bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of mouse crystallins in 2D protein patterns by sequencing and mass spectrometry. Application to cataract mutants
Authors: Jungblut P.R , Otto A , Favor J , Löwe M , Müller E.-C , Kastner M , Sperling K , Klose J
Published: July 2002

The eye lens proteins of the mouse were separated into 1940 polypeptide spots by two‐dimensional electrophoresis in large gels. All 16 crystallins ubiquitous in mammals were identified by protein sequencing and mass spectrometry except for (γ)‐F, which shows an almost identical sequence with (γ)‐E. Two crystallins, (β)‐A2 and (γ)‐S, were shown for the first time to occur in the mouse lens. An investigation of the murine cataract mutant Cat2nop ((γ)‐B gene) demonstrated that a monogenic mutation might affect a broad spectrum of proteins.
Priming of human neutrophil superoxide generation by tumour necrosis factor‐α is signalled by enhanced phosphatidylinositol 3,4,5‐trisphosphate but not inositol 1,4,5‐trisphosphate accumulation
Authors: Condliffe Alison M , Hawkins Phillip T , Stephens Len R , Haslett Christopher , Chilvers Edwin R
Published: July 2002

In human neutrophils, significant agonist‐stimulated superoxide anion (O−
2) release is observed only after exposure to a priming agent such as TNFα. We have investigated the potential for TNFα to modulate N‐formyl‐Met‐Leu‐Phe (fMLP)‐triggered Ins(1,4,5)P3 and PtdIns(3,4,5)P3 accumulation. TNFα pretreatment did not affect basal or stimulated Ins(1,4,5)P3 levels but greatly upregulated fMLP‐stimulated PtdIns(3,4,5)P3 accumulation, in a manner that matched, both temporally and in magnitude, the increase in O−
2 generation implying a possible role for PtdIns(3,4,5)P3 in signalling primed O−
2 release.
Redox agents regulate ion channel activity in vacuoles from higher plant cells
Authors: Carpaneto Armando , Cantù Alberto M , Gambale Franco
Published: July 2002

The ability of redox agents to modulate certain characteristics of voltage‐ and calcium‐activated channels has been recently investigated in a variety of animal cells. We report here the first evidence that redox agents regulate the activation of ion channels in the tonoplast of higher plants. Using the patch‐clamp technique, we have demonstrated that, in tonoplasts from the leaves of the marine seagrass Posidonia oceanica and the root of the sugar beet, a variety of sulphydryl reducing agents, added at the cytoplasmic side of the vacuole, reversibly favoured the activation of the voltage‐dependent slow vacuolar (SV) channel. Antioxidants, like dithiothreitol (DTT) and the reduced form of glutathione, gave a reversible increase of the voltage‐activated current and faster kinetics of channel activation. Other reducing agents, such as ascorbic acid, also increased the SV currents, although to a lesser extent in comparison with DTT and glutathione, while the oxidising agent chloramine‐T irreversibly abolished the activity of the channel. Single channel experiments demonstrated that DTT reversibly increased the open probability of the channel, leaving the conductance unaltered. The regulation of channel activation by glutathione may correlate ion transport with other crucial mechanisms that in plants control turgor regulation, response to oxidative stresses, detoxification and resistance to heavy metals.
Activation pattern of mitogen‐activated protein kinases elicited by peroxynitrite: attenuation by selenite supplementation
Authors: Schieke Stefan M , Briviba Karlis , Klotz Lars-Oliver , Sies Helmut
Published: July 2002

Peroxynitrite is a mediator of toxicity in pathological processes in vivo and causes damage by oxidation and nitration reactions. Here, we report a differential induction of mitogen‐activated protein kinases (MAPKs) in WB‐F344 rat liver epithelial cells by peroxynitrite. For the exposure of cultured cells with peroxynitrite, we employed a newly developed infusion method. At 6.5 μM steady‐state concentration, the activation of p38 MAPK was immediate, while JNK1/2 and ERK1/2 were activated 60 min and 15 min subsequent to 3 min of exposure to peroxynitrite, respectively. Protein‐bound 3‐nitrotyrosine was detected. When cells were grown in a medium supplemented with sodium selenite (1 μM) for 48 h, complete protection was afforded against the activation of p38 and against nitration of tyrosine residues. These data suggest a new role for peroxynitrite in activating signal transduction pathways capable of modulating gene expression. Further, the abolition of the effects of peroxynitrite by selenite supplementation suggests a protective role of selenium‐containing proteins.
Structure of VAT, a CDC48/p97 ATPase homologue from the archaeon Thermoplasma acidophilum as studied by electron tomography
Authors: Rockel Beate , Walz Jochen , Hegerl Reiner , Peters Jürgen , Typke Dieter , Baumeister Wolfgang
Published: July 2002

Valosine‐containing protein‐like ATPase from Thermoplasma acidophilum is a member of the superfamily of ATPases associated with a diversity of cellular activities and is closely related to CDC48 from yeast and p97 from higher eukaryotes and more distantly to N‐ethylmaleimide‐sensitive fusion protein. We have used electron tomography to obtain low‐resolution (2–2.5 nm) three‐dimensional maps of both the whole 500 kDa complex and the N‐terminally truncated valosine‐containing protein‐like ATPase from T. acidophilum complex lacking the putative substrate binding domain.
Use of a drug‐resistant mutant of stress‐activated protein kinase 2a/p38 to validate the in vivo specificity of SB 203580
Authors: Eyers Patrick A. , van den IJssel Paul , Quinlan Roy A. , Goedert Michel , Cohen Philip
Published: July 2002

