Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-to-cell propagation of infectious cytosolic protein aggregates

Prions are self-templating protein conformers that replicate by recruitment and conversion of homotypic proteins into growing protein aggregates. Originally identified as causative agents of transmissible spongiform encephalopathies, increasing evidence now suggests that prion-like phenomena are more common in nature than previously anticipated. In contrast to fungal prions that replicate in the cytoplasm, propagation of mammalian prions derived from the precursor protein PrP is confined to the cell membrane or endocytic vesicles. Here we demonstrate that cytosolic protein aggregates can also behave as infectious entities in mammalian cells. When expressed in the mammalian cytosol, protein aggregates derived from the prion domain NM of yeast translation termination factor Sup35 persistently propagate and invade neighboring cells, thereby inducing a self-perpetuating aggregation state of NM. Cell contact is required for efficient infection. Aggregates can also be induced in primary astrocytes, neurons, and organotypic cultures, demonstrating that this phenomenon is not specific to immortalized cells. Our data have important implications for understanding prion-like phenomena of protein aggregates associated with human diseases and for the growing number of amyloidogenic proteins discovered in mammals.
A comparison of leucocyte responses to heat‐killed bacillus Calmette‐Guérin in different CNS compartments

We have previously shown that heat‐killed bacillus Calmette‐Guérin (BCG) injected into the CNS parenchyma does not produce a typical delayed‐type hypersensitivity (DTH) response [23]. In this paper we have compared the initial leucocyte response in the CNS parenchyma, ventricles and skin to gain insight into the mechanisms by which the DTH response in the CNS might be controlled. We have found that 105 organisms of heat‐killed BCG injected into either the CNS parenchyma or the lateral ventricles produced a rapid neutrophil response at the site of the injection, which was comparable with that in the skin. The neutrophil response resolved within the first week. Unlike the neutrophil response, the mononuclear phagocyte response in the CNS parenchyma was much smaller than that seen in the ventricles and the skin and it resolved within 4 weeks. Furthermore, the myelomonocytic response in the CNS parenchyma failed to clear the BCG. The acute inflammatory response in the choroid plexus/ventricles and skin developed with a similar time‐course into a typical DTH response. After the first week, lesions at these two sites were composed predominantly of T‐cells and macrophages. DTH lesions were still detected at both sites after 6 weeks. The failure of the immune system to recognize foreign antigens sequestrated in the CNS parenchyma may have significant implications especially in studies of inflammatory responses in the CNS of unknown origin.
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Are insurgents affected by new information about the United States' sensitivity to costs? Using data on attacks and variation in access to international news across Iraqi provinces, we identify an "emboldenment" effect by comparing the rate of insurgent attacks in areas with higher and lower access to information about U.S news after public statements critical of the war. We find that in periods after a spike in war-critical statements, insurgent attacks increases by 7-10 percent, but that this effect dissipates within a month. Additionally, we find that insurgents shift attacks from Iraqi civilian to U.S. military targets following new information about the United States' sensitivity to costs, resulting in more U.S. fatalities but fewer deaths overall. These results suggest that there is a small but measurable cost to open public debate in the form of higher attacks in the short-term, and that Iraqi insurgent organizations - even those motivated by religious or ideological goals - are strategic actors that respond rationally to the expected probability of US withdrawal. However, the implied costs of open, public debate must be weighed against the potential gains. We conclude that to the extent insurgent groups respond rationally to the incentives set by the policies of pro-government forces, effective counterinsurgency should prioritize manipulating costs and inducements, rather than focus simply on search and destroy missions.
Independent prognostic importance of microvessel density in clinically localized prostate cancer.

