bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and in vitro activities of new non‐peptidic APA Inhibitors
Authors: Inguimbert N. , Coric P. , Dhotel H. , Bonnard E. , Llorens‐Cortes C. , De Mota N. , Fournié‐Zaluski M.‐C. , Roques B.‐P.
Published: February 2005

Abstract:  Aminopeptidase A (APA) is involved in the maturation of angiotensin III, a peptide which seems to be implicated in blood pressure regulation at the brain level. Therefore APA inhibitors are potential new antihypertensive agents with possible novel applications. With the aim of enhancing the bioavailability and potency of EC 33, the APA inhibitor (Ki = 300 nm) initially used in the earlier studies, we have synthesized new non‐peptidic inhibitors able to interact with the S1 and S subsites of the targeted enzyme. Compound 10a, (3S,4S)‐3‐amino‐4‐mercapto‐6‐phenyl‐hexane‐1‐sulfonic acid was obtained using an asymmetric synthesis. Inhibitor 10a exhibits a Ki value of 30 nm.
Solid‐phase synthesis and characterization ofN‐methyl‐rich peptides
Authors: Teixidó M. , Albericio F. , Giralt E.
Published: February 2005

Abstract: A library of peptides required for a project investigating the factors relevant for blood–brain barrier transport was synthesized on solid phase. As a result of the highN‐methylamino acid content in the peptides, their syntheses were challenging and form the basis of the work presented here. The coupling of protectedN‐methylamino acids withN‐methylamino acids generally occurs in low yield. (7‐azabenzotriazol‐1‐yloxy)‐tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) or PyBOP/1‐hydroxy‐7‐azabenzotriazole (HOAt), are the most promising coupling reagents for these couplings. When a peptide contains an acetylatedN‐methylamino acid at the N‐terminal position, loss of Ac‐N‐methylamino acid occurs during trifluoroacetic acid (TFA) cleavage of the peptide from the resin. Other side reactions resulting from acidic cleavage are described here, including fragmentation between consecutiveN‐methylamino acids and formation of diketopiperazines (DKPs). The time of cleavage is shown to greatly influence synthetic results. Finally, high‐performance liquid chromatography (HPLC) profiles ofN‐methyl‐rich peptides show multiple peaks because of slow conversion between conformers.
Stability and specificity of heterodimer formation for the coiled‐coil neck regions of the motor proteins Kif3A and Kif3B: the role of unstructured oppositely charged regions
Authors: Chana M.S. , Tripet B.P. , Mant C.T. , Hodges R.
Published: February 2005

Abstract:  We investigated the folding, stability, and specificity of dimerization of the neck regions of the kinesin‐like proteins Kif3A (residues 356–416) and Kif3B (residues 351–411). We showed that the complementary charged regions found in the hinge regions (which directly follow the neck regions) of these proteins do not adopt any secondary structure in solution. We then explored the ability of the complementary charged regions to specify heterodimer formation for the neck region coiled‐coils found in Kif3A and Kif3B. Redox experiments demonstrated that oppositely charged regions specified the formation of a heterodimeric coiled‐coil. Denaturation studies with urea demonstrated that the negatively charged region of Kif3A dramatically destabilized its neck coiled‐coil (urea1/2 value of 3.9 m compared with 6.7 m for the coiled‐coil alone). By comparison, the placement of a positively charged region C‐terminal to the neck coiled‐coil of Kif3B had little effect on stability (urea1/2 value of 8.2 m compared with 8.8 m for the coiled‐coil alone). The pairing of complementary charged regions leads to specific heterodimer formation where the stability of the heterodimeric neck coiled‐coil with charged regions had similar stability (urea1/2 value of 7.8 m) to the most stable homodimer (Kif3B) with charged regions (urea1/2 value of 8.0 m) and dramatically more stable than the Kif3A homodimer with charged regions (urea1/2, value of 3.9 m). The heterodimeric coiled‐coil with charged extensions has essentially the same stability as the heterodimeric coiled‐coil on its own (urea1/2 values of 7.8 and 8.1 m, respectively) suggesting that specificity of heterodimerization is driven by non‐specific attraction of the oppositely unstructured charged regions without affecting stability of the heterodimeric coiled‐coil.
Granite gneiss basement on Flinders Island, South Australia
Authors: COOPER S. A. , BELOUSOVA E. A.
Published: February 2005

A U–Pb zircon age of 1762 ± 11 Ma is reported for granite gneiss located on Flinders Island, South Australia. This age is identical, within analytical uncertainty, to a previously reported age for schists of the Price Metasediments located 100 km to the southeast on the southwestern coast of the Eyre Peninsula. The outcrop represents the only known country rock to the Early Mesoproterozoic Calca Granite (Hiltaba Suite) of Flinders Island, the largest island of the Investigator Group of islands, in the southwestern Gawler Craton. The stratigraphic name Investigator Granite Gneiss is proposed for this rock unit. The discovery of the Investigator Granite Gneiss now considerably increases the extent of known Late Palaeoproterozoic rocks on the eastern side of the peninsula. The outcrop was previously included with the considerably younger St Peter Suite granite–monzogranite, and grouped together with other islands in the Investigator Group. This new dating suggests that the geology on the other islands may require revision. For the first time, detailed major and trace‐element geochemistry is supplied for the granite gneiss on Flinders Island.
Psychiatric disorders and large interdialytic weight gain in patients on chronic haemodialysis
Authors: TASKAPAN HULYA , ATES FEHMI , KAYA BURHANETTIN , EMUL MURAT , KAYA MINE , TASKAPAN ÇAGATAY , SAHIN IBRAHIM
Published: February 2005