Stress‐activated protein kinase 2a, also called p38, is inhibited by SB 203580 and this drug has been used widely to implicate this enzyme in the regulation of many physiological processes. Here, we introduce a novel method of general application, which can be used to establish whether the effects of SB 203580 are mediated via inhibition of stress‐activated protein kinase 2a/p38 or whether they result from ‘non‐specific’ effects. Four events thought to occur upon activation of stress‐activated protein kinase 2a/p38 have been established unequivocally. These are the activation of mitogen‐activated protein kinase‐activated protein kinase‐2 and mitogen‐ and stress‐activated protein kinase‐1 and the phosphorylation of their presumed substrates, heat shock protein 27 and the transcription factor cyclic AMP response element binding protein, respectively. In contrast, the SB 203580‐induced activation of c‐Raf is independent of stress‐activated protein kinase 2a/p38 inhibition.
An 86 kDa diapause protein 1‐like protein is a component of early‐staged encapsulation‐relating proteins in coleopteran insect, Tenebrio molitor larvae1
Authors: Cho Mi Young , Choi Hye Won , Moon Ga Young , Kim Mi Hee , Kwon Tae Hyuk , Homma Ko-ichi , Natori Shunji , Lee Bok Luel
Published: July 2002

Recently, we reported two novel early‐staged encapsulation‐relating proteins (56 kDa and 48 kDa ERPs) isolated from the hemolymph of coleopteran insect, Tenebrio molitor larvae [Cho et al. (1999) Eur. J. Biochem. (in press)]. Here, a cDNA clone for another early‐staged encapsulation‐relating protein (86 kDa) was isolated. We found that the 86 kDa protein shows high homology with insect diapause protein 1. The 86 kDa protein was localized in the fat body and hemolymph, but not hemocyte lysate. A significant level of 86 kDa protein was detected in pre‐pupae stage, but it decreased rapidly at late larvae and pupae, and no protein was found in embryo, early larvae and adult stages. This diapause protein 1‐like protein is likely to be a component of early‐staged encapsulation‐relating proteins in the insect cellular defense reaction.
Ricin A chain utilises the endoplasmic reticulum‐associated protein degradation pathway to enter the cytosol of yeast
Authors: Simpson Jeremy C. , Roberts Lynne M. , Römisch Karin , Davey John , Wolf Dieter H. , Lord J.Michael
Published: July 2002

Cytotoxic proteins such as ricin A chain (RTA) have target substrates in the cytosol and therefore have to reach this cellular compartment in order to act. RTA is thought to translocate into the cytosol from the lumen of the endoplasmic reticulum (ER), although how it traverses the ER membrane has not been established. Using yeast mutants defective in various aspects of the ER‐associated protein degradation (ERAD) pathway, we show that RTA introduced into the yeast ER subverts this pathway to enter the cytosol via the Sec61p translocon. A significant proportion of the exported RTA avoided proteasomal degradation. These data are consistent with the contention that the RTA component from ricin endocytosed by mammalian cells may likewise exploit ERAD to translocate into the cytosol.
The antioxidant functions of cytochrome c
Authors: Korshunov Sergey S , Krasnikov Boris F , Pereverzev Mikhail O , Skulachev Vladimir P
Published: July 2002

Low (C1/2=1.5×10−7 M) concentrations of horse cytochrome c strongly inhibit H2O2 production by rat heart mitochondria under conditions of reverse electron transfer from succinate to NAD+. The effect is abolished by binding of cytochrome c with liposomes and is not prevented by SOD. Yeast cytochrome c is much less effective than the horse protein whereas acetylated horse cytochrome c is without effect. H2O2 formation stimulated by antimycin A is resistant to added cytochrome c. In inside‐out submitochondrial vesicles, H2O2 production is suppressed by all three cytochrome c samples tested, but at higher concentrations (C1/2 is about 5×10−7 M). In vesicles, SOD abolishes the cytochrome c inhibition. We conclude that extramitochondrial cytochrome c is competent in down‐regulation of the Complex I H2O2 production linked to the reverse electron transfer. Such an effect is absent in the inside‐out submitochondrial vesicles where another antioxidant cytochrome c function can be observed, i.e. the oxidation of O2
−
to O2. A possible role of cytochrome c in the antioxidant defence is discussed.
Protein purification and gene isolation of chlamysin, a cold‐active lysozyme‐like enzyme with antibacterial activity
Authors: Nilsen Inge W. , Øverbø Kersti , Sandsdalen Erling , Sandaker Elin , Sletten Knut , Myrnes Bjørnar
Published: July 2002