BACKGROUND Previous studies have reported a possible prognostic importance of microvessel density (MVD) in prostate cancer, although the significance after radical prostatectomy is not clear. The purpose of this study was to assess the prognostic value of MVD in clinically localized prostatic adenocarcinomas, focusing on moderately-differentiated tumours. MATERIALS AND METHODS We examined a series of 104 patients treated for presumed organ-confined cancer in the period 1988-94. The area of highest tumour grade was selected from the prostatectomy specimens and vessels were high-lighted by staining for factor-VIII-related antigen. MVD was quantitated in the "hot spot" area and related to biochemical failure and clinical recurrence. RESULTS In moderately differentiated tumours (WHO grade) (n = 66), MVD was associated with preoperative s-PSA and positive surgical margins. In univariate 5-year analysis, microvessel density (MVDmean > 122 mm-2, median) (p = 0.0074), s-PSA, tumour dimension, capsular penetration, seminal vesicle invasion and positive surgical margins were all significant predictors of biochemical failure, while MVDmean (p = 0.0084) was the only statistically significant predictor of clinical recurrence. In multivariate Cox' analysis, MVDmean (p = 0.0003), capsular penetration and tumour dimension remained as independent predictors of biochemical failure. CONCLUSION Assessment of MVD in moderately differentiated prostatic adenocarcinomas may improve the prognostic stratification of patients after radical prostatectomy.
Design and Development of an Efficient Multilevel DC/AC Traction Inverter for Railway Transportation Electrification

This paper presents a new trend in the transportation industry to adopt the multilevel inverter-based propulsion systems and gives the design procedure of a new DC/AC three-phase six-level inverter for powering the rail metro cars. The proposed inverter is based on the multilevel converter as it possesses much lower component voltage stress compared with the pulsewidth-modulated (PWM) topologies. Space vector pulsewidth modulation (SVPWM) with back-to-back clamped diode voltage modulation operation is used to achieve voltage regulation and high efficiency at any loading condition. Zero-current-switching operation is achieved without using an auxiliary circuit, which leads to minimum switching losses. The novelty of the proposed inverter lies within the proposed control methodology, which uses a new switching pattern that guarantees a modified SVPWM to eliminate the unwanted harmonics from the output voltage. The new algorithm is developed using numerical iterative solution using the Newton-Raphson technique that was downloaded to the processor using digital signal processing developed code. The mathematical model is simple but proven to be effective. As a result, a higher operating efficiency at full load of 98.5% is achieved as compared to previous efficiency of 97%. Analytical, simulation, and experimental results of a 1500 Vdc/700 Vac 400-kW converter are presented to offer the proof of concept. The converter provides real estate savings for the train under floor layout, higher operating efficiency as well as better cost price than the conventional two-level PWM hard-switched converters.
The Wilhelmine E. Key 1987 invitational lecture. Genetic changes associated with the evolution of adaptedness in cultivated plants and their wild progenitors.

The results of long-term studies of changes in adaptedness in a number of experimental populations of annual plants are summarized. Measurements made of quantitative traits showed that cumulative increases in reproductive capacity continued in these experimental populations for more than 50 generations. Highly significant allelic frequency changes also occurred for marker loci governing morphological variants, disease resistance, allozymes, and rDNA restriction fragments. Individual effects of the marker loci on quantitative traits were determined by extensive progeny testing of selfed families descended from single plants isolated from various generations of the experimental populations. Comparisons between homozygotes and heterozygotes of marker loci for quantitative trait expression revealed that all the marker loci studied had statistically significant additive effects on several to many quantitative traits; thus, each Mendelian locus, in addition to being a locus for its discrete descriptive effect, was also a locus for several quantitative traits. Consistent associations were found between superior reproductive capacity (e.g., larger numbers of kernels per plant) and the alleles of marker loci that increased in frequency over generations; no other quantitative traits measured were clearly and consistently associated with alleles that increased in frequency. Multilocus analyses based on canonical correlation, log linear, and cluster analysis procedures showed that highly significant associations developed in early generations among alleles of different loci in all the predominantly selfing populations studied. Dynamic changes featuring amalgamations of alleles into fewer clusters involving larger numbers of loci continued into the late generations. Patterns of ecogenetic differentiation that developed under predominant selfing were found to be fine-scaled overlays of environmental heterogeneity. The picture of evolutionary change that emerges is one in which the incorporation of increasing numbers of favorably interacting alleles into large synergistic complexes was accompanied in inbreeding populations by increases in adaptedness to the local environment and also by striking ecogenetic differentiation among local populations that occupy unlike habitats, including differentiation between cultivated plants and their wild progenitors. Selfing appears to promote the development and maintenance of adaptedness within populations and at the same time to facilitate the development of spatial differentiation by retarding gene flow between populations. (ABSTRACT TRUNCATED AT 400 WORDS)
Comparison of intrathecal ropivacaine-fentanyl and bupivacaine-fentanyl for major lower limb orthopaedic surgery: A randomised double-blind study

