Miracle-dz/UniFAR-FTUs huggingface dataset:
Coordinate Expression of α-Tropomyosin and Caldesmon Isoforms in Association with Phenotypic Modulation of Smooth Muscle Cells*

Isoform diversity of tropomyosin is generated from the limited genes by a combination of differential transcription and alternative splicing. In the case of the α-tropomyosin (α-TM) gene, exon 2a rather than exon 2b is specifically spliced in α-TM-SM mRNA, which is one of the major tropomyosin isoforms in smooth muscle cells. Here we demonstrate that expressions of α-tropomyosin and caldesmon isoforms are coordinately regulated in association with phenotypic modulation of smooth muscle cells. Molecular cloning and Western and Northern blottings have revealed that in addition to the down-regulation of β-TM-SM, α-TM-SM converted to α-TM-F1 and α-TM-F2 by a selectional change from exon 2a to exon 2b during dedifferentiation of smooth muscle cells in culture. Simultaneously, a change of caldesmon isoforms from high M r type to low M r type was also observed by alternative selection between exons 3b and 4 in the caldesmon gene during this process. In contrast, cultured smooth muscle cells maintaining a differentiated phenotype continued to express α-TM-SM, β-TM-SM, and high M r caldesmon. In situhybridization revealed specific coexpression of α-TM-SM and highM r caldesmon in smooth muscle in developing embryos. These results suggest a common splicing mechanism for phenotype-dependent expression of tropomyosin and caldesmon isoforms in both visceral and vascular smooth muscle cells.
Effect of vaccination on transmission characteristics of highly virulent Newcastle disease virus in experimentally infected chickens

An experimental study was conducted to evaluate the effect of vaccines produced in Ethiopia from vaccine strains used worldwide on the transmission characteristics of velogenic Newcastle disease virus field strain after different vaccination schemes. Chickens were vaccinated with Hitchner B1, La Sota or I-2 via the intraocular and intranasal routes. Vaccine and challenge viruses induced high antibody levels, both in inoculated and contact birds. Prime-boost vaccination protected birds against morbidity and mortality and significantly reduced the incidence of viral shedding from chickens compared with single vaccinated and unvaccinated birds. Protection from disease and mortality was correlated with the presence of positive antibody titres (>4 log2) at day of challenge. Most of the unvaccinated and in-contact birds excreted the virus and showed a high level of antibody titres, indicating the high infectivity of the challenge virus. The detection of the challenge virus in most of vaccinated birds demonstrated that the tested vaccination protocols cannot fully protect birds from viral infection, replication and shedding, and vaccinated–infected birds can act as a source of infection for susceptible flocks. The high mortality observed in unvaccinated birds and their contacts confirmed the virulence of the challenge virus and indicated that this field virus strain can easily spread in an unvaccinated poultry population and cause major outbreaks. Progressive vaccinations supported by biosecurity measures should therefore be implemented to control the disease and introduction of the virus to the poultry farms.
Distribution of putative male sex pheromones among Lutzomyia sandflies (Diptera: Psychodidae)

Abstract Male Lutzomyia longipalpis produce terpene sex pheromones in glandular tissue underlying the cuticle. The pheromones are transmitted to the surface via cuticle-lined ducts (measuring 0.25 mmin diameter), each of which reaches the surface in the centre of a papule (measuring 3-3.5 mmin diameter). Similar papules, in a range of shapes but all characterized by the presence of a central pore and absence of macrosetae, occur in some other species of sandfly. The aim of the present study was to determine the distribution of sex pheromones in sandflies of the genus Lutzomyia that do and do not have the papules. The results indicate that sex pheromones are not widely distributed amongst male Lutzomyia spp. Male members of the genus can be subdivided into three groups: those that produce terpenes and have cuticular papules; those that do not produce terpenes but still have the associated papules; and those that have neither terpenes nor papules. The papules seen in the species that do not synthesise sex pheromones are presumably vestigial, non-functional structures. Such species may have stopped producing pheromone as the result of changes in the way in which the females found and selected mates or changing feeding preferences. A similar event has occurred in the Lepidoptera, where vestigial pheromone-secreting structures remain in some species which no longer produce pheromone. Lutzomyia lenti collected in southern Brazil produced a novel diterpene whereas male L. lenti from north-eastern Brazil did not, supporting suggestions by others that L. lenti is, like L. longipalpis, a species complex.
‘Iatrogenic’ Wernicke’s Encephalopathy in Japan