An antibacterial ∼11 kDa protein designated chlamysin was isolated from viscera of the marine bivalve Chlamys islandica. Chlamysin inhibited the growth of all Gram‐positive and Gram‐negative bacteria tested. The isolated protein was highly efficient in hydrolyzing Micrococcus luteus cells only at low pH (4.5–6.2) and at low temperature (4–35°C). No significant loss of enzyme activity was observed after 30 days storage at room temperature or after heating to 70°C for 15 min, suggesting relatively high protein structure stability. Sequence‐analyzed fragments of the protein revealed data which guided the isolation of the cDNA gene, encoding a 137 amino acid chlamysin precursor in scallops. The deduced protein contains a high portion of cysteine, serine and histidine residues and has a predicted isoelectric point below 7. The chlamysin protein was found to have sequence homology to an isopeptidase and to a recently published bivalve lysozyme.
Topical treatment of vaginal candidosis with sertaconazole and econazole sustained‐release suppositories
Authors: Dellenbach P. , Thomas J.‐L. , Guerin V. , Ochsenbein E. , Contet‐Audonneau N.
Published: July 2002

Objective: To compare the efficacy and safety of sertaconazole and econazole sustained‐release suppositories in the treatment of vulvovaginal candidosis. Study design: 369 women with symptoms and signs of vulvovaginitis were enrolled in this multicenter, randomized, double‐blind study. After clinical examination and vaginal sampling, 183 women were treated with a 300‐mg sertaconazole suppository and the other 186 with a 150‐mg econazole suppository. They were evaluated 1 week after treatment and those who were clinically uncured received a second suppository and were re‐assessed 1 week later. All women were evaluated 1 month after the last administration. At each follow‐up visit, clinical efficacy was assessed and a vaginal sampling was performed for microscopic examination and culture. Results: Of the 369 women included, only the 310 who had a positive culture for a strain of Candida were taken into account for efficacy analysis: 150 in the sertaconazole group and 160 in the econazole group. One hundred and five women (49 in the sertaconazole group and 56 in the econazole group) were not clinically cured after 1 week and received a second suppository. There were no differences between the two groups for the rates of clinical recovery (disappearance of signs and symptoms) and mycological recovery (negative culture), 1 week after the first application (62.1 and 67.7%, respectively), 1 week after the second application for women treated twice (72.3 and 80.6%, respectively) and for all patients 1 month after the last application (65.3 and 62.0%, respectively). Among the patients cured 1 week after the last application, the mycological recurrence rate after 1 month was significantly higher in the econazole group (32.7 vs. 19.8%, P=0.035). There was a trend towards better efficacy of sertaconazole after the first application, whereas the two treatments had similar efficacy in women treated twice. There were no serious adverse events and only local irritation was reported, without any statistically significant difference between the two groups. Conclusion: Single topical administration of sertaconazole and econazole had similar efficacy and safety but the former is associated with a lower rate of mycological recurrence one month after achieving a negative culture.
Laparoscopic diagnosis of acute lower abdominal pain in women of reproductive age
Authors: Gaitán H. , Angel E. , Sánchez J. , Gómez I. , Sánchez L. , Agudelo C.
Published: July 2002

Objectives: To compare the accuracy of laparoscopy performed within 24 h of admission and the conventional method based on clinical observation in the etiological diagnosis of non‐specific acute lower abdominal pain (NSLAP) in women of reproductive age. Methods: A total of 110 patients who met the selection criteria and were seen from November 1997 to June 2000 at the Instituto Materno Infantil, a referral hospital for maternal and perinatal care in Bogotá, were randomly divided into two groups. The effectiveness of each method was evaluated according to number of diagnoses reached, length of in‐patient stay before diagnosis, complications, and diagnostic accuracy when compared with a standard given by microbiological and histopathological findings as well as clinical course. Results: The early laparoscopy group did not experience more accurate diagnoses (85% vs. 79%, P=0.61) or a greater number of complications (11% vs. 9%, P=0.48), although the patients’ stay was shorter (1.3 vs. 2.3 days, P=0.008) than the stay of the conventional‐diagnosis group. Sensitivity analysis showed more accurate judgements with laparoscopy in four of the five NSLAP causes, but only in two of the cases did this greater accuracy have clinical significance. Conclusions: Early laparoscopy did not show a clear benefit in women with NSLAP.
Improving emergency obstetric care at a district hospital, Makeni, Sierra Leone
Authors: Leigh B , Kandeh H.B.S , Kanu M.S , Kuteh M , Palmer I.S , Daoh K.S , Moseray F ,   (The Freetown/ Makeni PMM Team)
Published: July 2002

Preliminary studies: A facility review and focus group discussions revealed poor capacity to manage obstetric complications. Interventions: In response, a physician with obstetric skills was posted, and a second physician was trained. Courses in life‐saving obstetric skills were held for nurses and midwives. An unused operating theater was made functional with simple modifications. A generator and blood bank were installed. Drugs and supplies were made available through a revolving fund. Subsequently, community interventions focused on improving utilization. Results: The number of women seeking treatment for major obstetric complications at the district hospital increased from 31 in 1990 to 98 in 1995, while the case fatality rate (CFR) among these women dropped from 32% to 5%. Cesarean sections increased from two in 1990 to 38 in 1995. In 1995, 444 abortion‐related procedures were performed — almost all of them for unwanted pregnancy — compared with only 22 in 1990. Costs: The cost of material improvements and training was approximately US$39 000, of which 46% was from project funds, 41% from non‐governmental organizations and 13% from government. Conclusions: Women with obstetric complications will seek hospital care if services are available. Government hospital services can be improved by building on existing resources. Obstetric CFR can be dramatically reduced. The need for safe abortion services, which are currently illegal in Sierra Leone, is demonstrated. © 1997 International Federation of Gynecology and Obstetrics
Involving the private sector in improving obstetric care, Anambra State, Nigeria
Authors: Chukudebelu W , Ikeme A , Okaro J , Egbuciem P , Onah B , Okeke V , Nwakoby B , Akpala O , Nwagbo D , Ikeagu A ,   (The Enugu PMM Team)
Published: July 2002

