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Amyotrophic lateral sclerosis, or motor neuron disease, is an uncommon progressive neurological disorder. Professionals working in the perioperative field may encounter patients with amyotrophic lateral sclerosis only rarely. The relevant published literature on amyotrophic lateral sclerosis is broad in scope, but a contemporary review focused on the perioperative period is absent. This structured narrative review seeks to provide a summary of the contemporary management of patients and then focuses on eliciting if there are perioperative management considerations specific to amyotrophic lateral sclerosis that can be optimised. A comprehensive structured narrative literature review, including grey literature searching, indicated worsening ventilatory failure is of prime concern but that patients may present with a broad range of neurological symptoms, and that cardiovascular and cognitive dysfunction specific to amyotrophic lateral sclerosis may exist and be occult. Exacerbation of neuromuscular weakness during the perioperative period is multifaceted and requires the application of a high standard of the core principles of surgical and anaesthetic management of neuromuscular disease. Standard perioperative approaches require rigorous attention and potential exists for significant alteration. There is a potential high risk of postoperative increased morbidity from neurological decline and mortality from pulmonary complications. A meticulous approach to planning preoperative assessment, shared decision-making, intraoperative and postoperative care is required.

This paper addresses a capacitated transportation plant location-allocation problem with an objective of maximizing expected net profits. A quantitative model is developed which includes price sensitivity and stochastic demand. A heuristic algorithm and two optimizing algorithms are proposed as solution methodologies for location and allocation decisions. Both a normal and uniform distribution of demands are considered, and the relationships between price and quantity demanded are accounted for in the model. A heuristic which produces near optimal solutions within reasonable limits of percentage deviation is required for solving medium and large size problems. The heuristic algorithm also has a lower computation time. (Reprinted by permission of the publisher.), I. Introduction Private sector plant location-allocation problems can be classified broadly into transportation type or transshipment type plant location-allocation problems. [11] A transportation location-allocation problem is considered in this study, [...]

Fewer women attain tenure and reach the rank of professor than their male counterparts. The extant literature is rich in descriptions of barriers that women encounter while on the tenure track. This study was designed to focus on the environment of one large, public, high research university to determine the types of environmental barriers that exist that affect women. Of interest to the researchers was whether the barriers identified can be attributed to the culture and climate of academe in general or are institution centric. To examine these barriers, this study was guided by one research question, framed by the perceptions and experiences of women on the tenure track at the study institution, which focused on the identification of environmental barriers that women encountered. This mixed method study identified environment barriers that were categorized into the four areas of work environment, assistance, policy, and genderedness and socialization. The results of the study support the national research discussions that the tenure process is flawed and ambiguous, and further emphasize that though the barriers are known to exist, universities continue to be slow to address them. The findings of the study need to be analyzed with caution due to it being conducted at one university, but the response rate of the participants supports that women seeking tenure at this institution want to discuss their perceptions and experiences of the process.

The first bulk n = 3 brownmillerite structure Ca2MnAlO5.5 has been synthesized by high-pressure oxidation of the n = 1 brownmillerite phase, Ca2MnAlO5, such that alternate AlO4 tetrahedral layers are oxidized to AlO6 octahedra. Rietveld analysis of room-temperature neutron powder diffraction (NPD) data shows a body-centered material (Imma, a = 5.2860(1) Å, b = 29.5334(6) Å, c = 5.4027(1) Å). Although magnetic measurements detected an increase in antiferromagnetic ordering at around 40 K, low-temperature NPD measurements implied the presence of no long-range magnetic order.

Ciprofloxacin-resistant gonococci have been isolated from patients in the United Kingdom since 1993. Until recently, evidence has suggested that the majority of infections are not endemic but have been acquired abroad. In October 1999, increasing numbers of ciprofloxacin resistant isolates of the non-requiring auxotype were reported in Oldham and Rochdale (Northwest England). These and similar isolates from elsewhere in England and Wales were genetically characterized using a simplified opa-typing method (a non-radioactive PCR–RFLP method targeting the opa family of genes). Of 73 isolates studied, 24 had unique opa-types (10 from infections acquired abroad), whilst the remaining 49 were indistinguishable (none were known to be acquired abroad). This cluster included 31 isolates from Oldham and Rochdale, 16 from elsewhere in the north of England, and 2 from Southern England and South Wales with known epidemiological links to cases from Manchester and Rochdale respectively. This study illustrates the potential for spread of an antibiotic resistant clone of N. gonorrhoeae both locally and nationally and demonstrates that endemic acquisition of ciprofloxacin-resistant gonococci is now a significant problem in the United Kingdom.

