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We describe a new method for solving the linearized 1D Vlasov–Poisson system by using properties of Cauchy-type integrals. Our method remedies critical flaws of the two standard methods, reveals a previously unrecognized Gaussian-in-time-like decay, and can also account for an externally applied electric field. The Landau approximation involves deforming the Bromwich contour around the poles closest to the real axis due to the analytically continued dielectric function, finding the long-time behavior for a stable system: Landau damping. Jackson's generalization encircles all poles while sending the contour to infinity, assuming its contribution vanishes, which is not true in general. This gives incorrect solutions for physically reasonable configurations and can exhibit pathological behavior, of which we show examples. The van Kampen method expresses the solution for a stable equilibrium as a continuous superposition of waves, resulting in an opaque integral. Case's generalization includes unstable systems and predicts a decaying discrete mode for each growing discrete mode, an apparent contradiction to both the Jackson solution and ours. We show, without imposing additional constraints, that the decaying modes are never present in the time evolution due to an exact cancellation with part of the continuum. Our solution is free of integral expressions, is obtained using algebra and Laurent series expansions, does not rely on analytic continuations, and results in a correct asymptotically convergent form in the case of infinite sums. The analysis used can be readily applied in higher-dimensional, electromagnetic systems and also provides a new technique for evaluating certain inverse Laplace transforms. [ABSTRACT FROM AUTHOR]

Many high-altitude mammals, including humans, display signatures of selection on genes of the Hypoxia Inducible Factor (HIF) pathway, particularly HIF2A and PHD2. HIF2A , encoding the transcription factor HIF-2α, is a recurrent target of selection. Mechanisms of convergent evolution include impaired heterodimerization, defective coactivator recruitment, and possibly decreased transcription of the HIF2A gene. It has been observed that high altitude-associated amino acid changes in PHD2 and HIF-2α occur in nonconserved, unstructured regions of these proteins, and these changes can selectively alter interactions with other proteins, producing partial as opposed to complete loss of function. In Tibetans, pairing of a partial loss-of-function PHD2 allele with a partial loss-of-function HIF2A allele could produce a panel of adaptive phenotypes that neither allele alone could produce, raising the possibility that this could be mimicked pharmacologically. Humans and other mammals inhabit hypoxic high-altitude locales. In many of these species, genes under positive selection include ones in the Hypoxia Inducible Factor (HIF) pathway. One is PHD2 (EGLN1), which encodes for a key oxygen sensor. Another is HIF2A (EPAS1), which encodes for a PHD2-regulated transcription factor. Recent studies have provided insights into mechanisms for these high-altitude alleles. These studies have (i) shown that selection can occur on nonconserved, unstructured regions of proteins, (ii) revealed that high altitude-associated amino acid substitutions can have differential effects on protein–protein interactions, (iii) provided evidence for convergent evolution by different molecular mechanisms, and (iv) suggested that mutations in different genes can complement one another to produce a set of adaptive phenotypes. [ABSTRACT FROM AUTHOR]

We report a proof-of-principle lattice QCD simulation of the electric and magnetic polarizabilities for a neutral pion in the four-point function method. The results are based on the same quenched Wilson ensembles on a 24 3 × 48 lattice at β = 6.0 with pion mass from 1100 to 370 MeV previously used for a charged pion. For electric polarizability, the results are largely consistent with those from the background field method and ChPT. In contrast, there are significant differences for magnetic polarizability among the four-point function method, the background field method, and ChPT. The situation points to the important role of disconnected diagrams for a neutral pion. We elucidate a transparent quark decomposition in the four-point function method that can be used to shed light on the issue. [ABSTRACT FROM AUTHOR]

The article titled "Publisher's Note: 'A new method for solving the linearized 1D Vlasov-Poisson system yielding a new class of solutions'" was originally published online on May 30, 2024 with errors on pages 2, 6, and 10. These errors have been corrected in all online versions of the article as of June 3, 2024. The corrections include adding a semi-colon to the third line of the last paragraph on page 2, correcting a sentence on page 6 regarding the numerical solutions of the Vlasov-Poisson equation, and correcting a sentence on page 10 below Equation 60. The authors of the article are Frank M. Lee and B. A. Shadwick. [Extracted from the article]

Optogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage-specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+ sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardio-myocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3 (optoa1AR) and cAMP (optoβ2AR), or Ca2+-permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+ imaging in Hcn4BAC-CatCh2/Myh6-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signaling in vivo, in complex tissue networks. [ABSTRACT FROM AUTHOR]