Aims:  Psychiatric disorders have been considered in terms of non‐compliant behaviour and low life quality in haemodialysis patients. The aim of this study is to investigate the potential association of psychiatric disorders with compliance of fluid restriction and nutritional status and to measure the effects of psychiatric disorders on the life quality in chronic renal failure patients on haemodialysis.

Methods:  The study was conducted between April 2002 and December 2002 at a University hospital haemodialysis unit. The study population included 40 chronic renal failure patients (15 females/25 males). The Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS) and Primary Care Evaluation of Mental Disorders (PRIME‐MD), The Mini Mental State Examination (MMSE) and Short Form Health Survey 36 (SF‐36) were used for patient assessment by a trained psychiatrist. The subjects’ medical charts were reviewed by a physician who was unaware of the the results of the psychiatric assesments. Interdialytic weight gain (IDWG %) and nutritional status were used as an index of diet compliance. Nutrition was assessed by using subjective global assessment (SGA), serum albumin, predialysis phosphorus and potassium levels.

Results:  All patients’ MMSE were normal. A diagnosis of a depressive or anxiety or somatoform disorder by the PRIME MD was made in 65% of the patients. Fourteen (35%) of the patients had a depressive disorder, 13 (32.5%) of the patients had a somatoform disorder, and 12 (30%) had an anxiety disorder. We found no relationship between any psychiatric disorder and age, sex, duration of dialysis therapy, education, marital status, employment, socioeconomic status, serum albumin, phosphorus, potassium or SGA (P > 0.05). In patients with depression or a somatoform disorder, the interdialytic weight (%) was significantly higher than those of the patients without these disorders (P < 0.05). All indices of quality of life decreased in patients diagnosed with a psychiatric disorder.

Conclusion:  Depressive symptoms are important determinants of patients’ large interdialytic weight gain and psychiatric disorders that effect a patients’ overall quality of life. Evaluation of psychiatric status should be part of the care provided to haemodialysis patients.
Rabeprazole‐induced acute interstitial nephritis
Authors: GEEVASINGA NIMESHAN , COLEMAN PATRICK L , ROGER SIMON D
Published: February 2005

SUMMARY:  Acute interstitial nephritis is an uncommon but important cause of acute renal failure. Proton pump inhibitors are now thought to be the most common class of drugs implicated in drug‐induced acute interstitial nephritis. This is the first reported case of rabeprazole‐induced acute interstitial nephritis.
Migraine, Botulinum Toxin type‐A, and the Disappearing Sebaceous Cyst
Authors: Turner Ira M. , Agrillo Tiffany
Published: February 2005

Botulinum toxin type‐A has been used with increasing frequency as a migraine prophylactic agent. A recent case of ours had an unexpected beneficial effect on a local comorbid condition.
Emergency Department and Community Health Center Visits and Costs in an Uninsured Population
Authors: Smith‐Campbell Betty
Published: February 2005

Purpose:

To assess how a Community Health Center (CHC) influenced access to care for uninsured people and to describe the economic effect on the local hospital.

Design:

A framework on access to health care was used in this community‐level, descriptive study.

Methods:

Data were collected on emergency department (ED) use before state funding of the CHC, 1988 and through 2001. Information included insurance status, charges, diagnosis, and complexity of services received. This study is a population study, and descriptive statistics were used to analyze the data.

Findings:

Within 3 years after state funding of a CHC began, uninsured visits to the local hospital ED decreased by almost 40%. After 10 years, uninsured ED visits remained 25% lower than before state funding began, whereas insured visits had almost doubled (98%). The decrease in number of uninsured visits saved the hospital and uninsured patients almost $14 million.

Conclusions:

After establishment of the CHC, ED visits by uninsured patients declined. Although a causal link cannot be made between the CHC and ED, the descriptive data provide information about a linkage between the decline of uninsured ED visits and the CHC.
Visualizing the extra symmetry of the Kepler problem
Authors: Morehead Jim
Published: February 2005

The extra symmetry of the Kepler problem corresponding to the conservation of the Runge–Lenz vector can be visualized by studying how entire Kepler ellipses evolve under symmetry transformations. After discussing the general case, we show that the evolution generated by a component of the Runge–Lenz vector in the plane of the orbit yields the same family of ellipses in the plane as the projection onto the plane of a rotation of a certain circle in three dimensions.
Active learning in lectures introducing magnetic induction
Authors: Cohen Scott M.
Published: February 2005