Despite coupling to the same class of inhibitory G proteins and binding the same physiological ligand, the human A(1) and rat A(3) adenosine receptors (ARs) desensitize at different rates in response to sustained agonist exposure. This is due to the ability of the A(3)AR, but not the A(1)AR, to serve as a substrate for rapid phosphorylation and desensitization by members of the G protein-coupled receptor kinase (GRK) family. The aim of this study was to investigate whether these differences were also manifested in their abilities to undergo agonist-dependent receptor internalization. For the first time, we report that A(3)ARs internalize profoundly in response to short-term exposure to agonist but not activators of second messenger-regulated kinases. The A(3)AR-selective antagonist MRS1523 blocked both A(3)AR phosphorylation and internalization. Moreover, in contrast to the A(1)AR, which internalized quite slowly (t(1/2) = 90 min), A(3)ARs internalized rapidly (t(1/2) = 10 min) over a time frame that followed the onset of receptor phosphorylation. A nonphosphorylated A(3)AR mutant failed to internalize over a 60-min time course, suggesting that receptor phosphorylation was essential for rapid A(3)AR internalization to occur. In addition, fusion onto the A(1)AR of the A(3)AR C-terminal domain containing the sites for phosphorylation by GRKs conferred rapid agonist-induced internalization kinetics (t(1/2) = 10 min) on the resulting chimeric AR. In conclusion, these data suggest that GRK-stimulated phosphorylation of threonine residues within the C-terminal domain of the A(3)AR is obligatory to observe rapid agonist-mediated internalization of the receptor.

Activation of the A(3) adenosine receptor (A(3)AR) contributes to the cardioprotective, bronchoconstrictive, and hypotensive effects of adenosine. Agonist occupation of the A(3)AR results in a rapid desensitization of receptor function, which is associated with the phosphorylation of the receptor protein by one or more members of the G protein-coupled receptor kinase family of protein kinases. Although we demonstrated previously that phosphorylation of the C-terminal 14 amino acids of the rat A(3)AR is crucial for rapid desensitization to occur, the identity of the critical phosphorylation sites has remained unknown. Here, we demonstrate that the simultaneous mutation of Thr(307), Thr(318), and Thr(319) to Ala residues dramatically reduces agonist-stimulated phosphorylation and rapid desensitization of the rat A(3)AR. Individual mutation of each residue demonstrated that Thr(318) and Thr(319) are the major sites of phosphorylation. Phosphorylation at Thr(318) appeared to be necessary to observe phosphorylation at Thr(319), but not vice versa. However, the replacement of Thr(318) with a glutamate residue demonstrated that the simple addition of negative charge at position 318 was not sufficient to rescue phosphorylation at position 319. In addition, the mutation of two predicted palmitoylation-site cysteine residues proximal to the regulatory domain resulted in the appearance of an agonist-independent basal phosphorylation. Therefore, G protein-coupled receptor kinase-mediated phosphorylation of the C-terminal tail of the A(3)AR in situ appears to follow a sequential mechanism, perhaps involving receptor depalmitoylation, with phosphorylation at Thr(318) being particularly important.

Enteric infections in animals and humans have proven the link between mucosal inflammation and gastrointestinal motor dysfunction. The goal of the present investigation was to study the long-term effects of mucosal inflammation on the neuromuscular functions of the small intestine in a ferret model of primary Trichinella spiralis infection. Myeloperoxidase activity and isometric contractions of isolated jejunal muscles were studied on days 8, 30, and 60 postinfection (PI). The peak increase in myeloperoxidase activity seen on day 8 PI returned to normal levels by day 60 PI. Contractions of the longitudinal and circular muscles evoked by electrical field stimulation of enteric nerves on day 8 PI showed no difference when compared with uninfected controls. However, during this enteric phase of the infection, neurally mediated responses were characterized by a disturbance in the balance between cholinergic and nonadrenergic, noncholinergic (NANC) excitation with both a reduction of cholinergic and a reciprocal enhancement of NANC neurotransmission. On days 30 and 60 PI the amplitude of neurally mediated responses and the balance between cholinergic and NANC excitation were restored in the circular but not in the longitudinal muscle. In addition, there were changes in the effector function involving smooth muscle hyperresponsiveness to high K+ or carbachol on days 8, 30, and 60 PI. However, a significant reduction in EC50 for carbachol was found only on day 60 PI. The results demonstrate that T. spiralis infection results in alterations of muscle contractility and enteric neurotransmission that persist after the resolution of mucosal inflammation.