[Display omitted] • LPS-induced alternative splicing of MyD88 terminates chronic inflammation. • The RNA binding proteins SRSF1 and HNRNPU regulate MyD88 alternative splicing. • SRSF1 and HNRNPU binding to MyD88 pre-mRNA is regulated by LPS. • LPS exposure decreases SRSF1 expression. • SRSF1 and HNRNPU regulate the extent of the innate immune response. Inflammation driven by Toll-like receptor (TLR) signaling pathways is required to combat infection. However, inflammation can damage host tissues; thus it is essential that TLR signaling ultimately is terminated to prevent chronic inflammatory disorders. One mechanism that terminates persistent TLR signaling is alternative splicing of the MyD88 signaling adaptor, which functions in multiple TLR signaling pathways. While the canonical long isoform of MyD88 (MyD88-L) mediates TLR signaling and promotes inflammation, an alternatively-spliced shorter isoform of MyD88 (MyD88-S) produces a dominant negative inhibitor of TLR signaling. MyD88-S production is induced by inflammatory agonists including lipopolysaccharide (LPS), and thus MyD88-S induction is thought to act as a negative feedback loop that prevents chronic inflammation. Despite the potential role that MyD88-S production plays in inflammatory disorders, the mechanisms controlling MyD88 alternative splicing remain unclear. Here, we identify two RNA binding proteins, SRSF1 and HNRNPU, that regulate LPS-induced alternative splicing of MyD88. [ABSTRACT FROM AUTHOR]

We aim to compute the discrete energy spectrum for two-body scattering in a three-dimensional box under periodic boundary conditions. The spectrum in the center of mass is obtained by solving the Schödinger equation in a test potential using the Fourier basis. The focus is on how to project the spectrum into the various irreducible representations of the symmetry groups of the box. Four examples are given to show how the infinite-volume spectrum (including both bound and scattering states) is resolved in cubic or elongated boxes, and in systems with integer or half-integer total spin. Such a demonstration is a crucial step in relating the discrete spectrum in the box to the infinite-volume scattering phaseshifts via the Lüscher method. [ABSTRACT FROM AUTHOR]

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. [ABSTRACT FROM AUTHOR]

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. (Korean J Pain 2014; 27: 3-15) [ABSTRACT FROM AUTHOR]

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. [ABSTRACT FROM AUTHOR]

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled. [ABSTRACT FROM AUTHOR]

Introduction: Opioid dependency is a major epidemiologic problem with profound morbidity and mortality. Despite the availability of effective treatments, there are often overwhelming barriers to those treatments. Case Presentations: We present a case series involving a novel approach to the induction phase of buprenorphine or buprenorphine-naloxone therapy using transdermal buprenorphine. This approach has been demonstrated in inpatient settings but has not been widely explored in the outpatient setting. We demonstrated that a range of patients, from the highly medically complex to relatively straightforward cases, benefited from this approach. Discussion: We believe that this approach can be used in a wide range of patients to transition from opioid use to buprenorphine therapy without the patient having to experience withdrawal or wait to start treatment. This should reduce the risk of lack of return for follow-up as well as decrease the dropout rate caused by patients being unable to tolerate withdrawal symptoms. [ABSTRACT FROM AUTHOR]

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. [ABSTRACT FROM AUTHOR]

Abstract Hemostasis is the physiological control of bleeding and is initiated by subendothelial exposure. Platelets form the primary vascular seal in three stages (localization, stimulation and aggregation), which are triggered by specific interactions between platelet surface receptors and constituents of the subendothelial matrix. As a secondary hemostatic plug, fibrin clot formation is initiated and feedback-amplified to advance the seal and stabilize platelet aggregates comprising the primary plug. Once blood leakage has been halted, the fibrinolytic pathway is initiated to dissolve the clot and restore normal blood flow. Constitutive and induced anticoagulant and antifibrinolytic pathways create a physiological balance between too much and too little clot production. Hemostatic imbalance is a major burden to global healthcare, resulting in thrombosis or hemorrhage. [ABSTRACT FROM AUTHOR]

Hepcidin is the master regulator of iron metabolism. It plays a key role in the regulation of iron transport across the duodenal epithelium, which in turn is dependent on the oxygen-regulated transcription factor hypoxia-inducible factor 2α (HIF-2α). In this issue of the JCI, Schwartz and colleagues show that duodenal HIF-2α is itself regulated by hepcidin, thereby indicating that this transcription factor is not only regulated by oxygen, but also by iron. This work indicates that the crosstalk between liver hepcidin and intestinal HIF-2α plays an important role during iron overload, systemic iron deficiency, and anemia. [ABSTRACT FROM AUTHOR]