I describe a method of introducing magnetic induction to an introductory physics class, which encourages active participation by students in the process of learning.
Glycolipids as Receptors for
Bacillus thuringiensis
Crystal Toxin
Authors: Griffitts Joel S. , Haslam Stuart M. , Yang Tinglu , Garczynski Stephan F. , Mulloy Barbara , Morris Howard , Cremer Paul S. , Dell Anne , Adang Michael J. , Aroian Raffi V.
Published: February 2005

The development of pest resistance threatens the effectiveness of
Bacillus thuringiensis
(Bt) toxins used in transgenic and organic farming. Here, we demonstrate that (i) the major mechanism for Bt toxin resistance in
Caenorhabditis elegans
entails a loss of glycolipid carbohydrates; (ii) Bt toxin directly and specifically binds glycolipids; and (iii) this binding is carbohydrate-dependent and relevant for toxin action in vivo. These carbohydrates contain the arthroseries core conserved in insects and nematodes but lacking in vertebrates. We present evidence that insect glycolipids are also receptors for Bt toxin.
Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae
Authors: Csutora Péter , Strassz András , Boldizsár Ferenc , Németh Péter , Sipos Katalin , Aiello David P. , Bedwell David M. , Miseta Attila
Published: February 2005

Phosphoglucomutase is a key enzyme of glucose metabolism that interconverts glucose-1-phosphate and glucose-6-phosphate. Loss of the major isoform of phosphoglucomutase in Saccharomyces cerevisiae results in a significant increase in the cellular glucose-1-phosphate-to-glucose-6-phosphate ratio when cells are grown in medium containing galactose as carbon source. This imbalance in glucose metabolites was recently shown to also cause a six- to ninefold increase in cellular Ca2+ accumulation. We found that Li+ inhibition of phosphoglucomutase causes a similar elevation of total cellular Ca2+ and an increase in 45Ca2+ uptake in a wild-type yeast strain grown in medium containing galactose, but not glucose, as sole carbon source. Li+ treatment also reduced the transient elevation of cytosolic Ca2+ response that is triggered by exposure to external CaCl2 or by the addition of galactose to yeast cells starved of a carbon source. Finally, we found that the Ca2+ overaccumulation induced by Li+ exposure was significantly reduced in a strain lacking the vacuolar Ca2+-ATPase Pmc1p. These observations suggest that Li+ inhibition of phosphoglucomutase results in an increased glucose-1-phosphate-to-glucose-6-phosphate ratio, which results in an accelerated rate of vacuolar Ca2+ uptake via the Ca2+-ATPase Pmc1p.
Integrator Function in the Oculomotor System Is Dependent on Sensory Context
Authors: Chan W.W.P. , Galiana H. L.
Published: February 2005

The oculomotor integrator is usually defined by the characteristics of decay in gaze after saccades to flashed targets or after spontaneous gaze shifts in the dark. This property is then presumed fixed and accessed by other ocular reflexes, such as the vestibuloocular reflex (VOR) or pursuit, to shape motoneural signals. An alternate view of this integrator proposes that it relies on a distributed network, which should change its properties with sensory-motor context. Here we demonstrate in 10 normal subjects that the function of integration can vary in an individual with the imposed test. The value of the time constant for the decay of gaze holding in the dark can be significantly different from the effective integration time constant estimated from VOR responses. Hence analytical tools for the study of dynamics in ocular reflexes must allow for nonideal and labile integrator function. The mechanisms underlying such labile integration remain to be explored and may be different in various ocular reflexes (e.g., visual versus vestibular).
Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults
Authors: Elman Elyssa , Bornais Chantal , Blostein Mark , Wells Phillip , Kahn Susan
Published: February 2005

The post-thrombotic syndrome (PTS) after upper extremity deep venous thrombosis (UEDVT) has not been well characterized. The objective of our study was to describe and quantify residual symptoms, functional disability and quality of life associated with PTS after UEDVT in adults. Twenty-four patients with objectively diagnosed UEDVT (bilateral in 1 patient) at least 6 months previously were recruited from two Canadian thrombosis clinics. Data were collected on demographic characteristics, DVT risk factors and affected venous segments. The Villalta PTS scale, modified for the upper extremity, was used to diagnose PTS. Patients completed questionnaires on degree of functional disability (DASH questionnaire), and generic (SF-36) and disease-specific (VEINES-QOL) quality of life. Results were compared in patients with and without PTS. Patients were assessed a median of 13 months after the diagnosis of UEDVT. Daily ipsilateral arm or hand swelling was reported by 52% of patients and daily ipsilateral arm pain by 20% of study patients, compared with 0% and 0%, respectively, in the contralateral arm. PTS was present in 11/25 (44%) limbs (11/24 patients). One patient had severe PTS. Patients with PTS, compared with those without PTS, had significantly more functional disability (mean DASH score 20.9 vs. 3.7, p= 0.009) and poorer quality of life (mean VEINES-QOL score 45.6 vs. 53.6; p=0.001; mean SF-36 Physical Component Score (PCS) 40.8 vs.50.2; p= 0.12). PTS scores were higher and quality of life was poorer when PTS involved the dominant arm. In conclusion, PTS occurs frequently after UEDVT and is associated with significant functional disability and reduced quality of life. Patients with dominant arm PTS appear to fare worse than those with non-dominant arm PTS. Larger, prospective studies to identify prognostic factors that lead to PTS after UEDVT are warranted.
Antithrombotic potential of new direct thrombin inhibitors built on the azaphenylalanine scaffold in two rat venous thrombosis models
Authors: Stegnar Mojca , Drevenšek Gorazd , Budihna Metka , Božič Mojca , Zega Anamarija , Štalc Anton , Černe Manica , Urleb Uroš , Peternel Luka
Published: February 2005