Preliminary studies: Of 11 facilities providing obstetric services in the Njikoka Local Government Area, four were private, for‐profit institutions. Focus group discussions in seven communities revealed a preference for private facilities due to flexible payment schedules, proximity, reliable availability of a medical doctor and poor quality government services. Each of the private facilities had one doctor and one midwife and the bulk of patient care was performed by health aides with no formal midwifery training. Interventions: In 1992, 15 aides from the private facilities were trained in the recognition and management of obstetric complications. The training consisted of one week of classroom instruction and two weeks of practical training in local missionary hospitals. Results: Improvements were assessed by a written test. The percent of trainees obtaining a passing test mark increased from 33% (pre‐training) to 61% (post‐classroom) to 77% (post‐practicum). Costs: The cost of this intervention was approximately US $18 000. Conclusions: Auxiliaries' skills can be improved with classroom and practical training. The involvement of private sector institutions is important where they provide a substantial proportion of emergency obstetric services. However, maintaining improvements requires sustained efforts. © 1997 International Federation of Gynecology and Obstetrics
Community education to improve utilization of emergency obstetric services in Ghana
Authors: Opoku S.A , Kyei‐Faried S , Twum S , Djan J.O , Browne E.N.L , Bonney J ,   (The Kumasi PMM Team)
Published: July 2002

Preliminary studies: Focus group studies in the Ashanti region showed that people avoided utilizing health facilities because of lack of confidence in the services and concern about the availability of drugs and supplies, among other reasons. Interventions: After services at the health center were upgraded, community education activities began in early 1994. These activities were carried out through existing mechanisms — e.g. Ministry of Health (MOH) outreach workers and village health workers, public health nurses and midwives, and village health committees. They addressed a variety of audiences, including women's and church groups, emphasizing early recognition and treatment of obstetric complications, and the improved availability of services. Results: The number of women with obstetric complications admitted to the health center rose from 26 in 1993 to 73 in 1995. It was the impression of the health center staff that women were also coming for treatment more promptly. Costs: The cost of this intervention was US$1950. This was mostly project funds, with the government and community together contributing approximately one‐fifth. Conclusions: Once services are available, community education and information activities can enhance utilization. The cost of such activities can be reduced, and sustainability promoted, by involving MOH personnel and community groups. © 1997 International Federation of Gynecology and Obstetrics
Emergency loan funds to improve access to obstetric care in Ekpoma, Nigeria
Authors: Chiwuzie J , Okojie O , Okolocha C , Omorogbe S , Oronsaye A , Akpala W , Ande B , Onoguwe B , Oikeh E ,   (The Benin PMM Team)
Published: July 2002

Preliminary studies: Focus group discussions in the community identified difficulties in paying for transport as a major barrier to seeking and reaching emergency care for obstetric complications. Interventions: After emergency obstetric services in local health facilities had been upgraded, the clans in Ekpoma were mobilized in 1995 to set up emergency loan funds for women with complications. Funds were managed entirely by the clans, with ongoing monitoring and supervision by project staff. Two percent simple interest was charged. Results: Of the 13 clans contacted, 12 successfully launched loan funds. Total donations amounted to US$793, of which four‐fifths were contributed by the community. In the 1st year of the operation, 456 women/families requested loans (ranging from US$7 to US$15), and 380 (83%) were granted. Three‐hundred and fifty‐four (93%) loans were repaid in full. In addition to being used for transport, loans were used to help pay for drugs, blood and hospital fees. Costs: The cost of establishing the loan fund was US$1360, including initial donations to the loan funds. The PMM project paid 55% of the total. Conclusions: With relatively little outside financial input, communities can set up and administer loan funds for emergency obstetric transport and care. However, sustaining the funds over the long term requires continuing effort and involvement with the communities. © 1997 International Federation of Gynecology and Obstetrics
Epidemiology of behavioral dependence: literature review and results of original studies
Authors: Lejoyeux M. , Mc Loughlin M. , Adès J.
Published: July 2002

The extension of the definition of dependence leads to the consideration of some impulsive disorders as a form of dependence disorder. This pathological condition is characterized by the repetitive occurrence of impulsive and uncontrolled behaviors. Other clinical characteristics are failure to resist an impulse, drive or temptation to perform some act harmful to oneself and/or others, an increasing sense of tension or excitement before acting out, and a sense of pleasure, gratification or release at the time of the behavior or shortly thereafter. Behavioral dependences most often described are pathological gambling, kleptomania, trichotillomania and compulsive buying.

Studies using a specific assessment scale, the South Oaks Gambling Screen, distinguished problem gambling from pathological gambling. Social gamblers spend 5% of their money and pathological gamblers 14 to 45%. Prevalence of ‘problem gambling’ is 4% and pathological gambling 2%. Several studies have suggested that the incidence of pathological gambling is eight to ten times greater in alcohol-dependent patients than in the general population.