Background and Aims: Intrathecal bupivacaine results in complete anaesthetic block of longer duration than ropivacaine. Fentanyl as an adjuvant may improve the quality of spinal block of ropivacaine while maintaining its advantage of early motor recovery. In this study, we proposed to compare the efficacy and safety of intrathecal ropivacaine-fentanyl (RF) with bupivacaine-fentanyl (BF) for major lower limb orthopaedic surgeries. Methods: Sixty patients were randomly allocated to receive either intrathecal 15 mg 0.5% ropivacaine with 25 mcg fentanyl (Group RF) or 15 mg 0.5% bupivacaine with 25 mcg fentanyl (Group BF). The onset, duration, spread of sensory and motor block, haemodynamic parameters and side effects were recorded. Statistical Package for Social Sciences 20 software was used for statistical analysis. Results: Time to reach highest sensory level and complete motor block were comparable. Sensory regression to L1 dermatome was 226 ± 46.98 min in Group RF and 229.33 ± 50.51 min in Group BF, P = 0.36. The motor recovery to Bromage scale 1 was faster in Group RF (242.8 ± 47.06 min) than Group BF (268 ± 49.9 min) P = 0.023. Time for rescue analgesia was prolonged in Group BF (263.33 ± 63 min) when compared to Group RF (234.44 ± 58.76 min), P = 0.021. The haemodynamic stability was better in Group RF than Group BF. Conclusion: Intrathecal RF provided satisfactory anaesthesia with haemodynamic stability for major lower limb orthopaedic surgery. It provided similar sensory but shorter duration of motor block compared to BF which is a desirable feature for early ambulation, voiding and physiotherapy.
The influence of pro-environmental managers’ personal values on environmental disclosure

PurposeThe purpose of this paper is to examine in greater depth the influence of internal factors on the disclosure of environmental information by companies. The influence of pro-environmental managers´ personal values on environmental disclosure quality is analyzed and the extent to which the influence of those values is mediated by the practices associated with the environmental organizational structure of the company.Design/methodology/approachThe authors use a partial least squares structural equation model to analyze the relationship between the quality of the environmental information disclosed by 137 environmentally sensitive Spanish firms, their level of commitment towards the environment and the personal values of the directors in charge of those reports.FindingsA central finding of this work is that a positive relationship between the pro-environmental managers’ personal values and environmental disclosure quality is fully mediated by the environmental organizational structures of their companies.Practical implicationsA better understanding of the relationship between the personal values of managers and corporate environmental reporting quality will contribute to the design of policies that can enhance firm transparency and accountability, for example, by educating future managers in sustainability values.Social implicationsLight is cast on the mechanisms that can enhance corporate transparency and accountability in relation to environmental matters.Originality/valueIn this paper, a quantitative study of the internal driving forces of environmental disclosure is conducted, an aspect that has often been ignored in the literature on quantitative voluntary social reporting. The merit of this approach is its contribution to the literature through the analysis of the reasons why powerful actors within firms could (or could not) develop corporate social reporting practices.
Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested. METHOD Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment. RESULTS With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups. CONCLUSION Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov identifier: NCT00159081.
Susceptibility of the different developmental stages of the asexual (schizogonic) erythrocyte cycle of Plasmodium chabaudi chabaudi to hyperimmune serum, immunoglobulin (Ig)G1, IgG2a and F(ab′)2 fragments