The antithrombotic potential of new direct thrombin inhibitors built on the azaphenylalanine scaffold (LK-732, LK-639 and LK-731) and their amidoxime prodrugs (LK-658, LK-633 and LK-730) was studied in comparison to argatroban and nadroparin in two rat models of venous thrombosis, induced either by complete stasis combined with hypercoagulability (model 1) or by partial stasis combined with vessel injury (model 2). In initial experiments LK-732 was established as the most promising antithrombotic of the LK inhibitors and as such was further tested. In model 1, intravenous bolus administration of LK-732 produced a dose-dependent inhibition of thrombus formation with an ID50 value of 1.3 mg/kg. This ID50 value was approximately four times higher than the ID50 value of argatroban (0.3 mg/kg; p=0.011). However, in model 2, LK-732 and argatroban decreased thrombus weight by 50% at similar ID50 values (3.8 mg/kg vs 3.0 mg/kg, respectively; p=0.726). The ex vivo anticoagulant effect of LK-732 was substantially weaker compared to argatroban at doses that produced comparable antithrombotic effects. After subcutaneous administration, in vivo thrombus weight reduction of LK inhibitors (10 mg/kg) ranged between 22 to 48%. However, their oral antithrombotic effect at a dose of 30 mg/kg was rather low. LK amidoxime prodrugs failed to produce a substantial antithrombotic effect after subcutaneous (10 mg/ kg) as well as after oral administration (30 mg/kg). In conclusion, thrombin inhibitors built on the azaphenylalanine scaffold represent a new group of intravenously effective antithrombotics. However, optimisation of the oral antithrombotic effect of amid-oxime prodrug LK-658 of the lead inhibitor LK-732 is required for justifying further development of these inhibitors.
Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B
Authors: Béguin Suzette , Lienhart Anne , Al Dieri Raed , Trzeciak Christine , Bordet Jean , Hemker Coenraad , Negrier Claude , Dargaud Yesim
Published: February 2005

In haemophilia patients, a relationship is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX (FVIII/FIX) activity. However, it is known from clinical experience, that some haemophilia patients, despite similar FVIII/FIX plasma levels, could exhibit different bleeding phenotype. After determining preanalytical test conditions, we evaluated the thrombin generation capacity from haemophilia plasma samples in various conditions and the potential usefulness of thrombin generation test (TGT) in haemophilia patients. In a series of 46 haemophilia patients (34 haemophilia A and 12 haemophilia B patients), we found a significant correlation between plasmatic FVIII/FIX levels and endogenous thrombin potential (ETP), peak and time to peak obtained by thrombin generation measurement. In addition, a correlation was found between severe clinical bleeding phenotype and ETP. Our results suggest that TGT could be a promising tool to evaluate haemostasis capacity in patients with haemophilia. Our ex vivo results, obtained 24 hours after FVIII concentrate administration, showed that in patients presenting similar plasmatic FVIIII levels, thrombin generation capacity may be significantly different. These results suggest that in patients with haemophilia, TGT could be useful for individually tailoring prophylactic regimens as well as for adapting clotting factors infusions in surgical situations, in addition to FVIII/FIX plasma clotting activities.
Single cell studies of the cell cycle and some models
Authors: Mitchison JM
Published: February 2005

Analysis of growth and division often involves measurements made on cell populations, which tend to average data. The value of single cell analysis needs to be appreciated, and models based on findings from single cells should be taken into greater consideration in our understanding of the way in which cell size and division are co-ordinated. Examples are given of some single cell analyses in mammalian cells, yeast and other microorganisms. There is also a short discussion on how far the results are in accord with simple models.
Epitope mapping of Ly-49G and G-like receptors: CK-1 antibody defines a polymorphic site of functional interaction with class I ligand
Authors: Osman Mohammed S , Silver Elizabeth T , Varghese Jay C , Chang Chew Shun , Gong Dong-Er , Audette Gerald F , Hazes Bart , Kane Kevin P
Published: February 2005