Similar to its mammalian counterparts, teleost Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA presented in the genome of bacteria or DNA viruses and initiates signaling pathway(s) for immune responses. We have previously shown that the TLR9 pathway in grouper, an economically important teleost, can be debilitated by an inhibitory gTLR9B isoform, whose production is mediated by RNA alternative splicing. However, how does grouper TLR9 (gTLR9) signaling impinge on the RNA splicing machinery to produce gTlr9B is unknown. Here we show that the gTlr9 alternative splicing is regulated through ligand-induced phosphorylation of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II). We first observed that ligand-activated NF- κB pathway biased the production of the gTlr9B isoform. Because NF- κB is known to recruit p-TEFb kinase, which phosphorylates the Pol II CTD at Ser2 residues, we examined p-TEFb’s role in alternative splicing. We found that promoting p-TEFb kinase activity significantly favored the production of the gTlr9B isoform, whereas inhibiting p-TEFb yielded an opposite result. We further showed that p-TEFb-mediated production of the gTlr9B isoform down-regulates its own immune responses, suggesting a self-limiting mechanism. Taken together, our data indicate a feedback mechanism of the gTLR9 signaling pathway to regulate the alternative splicing machinery, which in turn produces an inhibitor to the pathway. [ABSTRACT FROM AUTHOR]

Toll-like receptor 9 (TLR9) recognizes and binds unmethylated CpG motifs in DNA, which are found in the genomes of bacteria and DNA viruses. In fish, Tlr9 is highly diverse, with the number of introns ranging from 0 to 4. A fish Tlr9 gene containing two introns has been reported to express two alternatively spliced isoforms, namely gTLR9A (full-length) and gTLR9B (with a truncated Cʹ-terminal signal transducing domain), whose regulation and function remain unclear. Here, we report a unique regulatory mechanism of gTLR9 signaling in orange-spotted grouper (Epinephelus coioides), whose gTlr9 sequence also contains two introns. We demonstrated that the grouper gTlr9 gene indeed has the capacity to produce two gTLR9 isoforms via alternative RNA splicing. We found that gTLR9B could function as a negative regulator to suppress gTLR9 signaling as demonstrated by the suppression of downstream gene expression. Following stimulation with CpG oligodeoxynucleotide (ODN), gTLR9A and gTLR9B were observed to translocate into endosomes and co-localize with ODN and the adaptor protein gMyD88. Both gTLR9A and gTLR9B could interact with gMyD88; however, gTLR9B could not interact with downstream IRAK4 and TRAF6. Further analysis of the expression profile of gTlr9A and gTlr9B upon immune-stimulation revealed that the two isoforms were differentially regulated in a time-dependent manner. Overall, these data suggest that fish TLR9B functions as a negative regulator, and that its temporal expression is mediated by alternative RNA splicing. This has not been observed in mammalian TLR9s and might have been acquired relatively recently in the evolution of fish. [ABSTRACT FROM AUTHOR]

Humans have adapted to the chronic hypoxia of high altitude in several locations, and recent genome-wide studies have indicated a genetic basis. In some populations, genetic signatures have been identified in the hypoxiainducible factor (HIF) pathway, which orchestrates the transcriptional response to hypoxia. In Tibetans, they have been found in the HIF2A (EPAS1) gene, which encodes for HIF-2a, and the prolyl hydroxylase domain protein 2 (PHD2, also known as EGLN1) gene, which encodes for one of its key regulators, PHD2. High-altitude adaptation may be due to multiple genes that act in concert with one another. Unraveling their mechanism of action can offer new therapeutic approaches toward treating common human diseases characterized by chronic hypoxia. [ABSTRACT FROM AUTHOR]

Background: Health Care Providers (HCPs) report that manual techniques of intravascular fluid resuscitation are commonly used during pediatric shock management. The optimal pediatric fluid resuscitation technique is currently unknown. We sought to determine HCP test-retest reliability (repeatability) and inter-subject variability of fluid resuscitation performance outcomes to inform the design of future studies. Methods: Fifteen consenting HCPs from McMaster Children's Hospital, in Hamilton, Canada participated in this single-arm interventional trial. Participants were oriented to a non-clinical model representing a 15 kg toddler, which incorporated a 22-gauge IV catheter. Following a standardization procedure, participants administered 600 mL (40 mL/kg) of saline to the simulated child under emergency conditions using prefilled 60-mL syringes. Each participant completed 5 testing trials. All testing was video recorded, with fluid administration time outcome data (in seconds) extracted from trial videos by two blinded outcome assessors. Data describing catheter dislodgement events, volume of saline effectively delivered, and participant demographics were also collected. The primary outcome of fluid administration time test-retest reliability was analyzed by one-way analysis of variance (ANOVA) and intra-class correlation (ICC), with good reliability defined as ICC > 0.70. Results: Differences in HCP fluid administration times are attributable to inter-subject variability rather than intra-subject variability based on one-way ANOVA analysis, F (14,60) = 43.125; p < 0.001. Test-retest reliability of subjects was excellent with ICC = 0.97 (95% CI: 0.95-0.99); p < 0.001. Conclusions: Findings demonstrate excellent test-retest reliability of HCP fluid resuscitation performance in a setting involving a non-clinical model. Investigators can justify a single evaluation of HCP performance in future studies. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC) and activated PCC (aPCC) are three non-specific haemostatic agents sometimes employed to reverse new, factor-specific oral anticoagulants. Methods: We conducted a review in the literature to compare the abilities of rFVIIa, PCC and aPCC to reverse factor-specific anticoagulants. MEDLINE and EMBASE databases were searched up to Oct 2013. Results: Eleven animal studies and two human trials met predefined inclusion criteria. To account for dosing variations of anticoagulants among studies, data were interpreted based on standards referenced from human trials at therapeutic doses. In animal studies, inconsistencies in the reversal abilities of rFVIIa, PCC and aPCC can be partly attributed to inter-species differences in the affinity among various clotting factors and tissue factors. Moreover, the differences in the affinity between species-specific clotting factors and anticoagulants that were initially designed to inhibit human factor may impose additional obstacles when comparing single factor rFVIIa with agents that contained multiple clotting factors. In the absence of a common clinical indication for the utilization of rFVIIa, PCC and aPCC, it is difficult, if not impossible, to establish an equivalent dose among these haemostatic agents when comparing their effectiveness in reversing factor-specific oral anticoagulants. Human trials were too few and sub-optimally designed to draw definite conclusions. Conclusion: While preclinical studies may hint at a role for these haemostatic agents in reversing the anticoagulant effects of oral, factor-specific anticoagulants, existing trials offer inconclusive evidence to guide a clinical decision among individual agents with respect to potency and thrombosis risk. The mechanistic differences of these hemostatic agents in terms of their interactions with other coagulation factors impose major obstacles for the scientists using animal models to compare the efficacy of these reversal agents. [Copyright &y& Elsevier]