No systematic study has assessed the prevalence of kleptomania. Data come from case reports. Among subjects arrested after a theft, prevalence of kleptomania varied between 0 and 24%. Trichotillomania prevalence rate is 0.6% among students. Studies using less restrictive diagnostic criteria found a prevalence rate of 3.4% in women and 1.5% in men. The disorder is often unrecognized; 40% of the cases are not diagnosed and 58% of the patients have never been treated.

Prevalence studies of compulsive buying found a rate between 1 and 6% in the general population. Compulsive buying is significantly more frequent among women (90% of the cases). Study of family history of compulsive buyers showed a high frequency of alcohol-dependence disorder (20%) and depression (18%). In all cases of behavioral dependence disorders, a high level of impulsivity and sensation-seeking could determine an increased risk.
Has the attempt to reduce psychiatric inpatient treatment been successful in Finland?
Authors: Kaltiala-Heino R. , Laippala P. , Joukamaa M.
Published: July 2002

The deinstitutionalisation process in Finland’s psychiatric healthcare did not start until the late 1980s. Our aim is to evaluate how the use of psychiatric inpatient treatment was associated with deinstitutionalisation given the changes in the modality of treatment ideology (years 1987–1991) as well as being due to economic pressures (years 1991–1995). Special emphasis is given on the inpatient treatment of schizophrenia and other psychotic disorders.

Data was retrieved using the national hospital discharge register of all treatment periods in psychiatric hospitals and treatment periods due to psychiatric disorders in other hospitals. Three years (1987, 1991, and 1995) were compared. Four healthcare districts in northern Finland were studied. Resource use was measured by number of treatment periods and inpatient days in relation to population. Psychiatric inpatient treatment was reduced in 1987–1991, when resources in community care increased. During the period of economic pressures (1991–1995), when community care resources no longer increased, inpatient treatment started to rise again. Over the whole period, psychiatric treatment in primary care institutions increased.

Reduction of psychiatric beds results in increasing inpatient treatment in non-specialist institutions, especially when community care fails to serve the patients. In the future it is important to evaluate whether the quality of care remains in the standard of specialised services when treatment shifts away from the specialist level.
Mutual fund shareholders
Authors: Alexander Gordon J. , Jones Jonathan D. , Nigro Peter J.
Published: July 2002

This paper examines responses from a survey of 2,000 randomly selected mutual fund investors who purchased shares from six different distribution channels. The survey provides data on the demographic, financial, and fund ownership characteristics of mutual fund investors. It also provides data on investors’ knowledge of the costs and investment risks of mutual funds and the information sources these investors use to learn about these costs and risks. Our survey results strongly suggest there is room for improvement in the level of financial literacy of mutual fund investors. © 1999 Elsevier Science Inc. All rights reserved.
The prediction of default for high yield bond issues
Authors: Huffman Stephen P. , Ward David J.
Published: July 2002

Bondholders and financial analysts have long sought models which will predict financial distress in corporations. Prior research has produced a number of useful models to predict bankruptcy in the short term. This paper looks at four models which predict default based upon public information at the time of issuance of high yield bonds.

Multivariate results using logistic regression analysis indicate that high yield issues that default are characterized by having higher asset growth rates, lower operating profit margins, larger levels of collateralizable assets, and larger changes in net working capital. Models using Altman (1968) variables have lower likelihood ratio indexes than models employing alternative explanatory variables. Predictive ability tests of models excluding the traditional variables on a holdout sample are able to correctly predict 73.3 percent of the defaulted bonds and 68.6 percent of the nondefaulted bonds.
Negative inotropic effects of recombinant interleukin 2 in patients without left ventricular dysfunction
Authors: Tio René A. , Nieken Judith , de Vries Elisabeth G.E. , Pfeiffer Carolein , de Jongste Mike J.L. , Pieper Els , Moshage Han , Limburg Piet C. , Mulder Nanno H.
Published: July 2002

Experimental data have shown that rIL2 has negative inotropic properties. This has not been investigated in humans with normal left ventricular function. Seventeen consecutive renal cell carcinoma patients who received rIL2 therapy because of dissemination were analyzed before and after treatment with a low dose of rIL2 subcutaneously. Left ventricular ejection fraction (echocardiography), heart rate variability parameters (24 h electrocardiography), and TNFα, IL1β and nitric oxide metabolites (NOx) were measured. LVEF decreased from 54 ± 7 to 50 ± 6% (mean ± S.D.; P = 0.012), with a concomitant increase in heart rate from 87 ± 13 to 94 ± 13 beats/min (P = 0.031). All frequency domain HRV parameters decreased: the total power from 18.0 ± 7.9 to 14.0 ± 5.0 ms (P = 0.001), the low frequency from 10.3 ± 5.4 to 8.3 ± 3.4 ms (P = 0.001), and the high frequency from 6.3 ± 2.6 to 4.5 ± 1.1 ms (P = 0.001). There was no measurable effect on TNFα, IL1β concentrations. Plasma levels of nitrate (NOx) increased from 22.8 ± 14.4 to 41.8±26.6 μmol/l (P = 0.007).