Ly-49 receptors regulate mouse natural killer cell functions. Members of the polymorphic Ly-49 multigene family recognize specific alleles of major histocompatibility complex class I (MHC I) or MHC I-like proteins. Previous studies have provided insight into the nature of Ly-49A and -C interaction with their high-affinity MHC I ligands, H-2Dd and Kb, respectively. Unlike Ly-49C, recognition of MHC I by Ly-49A is regulated in part by residues within the β4–β5 loop of its ectodomain. Ly-49A and -G are within the same Ly-49 subfamily, and both receptors recognize Dd. However, there have been no studies that define specific sites on Ly-49G that mediate class I MHC recognition. The Ly-49G receptors of different inbred mouse strains can differ as a result of amino acid polymorphisms within their ectodomains. In this report, we have generated a novel antibody, CK-1, which recognizes Ly-49GB6 and a Ly-49GB6-like receptor, Ly-49Mnonobese diabetic, but not Ly-49GBALB/c. By exploiting the differences within ectodomains of C57BL/6 and BALB/c Ly-49G allele products, we identified epitopes recognized by the Ly-49G-specific antibodies CK-1 and Cwy-3, whose epitopes mapped within the β4–β5 loop and the β1 strand, respectively, and were nonoverlapping. Although both antibodies specifically recognized the Ly-49GB6 ectodomain, Cwy-3 was unable to block its interaction with MHC I, and CK-1 significantly inhibited it. The importance of residues within the β4–β5 loop in Ly-49G recognition demonstrates that its interaction with MHC I is similar to that of Ly-49A but not Ly-49C.
twin, aCCR4homolog, regulates cyclin poly(A) tail length to permitDrosophilaoogenesis
Authors: Morris Jason Z. , Hong Amy , Lilly Mary A. , Lehmann Ruth
Published: February 2005

Cyclins regulate progression through the cell cycle. Control of cyclin levels is essential in Drosophila oogenesis for the four synchronous divisions that generate the 16 cell germ line cyst and for ensuring that one cell in each cyst, the oocyte, is arrested in meiosis, while the remaining fifteen cells become polyploid nurse cells. Changes in cyclin levels could be achieved by regulating transcription, translation or protein stability. The proteasome limits cyclin protein levels in the Drosophila ovary, but the mechanisms regulating RNA turnover or translation remain largely unclear. Here, we report the identification of twin, a homolog of the yeast CCR4 deadenylase. We show that twin is important for the number and synchrony of cyst divisions and oocyte fate. Consistent with the deadenylase activity of CCR4 in yeast, our data suggest that Twin controls germ line cyst development by regulating poly(A) tail lengths of several targets including Cyclin A (CycA) RNA. twin mutants exhibit very low expression of Bag-of-marbles (Bam), a regulator of cyst division, indicating that Twin/Ccr4 activity is necessary for wild-type Bam expression. Lowering the levels of CycA or increasing the levels of Bam suppresses the defects we observe in twin ovaries, implicating CycA and Bam as downstream effectors of Twin. We propose that Twin/Ccr4 functions during early oogenesis to coordinate cyst division, oocyte fate specification and egg chamber maturation.
Bad Beta, Good Beta
Authors: Campbell John Y , Vuolteenaho Tuomo
Published: February 2005

This paper explains the size and value “anomalies” in stock returns using an economically motivated two-beta model. We break the beta of a stock with the market portfolio into two components, one reflecting news about the market's future cash flows and one reflecting news about the market's discount rates. Intertemporal asset pricing theory suggests that the former should have a higher price of risk; thus beta, like cholesterol, comes in “bad” and “good” varieties. Empirically, we find that value stocks and small stocks have considerably higher cash-flow betas than growth stocks and large stocks, and this can explain their higher average returns. The poor performance of the capital asset pricing model (CAPM) since 1963 is explained by the fact that growth stocks and high-past-beta stocks have predominantly good betas with low risk prices.
When Does Learning in Games Generate Convergence to Nash Equilibria? The Role of Supermodularity in an Experimental Setting
Authors: Chen Yan , Gazzale Robert
Published: February 2005

This study clarifies the conditions under which learning in games produces convergence to Nash equilibria in practice. We experimentally investigate the role of supermodularity, which is closely related to the more familiar concept of strategic complementarities, in achieving convergence through learning. Using a game from the literature on solutions to externalities, we find that supermodular and “near-supermodular” games converge significantly better than those far below the threshold of supermodularity. From a little below the threshold to the threshold, the improvement is statistically insignificant. Increasing the parameter far beyond the threshold does not significantly improve convergence.
Strategic information management in health care - myth or reality?
Authors: Curry Adrienne , Knowles Gail
Published: February 2005

This paper uses data gathered from a case NHS Trust in Scotland to demonstrate progress in terms of operational and strategic information management and to highlight some of the problems currently experienced in the health-care environment in striving to comply with governmental policies relating to information sharing.

Progress has certainly been made and there is recognition of the potential to be achieved from more efficient and effective information management in health care. Problems exist, however, and there is still a considerable gap to be filled between the policy objectives and what is actually achievable in reality on a day-to-day basis. Data have been gathered from a hospital and a health centre to illustrate information flow between two of the Trust entities and a benchmark has been provided, showing that best practice can be achieved and how it can be achieved.
Ribozyme motif structure mapped using random recombination and selection
Authors: WANG QING S. , UNRAU PETER J.
Published: February 2005