We present a method to determine, using only velocity field data, the time-averaged energy flux J and total radiated power P for two-dimensional internal gravitywaves. Both J and P are determined from expressions involving only a scalar function, the stream function ?.We test the method using data from a direct numerical simulation for tidal flow of a stratified fluid past a knife edge. The results for the radiated internal wave power given by the stream function method agree to within 0.5% with results obtained using pressure and velocity data from the numerical simulation. The results for the radiated power computed from the stream function agree well with power computed from the velocity and pressure if the starting point for the stream function computation is on a solid boundary, but if a boundary point is not available, care must be taken to choose an appropriate starting point. We also test the stream function method by applying it to laboratory data for tidal flow past a knife edge, and the results are found to agree with the direct numerical simulation. The supplementary material includes a Matlab code with a graphical user interface that can be used to compute the energy flux and power from two-dimensional velocity field data. [ABSTRACT FROM AUTHOR]

As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Traditionally, surgical management of mesh/suture erosions has involved excision through a transvaginal or endoscopic approach for urethral erosions, and a transabdominal approach (open or laparoscopic) for bladder exposures. In the majority of published studies, urethral erosions appear to be a complication of retropubic mid-urethral sling insertion, with incidence rates in the range 0.03-0.8%. The present study confirms that transurethral endoscopic management has low morbidity, good functional outcomes and potentially low rates of recurrent stress incontinence. Urethral tape erosions were excised successfully with a transurethral approach, whereas mesh eroded in the bladder required an open procedure. OBJECTIVES • To evaluate transurethral endoscopic excision using the holmium laser (TEEH) for the management of lower urinary tract mesh or suture complications of continence intervention. • To compare the outcomes, complications and recurrence rates of TEEH with the published results from studies using other techniques. PATIENTS AND METHODS • A retrospective review of six patients who underwent TEEH for eroded mid-urethral tape or suture into the urethra or bladder. • Patients with urethral and bladder exposure of mesh or suture material managed by TEEH were identified from the operating records, electronic data records and the Holmium Laser Registry at our institution. • Outcome variables included resolution of the presenting symptoms and continence status, recurrent mesh or suture exposure, and symptoms or other morbidity, including haematoma, urinary sepsis, voiding dysfunction and recurrent stress incontinence. • A literature review on the available evidence on holmium laser for lower urinary tract complications of continence surgery was undertaken. RESULTS • Between September 2006 and March 2010, six women underwent TEEH. All presented with bladder storage symptoms and/or haematuria with recurrent cystitis. The interval between surgery and the diagnosis of erosion was 1-13 years. • Four women had previously undergone retropubic mid-urethral tape, one colposuspension and one a suprapubic arc procedure followed by a transobturator tape insertion. • Complete excision with TEEH was achieved in all cases. • Two women had postoperative haematuria, which resolved after 2 weeks. There were no other immediate complications. • Four patients had recurrent erosion at follow-up. Two of them were symptomatic, requiring repeat TEEH. One was asymptomatic and managed expectantly. In one case, recurrent mesh erosion occurred at the bladder neck in the submucosal layer. This was considered unsuitable for further TEEH. A laparotomy and open excision was undertaken. CONCLUSIONS • TEEH is a minimally invasive technique, with minimal morbidity and complications, compared to open vaginal or abdominal excision of mesh or suture exposure into the lower urinary tract. Open urethrotomy involves risks of damage to the continence (sphincter) mechanism, with subsequent stress incontinence. In addition, anterior wall scarring may lead to dyspareunia, vaginal pain, urethral stricture and/or fistula. When mesh erosion involves the bladder, transabdominal open or laparoscopic excision may be required. • Although the recurrence rates in our series are high, the majority of them were managed easily by repeat TEEH, with minimal morbidity or expectantly if asymptomatic. • In selected patients, TEEH is an acceptable novel technique for the first-line management of this complication of continence interventions, although longer or pooled prospective studies evaluating TEEH are now required. [ABSTRACT FROM AUTHOR]

