Cumulative Trauma Disorders: OSHA\u27s General Duty Clause and the Need for an Ergonomics Standard

This Note argues that neither the Act nor its underlying policies supports OSHA\u27s current use of the general duty clause to prosecute alleged ergonomics violations and that the only way to protect workers from CTDs fairly and effectively is through the promulgation of an ergonomics standard. Part I examines the purposes of the Act, as well as the function of the Act\u27s general duty clause. Part II analyzes the four requirements of the general duty clause in the context of CTDs and finds that the clause does not apply to CTDs. Part III argues that the Act\u27s intended policies support the promulgation of an ergonomics standard rather than the use of the general duty clause. This Note concludes that the Secretary of Labor should promulgate an ergonomics standard33 as soon as possible and that, until then, the general duty clause should not be used to prosecute employers for alleged ergonomics violations

Analysis of CO₂ leakage through "low-permeability" faults from natural reservoirs in the Colorado Plateau, southern Utah

The numerous CO2 reservoirs in the Colorado Plateau region of the United States are natural analogues for potential geologic CO2 sequestration repositories. To better understand the risk of leakage from reservoirs used for long-term underground CO2 storage, we examine evidence for CO2 migration along two normal faults from a reservoir in east-central Utah. CO2 -charged springs, geysers, and a hydrocarbon seep are localised along these faults. These include natural springs that have been active for long periods of time, and springs that were induced by recent drilling. The CO2 -charged spring waters have deposited travertine mounds and carbonate veins. The faults cut siltstones, shales, and sandstones and the fault rocks are fine-grained, clay-rich gouge, generally thought to be barriers to fluid flow. The geologic and geochemical data are consistent with these faults being conduits for CO2 to the surface. Consequently, the injection of CO2 into faulted geologic reservoirs, including faults with clay gouge, must be carefully designed and monitored to avoid slow seepage or fast rupture to the biosphere

Convergence properties of η→3π\eta\to 3\pi decays in chiral perturbation theory

Theoretical efforts to describe and explain the $\eta\to 3\pi$ decays reach far back in time. Even today, the convergence of the decay widths and some of the Dalitz plot parameters seems problematic in low energy QCD. In the framework of resummed CHPT, we explore the question of compatibility of experimental data with a reasonable convergence of a carefully defined chiral series, where NNLO remainders are assumed to be small. By treating the uncertainties in the higher orders statistically, we numerically generate a large set of theoretical predictions, which are then confronted with experimental information. In the case of the decay widths, the experimental values can be reconstructed for a reasonable range of the free parameters and thus no tension is observed, in spite of what some of the traditional calculations suggest. The Dalitz plot parameters $a$ and $d$ can be described very well too. When the parameters $b$ and $\alpha$ are concerned, we find a mild tension for the whole range of the free parameters, at less than 2$\sigma$ C.L. This can be interpreted in two ways - either some of the higher order corrections are indeed unexpectedly large or there is a specific configuration of the remainders, which is, however, not completely improbable. Also, the distribution of the theoretical uncertainties is found to be significantly non-gaussian, so the consistency cannot be simply judged by the 1$\sigma$ error bars.Comment: 57 pages, 5 figure

Low-energy interactions of Nambu-Goldstone bosons with DD mesons in covariant chiral perturbation theory

We calculate the scattering lengths of Nambu-Goldstone bosons interacting with $D$ mesons in a covariant formulation of chiral perturbation theory, which satisfies heavy-quark spin symmetry and analytical properties of loop amplitudes. We compare our results with previous studies performed using heavy meson chiral perturbation theory and show that recoil corrections are sizable in most cases.Comment: 3 figures and 4 table

The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex

The MAGE (Melanoma-associated antigen) protein family members are structurally related to each other by a MAGEhomology domain comprised of 2 winged helix motifs WH/A and WH/B. This family specifically evolved in placental mammals although single homologs designated NSE3 (non-SMC element) exist in most eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight subcomplex of the structural maintenance of chromosomes SMC5–6 complex. Previously, we showed that interactions of the WH/B motif of the MAGE proteins with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1-NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs acquired new RING-finger containing partners through their evolution and form MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed the yeast 2-hybrid system to screen a human RING-finger protein library against several MAGE baits. We identified a number of potential MAGE-RING interactions and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41) in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co-factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may have evolved from an ancestral NSE1-NSE3-NSE4 complex

A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6

The SMC (Structural Maintenance of Chromosomes) complexes are composed of SMC dimers, kleisin and kleisin-interacting (HAWK or KITE) subunits. Mutual interactions of these subunits constitute the basal architecture of the SMC complexes. In addition, binding of ATP molecules to the SMC subunits and their hydrolysis drive dynamics of these complexes. Here, we developed new systems to follow the interactions between SMC5/6 subunits and the relative stability of the complex. First, we show that the N-terminal domain of the Nse4 kleisin molecule binds to the SMC6 neck and bridges it to the SMC5 head. Second, binding of the Nse1 and Nse3 KITE proteins to the Nse4 linker increased stability of the ATP-free SMC5/6 complex. In contrast, binding of ATP to SMC5/6 containing KITE subunits significantly decreased its stability. Elongation of the Nse4 linker partially suppressed instability of the ATP-bound complex, suggesting that the binding of the KITE proteins to the Nse4 linker constrains its limited size. Our data suggest that the KITE proteins may shape the Nse4 linker to fit the ATP-free complex optimally and to facilitate opening of the complex upon ATP binding. This mechanism suggests an important role of the KITE subunits in the dynamics of the SMC5/6 complexes

Mithramycin and Analogs for Overcoming Cisplatin Resistance in Ovarian Cancer

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, in the treatment of platinum-resistant ovarian cancer