Isolating the core functional elements of an RNA is normally performed during the characterization of a new RNA in order to simplify further biochemical analysis. The removal of extraneous sequence is challenging and can lead to biases that result from the incomplete sampling of deletion variants. An impartial solution to this problem is to construct a library containing a large number of deletion constructs and to select functional RNA isolates that are at least as efficient as their full-length progenitors. Here, we use nonhomologous recombination and selection to isolate the catalytic core of a pyrimidine nucleotide synthase ribozyme. A variable-length pool of ~108 recombinant molecules that included deletions, inversions, and translocations of a 271-nucleotide-long ribozyme isolate was constructed by digesting and randomly religating its DNA genome. In vitro selection for functional ribozymes was then performed in a size-dependent and a size-independent manner. The final pools had nearly equivalent catalytic rates even though their length distributions were completely different, indicating that a diverse range of deletion constructs were functionally active. Four short sequence islands, requiring as little as 81 nt of sequence, were found within all of the truncated ribozymes and could be folded into a secondary structure consisting of three helix–loops. Our findings suggest that nonhomologous recombination is a highly efficient way to isolate a ribozyme’s core motif and could prove to be a useful method for evolving new ribozyme functions from pre-existing sequences in a manner that may have played an important role early in evolution.
Load-Carrying Capacity Evaluation of Damaged Reinforced Concrete Structures by Dynamic Testing and Finite-Element Model Updating
Authors: Xia P-Q , Brownjohn JMW
Published: February 2005

There are many nondestructive test methods for the detailed condition evaluation of existing bridges. However, on detection of damage or deterioration, it may be possible only to make a subjective or qualitative judgement on safety. Resulting from research aimed at providing quantitative measures of bridge condition and fitness for purpose, this paper presents a practical method for evaluating the load-carrying capacity of damaged reinforced concrete (RC) beam structures based on dynamic testing and finite-element (FE) model updating. The distribution of the second moment of the cross section along an RC beam structure that had been loaded until failure was identified using FE model updating. Based on the identified second moment of cross section, the effective steel ratio and the ultimate moment of the damaged structure were estimated, leading to an estimate of load-carrying capacity. The paper describes a laboratory study using techniques that can be applied to prototype structures.
Quantifying the Confidence Levels of Deformation Measurements in Asphalt Concrete
Authors: Levenberg E , Uzan J
Published: February 2005

An experimental approach for measuring surface strains in asphalt concrete (AC) samples is presented in this paper. It is equivalent to the local attachment of a large number of linear variable displacement transducers (LVDTs) with gage lengths ranging from 5 to 80 mm. The strain distribution properties developed under conditions of uniaxial tension are studied and analyzed for one AC mixture. It is shown that gage lengths of the order of the nominal maximum aggregate size measure a wide range of strain values: from zero strain up to 5 times the average strain. Moreover, as the gage length is increased, the scatter is reduced and the individual measurements yield values that are closer to their average. Subsequently, the confidence levels associated with using a limited number of gages with a given gage length are quantified. The results are then used to assess test protocol recommendations related to AC sample instrumentation. The size scale of the material's Representative Volume Element (RVE) is also addressed.
Heat, Air, and Moisture Transport Properties of Several North American Bricks and Mortar Mixes
Authors: Kumaran MK , Lackey JC , Normandin N , Tariku F , van Reenen D
Published: February 2005

Hygrothermal models are emerging as practical building design tools. These models require a set of reliable inputs to provide results that are meaningful to the designers. One of these inputs is the set of heat, air, and moisture transport properties of materials. For any given class of building materials, the properties may vary within a broad range. This paper reports the porosity, density, matrix density, thermal conductivity, equilibrium moisture content, water vapor permeability, water absorption coefficient, liquid diffusivity, and air permeability of six types of bricks and four mortar mixes that are used commonly in North America. The experimental and analytical procedures follow either international standards or well-established methodologies.
Medicare Eligibility and Reported Support for Proposals to Expand Medicare
Authors: Kavanagh Nolan M. , Campbell Andrea L. , McIntyre Adrianna
Published: February 2024

This study estimates the association between Medicare eligibility and support for recent proposals to expand program participation and benefits.
Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease
Authors: Jang Heejoon , Kim Yeonjin , Lee Dong Hyeon , Joo Sae Kyung , Koo Bo Kyung , Lim Soo , Lee Woojoo , Kim Won
Published: February 2024

Importance

Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking.

Objective

To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D).

Design, Setting, and Participants

This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD.

Exposures

Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days.

Main Outcomes and Measures

The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks.

Results

In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas.

Conclusions and Relevance

The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.
Alfaxalone does not have long‐term effects on goldfish pyramidal neuron action potential properties or GABAA receptor currents
Authors: Di Stefano Domenic , Suganthan Haushe , Buck Leslie
Published: February 2024

Anesthetics have varying physiological effects, but most notably alter ion channel kinetics. Alfaxalone is a rapid induction and washout neuroactive anesthetic, which potentiates γ‐aminobutyric acid (GABA)‐activated GABAA receptor (GABAA‐R) currents. This study aims to identify any long‐term effects of alfaxalone sedation on pyramidal neuron action potential and GABAA‐R properties, to determine if its impact on neuronal function can be reversed in a sufficiently short timeframe to allow for same‐day electrophysiological studies in goldfish brain. The goldfish (Carassius auratus) is an anoxia‐tolerant vertebrate and is a useful model to study anoxia tolerance mechanisms. The results show that alfaxalone sedation did not significantly impact action potential properties. Additionally, the acute application of alfaxalone onto naive brain slices caused the potentiation of whole‐cell GABAA‐R current decay time and area under the curve. Following whole‐animal sedation with alfaxalone, a 3‐h wash of brain slices in alfaxalone‐free saline, with saline exchanged every 30 min, was required to remove any potentiating impact of alfaxalone on GABAA‐R whole‐cell currents. These results demonstrate that alfaxalone is an effective anesthetic for same‐day electrophysiological experiments with goldfish brain slices.
A CNN‐based denoising method trained with images acquired with electron density phantoms for thin‐sliced coronary artery calcium scans
Authors: Yang Ching‐Ching , Hou Kuei‐Yuan
Published: February 2024