Iron-sulfur proteins play an essential role in a variety of biologic processes and exist in multiple cellular compartments. The biogenesis of these proteins has been the subject of extensive investigation, and particular focus has been placed on the pathways that assemble iron-sulfur clusters in the different cellular compartments. Iron-only hydrogenase-like protein 1 (IOP1; also known as nuclear prelamin A recognition factor like protein, or NARFL) is a human protein that is homologous to Nar1, a protein in Saccharomyces cerevisiae that, in turn, is an essential component of the cytosolic iron-sulfur protein assembly pathway in yeast. Previous siRNA-induced knockdown studies using mammalian cells point to a similar role for IOP1 in mammals. In the present studies, we pursued this further by knocking out Iop1 in Mus musculus. We find that Iop1 knock-out results in embryonic lethality before embryonic day 10.5. Acute, inducible global knock-out of Iop1 in adult mice results in lethality and significantly diminished activity of cytosolic aconitase, an iron-sulfur protein, in liver extracts. Inducible knock-out of Iop1 in mouse embryonic fibroblasts results in diminished activity of cytosolic but not mitochondrial aconitase and loss of cell viability. Therefore, just as with knock-out of Nar1 in yeast, we find that knock-out of Iop1/Narfl in mice results in lethality and defective cytosolic iron-sulfur cluster assembly. The findings demonstrate an essential role for IOP1 in this pathway. [ABSTRACT FROM AUTHOR]

We study the ηNN coupling constant using the method of QCD sum rules starting from the vacuum-to-eta correlation function of the interpolating fields of two nucleons. The matrix element of this correlation has been taken with respect to nucleon spinors to avoid unwanted pole contribution. The SU(3)-flavor symmetry breaking effects have been accounted for via the η-mass, s-quark mass and eta decay constant to leading order. Out of the four sum rules obtained by taking the ratios of the two sum rules in conjunction with the two sum rules in nucleon mass, three are found to give mutually consistent results. We find the SU(3) breaking effects significant, as large as 50% of the SU(3) symmetric part. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare the 1-h pad test in women who have urodynamically confirmed stress incontinence (USI) with a patient-based 3-point symptom severity scale and validated quality of life (QoL) questionnaires. PATIENTS AND METHODS In all, 98 women with USI were prospectively recruited; all had a 1-h pad test and completed the validated disease-specific QoL questionnaires, including short forms of the International Consultation on Incontinence Questionnaire (ICIQ-SF), Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7). In addition, the severity of incontinence was determined using the Stamey grading scale, a visual analogue scale (VAS) score, and a patient-based 3-point symptom severity scale. RESULTS The VAS, symptom severity scale, Stamey grade, UDI-6, and IIQ-7 failed to correlate significantly with the 1-h pad test. Only the ICIQ-SF correlated significantly with this test. CONCLUSION The ICIQ-SF is easy to administer and, in this study, correlated best with the 1-h pad test in women with pure primary or secondary USI. It incorporates both symptom severity and QoL variables. We recommend its routine use in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Parkinson''s disease (PD) is a neurodegenerative disease characterized by a loss of nigrostriatal dopaminergic neurons. Recently, PD research has been stimulated by the identification of genes that are implicated in rare familial forms of PD. However, despite these discoveries, the primary cause of PD is still unclear. Various pathogenic mechanisms may be involved including mitochondrial dysfunction, proteasomal dysfunction/protein aggregation, oxidative damage, environmental factors and genetic disposition. Furthermore, dopamine has also been implicated in contributing to the pathogenesis of PD. This review will focus on the genes that have been identified to be associated with PD and how they may impair dopamine metabolism. Understanding the role of these PD-related genes in dopamine neurobiology may provide insight into the underpinning pathogenic mechanisms of PD. [Copyright &y& Elsevier]

