ordvar calculates measures of ordinal consensus and dispersion. These include lsq and 1-lsq, which are 0/1 normed ordinal consensus and dispersion statistics described in Blair and Lacy (2000). The ...latter statistic is essentially identical to the IOV measure of Berry and Mielke (1992). The non-normed version of the dispersion statistic, termed d-squared by Lacy (2006), is also calculated, as are delta-method standard errors for these statistics. These measures do not rely on assumptions about intercategory distances or distributional form.
r2o calculates the ordinal explained variation statistic (i.e., R-squared) described by Lacy (2006), which is used to summarize the fit of a regression model for an ordinal response. It rests on an ...ordinal variation measure that entails no assumptions about intercategory distances or distributional form. This measure is valid regardless of the method used to estimate the model, and was shown to outperform various pseudo-R-squared measures in estimating the value of the true R-squared for a regression model for an underlying continuous response, even though its sense does not require such. -r2o- is to be used after a relevant categorical response model has been run, while the e() list is still intact. By default, the program recognizes the following as relevant response models: -ologit-, -oprobit-, -mlogit-, and -gologit2-. However, -r2o- should work after any estimation command for which –predict- p1,..., pk will calculate predicted probabilities, and which follows official Stata's conventions for naming items in the e() list.
•Hypervelocity impact testing of fluid-filled metallic honeycomb core sandwich panels•Comparison of hypervelocity impacts to PEG-filled and STF-filled Panels•STF-filled panels provide greater impact ...mitigation than PEG-filled panels at 21°C•STF-filled panels subjected to hypervelocity impacts at low-temperatures (-80°C)•2D and 3D CT scans of all tested panels for damage evaluation
The use of honeycomb core sandwich panels filled with a shear thickening fluid (STF) as a component of spacecraft micrometeoroid/orbital debris (MMOD) shielding was investigated using hypervelocity impact (HVI) testing. Incorporating a STF into shielding has the potential to reduce damage to the core and the likelihood of back-side facesheet perforation in the event of a HVI. The sandwich panels tested consisted of 1.27 cm thick hexagonal aluminum honeycomb core bonded between 0.064 cm thick aluminum facesheets. The STF displayed a marked rise in viscosity with increasing shear rate above a critical shear rate. It was based on low molecular weight polyethylene glycol (PEG) and hydrophilic fumed silica. Sandwich panel target specimens filled with the STF were subjected to HVIs by 1 mm diameter stainless steel spheres at nominal temperatures of -80°C or 21°C with nominal impact velocities of 4.8 km/s or 6.8 km/s. Additional specimens filled with PEG only were also impacted for comparison.
Visual inspections and X-ray computerized tomography were used to assess impact damage. All of the panels experienced perforation of the impacted facesheet, facesheet bulging, localized delamination, and the formation of a cavity in the damaged core. STF-filled panels sustained significantly less damage than PEG-filled panels. None of the STF-filled panels were completely perforated during impact. In contrast, one of the PEG-filled panels impacted at the peak velocity was perforated. The remaining PEG-filled panel sustained substantially more honeycomb core damage and facesheet-core delamination compared to an analogous STF-filled panel. Sandwich panels filled with the STF provide superior HVI mitigation in comparison to panels filled with a Newtonian fluid (i.e., PEG). These experiments show that incorporation of STFs into MMOD shielding components has the potential to dramatically improve the HVI penetration resistance over a broad range of impact velocities and temperatures.
Ebola virus is highly lethal for great apes. Estimated mortality rates up to 98% have reduced the global gorilla population by approximately one-third. As mountain gorillas (Gorilla beringei ...beringei) are endangered, with just over 1000 individuals remaining in the world, an outbreak could decimate the population. Simulation modeling was used to evaluate the potential impact of an Ebola virus outbreak on the mountain gorilla population of the Virunga Massif. Findings indicate that estimated contact rates among gorilla groups are high enough to allow rapid spread of Ebola, with less than 20% of the population projected to survive at 100 days post-infection of just one gorilla. Despite increasing survival with vaccination, no modeled vaccination strategy prevented widespread infection. However, the model projected that survival rates greater than 50% could be achieved by vaccinating at least half the habituated gorillas within 3 weeks of the first infectious individual.