Conclusions:

A low dose of rIL2 has a negative inotropic effect that may be mediated by increased NO concentrations. It also reduces sympathetic activity as reflected in HRV parameters.
Perindopril for elderly people with chronic heart failure: the PEP‐CHF study
Authors: Cleland John G.F. , Tendera Michal , Adamus Jerzy , Freemantle Nick , Gray Christopher S. , Lye Michael , O'Mahony Denis , Polonski Lech , Taylor Jacqueline ,   on behalf of the PEP investigators
Published: July 2002

Background:

The prevalence of chronic heart failure (CHF) rises with increasing age, from <1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general.

Aims:

The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction.

Subjects:

One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography.

Methods:

Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub‐studies of this trial include a 6‐min walking test and more detailed evaluation of ventricular function (as assessed by echocardiography). Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year. This trial is due to report in the year 2001.
De novo filament formation by human hair keratins K85 and K35 follows a filament development pattern distinct from cytokeratin filament networks
Authors: Yamamoto Masaki , Sakamoto Yasuko , Honda Yuko , Koike Kenzo , Nakamura Hideaki , Matsumoto Toshihiko , Ando Shoji
Published: February 2021

In human hair follicles, the hair‐forming cells express 16 hair keratin genes depending on the differentiation stages. K85 and K35 are the first hair keratins expressed in cortical cells at the early stage of the differentiation. Two types of mutations in the gene encoding K85 are associated with ectodermal dysplasia of hair and nail type. Here, we transfected cultured SW‐13 cells with human K85 and K35 genes and characterized filament formation. The K85–K35 pair formed short filaments in the cytoplasm, which gradually elongated and became thicker and entangled around the nucleus, indicating that K85–K35 promotes lateral association of short intermediate filaments (IFs) into bundles but cannot form IF networks in the cytoplasm. Of the K85 mutations related to ectodermal dysplasia of hair and nail type, a two‐nucleotide (C1448T1449) deletion (delCT) in the protein tail domain of K85 interfered with the K85–K35 filament formation and gave only aggregates, whereas a missense mutation (233A>G) that replaces Arg78 with His (R78H) in the head domain of K85 did not interfere with the filament formation. Transfection of cultured MCF‐7 cells with all the hair keratin gene combinations, K85–K35, K85(R78H)–K35 and K85(delCT)–K35, as well as the individual hair keratin genes, formed well‐developed cytoplasmic IF networks, probably by incorporating into the endogenous cytokeratin IF networks. Thus, the unique de novo assembly properties of the K85–K35 pair might play a key role in the early stage of hair formation.
Facile Total Syntheses of Putative and Revised Structures of Pethybrene
Authors: Jee Dong Whan , Lee Hee‐Yoon
Published: February 2021

The structural identity of pethybrene was confirmed as theoretically proposed 6‐5‐5 tricyclic structure through total syntheses of two putative structures. The originally proposed structure 1 was synthesized in 13 steps via Intramolecular Pauson‐Khand reaction to form the triquinane skeleton and the newly proposed structure from a theoretical study 2 was obtained from a known [2+2] cycloaddition product in 3 steps.
Magneto‐dielectricandmagneto‐conductingfillers based polymer composites: Effect of functionalization, coating and dispersion process on electromagnetic shielding properties
Authors: Vyas Manoj Kumar , Chandra Amita
Published: February 2021

Electromagnetic interference shielding of magneto‐dielectric (BaTiO3‐Fe3O4) and magneto‐conducting (f‐MWCNT‐Fe3O4) fillers based polymer electrolyte composites in the X‐band have been studied in the present work. Magneto‐dielectric and magneto‐conducting fillers have been obtained by in situ preparation of Fe3O4nanoparticles by chemical precipitation in the presence of BaTiO3and functionalized multiwalled carbon nanotubes (f‐MWCNT). Functionalization of MWCNT has resulted in their strong bonding with the polymer electrolyte adversely affecting the charge transport properties and shielding effectiveness. Dielectric, magnetic and conducting properties of the magneto‐dielectric and magneto‐conducting fillers are found to be significantly different as a result of coating by Fe3O4nanoparticles on BaTiO3andf‐MWCNT. Combining two fillers in a single nanocomposite has exhibited non‐complimentary addition of their individual properties. The ultra‐sonication method of dispersion of the magneto‐conducting filler has been found to give better conducting and shielding effectiveness in comparison to the homogenization method due to better disentanglement of the nanotubes.
Urban heat islands in Hong Kong: Bonding with atmospheric stability
Authors: Wang Weiwen , Chen Bingyin , Xu Yong , Zhou Wen , Wang Xuemei
Published: February 2021