‘Iatrogenic’ Wernicke’s encephalopathy has appeared to occur more frequently in Japan, probably induced by the change of our Japanese national health insurance policy in 1992. We report 4 nonalcoholic patients with such Wernicke’s encephalopathy, which occurred during the early postoperative oral food intake period following intravenous nutrition without vitamin supplements. We analyzed the medical records of 4 patients, 3 men and 1 woman, aged between 55 and 71 years, who were admitted to our hospital between 1992 and 1995. Three patients underwent gastrointestinal surgery and 1 suffered chronic pyothorax. We diagnosed our patients as having Wernicke’s encephalopathy based on typical neurological abnormalities, in addition to typical cranial magnetic resonance image findings, low serum vitamin B1 levels, or both. Although all of the patients were treated with vitamin B1 and showed some improvement, 1 patient developed Korsakoff syndrome, 2 made incomplete neurological recovery, and 1 died. We speculated that the body vitamin B1 stores had been decreasing in our patients who did not receive any vitamin supplements during intravenous hyperalimentation or hydration. Subsequent administration of high calorie and high carbohydrate oral diets increased the demand for vitamin B1, further depleting the vitamin stores, thereby causing ‘iatrogenic’ Wernicke’s encephalopathy. The change of our national health insurance policy in 1992 discouraged the routine administration of vitamins, probably causing Wernicke’s encephalopathy in our patients.
Inhibition of the acrosome reaction by trypsin inhibitors and prevention of penetration of spermatozoa through the human zona pellucida.

In this study we evaluated the effect of several trypsin inhibitors (p-aminobenzamidine: pAB; N-alpha-p-tosyl-L-lysine-chloromethyl-ketone: TLCK and p-nitrophenyl-p'-guanidino-benzoate: NPGM) on sperm binding and penetration of the human zona pellucida. Motile spermatozoa, selected by a two-step Percoll gradient, were incubated at 1 x 10(7) cells ml-1 at 37 degrees C and in 5% CO2 for 4.5 h. This was followed by the addition of 1 mmol pAB l-1 or phosphate-buffered saline (control) for 30 min. Three to four non-viable human oocytes were then added to each sperm suspension and incubated for 3 h. The numbers of spermatozoa bound to the human zona pellucida and in the perivitelline space were determined by phase contrast microscopy. The results showed that pAB significantly inhibited zona penetration by spermatozoa (56 +/- 8% oocytes penetrated, control versus 0 +/- 0% oocytes penetrated, pAB, mean +/- SEM), without modifying spermatozoa-zona pellucida binding. The inhibition of zona penetration was due to a block of the acrosome reaction normally induced by the human zona pellucida. In separate experiments, sperm suspensions pretreated with 1 mmol pAB l-1 or 10 mumol NPGB l-1 exhibited a marked decrease in the percentage of acrosome reactions on the zona surface (85 +/- 4% and 76 +/- 3% inhibition, respectively). In addition, the inhibitors prevented the acrosome reaction induced by human follicular fluid (percentage of acrosome-reacted spermatozoa: control 8 +/- 2; follicular fluid 25 +/- 3; pAB 6 +/- 2; NPGB 8 +/- 1; TLCK 12 +/- 2). (ABSTRACT TRUNCATED AT 250 WORDS)
The Anti-Methicillin-Resistant Staphylococcus aureus Quinolone WCK 771 Has Potent Activity against Sequentially Selected Mutants, Has a Narrow Mutant Selection Window against Quinolone-Resistant Staphylococcus aureus, and Preferentially Targets DNA Gyrase

