lymphoma (NHL). Patients with aggressive NHL (AGG) require immediate chemotherapy for a potentially curable disease in contrast to patients with indolent NHL (IND) that is characterized by a chronic course with repeated relapses and progression despite therapy. This study examined the QOL in adult survivors of NHL >1 year from diagnosis and not currently on therapy; we hypothesized that fatigue and quality of life would be worse in patients with low grade NHL given the expectation of future progressive disease and repetition of multiple therapies.109 patients with NHL (58 AGG, 51 IND), more than one year from initial diagnosis, and at least three months from any active therapy, completed two health related quality of life assessments using the Medical Outcomes Study 36-Item Short-Form Healthy Survey (MOS SF-36) which assesses 8 subsets and 2 summary scores, and the Functional Assessment in Cancer Therapy – Fatigue (FACT-F). Physical and Mental SF-36 scores or FACT-F scores between IND and AGG were compared using a two sample t-test. Multiple linear regression* was performed to account for any potentially explanatory variables (age, use of chemotherapy, time from last treatment to survey).Median age was 60 years [61 years (33-88) IND and 57 years (22-90) AGG]. 48.6% were female (52.9% IND, 44.8% AGG). 74.3% were in complete remission at the time of the survey (52.9% IND, 93.1% AGG) (p<0.001). 70.6% had received chemotherapy (43.1% IND, 94.8% AGG) and 55% had received immunotherapy (31.4% IND, 75.9% AGG). 17.6% of IND had received no therapy. The overall physical (PCS) and mental (MCS) component quality of life scores of the SF-36 did not differ between survivors with aggressive and indolent NHL; the median PCS was 51.8 (11.2-66.5) [56.8 IND, 51.4 AGG, p=0.192] and the median MCS was 54.2 (10.8-65.8) [54.6 IND, 53.3 AGG, p=0.239]. Examining the eight subcategories of the SF-36, physical function in survivors of IND was significantly better when compared with those of AGG NHL. Using the FACT-F, fatigue scores also did not differ between the two populations; the median FACT-F score was 45 (8-52) [47 IND, 43 AGG, p=0.114).While some other studies have reported a decreased quality of life in NHL survivors, our study reports a similar overall quality of life between survivors of IND and AGG NHL more than one year from initial diagnosis; this may be explained by a significant proportion of our IND patients having never received therapy or an acclimation to the need for future therapy. Physical function may be more impaired in survivors of AGG NHL and warrants further investigation.No relevant conflicts of interest to declare.

We studied cytogenetic risk grouping schemes to stratify AML patients into prognostically distinct subgroups for relapse free (RFS) and overall survival (OS) after an allogeneic hematopoietic stem cell transplantation (HSCT).We retrospectively analyzed consecutive patients who underwent their first HSCT with a matched related donor (MRD) or cord blood (CB) at the University of Minnesota for AML in remission between January 1995 and December 2007. Patients were divided according to cytogenetic abnormalities based on the MRC, SWOG, CALGB, Dana-Farber (DF) and recently described monosomal karyotype (MK) classification schemes and study group was stratified based on first complete remission (CR1) and beyond (CR2+) at HSCT. Cox regression analysis evaluated the prognostic factors on OS and RFS.212 patients were analyzed with a median age 45 years (range 18-68); 27 had evolved from MDS. Disease status was, CR1 (n=134) and CR2+ (n=78). Donors were MRD (n=105) and CB (n=107). Conditioning intensity was myeloablative (MA, n=118) and non-myeloablative (NMA, n=94). Cytogenetic classification based on MRC, SWOG, CALGB and DF was concordant in 131 patients (62%). Ten (5%), 89 (42%) and 32 (15%) patients were in favorable, intermediate/standard and adverse/unfavorable groups in all 4 classification schemes. Fifty-five patients (26%) were classified as unfavorable/adverse in one scheme and standard/intermediate in another. Sixteen patients (7%) were classified as unknown significance and 10 (5%) were excluded in at least one classification scheme. Eighteen of 23 MK+ patients (78%) and 14 of 78 MK-patients (18%) were classified as adverse/unfavorable in all other schemes. The remaining 5 MK+ (22%) and 64 MK- patients (82%) were classified inconsistently in the other schemes. Five year probabilities were: OS 37 % (95% CI % 29%-45%), RFS 54% (95% CI 45%-64%). Six mo and 2 year cumulative incidence of transplant related mortality were 21% (95% CI 16%-27%) and 29% (95% CI 23%-35%).In multivariate analysis, after adjusting for age, conditioning intensity, disease status at HSCT, donor type and CMV status, only MK+ was associated with lower RFS in CR1 patients (HR=4.1, p=0.05). Cytogenetic classifications by the other 4 schemes were not predictive of RFS (SWOG HR=1.34 p=0.23, MRC HR=1.47, p=0.14, CALGB HR=1.43 p=0.15, DF HR=1.43 p=0.16). Median time to relapse was 6.1 mo for MK+ vs. 75.8 mo for MK- vs not reached for normal karyotype (NK) (Figure 1). In CR1, no covariates were associated with OS. In CR2+ patients, MK and CALGB predicted OS. MK+ (HR=2.93, p=0.04), MK- (HR=2.05, p=0.06) and NMA conditioning (HR=3.3, p=0.01) were associated with lower OS. All MK+ patients died within 3 years. CALGB adverse karyotype (HR=2.95, p=0.01) and NMA conditioning (HR=3.1, p=0.01) also associated with lower OS. All 5 classification schemes could predict RFS in CR2+. However, only MK could identify a very poor prognostic group, MK+ (HR=5.9, p<0.01, median RFS 2.5 mo) vs. a poor prognostic group, MK- (HR=2.0, p=0.06, median RFS 16.3 mo) (Figure 2).HSCT in CR1 overcomes the poor prognosis associated with higher risk cytogenetic abnormalities. The MK classification can best identify a very poor prognostic group. In CR2+, HSCT particularly with NMA conditioning may not overcome the poor prognosis from cytogenetic subgroups. Among all classification schemes, MK can best predict outcome in CR1 and CR2+ patients.No relevant conflicts of interest to declare.

