Surface Finish Analysis in Single Point Incremental Sheet Forming of Rib-Stiffened 2024-T3 and 7075-T6 Alclad Aluminium Alloy Panels

The article presents the results of the analysis of the interactions between the single point incremental forming (SPIF) process parameters and the main roughness parameters of stiffened ribs fabricated in Alclad aluminium alloy panels. EN AW-7075-T6 and EN AW-2024-T3 Alclad aluminium alloy sheets were used as the research material. Panels with longitudinal ribs were produced with different values of incremental vertical step size and tool rotational speed. Alclad is formed of high-purity aluminium surface layers metallurgically bonded to aluminium alloy core material. The quality of the surface roughness and unbroken Alclad are key problems in SPIF of Alclad sheets destined for aerospace applications. The interactions between the SPIF process parameters and the main roughness parameters of the stiffened ribs were determined. The influence of forming parameters on average roughness Sa and the 10-point peak–valley surface roughness Sz was determined using artificial neural networks. The greater the value of the incremental vertical step size, the more prominent the ridges found in the inner surface of stiffened ribs, especially in the case of both Alclad aluminium alloy sheets. The predictive models of ANNs for the Sa and the Sz were characterised by performance measures with R² values lying between 0.657 and 0.979. A different character of change in surface roughness was found for sheets covered with and not covered with a soft layer of technically pure aluminium. In the case of Alclad sheets, increasing the value of the incremental vertical step size increases the value of the surface roughness parameters Sa and Sz. In the case of the sheets not covered by Alclad, reduction of the tool rotational speed increases the Sz parameter and decreases the Sa parameter. An obvious increase in the Sz parameter was observed with an increase in the incremental vertical step size.     

Fabrication of Functionally Graded Diamond/Al Composites by Liquid–Solid Separation Technology

The electronic packaging shell, the necessary material for hermetic packaging of large microelectronic device chips, is made by mechanical processing of a uniform block. However, the property variety requirements at different positions of the shell due to the performance have not been solved. An independently developed liquid–solid separation technology is applied to fabricate the diamond/Al composites with a graded distribution of diamond particles. The diamond content decreases along a gradient from the bottom of the shell, which houses the chips, to the top of the shell wall, which is welded with the cover plate. The bottom of the shell has a thermal conductivity (TC) of 169 W/mK, coefficient of thermal expansion (CTE) of 11.0 × 10⁻⁶/K, bending strength of 88 MPa, and diamond content of 48 vol.%. The top of the shell has a TC of 108 W/mK, CTE of 19.3 × 10⁻⁶/K, bending strength of 175 MPa, and diamond content of 15 vol.%, which solves the special requirements of different parts of the shell and helps to improve the thermal stability of packaging components. Moreover, the interfacial characteristics are also investigated. This work provides a promising approach for the preparation of packaging shells by near-net shape forming.     

Hot melt extrusion: An industrially feasible approach for casting orodispersible film

Over the recent few decades, many groups of formulation scientists are concentrating on rapid release dosage forms in oral cavity. Among all fast release dosage forms, orodispersible films are successful to attract pharmaceutical industry due to ease of formulation and extension patent life. Films are popular in patients too because of quick onset and user friendliness of dosage form. From the beginning, solvent casting has been selected as method of choice for manufacturing of orodispersible films. Solvent casting has been proved as a benchmark technology because of ease in product development, process optimization, process validation and technology transfer to production scale despite of some drawbacks like more number of unit operations involved and consumption of large quantity of solvents with controlled limits of organic volatile impurities in final formulation. The application of hot-melt extrusion (HME) in the pharmaceutical industry is consecutively increasing due to its proven innumerable advantages like solvent free continuous process with fewer unit operations and better content uniformity. Very few development activities has been initiated in the field of hot melt extruded orodispersible films so far. This extensive review covers detailed discussion of heavy duty industrial extruders, selection of downstream equipments, selection of excipients, common problems found in formulations and their remedies. Successive part of review addresses identification of critical quality attributes, quality target profile of product, criticality in selection of process parameters and material for substantial simulation in laboratory scale and production for successful technology transfer.     

Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as Potent and Selective Pim-1 Inhibitors

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Single-Stroke Attachment of Sheets to Tube Ends Made from Dissimilar Materials

This paper presents a new joining method by a forming process for attaching sheets to tube ends. The process consists of two different forming stages carried out sequentially in a single stroke. Firstly, the free tube end is flared by compression with a contoured die, then is squeezed (indented) against the sheet surface to create a mechanical interlocking. The new process is carried out at an ambient temperature and, in contrast to existing joining by forming operations based on tube expansion, it avoids seal welds, tube protrusions above the sheet surfaces, and machining of grooves on the sheet holes to obtain the form-fit joints. The paper starts by analyzing the process deformation mechanics and its main operating variables and finishes by presenting examples that demonstrate its effectiveness for attaching sheets to tube ends made from polyvinylchloride and aluminum. Experimental and numerical simulation work provides support to the presentation.     

Ultimate Load-Carrying Ability of Rib-Stiffened 2024-T3 and 7075-T6 Aluminium Alloy Panels under Axial Compression

Stringer-stiffened panels made of aluminium alloys are often used as structural elements in the aircraft industry. The load-carrying capacity of this type of structure cannot relieve the reduction in strength in the event of local buckling. In this paper, a method of fabrication of rib-stiffened panels made of EN AW-2024-T3 Alclad and EN AW-7075-T6 Alclad has been proposed using single point incremental forming. Panels made of sheets of different thickness and with different values of forming parameters were tested under the axial compression test. A digital image correlation (DIC)-based system was used to find the distribution of strain in the panels. The results of the axial compression tests revealed that the panels had two distinct buckling modes: (i) The panels buckled halfway up the panel height towards the rib, without any appreciable loss of rib stability, and (ii) the rib first lost stability at half its height with associated breakage, and then the panel was deflected in the opposite direction to the position of the rib. Different buckling modes can be associated with the character of transverse and longitudinal springback of panels resulting from local interaction of the rotating tool on the surface of the formed ribs.     

Formability and Failure Evaluation of AA3003-H18 Sheets in Single-Point Incremental Forming Process through the Design of Experiments

The single-point incremental forming process (SPIF) is one of the emerging manufacturing methods because of its flexibility in producing the desired complex shapes with higher formability at low-cost compared to traditional sheet forming methods. In this research work, we experimentally investigate the forming process to determine the influence of process parameters and their contribution to enhancing the formability without causing a fracture by combining the design of experiments (DOE), grey relational analysis (GRA), and statistical analysis of variance (ANOVA). The surface morphology and the energy dispersive X-ray spectroscopy (EDS) method are used to perform elemental analysis and examine the formed parts during three forming stages. The DOE procedure, a central composite design with a face-centered option, is devised for AA3003-H18 Al alloy sheet for modeling the real-time experiments. The response surface methodology (RSM) approach is adopted to optimize the forming parameters and recognize the optimal test conditions. The statistically developed model is found to have agree with the test measurements. The prediction model’s capability in R2 is computed as 0.8931, indicating that the fitted regression model adequately aligns with the estimated grey relational grade (GRG) data. Other statistical parameters, such as root mean square error (RMSE) and average absolute relative error (AARE), are estimated as 0.0196 and 2.78%, respectively, proving the proposed regression model’s overall closeness to the measured data. In addition, the prediction error range is identified as −0.05 to 0.05, which is significantly lower and the residual data are distributed normally in the design space with variance and mean of 3.3748 and −0.1232, respectively. ANOVA is performed to understand the adequacy of the proposed model and the influence of the input factors on the response variable. The model parameters, including step size, feed rate, interaction effect of tool radius and step size, favorably influence the response variable. The model terms X₂ (0.020 and 11.30), X₃ (0.018 and 12.16), and X₁X₂ (0.026 and 9.72) are significant in terms of p-value and F-value, respectively. The microstructural inspection shows that the thinning behavior tends to be higher as forming depth advances to its maximum; the deformation is uniform and homogeneous under the predefined test conditions.     