Abstract: Dissolved organic matter (DOM) is a complex and poorly understood mixture of natural polymeric organic material, and plays an important role in material transport and carbon balance in aquatic ecosystems. Fluorescent dissolved organic matter (FDOM) represents a major portion of the total DOM and has often been used as a tracer to identify the source or track the movement of DOM in aquatic environment. In this work, we have applied Excitation/Emission Matrix spectroscopy (EEMs) to study the distribution and characteristics of FDOM in seawater of Bohai Sea in Northern China. Hierarchical Cluster method has been used to assess the similarities and dissimilarities of the entire EEMs data sets of seawater samples collected from different regions of the Bohai Sea. The distribution of different seawater samples as revealed by multivariate results has been used to track the movement of DOM material in the Bay, and the results from such analysis are in good agreement with those obtained from seawater circulation and dynamics models. [Copyright &y& Elsevier]

The biogenesis of cytosolic iron-sulfur (Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nan, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of hydrogen gas in anaerobic bacteria. There are two orthologues of Nan in mammalian cells, iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor). We examined IOP1 for a potential role in mammalian cytosolic Fe-S protein biogenesis, We found that knockdown of IOP1 in both HeLa and Hep3B cells decreases the activity of cytosolic aconitase, an Fe-S protein, but not that of mitochondrial aconitase. Knock-down of IOP2, in contrast, had no effect on either. The decrease in aconitase activity upon IOP1 knockdown is rescued by expression of a small interference RNA-resistant version of IOP1. Upon loss of its Fe-S cluster, cytosolic aconitase is known to be converted to iron regulatory protein 1, and consistent with this, we found that IOP1 knockdown increases transferrin receptor 1 mRNA levels and decreases ferritin heavy chain protein levels. IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation. [ABSTRACT FROM AUTHOR]

Dopamine is a major neurotransmitter in the mammalian central nervous system (CNS) that regulates neuroendocrine functions, locomotor activity, cognition and emotion. The dopamine system has been extensively studied because dysfunction of this system is linked to various pathological conditions including Parkinson's disease, schizophrenia, Tourette's syndrome, and drug addiction. Accordingly, intense efforts to delineate the full complement of signaling pathways mediated by individual receptor subtypes have been pursued. Dopamine D1-like receptors are of particular interest because they are the most abundant dopamine receptors in CNS. Recent work suggests that dopamine signaling could be regulated via dopamine receptor interacting proteins (DRIPs). Unraveling these DRIPs involved in the dopamine system may provide a better understanding of the mechanisms underlying CNS disorders related to dopamine system dysfunction and may help identify novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: A calculation of the mass spectrum in the baryon decuplet sector is presented using the method of QCD sum rules. Sum rules are derived for states of spin-parity and using both the conventional method and a parity-projection method. The predictive ability of the sum rules is explored by a Monte Carlo based analysis procedure in which the three phenomenological parameters (mass, coupling, threshold) are treated as free parameters and fitted simultaneously. Taken together, the results give an improved determination of the mass spectrum in this sector from the perspective of non-perturbative QCD. [Copyright &y& Elsevier]

Altered synaptic dopamine levels have been implicated in several neurological/neuropsychiatric disorders, including drug addiction and schizophrenia. However, it is unclear what precipitates these changes in synaptic dopamine levels. One of the key presynaptic components involved in regulating dopaminergic tone is the dopamine transporter (DAT). Here, we report that the DAT is also regulated by the dopamine D2 receptor through a direct protein–protein interaction involving the DAT amino-terminus and the third intracellular loop of the D2 receptor. This physical coupling facilitates the recruitment of intracellular DAT to the plasma membrane and leads to enhanced dopamine reuptake. Moreover, mice injected with peptides that disrupt D2–DAT interaction exhibit decreased synaptosomal dopamine uptake and significantly increased locomotor activity, reminiscent of DAT knockout mice. Our data highlight a novel mechanism through which neurotransmitter receptors can functionally modulate neurotransmitter transporters, an interaction that can affect the synaptic neurotransmitter levels in the brain. [ABSTRACT FROM AUTHOR]

Abstract: Licorice, the roots of Glycyrrhizia uralensis Fisch, is used as a medicinal herb and food additive in China. At present, the quality grading and authentication of licorice products is generally done by visual inspection, which is subjective and often biased. In this study, a rapid and nondestructive method for the classification of licorice samples according to their growing conditions, geographic areas and plant parts was developed using fiber optic diffuse reflectance near-infrared spectroscopy (FODR-NIR). With the use of multiplicative signal correlation (MSC) and Norris derivative filter, the differences of the NIR spectra among different licorice samples were enhanced even though the raw spectra were very similar. The results showed that the NIR spectra of the samples were moderately clustered in the principle component spaces, and pattern recognition technique of soft independent modeling of class analogy (SIMCA) provided satisfactory classification results. Additionally, a partial least square (PLS) method using HPLC data set as reference was constructed to predict the value of glycyrrhizic acid (GA) in licorice. The results showed that PLS models with both data normalization (DN) coupled with first derivative pretreatments, and MSC coupled with first derivative pretreatments provided acceptable results. [Copyright &y& Elsevier]