Many architects believe that major improvements in cost-energy-performance must now come from domain-specific hardware. This paper evaluates a custom ASIC - called a Tensor Processing Unit (TPU) - ...deployed in datacenters since 2015 that accelerates the inference phase of neural networks (NN). The heart of the TPU is a 65,536 8-bit MAC matrix multiply unit that offers a peak throughput of 92 TeraOps/second (TOPS) and a large (28 MiB) software-managed on-chip memory. The TPU's deterministic execution model is a better match to the 99th-percentile response-time requirement of our NN applications than are the time-varying optimizations of CPUs and GPUs that help average throughput more than guaranteed latency. The lack of such features helps explain why, despite having myriad MACs and a big memory, the TPU is relatively small and low power. We compare the TPU to a server-class Intel Haswell CPU and an Nvidia K80 GPU, which are contemporaries deployed in the same datacenters. Our workload, written in the high-level TensorFlow framework, uses production NN applications (MLPs, CNNs, and LSTMs) that represent 95% of our datacenters' NN inference demand. Despite low utilization for some applications, the TPU is on average about 15X-30X faster than its contemporary GPU or CPU, with TOPS/Watt about 30X-80X higher. Moreover, using the GPU's GDDR5 memory in the TPU would triple achieved TOPS and raise TOPS/Watt to nearly 70X the GPU and 200X the CPU.
Protein aggregation is of great concern to pharmaceutical formulations and has been implicated in several diseases. We engineered an anti-IL-13 monoclonal antibody CNTO607 for improved solubility. ...Three structure-based engineering approaches were employed in this study: (i) modifying the isoelectric point (pI), (ii) decreasing the overall surface hydrophobicity and (iii) re-introducing an N-linked carbohydrate moiety within a complementarity-determining region (CDR) sequence. A mutant was identified with a modified pI that had a 2-fold improvement in solubility while retaining the binding affinity to IL-13. Several mutants with decreased overall surface hydrophobicity also showed moderately improved solubility while maintaining a similar antigen affinity. Structural studies combined with mutagenesis data identified an aggregation ‘hot spot’ in heavy-chain CDR3 (H-CDR3) that contains three residues (99FHW100a). The same residues, however, were found to be essential for high affinity binding to IL-13. On the basis of the spatial proximity and germline sequence, we reintroduced the consensus N-glycosylation site in H-CDR2 which was found in the original antibody, anticipating that the carbohydrate moiety would shield the aggregation ‘hot spot’ in H-CDR3 while not interfering with antigen binding. Peptide mapping and mass spectrometric analysis revealed that the N-glycosylation site was generally occupied. This variant showed greatly improved solubility and bound to IL-13 with affinity similar to CNTO607 without the N-linked carbohydrate. All three engineering approaches led to improved solubility and adding an N-linked carbohydrate to the CDR was the most effective route for enhancing the solubility of CNTO607.
We prepared and characterized golimumab (CNTO148), a human IgG1 tumor necrosis factor alpha (TNFα) antagonist monoclonal antibody chosen for clinical development based on its molecular properties. ...Golimumab was compared with infliximab, adalimumab and etanercept for affinity and in vitro TNFα neutralization. The affinity of golimumab for soluble human TNFα, as determined by surface plasmon resonance, was similar to that of etanercept (18 pM versus 11 pM), greater than that of infliximab (44 pM) and significantly greater than that of adalimumab (127 pM, p=0.018). The concentration of golimumab necessary to neutralize TNFα-induced E-selectin expression on human endothelial cells by 50% was significantly less than those for infliximab (3.2 fold; p=0.017) and adalimumab (3.3-fold; p=0.008) and comparable to that for etanercept. The conformational stability of golimumab was greater than that of infliximab (primary melting temperature Tm 74.8 °C vs. 69.5 °C) as assessed by differential scanning calorimetry. In addition, golimumab showed minimal aggregation over the intended shelf life when formulated as a high concentration liquid product (100 mg/mL) for subcutaneous administration. In vivo, golimumab at doses of 1 and 10 mg/kg significantly delayed disease progression in a mouse model of human TNFα-induced arthritis when compared with untreated mice, while infliximab was effective only at 10 mg/kg. Golimumab also significantly reduced histological scores for arthritis severity and cartilage damage, as well as serum levels of pro-inflammatory cytokines and chemokines associated with arthritis. Thus, we have demonstrated that golimumab is a highly stable human monoclonal antibody with high affinity and capacity to neutralize human TNFα in vitro and in vivo.
Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens ...are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4(+) T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-alpha secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-alpha after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging.
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