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Abstract 525

FA is the most common heritable marrow failure syndrome with a high predisposition to myelodysplastic syndrome and leukemia. Great strides have been made in optimizing the conditioning regimen and GVHD prophylaxis, necessarily tailored to these patients as a result of their underlying defect in DNA repair. Prior to 1995, survival rates after alternate donor hematopoietic cell transplantation (AD-HCT) were exceptionally poor (<20%). After 1999, the addition of fludarabine (FLU) significantly improved engraftment and survival. However, risks of infection and late effects remained important challenges. Seeking to reduce these risks, we conducted a single center, single arm, TBI dose deescalation trial designed to determine the lowest possible dose of TBI required for engraftment in recipients of T cell depleted AD marrow (TCD BM). All patients received cyclophosphamide (CY) 10 mg/kg × 4 days, FLU 35 mg/m2 × 4 days, ATG 30 mg/kg ×5 days and a single fraction of TBI with CT guided thymic shielding (TS). TBI dose deescalation strata were: TBI 300 cGy (cohort 1); TBI 150 cGy (cohort 2); no TBI (cohort 3). All patients received CSA and methylprednisolone as GVHD prophylaxis and G-CSF 5 ug/kg/day until engraftment. The decision to proceed with each stepwise decrease in TBI was based upon achieving primary neutrophil engraftment in 10 of 10 patients at each dose level, or 14 of 15 patients if one graft failure is observed in any of the first 10 patients. More than 1 graft failure in 15 patients was considered unacceptable and the next higher TBI dose level was then considered the optimal dose. Between July 2006-May 2008, 19 FA patients were enrolled with 17 in cohort 1 and 2 in cohort 2. Five patients received 5–6/6 unmanipulated UCB because a marrow donor could not be identified. All patients achieved primary engraftment at a median of 11 days after AD-HCT. However, 2/2 patients who received TBI 150 developed secondary graft failure at 76 and 114 days after HCT. The dose de-escalation was stopped with TBI 300 cGy identified as the lowest possible dose in the context of FLU/CY given concomitantly. Thus far, 17 patients have been treated with TBI 300. As shown, results compare favorably with prior regimens using TBI 450 with and without TS (table). Outcomes after AD-HCT in Standard Risk FA Patients N Neutrophil Engraftment Acute GVHD Chronic GVHD 1 Year Survival TS = thymic shielding TBI 450 no TS 21 95% 24% 19% 67% TBI 450 +TS 12 92% 42% 8% 83% TBI 300 +TS 17 94% 25% 0% 92% Our results demonstrate that TBI 300 cGy is sufficient for consistent engraftment in recipients of CY-FLU-ATG and HLA matched or mismatched TCD AD BM or UCB and represents a new standard of care for this patient population. Longer follow up is needed to quantitate the impact of lower dose radiation on immune recovery, risks of infection, cancer risk and other therapy-related late effects.

FA is the most common heritable marrow failure syndrome with a high predisposition to myelodysplastic syndrome and leukemia. Great strides have been made in optimizing the conditioning regimen and GVHD prophylaxis, necessarily tailored to these patients as a result of their underlying defect in DNA repair. Prior to 1995, survival rates after alternate donor hematopoietic cell transplantation (AD-HCT) were exceptionally poor (<20%). After 1999, the addition of fludarabine (FLU) significantly improved engraftment and survival. However, risks of infection and late effects remained important challenges. Seeking to reduce these risks, we conducted a single center, single arm, TBI dose deescalation trial designed to determine the lowest possible dose of TBI required for engraftment in recipients of T cell depleted AD marrow (TCD BM). All patients received cyclophosphamide (CY) 10 mg/kg × 4 days, FLU 35 mg/m2 × 4 days, ATG 30 mg/kg ×5 days and a single fraction of TBI with CT guided thymic shielding (TS). TBI dose deescalation strata were: TBI 300 cGy (cohort 1); TBI 150 cGy (cohort 2); no TBI (cohort 3). All patients received CSA and methylprednisolone as GVHD prophylaxis and G-CSF 5 ug/kg/day until engraftment. The decision to proceed with each stepwise decrease in TBI was based upon achieving primary neutrophil engraftment in 10 of 10 patients at each dose level, or 14 of 15 patients if one graft failure is observed in any of the first 10 patients. More than 1 graft failure in 15 patients was considered unacceptable and the next higher TBI dose level was then considered the optimal dose. Between July 2006-May 2008, 19 FA patients were enrolled with 17 in cohort 1 and 2 in cohort 2. Five patients received 5–6/6 unmanipulated UCB because a marrow donor could not be identified. All patients achieved primary engraftment at a median of 11 days after AD-HCT. However, 2/2 patients who received TBI 150 developed secondary graft failure at 76 and 114 days after HCT. The dose de-escalation was stopped with TBI 300 cGy identified as the lowest possible dose in the context of FLU/CY given concomitantly. Thus far, 17 patients have been treated with TBI 300. As shown, results compare favorably with prior regimens using TBI 450 with and without TS (table).