ABSTRACT WCK 771 is a broad-spectrum fluoroquinolone with enhanced activity against quinolone-resistant staphylococci. To understand the impact of the target-level interactions of WCK 771 on its antistaphylococcal pharmacodynamic properties, we determined the MICs for genetically defined mutants and studied the mutant prevention concentrations (MPCs), the frequency of mutation, and the cidality against the wild type and double mutants. There was a twofold increase in the MICs of WCK 771 for single gyrA mutants, indicating that DNA gyrase is its primary target. All first- and second-step mutants selected by WCK 771 revealed gyrA and grlA mutations, respectively. The MICs of WCK 771 and clinafloxacin were found to be superior to those of other quinolones against strains with double and triple mutations. WCK 771 was also cidal for high-density double mutants at low concentrations. WCK 771 and clinafloxacin showed narrow mutant selection windows compared to those of the other quinolones. Against a panel of 50 high-level quinolone-resistant clinical isolates of staphylococci (ciprofloxacin MIC ≥ 16 μg/ml), the WCK 771 MPCs were ≤2 μg/ml for 68% of the strains and ≤4 μg/ml for 28% of the strains. Our results demonstrate that gyrA is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin). WCK 771 displayed an activity profile comparable to that of clinafloxacin, a dual-acting quinolone with a high affinity to DNA gyrase. Overall, the findings signify the key role of DNA gyrase in determining the optimal antistaphylococcal features of quinolones.
Health economic evaluation of treating anemia in cancer patients receiving chemotherapy: a study in Belgian hospitals.

BACKGROUND Erythropoiesis-stimulating agents (ESAs) are used in chemotherapy-induced anemia (CIA) with the goal of improving quality of life and preventing RBC transfusions. This retrospective database study compared the three currently available ESAs, epoetin alfa (EPO-A), epoetin beta (EPO-B), and darbepoetin alfa (DARB), regarding costs and outcomes. METHODS Data were obtained from a Belgian longitudinal database, including medical and financial data on cancer patients receiving chemotherapy and ESAs, submitted by 46 Belgian hospitals. Propensity score matching was applied to correct for selection bias. The main effectiveness parameter was defined as transfusion- and anemia-readmission-free survival (TA-free survival) at 3 months. Costs were analyzed taking the health care payer perspective. RESULTS Including 1,584 EPO-A, 380 EPO-B, and 429 DARB propensity-matched patients, TA-free survival rates were similar for the three groups (DARB, 84.37%; EPO-A, 84.60%; EPO-B, 84.94%). Overall inpatient costs were euro 16,949 +/- euro 1,025, euro 19,472 +/- euro 901, and euro 19,295 +/- euro 1,048 for DARB, EPO-A, and EPO-B, respectively (DARB versus EPO-A, p < .0001 and DARB versus EPO-B, p = .008). Anemia-associated costs were euro 3,051 +/- euro 218 in the DARB group, compared with euro 3,995 +/- euro144 for EPO-A (p < .0001) and euro 3,752 +/- euro 229 for EPO-B (p = .0132). CONCLUSION To our knowledge, this is the first real-life matched retrospective study comparing ESAs with regard to both costs and effects. For similar patient profiles, the patients in the DARB group consumed the smallest amounts of ESAs, with similar clinical outcomes. These data therefore suggest a greater efficiency of DARB in the treatment of CIA.
The cost-effectiveness of an inner-city asthma intervention for children.

BACKGROUND Comprehensive management efforts to reduce asthma morbidity among children in urban areas with high levels of poverty and large minority populations have been inconclusive. The National Cooperative Inner-City Asthma Study (NCICAS) demonstrated improved symptom outcomes but did not evaluate cost-effectiveness in this population. OBJECTIVE We sought to examine the incremental cost-effectiveness of a comprehensive social worker-based education program and environmental control in children with asthma stratified by baseline level of asthma control. METHODS We performed a prospective cost-effectiveness analysis alongside a randomized trial. A total of 1033 children and their families residing in 8 inner-city urban areas in the United States were enrolled in the NCICAS. Outcomes included symptom-free days, cost per symptom-free day gained, and annual costs of asthma morbidity compared by baseline symptom control, previous hospitalization, and previous unscheduled physician visits. RESULTS The NCICAS intervention significantly reduced asthma symptoms. First-year intervention costs were 245 US dollars higher for the intervention children compared with those receiving usual care. There were no additional intervention-related costs during the second year. When compared with usual care, the intervention improved outcomes at an average additional cost of 9.20 US dollars per symptom-free day gained (95% CI, -12.56 to 55.29 US dollars). The intervention was cost saving in 3 strata of children with increasing asthma severity. CONCLUSIONS A multifaceted asthma intervention program reduced symptom days and was cost-effective for inner-city children with asthma. In children with more severe disease, the intervention was substantially more effective and reduced costs compared with that seen in control children. Organizations serving this population should consider this strategy as part of a comprehensive disease-management program for asthma.
Randomized controlled clinical trial of a combination of somatostatin analog and dexamethasone plus zoledronate vs. zoledronate in patients with androgen ablation-refractory prostate cancer.