Purpose

This work proposed a convolutional neural network (CNN)‐based method trained with images acquired with electron density phantoms to reduce quantum noise for coronary artery calcium (CAC) scans reconstructed with slice thickness less than 3 mm.

Methods

A DenseNet model was used to estimate quantum noise for CAC scans reconstructed with slice thickness of 0.5, 1.0 and 1.5 mm. Training data was acquired using electron density phantoms in three different sizes. The label images of the CNN model were real noise maps, while the input images of the CNN model were pseudo noise maps. Image denoising was conducted by subtracting the CNN output images from thin‐sliced CAC scans. The efficacy of the proposed method was verified through both phantom study and patient study.

Results

By means of phantom study, the proposed method was proven effective in reducing quantum noise in CAC scans reconstructed with 1.5‐mm slice thickness without causing significant texture change or variation in HU values. With regard to patient study, calcifications were more clear on the denoised CAC scans reconstructed with slice thickness of 0.5, 1.0 and 1.5 mm than on 3‐mm slice images, while over‐smooth changes were not observed in the denoised CAC scans reconstructed with 1.5‐mm slice thickness.

Conclusion

Our results demonstrated that the electron density phantoms can be used to generate training data for the proposed CNN‐based denoising method to reduce quantum noise for CAC scans reconstructed with 1.5‐mm slice thickness. Because anthropomorphic phantom is not a necessity, our method could make image denoising more practical in routine clinical practice.
A Glance into the Destiny of Transcriptomic Activity, Embodied by the HOX Genes, in Neonatal and Aging Dermal Cells
Authors: Ko Doyeong , Mun Seyoung , Kim Minji , Nho Youn‐Hwa , Lee Dong‐Geol , Kang Seunghyun , Han Kyudong , Kim Misun
Published: February 2024

Skin is an organ having a crucial role in the protection of muscle, bone, and internal organs and undergoing continuous self‐renewal and aged. The growing interest in the prevention of skin aging and rejuvenation has sparked a surge of industrial and research studies focusing on the biological and transcriptional changes that occur during skin development and aging. In this study, the aim is to identify transcriptional differences between two main types of human skin cells: the human dermal fibroblasts (HDFs) and the human epidermis keratinocytes (HEKs) isolated from 30 neonatal and 30 adults (old) skin. Through differentially expressed gene (DEG) profiling using DEseq2, 604 up‐, and 769 down‐regulated genes are identified in the old group. A functional analysis using Metascape Gene Ontology and Reactome pathways revealed systematic transcriptomic shifts in key skin formation and maintenance markers, alongside a distinct difference in HOX gene families crucial for embryonic development and diverse biological processes. Among the 39 human HOX gene family, ten posterior HOX genes (HOXA10, 11, 13, HOXB13, HOXC11, and HOXD9‐13) are significantly downregulated, and anterior 25 genes (HOXA2‐7, HOXB1‐9, HOXC4‐6 and 8–9, and HOXD1,3,4 and 8) are upregulated, especially in the old HDFs. The study successfully demonstrates the correlation between HOX genes and the skin aging process, providing strong evidence that HOX genes are proposed as a new marker for skin aging assessment.
Effect of Homogenization on Microstructure and Mechanical Properties of Al–Mg–Mn–Er Alloy
Authors: Shen Song , Yao Shun , Yang Xinhe , Xu Chen , Ma Zhikun , Zhang Hui , Wu Ruizhi , Hou Legan , Cong Fuguan , Ma Xaochun
Published: February 2024

As a traditional nonage‐hardenable aluminum alloy, 5XXX aluminum alloy has a limited dispersion‐strengthening effect since it is challenging to obtain high‐density and fine‐sized dispersoids by a conventional homogenization treatment process. In this work, three different homogenization treatments, single‐stage homogenization, slope heating homogenization, and double‐stage homogenization are used in a new type Al–Mg–Mn–Er alloy to exploit the dispersion strengthening. The precipitation behavior of submicron‐sized Mn‐containing dispersoids and nanosized Al3Er precipitates is investigated. In single‐stage homogenization, the nucleation of the Mn‐containing dispersoid is completed within a span of 2 h at 460 °C, accompanied by noticeable coarsening and the Al3Er precipitate tended to nucleate at dislocation sites and form a chain‐like structure. In slope heating and double‐stage homogenization, during the initial phase of heat treatment, lower temperatures facilitate the nucleation of dispersoids. This leads to the uniform precipitation of Mn‐containing dispersoids within the grain interior and improves the chain distribution of the Al3Er precipitates. The double‐stage homogenization generates the finest dispersoids. The alloy reaches maximum strength in the double‐stage homogenization, and the yield strength is 177 MPa, representing a 22% increase compared to the single‐stage homogenization.
Sponge Inspired Flexible, Antibacterial Aerogel Electrode with Long‐Term High‐Quality Electrophysiological Signal Recording for Human‐Machine Interface
Authors: Wang Junjie , Zhou Qian , Wang An , Zhu Zhijun , Moses Kumi , Wang Tengjiao , Li Peng , Huang Wei
Published: February 2024