The crystallographic and magnetic structures of Fe0.5Cu0.5Cr2S4 have been examined in order to generate a possible mechanism to explain the CMR behaviour of such spinels. Neutron powder diffraction has revealed that the tetrahedrally coordinated Fe3+ and Cu+ ions are fully ordered, with the magnetic moments of Fe3+ (µ300=–1.97(5) µB) aligned antiparallel to those of the octahedrally coordinated Cr3+ (µ300=1.49(3) µB). The results suggest a new CMR mechanism, which involves exchange on three cation centres (‘triple exchange’) and requires antiferromagnetic coupling of magnetic spins, in contrast to the manganite perovskites for which double-exchange provides a ferromagnetic state.

This paper presents an application of chance‐constrained goal programming methodology to a system of multipurpose reservoirs. Several objectives which may be conflicting and noncommensurate such as flood protection, municipal and industrial (M&I) water supply, hydroelectric power generation, recreation, etc. are considered in the model. The system goals and constraints are expressed either deterministically or probabilistically depending on whether the random variable term for inflow into a reservoir is present or not. For a constraint, the requirement must be strictly satisfied. For a goal, it is desired to achieve the solution which is as close as possible to the specified target. Stochastic inflows with one period correlation in successive periods are explicitly considered with conditional distribution functions based on normal and lognormal distributions of inflows provided. The application of the methodology to a three‐reservoir system in Oklahoma is reported. The proposed model uses a time period of a month and may be employed for planning rather than real‐time applications.

The A3 adenosine receptor (A3AR) contributes to several cardiovascular effects of adenosine, including antihypertensive and cardioprotective effects. Although several studies have detailed the mechanisms underlying agonist-mediated desensitization of the rat A3AR, the regulation of the human A3AR, which displays only a 70% amino acid identity with the rat homologue, has not been addressed. Using a Chinese hamster ovary cell line stably expressing a recombinant human A3AR, we demonstrated that prolonged treatment with the AR agonist 5'-N-ethylcarboxamidoadenosine induces uncoupling of the A3AR from G proteins and functional desensitization. In addition to A3AR desensitization, a 1.5-2.5-fold increase was noted in the adenylyl cyclase (AC) activity achieved in the presence of GTP with or without forskolin. This sensitization of AC activity was not a consequence of the down-regulation of Gi proteins induced by NECA treatment and was not associated with sustained or transient increases in the expression of Gs. Time course experiments revealed that the onset of sensitization was half-maximal between 2 and 3 hr but was not due to the synthesis of new proteins because cycloheximide treatment failed to inhibit sensitization. The inability of the sensitization process to alter the AC activity obtained in the presence of manganese chloride suggests that prolonged A3AR activation increases the coupling efficiency between Gs and AC catalytic units. This phenomenon has implications for long term cellular adaptation to agonist because in agonist-treated cells, the extent to which a suboptimal concentration of forskolin could increase phosphorylation of the cAMP-responsive element binding protein was elevated compared with vehicle-treated controls.

A partitioning procedure is proposed for obtaining approximate solutions to pseudo-Boolean optimization problems (e.g., zero-one polynomial programs). Such a procedure is useful not only in its ability to provide a bound value but further as a means for initializing optimum seeking methods, such as implicit enumeration techniques, employed to insure optimality.

We demonstrate that viscoelastic mechanics of striated muscle, measured as elastic and viscous moduli, emerge directly from the myosin crossbridge attachment time, 𝑡att, also called time-on. The distribution of 𝑡att was modeled using a gamma distribution with shape parameter, 𝑝, and scale parameter, 𝛽. At 5 mM MgATP, 𝛽 was similar between mouse 𝛼-MyHC (16.0±3.7 ms) and 𝛽-MyHC (17.9±2.0 ms), and 𝑝 was higher (𝑃<0.05) for 𝛽-MyHC (5.6±0.4 no units) compared to 𝛼-MyHC (3.2±0.9). At 1 mM MgATP, 𝑝 approached a value of 10 in both isoforms, but 𝛽 rose only in the 𝛽-MyHC (34.8±5.8 ms). The estimated mean 𝑡att (i.e., 𝑝𝛽 product) was longer in the 𝛽-MyHC compared to 𝛼-MyHC, and became prolonged in both isoforms as MgATP was reduced as expected. The application of our viscoelastic model to these isoforms and varying MgATP conditions suggest that 𝑡att is better modeled as a gamma distribution due to its representing multiple temporal events occurring within 𝑡att compared to a single exponential distribution which assumes only one temporal event within 𝑡att.