BACKGROUND As previously shown, the combination of standard androgen ablation therapy with somatostatin analog and dexamethasone in metastatic androgen ablation-refractory (stage D3) prostate cancer (PrCa) patients has a favorable profile of side-effects, durable objective antitumor activity (up to 60% partial response rate) and palliative effects. Bisphosphonates interfere with bone remodeling at the sites of PrCa bone metastases and have been postulated to have indirect and/or direct anti-PrCa activity. MATERIALS AND METHODS A randomized controlled clinical trial was conducted to compare a combination of somatostatin analog (octreotide 20 mg i.m. every 28 days) and oral dexamethasone (4 mg daily for 1 month, gradually reduced to 1 mg daily by the fourth month, with a 1 mg daily maintenance dose thereafter) plus zoledronate (4 mg i.v. every 4 weeks) vs. zoledronate only. All patients in both arms remained in basic androgen blockade throughout the study. RESULTS Thirty-eight stage D3 patients (mean age 72.8 +/- 6.8 years) were randomized to either treatment arm of the study. The trial was stopped after a pre-specified interim analysis met the criteria for early closure, i.e. significant difference in outcomes between the two treatment arms. Partial responses (PR, > or =50% PSA decline) were observed in 13 out of 20 patients with combination therapy vs. none with zoledronate. The combination therapy arm had significantly better outcome with respect to median progression-free survival (7.0 vs. 1.0 months, p < 0.0001), median overall survival (OS) (12.0 vs. 9.0 months, p = 0.0027), median PrCa-specific OS (defined as time from onset of therapy until PrCa-related death) (16 vs. 9.0 months, p = 0.0005) and median duration of bone pain improvement (>14 vs. 4 months p = 0.00001 by log-rank tests). CONCLUSION For androgen ablation-refractory metastatic PrCa patients under androgen ablation, the combination of dexamethasone, somatostatin analog and zoledronate offered superior objective and palliative clinical responses than zoledronate alone.
B‐cell epitopes of the allergen Chi t 1.01: peptide mapping of epitopes recognized by rabbit, murine, and human antibodies

Background: Chi t 1.01, a hemoglobin of the midge Chironomus thummi thummi, is a widespread environmental and occupational allergen. The aim of the present investigation was to identify and compare peptides involved in B‐cell epitopes of Chi t 1.01 recognized by 15 human IgE sera, six murine monoclonal antibodies (mAbs), and a polyclonal rabbit antiserum.
T-Cell Receptor-Mediated Anergy of a Human Immunodeficiency Virus (HIV) gp120-Specific CD4+ Cytotoxic T-Cell Clone, Induced by a Natural HIV Type 1 Variant Peptide

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection triggers a cytotoxic T-lymphocyte (CTL) response mediated by CD8+ and perhaps CD4+ CTLs. The mechanisms by which HIV-1 escapes from this CTL response are only beginning to be understood. However, it is already clear that the extreme genetic variability of the virus is a major contributing factor. Because of the well-known ability of altered peptide ligands (APL) to induce a T-cell receptor (TCR)-mediated anergic state in CD4+ helper T cells, we investigated the effects of HIV-1 sequence variations on the proliferation and cytotoxic activation of a human CD4+ CTL clone (Een217) specific for an epitope composed of amino acids 410 to 429 of HIV-1 gp120. We report that a natural variant of this epitope induced a functional anergic state rendering the T cells unable to respond to their antigenic ligand and preventing the proliferation and cytotoxic activation normally induced by the original antigenic peptide. Furthermore, the stimulation of Een217 cells with this APL generated altered TCR-proximal signaling events that have been associated with the induction of T-cell anergy in CD4+ T cells. Importantly, the APL-induced anergic state of the Een217 T cells could be prevented by the addition of interleukin 2, which restored their ability to respond to their nominal antigen. Our data therefore suggest that HIV-1 variants can induce a state of anergy in HIV-specific CD4+ CTLs. Such a mechanism may allow a viral variant to not only escape the CTL response but also facilitate the persistence of other viral strains that may otherwise be recognized and eliminated by HIV-specific CTLs.
An Improved Discrete Preisach Model of Open Circuit Voltage Hysteresis for LiFePO4 Batteries