A barrier to urban heat island (UHI) mitigation is the lack of quantitative attribution of the various contributions to UHI intensity. This study demonstrates the daily and seasonal dynamics of UHIs in Hong Kong, a subtropical high‐density city. The nocturnal UHIs of the city are grouped according to various dynamic stability conditions (neutral, weak stable, and strong stable) of the boundary layer. Results indicate that the stronger the atmospheric stability, the more intense the UHI. The atmospheric anomalies linked to these stability classifications are hence revealed. In summer, nights of neutral (strong stable) stratification are controlled by low (high) pressure with rising (sinking) motion, less (more) precipitation, and lower (higher) air temperature at the surface. In winter, the influence of the large‐scale circulation system of the East Asian winter monsoon is significant. In the upper layer, the East Asian jet stream retreats westward (is displaced northward) on nights with neutral (strong stable) atmospheric stratification. At the surface, southeast China is hot and humid on neutral nights, while on strong stable nights, the coastal regions of southeast China are dry, and East Asia is dominated by positive surface air temperature anomalies. Atmospheric anomalies are generally nonsignificant on nights with weak stable stratification in both summer and winter. These findings provide potential predictors for UHI intensity.
A tale of two algorithms: The appeal and repeal of calculated grades systems in England and Ireland in 2020
Authors: Kelly Anthony
Published: February 2021

The Covid pandemic and the cancellation of state examinations caused unprecedented turmoil in the education systems on both sides of the Irish Sea. As the policy of calculating grades using purpose‐built algorithms came undone in the face of a barrage of appeal, protest and legal action, the context in which the policies had been devised collapsed. The British and Irish governments had initially adopted similar approaches to issuing examination grades, but then diverged into different stratagems pre‐ and post‐results, with significantly different outcomes. The Irish examination system emerged relatively unscathed, while the system in England suffered what was probably its greatest policy failure of modern times. This article examines and memorialises how and why this happened, and draws lessons for a future in which school closures and substitute examinations become the ‘new normal’.
Detection of the SARS‐CoV‐2 D614G mutation using engineered Cas12a guide RNA
Authors: Meng Qingzhou , Wang Xinjie , Wang Yanqun , Dang Lu , Liu Xinyi , Ma Xiaodong , Chi Tian , Wang Xian , Zhao Qin , Yang Guang , Liu Ming , Huang Xingxu , Ma Peixiang
Published: February 2021

Detection of pathogens with single‐nucleotide variations is indispensable for the disease tracing, but remains technically challenging. The D614G mutation in the SARS‐CoV‐2 spike protein is known to markedly enhance viral infectivity but is difficult to detect. Here, we report an effective approach called “synthetic mismatch integrated crRNA guided Cas12a detection” (symRNA‐Cas12a) to detect the D614 and G614 variants effectively. Using this method, we systemically screened a pool of crRNAs that contain all the possible nucleotide substitutions covering the ‐2 to +2 positions around the mutation and identify one crRNA that can efficiently increase the detection specificity by 13‐fold over the ancestral crRNA. With this selected crRNA, the symRNA‐Cas12a assay can detect as low as 10 copies of synthetic mutant RNA and the results are confirmed to be accurate by Sanger sequencing. Overall, we have developed the symRNA‐Cas12a method to specifically, sensitively and rapidly detect the SARS‐CoV‐2 D614G mutation.
A real‐world data of Immune checkpoint inhibitors in solid tumors from India
Authors: Noronha Vanita , Abraham George , Patil Vijay , Joshi Amit , Menon Nandini , Mahajan Abhishek , Janu Amit , Jain Srushti , Talreja Vikas T , Kapoor Akhil , Kumar Singh Gunjesh , Khaddar Satvik , Gupta Kushal , Rathinasamy Narmadha , Srinivas Sujay , Agrawal Amit , Ventrapati Pradeep , Prabhash Kumar
Published: February 2021

Background

Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors.

Methods

This was a single center retrospective analysis of prospective data base of patients with non‐melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints.

Results

Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non‐small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non‐melanoma solid malignancies was 5.37 months (95% CI, 3.73–9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73–3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%.

Conclusion

Real‐world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non‐melanoma solid tumors.
Synthesis, Biological Evaluation, and Docking Study of Ring‐Opening Amide Analogs of Matrine as Antitumor Agents
Authors: Qian Mingcheng , Jiang Xinyu , Zhang Mingting , Hu Lijuan , Liu Huimin , Zhao Shuai , Zhou Xiaoying , Chen Xin
Published: February 2021

In this article, we designed and synthesized two series of matrine analogs with ring‐opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N‐(3‐bromophenyl)‐4‐[(1R,3aS,10aR,10bS)‐decahydro‐1H,4H‐pyrido[3,2,1‐ij][1,6]naphthyridin‐1‐yl]butanamide (B11) with a meta‐bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose‐dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert‐butyl (1R,3aS,10aR,10bS)‐1‐[4‐(3‐bromoanilino)‐4‐oxobutyl]octahydro‐1H,4H‐pyrido[3,2,1‐ij][1,6]naphthyridine‐2(3H)‐carboxylate (A11, an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11, which can be used for further study both in vitro and in vivo.
Toward a more perfect coronary intervention…
Authors: Agarwal Shiv Kumar , Uretsky Barry F.
Published: February 2021

Key Points

Angiographic assessment to determine adequacy of stent expansion is unsatisfactory with approximately half of stents being underexpanded when evaluated by intravascular ultrasound (IVUS).

Adequate stent expansion is significant higher using IVUS, ranging from about 70–80% depending on the definition of stent expansion used.

