Polyspecific immunoglobulins (IVIg) suppress proliferation of human (auto)antigen-specific T cells without inducing apoptosis

Polyspecific immunoglobulins (IVIg) have been shown to reduce disease activity in multiple sclerosis (MS). To investigate the mechanisms of action of IVIg, we studied the impact of IVIg on growth and death (apoptosis) of human (auto)antigen-specific T cells. We observed a substantial suppression of proliferation of specifically activated T cells, in absence of caspase activation or DNA fragmentation. Further, neither susceptibility of T cells to undergo CD95-mediated apoptosis nor expression of apoptosis-blocking bcl-2 was modulated by IVIg. We conclude that IVIg may inhibit the reactivity of antigen-specific T cells in MS through suppression of proliferation rather than modulation of apoptosis

Construction work and risk of occupational disability: a ten year follow up of 14 474 male workers

Aims: Most industrialised countries have public income maintenance programmes to protect workers in case of disability but studies addressing disability risk of specific professional groups are rare. The objective of this study was to establish a detailed pattern of the nature and extent of occupational disability among construction workers. Methods: A cohort study was set up including 14 474 male workers from the construction industry in Württemberg (Germany) aged 25–64 years who underwent occupational health exams between 1986 and 1992. The cohort was linked to the regional pension register of the manual workers' pension insurance institution to identify workers who were granted a disability pension during the 10 year follow up. All-cause and cause specific standardised incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using disability rates from the general workforce and from all blue collar workers in Germany as references. Results: In total, 2247 (16%) members of the cohort were granted a disability pension. Major causes of disability were musculoskeletal (45%) and cardiovascular diseases (19%). In comparison with the general workforce, construction workers experienced a higher risk of disability from cancer (SIR = 1.26; 95% CI 1.08 to 1.47), respiratory diseases (SIR = 1.27; 95% CI 1.03 to 1.55), musculoskeletal diseases (SIR = 2.16; 95% CI 2.03 to 2.30), injuries/poisoning (SIR = 2.52; 95% CI 2.06 to 3.05), and all causes combined (SIR = 1.47; 95% CI 1.41 to 1.53). When compared with the blue collar reference group, increased risks of disability among construction workers were found for musculoskeletal diseases (SIR = 1.53; 95% CI 1.44 to 1.63), injury/poisoning (SIR = 1.83; 95% CI 1.50 to 2.21), and all causes combined (SIR = 1.11; 95% CI 1.07 to 1.16). Conclusions: Musculoskeletal diseases and external causes are major factors limiting the work capability of construction workers and lead to an increased proportion of occupational disability

Reliability experiments of sintered silver based interconnections by accelerated isothermal bending tests

Integration of more functionality and smaller chips into decreasing package volume leads to increasing heat generation. In addition, the use of new compound semiconductors like SiC and GaN require a high thermal conductivity of the interconnect materials. One of the promising solutions is a layer of sintered silver between semiconductor and substrate. The advantages compared to conventional solders are significant. A higher thermal and electrical conductivity in combination with a higher duty temperature due to a higher melting point should enhance the reliability of the package. However, even as the large scale commercial usage of the material has been started by the industry recently, many important details of the mechanical properties and the reliability behavior are still unknown. While the thermal properties could be characterized relatively easy and are quite repeatable and stable, the mechanical properties - important for the reliability - are extremely process-dependent and wide-spreading. The hunt for lowest feasible sintering process parameters - such as temperature, time and especially pressure - even amplify that behavior and led to an impasse in some cases. Also their failure mechanisms, to be identified in lifetime investigations, are yet unknown as well as their stability and predictability. In order to enable prolonged function of these interfaces, thermo-mechanical reliability has to be assured. Within this paper, we show the status of silver sintering and the problems regarding mechanical material characterization found in literature. Additionally, we present a guideline for the mechanical acceleration of reliability experiments by isothermal bending tests. Finally a proof of concept by failure analysis will be presented