The relationship between open circuit voltage (OCV) and state of charge (SOC) is a critical characterization for batteries. The hysteresis that OCV differs between charge and discharge at the same SOC need to be carefully studied for some battery types such as NiMH and LiFePO4. In previous research, the discrete Preisach model has proven to be effective and accurate for describing the hysteresis of LiFePO4 batteries. However, the partitions of the Preisach triangle in the discrete Preisach model are assumed to be equal in the whole OCV range which will lead to large numbers of grids as well as much computational burden. In this paper, a non-equal partition method is proposed which can not only decrease the number of partitions in the Preisach triangle but also guarantee the model performances. The results show that the partitions number and grids number in the proposed method are only half and 25% of the previous ones respectively and the precisions of SOC output are still within 4%.
A New Design Approach of Dopingless Tunnel FET for Enhancement of Device Characteristics

Formation of abrupt tunneling junction for the sub-nanometer tunnel FET (TFET) is crucial for achieving better electrical behavior. This task is more challenging in the case of dopingless TFETs (DL TFETs). In this concern, we propose a novel design of DL TFET, wherein a metallic layer has been placed in the oxide region at the space present between gate and source electrode (used for inducing p+ region) of conventional dopingless n-TFET to overcome the issue of low on-state current (<inline-formula> <tex-math notation="LaTeX">$\text{I}_{\mathrm{on}}$ </tex-math></inline-formula>) due to presence of tunneling barrier. Proposed modification is helpful for achieving steeper tunneling junction at the source/channel interface, which enables higher tunneling generation rate of charge carriers at this interface. The optimization for work function of the metal layer (ML) has been performed for improving <inline-formula> <tex-math notation="LaTeX">$\text {I}_{\mathrm{on}}$ </tex-math></inline-formula>, point subthreshold swing and threshold voltage (<inline-formula> <tex-math notation="LaTeX">$\text {V}_{\text {th}}$ </tex-math></inline-formula>). Finally, the impact of the ML misalignment from the gate/source terminal and optimization of its length is also presented.
The major indole alkaloid N,β-D-glucopyranosyl vincosamide from leaves of Psychotria leiocarpa Cham. & Schltdl. is not an antifeedant but shows broad antioxidant activity

N,β-D-glucopyranosyl vincosamide (GPV), a major alkaloid of Psychotria leiocarpa, constitutes up to 2.5% of the dry weight in leaves. Alkaloid content was not elicited by mechanical wounding or jasmonate. At concentrations found in natural conditions or 2.5 fold higher, GPV did not inhibit herbivory in two unrelated generalist models (Helix aspersa and Spodoptera frugiperda) or in a specific interaction model (Heliconius erato fed with Passiflora suberosa). In situ staining assay showed quenching activity of hydrogen peroxide by GPV. Exposure of P. leiocarpa to acute UV-B stress did not change GPV or chlorophyll content, indicating high tolerance to this stress by the species. In vitro antioxidant tests against singlet oxygen, superoxide anions and hydroxyl radicals showed efficient quenching activity of the alkaloid. GPV was not effective as antifeedant, but it may act indirectly in P. leiocarpa protection against oxidative stress generated upon wounding, UV exposure and perhaps other environmental stresses.
Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs

Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the “athlete’s heart” in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling in these three athletic species. The available literature provides compelling evidence for exercise-induced cardiac remodeling in all three species. However, more work is required to understand the influence of species/breed specific genetics and exercise-related hemodynamics, in order to fully understand the impact of exercise on cardiac structure.