This study showed that using the diameter of the external elastic membrane distal to the lesion to size stent diameter and postdilatation with a noncompliant balloon appears safe and provides improved stent expansion in lesions with positive remodeling.
Flexible Free‐Standing VO2/MXene Conductive Films as Cathodes for Quasi‐Solid‐State Zinc‐Ion Batteries
Authors: Shi Zhenglu , Ru Qiang , Pan Zikang , Zheng Minhui , Chi‐Chun Ling Francis , Wei Li
Published: February 2021

Flexible rechargeable zinc‐ion batteries (ZIBs) have aroused tremendous attention owing to the good safety and abundant reserves, making it one of the most promising alternatives for novel energy storage devices. Herein, flexible, free‐standing hybrid films with a three‐dimensional interlaced network are reported for ZIBs. The flexible and pliable VO2/MXene hybrid films deliver a high specific capacity of 228.5 mAh g−1 at 0.2 A g−1 and display a reversible capacity over 126.6 mAh g−1 after 700 cycles at 2 A g−1. More impressively, the flexible electrode also shows exciting mechanical flexibility and outstanding Zn2+ storage capability with a moderate capacity retention of 72.1 % after 2500 cycles at 5 A g−1 in quasi‐solid‐state ZIBs. The special structure can boost the diffusion pathway of Zn2+ and effectively stabilize the structure of the electrode upon cycling. This work also evidences that the flexible VO2/MXene hybrid films own an immense potential for portable and flexible equipment.
Enabling forward uncertainty quantification and sensitivity analysis in cardiac electrophysiology by reduced order modeling and machine learning
Authors: Pagani Stefano , Manzoni Andrea
Published: February 2021

We present a new, computationally efficient framework to perform forward uncertainty quantification (UQ) in cardiac electrophysiology. We consider the monodomain model to describe the electrical activity in the cardiac tissue, coupled with the Aliev‐Panfilov model to characterize the ionic activity through the cell membrane. We address a complete forward UQ pipeline, including both: (i) a variance‐based global sensitivity analysis for the selection of the most relevant input parameters, and (ii) a way to perform uncertainty propagation to investigate the impact of intra‐subject variability on outputs of interest depending on the cardiac potential. Both tasks exploit stochastic sampling techniques, thus implying overwhelming computational costs because of the huge amount of queries to the high‐fidelity, full‐order computational model obtained by approximating the coupled monodomain/Aliev‐Panfilov system through the finite element method. To mitigate this computational burden, we replace the full‐order model with computationally inexpensive projection‐based reduced‐order models (ROMs) aimed at reducing the state‐space dimensionality. Resulting approximation errors on the outputs of interest are finally taken into account through artificial neural network (ANN)‐based models, enhancing the accuracy of the whole UQ pipeline. Numerical results show that the proposed physics‐based ROMs outperform regression‐based emulators relying on ANNs built with the same amount of training data, in terms of both numerical accuracy and overall computational efficiency.
Cotton root growth response to mepiquat chloride application in early reproductive stages are cultivar dependent
Authors: Cordeiro Carlos Felipe dos Santos , Santos Iago Fernandes , Mello Patrícia Rafaella de , Echer Fábio Rafael
Published: February 2021

Mepiquat chloride (MC) is essential to reduce shoot growth and improve cotton (Gossypium hirsutum L. var. latifolium Hutch) harvest index, but the effect of high rates on cotton root growth is not known yet. The objective of this study was to evaluate the effect of different rates of MC application on root and shoot growth of different cotton cultivars. Two studies were conducted in a greenhouse to (a) characterize the stage of greatest susceptibility to high rates of MC and (b) evaluate the response to MC on root growth of cultivars of different maturity cycles (FM 906GLT, early; TMG 44B2RF, mid‐early; TMG 81WS, late; and FM 985GLTP, late). Regardless of the cultivar, spraying of MC in the early reproductive stage (B3) reduced root length. These reductions began approximately 2 wk after spraying. But spraying MC in the late reproductive stage (F1) can increase root length. Application of up to 30 g ha−1 of MC hindered shoot growth for 2 wk, but applications of 60 g ha−1 hindered shoot growth for 3 wk. We recommend a maximum application of 30 g ha−1 of MC in the first application to reduce root growth damage and balance biomass production.
Structure–Reactivity Effects of Biomass‐based Hydroxyacids for Sustainable Electrochemical Hydrogen Production
Authors: Martín‐Yerga Daniel , White Jai , Henriksson Gunnar , Cornell Ann
Published: February 2021

Biomass electro‐oxidation is a promising approach for the sustainable generation of H2 by electrolysis with simultaneous synthesis of value‐added chemicals. In this work, the electro‐oxidation of two structurally different organic hydroxyacids, lactic acid and gluconic acid, was studied comparatively to understand how the chemical structure of the hydroxyacid affects the electrochemical reactivity under various conditions. It was concluded that hydroxyacids such as gluconic acid, with a considerable density of C−OH groups, are highly reactive and promising for the sustainable generation of H2 by electrolysis at low potentials and high conversion rates (less than −0.15 V vs. Hg/HgO at 400 mA cm−2) but with low selectivity to specific final products. In contrast, the lower reactivity of lactic acid did not enable H2 generation at very high conversion rates (<100 mA cm−2), but the reaction was significantly more selective (64 % to pyruvic acid). This work shows the potential of biomass‐based organic hydroxyacids for sustainable generation of H2 and highlights the importance of the chemical structure on the reactivity and selectivity of the electro‐oxidation reactions.