The mass spectrum of spin-1/2 baryons in both parity channels is computed using the methods of lattice QCD in the quenched approximation. An anisotropic action with anisotropy as/at = 3 is employed, using tree-level coefficients with tadpole improvement. Clear splittings from the nucleon ground state are observed with smeared operators and 500 configurations. Methods for extracting the first excited states are investigated. Using the quark mass dependence of the masses, qualitative comparisons are made with previous calculations and experiment. [ABSTRACT FROM AUTHOR]

Abstract: Camellia oil is often the target for adulteration or mislabeling in China because of it is a high priced product with high nutritional and medical values. In this study, the use of attenuated total reflectance infrared spectroscopy (MIR-ATR) and fiber optic diffuse reflectance near infrared spectroscopy (FODR-NIR) as rapid and cost-efficient classification and quantification techniques for the authentication of camellia oils have been preliminarily investigated. MIR spectra in the range of 4000–650cm−1 and NIR spectra in the range of 10,000–4000cm−1 were recorded for pure camellia oils and camellia oil samples adulterated with varying concentrations of soybean oil (5–25% adulterations in the weight of camellia oil). Identifications is successfully made base on the slightly difference in raw spectra in the MIR ranges of 1132–885cm−1 and NIR ranges of 6200–5400cm−1 between the pure camellia oil and those adulterated with soybean oil with soft independent modeling of class analogy (SIMCA) pattern recognition technique. Such differences reflect the compositional difference between the two oils with oleic acid being the main ingredient in camellia oil and linoleic acid in the soybean oil. Furthermore, a partial least squares (PLS) model was established to predict the concentration of the adulterant. Models constructed using first derivative by combination of standard normal variate (SNV), variance scaling (VS), mean centering (MC) and Norris derivative (ND) smoothing pretreatments yielded the best prediction results With MIR techniques. The R value for PLS model is 0.994.The root mean standard error of the calibration set (RMSEC) is 0.645, the root mean standard error of prediction set (RMSEP) and the root mean standard error of cross validation (RMSECV) are 0.667 and 0.85, respectively. While with NIR techniques, NIR data without derivative gave the best quantification results. The R value for NIR PLS model is 0.992. The RMSEC, RMSEP and RMSECV are 0.70, 1.78 and 1.79, respectively. Overall, either of the spectral method is easy to perform and expedient, avoiding problems associated with sample handling and pretreatment than the conventional technique. [Copyright &y& Elsevier]

I review recent progress in computing the mass spectrum of excited baryons and pentaquarks in lattice QCD. [ABSTRACT FROM AUTHOR]

Abstract: High-speed counter-current chromatography (HSCCC) technique in semi-preparative scale has been applied to isolate and purify bioactive flavone compounds from the ethanol extract of Glycyrrhiza inflata Bat., a particular plant species of licorice. HSCCC separation was performed with a two-phase solvent system composed of n-hexane–chloroform–methanol–water (5:6:3:2, v/v) by eluting the lower mobile phase at a flow rate of 1.8ml/min and a revolution speed of 800rpm. Purification was performed with a two-phase solvent system composed of n-hexane–chloroform–methanol–water (1.5:6:3:2, v/v) by eluting the lower mobile phase at a flow-rate of 1.5ml/min and a revolution speed of 800rpm. Two major flavone peaks: inflacoumarin A and licochalcone A were collected and the respective yields of the peaks amount to 6mg (8.6%, w/w) and 8mg (11.4%, w/w) from 70mg of the crude extract sample. The purities of inflacoumarin A and licochalcone A reached 99.6% and 99.1%, respectively, after a sequential purification run. The structures of inflacoumarin A and licochalcone A were positively confirmed by 1H NMR and 13C NMR, 1H–13C-COSY, UV, FT-IR and electron ionization MS analyses. [Copyright &y& Elsevier]

Functional interactions between dopamine D1-like receptors and NMDA subtype glutamate receptors have been implicated in the maintenance of normal brain activity and neurological dysfunction. Although modulation of NMDA receptor functions by D1 receptor activation has been the subject of extensive investigation, little is known as to how the activation of NMDA receptors alters D1 function. Here we report that NMDA receptors regulate D1 receptor function via a direct protein-protein interaction mediated by the carboxyl tail regions of both receptors. In both cotransfected cells and cultured hippocampal neurons the activation of NMDA receptors increases the number of D1 receptors on the plasma membrane surface and enhances D1 receptor-mediated cAMP accumulation via a SNARE-dependent mechanism. Furthermore, overexpression of mini-genes encoding either NR1 or D1 carboxyl tail fragments disrupts the D1-NR1 direct protein-protein interaction and abolishes NMDA-induced changes in both D1 cell surface expression and D1-mediated cAMP accumulation. Our results demonstrate that the D1-NR1 physical interaction enables NMDA receptors to increase plasma membrane insertion of D1 receptors and provides a novel mechanism by which the activation of NMDA receptors upregulates D1 receptor function. Understanding the molecular mechanisms by which D1 and NMDA receptors functionally interact may provide insight toward elucidating the molecular neurobiological mechanisms involved in many neuropsychiatric illnesses, such as schizophronia. [ABSTRACT FROM AUTHOR]