Flexible bioelectronics have a large range of applications in the field of human health monitoring and human‐machine interfaces. Among various bioelectronics, flexible electrodes have been widely studied. However, it is still lack of investigation in the development of electrodes with high signal quality and long service life. Here, a sponge inspired flexible electrode based on cellulose aerogel is developed via thermally induced phase separation. Due to its flexibility, the electrode can easily conform to skin and achieve a higher signal‐to‐noise ratio (SNR) than the commercial rigid electrode. At the same time, the aerogel electrode with a sponge‐like structure can absorb solutions several times their own weight (≈800%). In addition, the dope of polypyrrole coated silver nanowires (AgNWs@PPy) improves its intrinsic bactericidal activity (antibacterial rate above 97.8%) and the cellulose‐based material itself offers good skin compatibility. Therefore, all these features contribute to a longer service life, while has been proven in electrophysiological signals recording. The SNR of electrocardiogram (ECG) signals recorded by aerogel electrode in 24 h is ≈15% higher than that of commercial electrode. Apart from that, when the commercial electrode is unavailable for eye‐open (EO) and eye‐closed (EC) paradigm in 12 h, the aerogel electrode can still record clear electroencephalogram (EEG) features.
A Sweat Absorbing Skin Electrode for Electrophysiology During Exercise
Authors: Shi Xiaohu , Song Dekui , Hu Wenya , Li Chuqi , Zhang Weifeng , Wang Shiyu , Hu Qianhuiwen , Wang Yifang , Wang Xin , Zhang Yingying , Peng Banghua , Wang Zijun , Liu Nan
Published: February 2024

Electrophysiological signals are commonly used to assess health performance, providing valuable information on body status. However, stable signal acquisition by commercial Ag/AgCl gel or metal electrodes is susceptible to electrode/skin interface interferences due to perspiration and motion during exercise. To address this challenge, herein a sweat absorbing skin electrode (SAE) is designed, which can not only become softer and more adhesive but also enhance conductivity after sweat during exercise. The resulting stable interface between SAE/skin after sweat enables accurate and continuous electrophysiological measurement during exercise. SAE is demonstrated by assembly of MXene (Ti3C2TX) aerogel and zwitterionic polymer, where Ti3C2TX aerogel works as conductive skeleton and zwitterionic polymer endows skin conformability as well as expediting interfacial charge transfer by the inherent ions. SAE can monitor a variety of electrophysiological signals during exercise. As an example, electromyogram (EMG) signals are acquired to assess muscle fatigue, which is impossible by commercial gel electrodes. Via machine learning, the correlation between EMG and physiological markers (body fat percentage (BF) and body mass index (BMI)) are constructed. The research shows that sweat‐absorbing SAEs can reliably monitor electrophysiological signals during exercise, such as muscle status, leading to evidence‐based scientific guidelines for sports and rehabilitation training.
A Point‐of‐Care Sensing Platform for Multiplexed Detection of Chronic Kidney Disease Biomarkers Using Molecularly Imprinted Polymers
Authors: Li Yixuan , Luo Liuxiong , Kong Yingqi , George Sophiamma , Li Yujia , Guo Xiaotong , Li Xin , Yeatman Eric , Davenport Andrew , Li Ying , Li Bing
Published: February 2024

Chronic kidney disease (CKD) is one of the most serious non‐communicable diseases affecting the population. In the early‐stages patients have no obvious symptoms, until it becomes life‐threatening leading end‐stage kidney failure. Therefore, it is important to early diagnose CKD to allow therapeutic interventions and progression monitoring. Here, a point‐of‐care (POC) sensing platform is reported for the simultaneous detection of three CKD biomarkers, namely creatinine, urea, and human serum albumin (HSA), using reduced graphene oxide/polydopamine‐molecularly imprinted polymer (rGO/PDA‐MIP) fabricated with novel surface‐molecularly imprinting technology. A multi‐channel electrochemical POC readout system with differential pulse voltammetry (DPV) function is developed, allowing the simultaneous detection of the three biomarkers, in combination with the surface‐MIP electrodes. This sensing platform achieves the record low limit‐of‐detection (LoD) at a femtomolar level for all three analytes, with wide detection ranges covering their physiological concentrations. Clinical validation is performed by measuring these analytes in serum and urine from healthy controls and patients with CKD. The average recovery rate is 81.8–119.1% compared to the results obtained from the hospital, while this platform is more cost‐effective, user‐friendly, and requires less sample‐to‐result time, showing the potential to be deployed in resource‐limited settings for the early diagnosis and tracking progression of CKD.