雌二醇对系统性红斑狼疮患者骨髓造血干/祖细胞的影响

目的 体外观察雌二醇（E2）对系统性红斑狼疮（SLE）患者骨髓干／祖细胞的影响。方法 分别用流式细胞仪、半固体休落培养观察17例SLE患者骨髓CD34^ 细胞、CD34^ CD38^－亚群、混合细胞集落（GEMM－CFU）和粒巨噬细胞集落（GM－CFU）的改变。体外观察E2、E2＋其拮抗剂他莫西芬对SLE患者骨髓GM－CFU的作用。结果 ①SLE患者CD34^ 细胞、GEMM－CFU、GM－CFU的形成校正这对照组明显减少；②E2对女性SLE较男性SLE、正常对照组的GM－CFU集落形成有明显的抑制作用；③他莫西芬可逆转E2对女性SLE患者的GM－CFU抑制作用。结论 SLE患者较后期的干细胞、祖细胞存在异常，雌激素可能介导了SLE患者骨髓造血干／祖细胞异常的发生。     

The in vitro effects of cytokines on expansion and migration of megakaryocyte progenitors

Increasing the number of megakaryocyte progenitors in stem cell transplants by ex vivo expansion culture may be an approach to accelerate platelet recovery in patients undergoing high-dose chemotherapy. We evaluated the effect of three different cytokine combinations on expansion, with special emphasis on the type of colony formation and migration of megakaryocytic cells. The number of clonogenic megakaryocyte progenitors (colony-forming units-megakaryocyte; CFU-Mk) with high- (> 20 cells/colony) and low-proliferative capacity (5-20 cells/colony) and the number of megakaryocytic (CD61+) cells were significantly increased by including interleukin 3 (IL-3) or IL-3 + IL-6 + IL-11 + Flt3-ligand to cultures containing megakaryocyte growth and development factor (MGDF) plus stem cell factor (SCF). No difference in the maturation of megakaryocytes from all three cytokine combinations to platelets were observed, as demonstrated by electron microscopy. In chemotaxis experiments, the migration towards stromal cell-derived factor 1 (SDF-1) was shown to be reduced for CD61+ cells and megakaryocyte progenitors cultured in other cytokines besides MGDF + SCF. The reduced migration was related to a lower expression of CXCR4, the receptor for SDF-1, on megakaryocytes from the proliferating cultures. These in vitro results demonstrate that expansion in IL-3 and other cytokines besides MGDF + SCF significantly impair the capacity of megakaryocytic cells to migrate.     

Treatment of enteritis in chronic granulomatous disease with granulocyte colony stimulating factor

Background—In several diseases there is a relationbetween deficiency of neutrophil granulocytes and granulomatouslesions. Recently, in glycogen storage disease type Ib, this relationhas been supported by the beneficial effect of treatment of enteritis with granulocyte-macrophage colony stimulating factor.
Aim—To investigate whether chronic granulomatousdisease could be treated according to the same principle.
Patients and methods—Inflammatory lesions weremonitored in two brothers with chronic granulomatous diseasedemonstrated by very low superoxide production in neutrophilgranulocytes. The two patients were treated with recombinant humangranulocyte colony stimulating factor on three occasions when thedisease was active.
Results—In one patient, remission of an inflamedstenosis of the colon sigmoideum was shown by granulocytescintigraphy after one month of treatment with granulocyte colonystimulating factor. In the other patient, remission of colon diseaseand later of a non-malignant tumour in the right lung hilum was shownby colonoscopy and computed tomography scans respectively.
Conclusion—Remission of inflammatory lesions intwo brothers with chronic granulomatous disease was induced bygranulocyte colony stimulating factor on three occasions. The mechanismfor this effect is not known. The result is similar to the response found in patients with leucocyte deficiency due to glycogen storage disease type Ib.

Keywords:chronic granulomatous disease; enteritis; granulocyte colony stimulating factor