All-cause and cause specific mortality in a cohort of 20 000 construction workers; results from a 10 year follow up

Background: Construction workers are potentially exposed to many health hazards, including human carcinogens such as asbestos, silica, and other so-called "bystander" exposures from shared work places. The construction industry is also a high risk trade with respect to accidents. Methods: A total of 19 943 male employees from the German construction industry who underwent occupational health examinations between 1986 and 1992 were followed up until 1999/2000. Results: A total of 818 deaths occurred during the 10 year follow up (SMR 0.71; 95% CI 0.66 to 0.76). Among those were 299 deaths due to cancer (SMR 0.89; 95% CI 0.79 to 1.00) and 312 deaths due to cardiovascular diseases (SMR 0.59; 95% CI 0.51 to 0.68). Increased risk of mortality was found for non-transport accidents (SMR 1.61; 95% CI 1.15 to 2.27), especially due to falls (SMR 1.87; 95% CI 1.18 to 2.92) and being struck by falling objects (SMR 1.90; 95% CI 0.88 to 3.64). Excess mortality due to non-transport accidents was highest among labourers and young and middle-aged workers. Risk of getting killed by falling objects was especially high for foreign workers (SMR 4.28; 95% CI 1.17 to 11.01) and labourers (SMR 6.01; 95% CI 1.63 to 15.29). Conclusion: Fatal injuries due to falls and being struck by falling objects pose particular health hazards among construction workers. Further efforts are necessary to reduce the number of fatal accidents and should address young and middle-aged, semi-skilled and foreign workers, in particular. The lower than expected cancer mortality deserves careful interpretation and futher follow up of the cohort

Thermo-mechanical reliability of sintered all-Cu electrical fine pitch interconnects under isothermal fatigue testing benchmarked against soldered and TLP-bonded SnAg3.5 joints

Cu sintering is one of the emerging technologies in the field of micro- and power electronics where operating temperatures higher than 150°C are required. At these temperatures, solder joints reach their limits due to high homologous temperatures. Hence, Cu sintered joints can serve as a substitute for these soft solder joints, being advantageous also with respect to thermo-dynamic stability, fatigue resistance, electrical conductance and cost. This paper addresses failure analysis of sintered (neck-based) All-Cu electrical interconnects (NEI) along with soldered SnAg3.5 and transient liquid phase bonded (TLPB) specimens which form an SnCu intermetallic (IMC) and are used in a homogenous Si-Si flip chip assembly for fine pitch interconnects. The SnAg3.5 solder serves as a benchmark for the NEIs and the TLPB joints. All the flip chip specimens were free of underfill material. The test samples were assembled on spring steel substrates using a Silicone-based adhesive for a low stress bond and then put under isothermal accelerated fatigue tests using 4-point bending at low-homologous temperatures (R.T.). The reliability investigation involves monitoring of electrical resistance as a failure indicator for interconnect fatigue. A failure criterion at 20% increase in resistance is defined to establish a correlation between the experimental failure times and resistance. The fatigue behaviour of the joints was also studied using Finite Elements analysis (FEA). The focus of the modelling was towards the behaviour of the critical joint. Cross-sections were prepared and analysed using optical microscopy and SEM to investigate the failure mode and mechanism

Determination of residual stress with high spatial resolution at TSVs for 3D integration: Comparison between HR-XRD, Raman spectroscopy and fibDAC

Three different experimental methods have been used to determine mechanical stresses in silicon nearby tungsten TSVs - HR-XRD performed at a synchrotron beamline, microRaman spectroscopy and stress relief techniques put into effect by FIB ion milling. All methods possess, to a different extend, high spatial resolution capabilities. However they differ in their sensitivity and response to the particular stress tensor components relevant for the residual stress state nearby TSV structures. Stress measurements were performed on test samples with TSVs in thinned dies, which were SLID bonded to a thicker Si substrate die. The measurements captured stresses introduced by the W-TSV as well as by the wafer bonding process. A stress range from several MPa to hundreds of MPa could have been covered with a spatial allocation ranging from 100 nm to tens of microns. Measurement results were compared to each other and to simulated stresses from finite element analysis

