Contracts--Developing Concepts of Unconscionability

Section 2-302 of the Uniform Commercial Code is a widely discussed and controversial statement of the law of unconscionability. It was a part of the original UCC as adopted by Pennsylvania in 1953, but some states elected to omit that section when they accepted the UCC. There are three fundamental reasons for their not adopting the section. The first objection is that the section goes against the security of the transaction by allowing the courts to remake parts of the contract. The second stems from the fact that the section limits the parties\u27 freedom to contract because it is often interpreted to allow an inquiry into the fairness of the exchange. The third involves the vagueness of the section due to its lack of definitions or any precise explanation of the concept. All of these objections are legitimate to some extent, but there are other factors which outweigh the negative aspects and make the adoption of section 2-302 advantageous. The law of unconscionability under section 2-302 has expanded greatly in the last ten years and is still developing. The courts today are using the section more readily in settling disputes. This could be due either to a better understanding by the courts of what the section encompasses or to a feeling on the part of the courts that this is the best way to an equitable result in most cases. Whatever the reasons, the law has developed quickly, and it is important to see where the law stands at the present time

Endogenous cross-talk of fungal metabolites

Non-ribosomal peptide (NRP) synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent NRP via a thiotemplate mechanism catalyzed by NRP synthetases. Substrate amino acids can be modified prior to or during incorporation into the NRP, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases, and glutathione S-transferases which are essential to effect biosynthesis of the final NRP. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancillary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: coenzyme A (CoA), acetyl CoA, S-adenosylmethionine, glutathione (GSH), NADPH, malonyl CoA, and molecular oxygen, amongst others are required for NRP and polyketide synthesis (PKS). Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of NRPs, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids), along with localization to similar regions within fungi (e.g., conidia) suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in NRP and PKS play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite

A Covariant Approach To Ashtekar's Canonical Gravity

A Lorentz and general co-ordinate co-variant form of canonical gravity, using Ashtekar's variables, is investigated. A co-variant treatment due to Crnkovic and Witten is used, in which a point in phase space represents a solution of the equations of motion and a symplectic functional two form is constructed which is Lorentz and general co-ordinate invariant. The subtleties and difficulties due to the complex nature of Ashtekar's variables are addressed and resolved.Comment: 18 pages, Plain Te

Time-course analysis following initial warm-up to inform pre-pitch entry preparations of soccer substitutes.

The purpose of this study was to investigate the time-course of decrements in physical performance following a pre-match warm-up in soccer players. Knowledge of this information could be used to inform re-warm-ups and pre-pitch entry practices of soccer substitutes. Data were collected over five sessions with 12 male youth professionals (15-17 yrs). Across the five sessions each player performed countermovement jumps (CMJ) and drop jumps (30 and 40 cm), pre-warm-up, immediately post-warm-up, and following 10-, 20-, 30-, 40-, and 50-minutes of inactivity. Physical performance was assessed by jump height and calculation of reactive strength index (RSI). Hierarchical generalized linear models (HGLMs) were fitted within a Bayesian framework to identify plausible time to achieve 10 to 50% decrements of the initial pre to post warm-up improvement. Mean improvements of 5.4 cm (95%CrI: 4.8 to 6.0), 0.24 ms-1 (95%CrI: 0.19 to 0.29), and 0.32 ms-1 (0.27 to 0.36) were obtained for the CMJ, and RSI measured from the 30 and 45 cm box, respectively. Decrements for all assessments were non-linear with the steepest rates of decline measured in the initial periods following warm-up. High probabilities were calculated (p ≥ 0.979) that up to 50% of the initial warm-up improvement for the CMJ would be lost between 20 and 30 minutes. The results of this study provide a guide for future research and practitioners managing the pre-pitch entry of soccer substitutes. It is suggested that practitioners consider and assess the effectiveness of exposing players to a re-warm-up between 20- and 30-minutes prior to pitch entry to maintain performance capabilities