MAPK/ERK kinase kinase 1 (MEKK1) is a mitogenactivated protein kinase kinase kinase (MAP3K) of the stress-induced JNK pathway. Once activated, MEKK1 phosphorylates the MAP2K MKK4, which in turn phosphorylates JNK. MEKK1 also has the capacity to activate IKK, the central protein kinase of the NF-κB pathway. The molecular determinants responsible for the ability of MEKK1 to recognize specific substrates are poorly understood. We report here that select point mutations in subdomain VIII of the protein kinase domain of MEKK1 (MEKK1Δ) differentially affect its ability to activate MKK4 and IKK, and consequently AP1 and NF-κB reporter genes. Moreover, binding of MKK4 to MEKK1Δ protects the latter from cleavage at an engineered protease target site in subdomain VIII. Collectively these results provide evidence that subdomain VIII of MEKK1 is involved not only in binding to, but also in discrimination of, protein substrates. [ABSTRACT FROM AUTHOR]

The β-amyloid precursor protein (APP) is an integral membrane protein that is the subject of proteolytic processing. Sequential cleavage of APP by β-secretase and subsequently γ-secretase generates the β-amyloid peptide as well as a cytoplasmic intracellular domain (AICD). AICD binds to the transcriptional coactivator Fe65, and this complex has been shown to display transcriptional activity. The regulation of this complex is poorly understood. We show here that activation of the NF-κB pathway, either by overexpression of NF-κB-inducing kinase (NIK) or by treatment with the proinflammatory cytokine IL-1β, downregulates the transcriptional activity of the AICD-Fe65 complex. This therefore provides a mechanism by which the activity of AICD might be modulated by extracellular stimuli. These results also identify an intracellular signal transduction pathway influenced by the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

In this article we describe production compilation, a mechanism for modeling skill acquisition. Production compilation has been developed within the ACT-Rational (ACT-R; J. R. Anderson, D. Bothell, M. D. Byrne, & C. Lebiere, 2002) cognitive architecture and consists of combining and specializing task-independent procedures into task-specific procedures. The benefit of production compilation for researchers in human factors is that it enables them to test the strengths and weaknesses of their task analyses and user models by allowing them to model the learning trajectory from the main task level and the unit task level down to the key-stroke level. We provide an example of this process by developing and describing a model learning a simulated air traffic controller task. Actual or potential applications of this research include the evaluation of user interfaces, the design of systems that support learning, and the building of user models. [ABSTRACT FROM AUTHOR]

Focuses on the dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Contents of Dopamine D1-like receptors; Calcium permeability of NMDA receptor; Dependence of NMDA-mediated excitoxicity on local cellular environment.

Intention superiority effect [J. Exp. Psychol. Learn. Mem. Cogn. 19 (1993) 1211; J. Exp. Psychol. Learn. Mem. Cogn. 24 (1998) 350] is the finding that the times to retrieve memory items related to uncompleted or partially completed intentions are faster than for those with no associated intentions. However, this relationship reverses when the intended tasks are completed [J. Exp. Psychol. Learn. Mem. Cogn. 24 (1998) 350; Mem. Cogn. 27 (1999) 320]. That is, the times to retrieve memory items related to completed intentions are slower than for those with no associated intentions. In this paper, we present a computational account of the intention superiority effect using the ACT-R cognitive architecture [Atomic components of thought. Mahwah, NJ: Lawrence Erlbaum Associates, 1998]. Our modeling approach is based on the idea that uncompleted or partially completed intentions are available as context in the current goal, and they prime related memory items while inhibiting unrelated memory items. However, once the intended tasks are completed, they are removed from the current goal, which produces an inhibitory effect on memory items associated with them. We describe an ACT-R model that is able to reproduce all of the effects reported in Marsh et al. [J. Exp. Psychol. Learn. Mem. Cogn. 24 (1998) 350]. [Copyright &y& Elsevier]

Examines the assumption about the scalability of skill acquisition in which complex tasks are made up of many smaller parts that are learned according to basic learning principles. Practice function; Discussions on the reducibility hypothesis; Information on the Kanfer-Ackerman Air-Traffic Controller task; Task analysis.

Presents information on a study which examined whether the sympathetic nervous system restrains limb blood flow and oxygen consumption in human subjects during exercise. Impact of bretylium tosylate bier block on muscle metabolism; Methodology; Results and discussion; Conclusions.

Examines the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis and attenuate reflex responses. Effects of sympathetic tone on forearm blood flow; Effects of sympathetic withdrawal on oxygen consumption.