Micro Bending Test on Double Cantilever Beams: A specimen-centred approach to accurate determination of the visco-plastic properties of Sintered Silver for Power Electronics applications

The increased attention for sintered silver as die attach attracts also interest in its reliability assessment. Since the porous joint material shows rate-dependent behaviour at elevated temperature, its visco-plastic behaviour needs to be quantified. Though tensile tests are frequently used for that task is still a challenge to manufacture homogeneous specimens large enough to be safely handled and tensile tested. In this paper the we have presented a comprehensive technology for manufacturing sintered silver specimen for micro bending test. The sample length is about 10 mm but can still be tested with nanoindenter equipment. These specimens were bent at 25 °C at different strain rates. The corresponding stress-strain curves were obtained with transformation functions computed by a FE model. Tensile specimens of sintered silver were manufactured and tensile tested at 25, 100 and 175 °C for investigation of rate dependency and relaxation behaviour. For 25 °C no rate dependency was observed. At 100 °C and 175 °C significant reduction of tensile strength and increase of tensile strain was observed at smaller strain rates. The creep was caused by thermal activation of inner surface diffusion

Residual stress investigations at TSVs in 3D micro structures by HR-XRD, Raman spectroscopy and fibDAC

In this paper the residual stress in single-crystalline Si around W-filled TSVs was determined experimentally by three methods with high spatial resolution and compared to one another. In contrast to Cu as TSV filler, W has the potential advantage of a lower CTE mismatch to Si resulting in lower thermally induced stress at the TSV-interface. As test layout a cross-sectioned double-die stack was used consisting of a top die with TSVs which is bonded by Cu-Sn Solid Liquid Interdiffusion Bonding (SLID) to the bottom die. Three different experimental methods have been used to determine mechanical stresses in silicon nearby tungsten TSVs - HR-XRD performed at a synchrotron beamline, microRaman spectroscopy and stress relief techniques put into effect by FIB milling. All methods possess, to a different extend, high spatial resolution capabilities. However they differ in their sensitivity and response to the particular stress tensor components relevant for the residual stress state nearby TSV structures. Stress measurements were performed on test samples with W-TSVs in thinned dies, which were SLID bonded to a thicker Si substrate die. The measurements captured stresses introduced by the W-TSV as well as by the wafer bonding process. A stress range from several MPa to hundreds of MPa could have been covered with a spatial resolution ranging from 100 nm to tens of microns. Measurement results were compared to one another and to simulated stresses from finite element analysis (FEA). All experimental methods show the influence of W and Cu-Sn-Bond in Si. The very high stress sensitivity for HR-XRD below 1 MPa could be shown. For small stress gradients the analysis of the peak position gives reasonable results and for larger stress gradients a profile analysis of the diffraction peak is more accurate. The results show that in intrinsic stress in W may have to be considered in FEA and more attention should be directed to the accuracy of the FE-modelled Cu-Sn SLID bond with resp- ct to shrinkage during phase formation of Cu3Sn

Review of percolating and neck-based underfills with thermal conductivities up to 3 W/m-K

Heat dissipation from 3D chip stacks can cause large thermal gradients due to the accumulation of dissipated heat and thermal interfaces from each integrated die. To reduce the overall thermal resistance and thereby the thermal gradients, this publication will provide an overview of several studies on the formation of sequential thermal underfills that result in percolation and quasi-areal thermal contacts between the filler particles in the composite material. The quasi-areal contacts are formed from nanoparticles self-assembled by capillary bridging, so-called necks. Thermal conductivities of up to 2.5 W/m-K and 2.8 W/m-K were demonstrated experimentally for the percolating and the neck-based underfills, respectively. This is a substantial improvement with respect to a state-of-the-art capillary thermal underfill (0.7 W/m-K)