Variation in Grazing Sward Chicory Content After Periods of Low Rainfall

Multispecies (MS) swards can reduce chemical nitrogen (N) fertiliser requirement due to the legume components of the sward mixtures, and have the potential to increase drought tolerance, particularly where chicory (CH, Chicorium intybus L.) is included in the sward mixture. A grazed plot experiment was established to investigate the persistency of forage herb species in MS swards under typical Irish grazing conditions. The swards contained three plant functional groups: grass, legume and herb; four sward types were established which included sward mixtures of the following species: perennial ryegrass (PRG, Lolium perenne L.) white clover (WC, Trifolium repens L.), red clover (RC, Trifolium pratense L.), CH and ribwort plantain (PL, Plantago lanceolata L.). The sward content of the various species in the sown mixtures was evaluated over three years (2020, 2021 and 2022). The summer of 2022 experienced dry weather conditions in which rainfall was well below average thus providing an opportunity to assess the drought tolerance of CH in grazed swards. The proportion of sward CH content from two late season cuts was assessed over the three years and this study reports the changes in sward CH content between years and grazing rotations. Average sward CH content was 14.7, 6.1, and 1.5% across all sward types in late summer of 2020, 2021 and 2022, respectively; average sward CH content was 13.7, 9.4 and 24.6 across all sward types in autumn of 2020, 2021 and 2022, respectively

Synthesis, antibacterial and anti-MRSA activity, in vivo toxicity and a structure-activity relationship study of a quinoline thiourea

We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure–activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds

Keep focussing: striatal dopamine multiple functions resolved in a single mechanism tested in a simulated humanoid robot

The effects of striatal dopamine (DA) on behavior have been widely investigated over the past decades, with "phasic" burst firings considered as the key expression of a reward prediction error responsible for reinforcement learning. Less well studied is "tonic" DA, where putative functions include the idea that it is a regulator of vigor, incentive salience, disposition to exert an effort and a modulator of approach strategies. We present a model combining tonic and phasic DA to show how different outflows triggered by either intrinsically or extrinsically motivating stimuli dynamically affect the basal ganglia by impacting on a selection process this system performs on its cortical input. The model, which has been tested on the simulated humanoid robot iCub interacting with a mechatronic board, shows the putative functions ascribed to DA emerging from the combination of a standard computational mechanism coupled to a differential sensitivity to the presence of DA across the striatum

The Aspergillus fumigatus Protein GliK Protects against Oxidative Stress and Is Essential for Gliotoxin Biosynthesis

The function of a number of genes in the gliotoxin biosynthetic cluster (gli) in Aspergillus fumigatus remains unknown. Here, we demonstrate that gliK deletion from two strains of A. fumigatus completely abolished gliotoxin biosynthesis. Furthermore, exogenous H2O2 (1 mM), but not gliotoxin, significantly induced A. fumigatus gliK expression (P 0.0101). While both mutants exhibited significant sensitivity to both exogenous gliotoxin (P<0.001) and H2O2 (P<0.01), unexpectedly, exogenous gliotoxin relieved H2O2-induced growth inhibition in a dose-dependent manner (0 to 10 g/ml). Gliotoxin-containing organic extracts derived from A. fumigatus ATCC 26933 significantly inhibited (P<0.05) the growth of the gliK26933 deletion mutant. The A. fumigatus gliK26933 mutant secreted metabolites, devoid of disulfide linkages or free thiols, that were detectable by reverse- phase high-performance liquid chromatography and liquid chromatography-mass spectrometry with m/z 394 to 396. These metabolites (m/z 394 to 396) were present at significantly higher levels in the culture supernatants of the A. fumigatus gliK26933 mutant than in those of the wild type (P0.0024 [fold difference, 24] and P0.0003 [fold difference, 9.6], respectively) and were absent from A. fumigatus gliG. Significantly elevated levels of ergothioneine were present in aqueous mycelial extracts of the A. fumigatus gliK26933 mutant compared to the wild type (P<0.001). Determination of the gliotoxin uptake rate revealed a significant difference (P0.0045) between that of A. fumigatus ATCC 46645 (9.3 pg/mg mycelium/min) and the gliK46645 mutant (31.4 pg/mg mycelium/min), strongly suggesting that gliK absence and the presence of elevated ergothioneine levels impede exogenously added gliotoxin efflux. Our results confirm a role for gliK in gliotoxin biosynthesis and reveal new insights into gliotoxin functionality in A. fumigatus

The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns

Correction to Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ: The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics 2007, 8:320