The mechanisms by which antibodies interfere with Plasmodium growth are still under debate. Characterizing the asexual erythrocyte stages susceptible to antibodies from hyperimmune individuals is therefore a relevant contribution to vaccine research. In this study, using a virulent and synchronous murine malaria parasite, Plasmodium chabaudi chabaudi AJ, we have shown that trophozoites and circulating schizonts are not the main targets for antibodies from hyperimmune serum. In drug‐cured mice challenged with a high inoculum of ring‐infected erythrocytes, parasitemias do not decline until the moment of erythrocyte rupture, suggesting that effector mechanisms operate immediately prior to reinvasion. Confirming these findings, treatment of primary‐infected mice with hyperimmune serum inhibited the generation of new ring forms, but did not alter the numbers of schizont‐infected erythrocytes, despite the fact that these cells were recognized by immunoglobulin (Ig)G antibodies. When these mice were treated with IgG1 or IgG2a purified from hyperimmune serum, both subclasses limited reinvasion, but IgG2a showed a stronger protective activity. The fact that Fc digestion decreases but does not abrogate protection suggests that both Fc‐dependent and independent mechanisms participate in this process. Treatment with cobra venom factor did not interfere with the antibody‐mediated protection, ruling out the participation of the complement system in both lysis and phagocytosis of merozoites or infected erythrocytes. Therefore, in mice suffering from P. c. chabaudi AJ malaria, merozoite neutralization seems to be a major mechanism of protection conferred by hyperimmune serum antibodies. However, FcγR‐mediated interactions, or other mechanisms not yet defined, may also contribute to inhibit erythrocyte reinvasion.
Lessons Learned about Human Stem Cell Responses to Ionizing Radiation Exposures: A Long Road Still Ahead of Us

Human stem cells (hSC) possess several distinct characteristics that set them apart from other cell types. First, hSC are self-renewing, capable of undergoing both asymmetric and symmetric cell divisions. Second, these cells can be coaxed to differentiate into various specialized cell types and, as such, hold great promise for regenerative medicine. Recent progresses in hSC biology fostered the characterization of the responses of hSC to genotoxic stresses, including ionizing radiation (IR). Here, we examine how different types of hSC respond to IR, with a special emphasis on their radiosensitivity, cell cycle, signaling networks, DNA damage response (DDR) and DNA repair. We show that human embryonic stem cells (hESCs) possess unique characteristics in how they react to IR that clearly distinguish these cells from all adult hSC studied thus far. On the other hand, a manifestation of radiation injuries/toxicity in human bodies may depend to a large extent on hSC populating corresponding tissues, such as human mesenchymal stem cells (hMSC), human hematopoietic stem cells (hHSC), neural hSC, intestine hSC, etc. We discuss here that hSC responses to IR differ notably across many types of hSC which may represent the distinct roles these cells play in development, regeneration and/or maintenance of homeostasis.
Predicting erectile dysfunction following surgical correction of Peyronie's disease without inflatable penile prosthesis placement: vascular assessment and preoperative risk factors.

INTRODUCTION Surgical therapy remains the gold standard treatment for Peyronie's Disease (PD). Surgical options include plication, grafting, and placement of inflatable penile prosthesis (IPP). Postoperative erectile dysfunction (ED) is a potential complication for PD surgery without IPP. We present our large series follow-up to evaluate preoperative risk factors for postoperative ED. AIMS The aim of this study is to evaluate preoperative risk factors for the development of ED following surgical correction of PD taking into account the degree of curvature, graft size, surgical approach, hypertension, hyperlipidemia, diabetes, smoking history, preoperative use of phosphodiesterase 5 inhibitors (PDE5), and preoperative duplex ultrasound findings including peak systolic and end diastolic velocities and resistive index. METHODS We identified 218 men undergoing either tunica albuginea plication (TAP) or partial plaque excision with pericardial grafting for PD following a previously published algorithm between November 1992 and April 2007. Preoperative and postoperative erectile function, curvature characteristics, presence of vascular risk factors, and duplex ultrasound findings were available on 109 patients. MAIN OUTCOME MEASURES Our primary outcome measure is the development of ED after surgery for PD. RESULTS Ten percent of TAP and 21% of plaque excision with grafting patients developed postoperative ED. Neither curve direction (P = 0.76), graft area (P = 0.78), surgical approach (P = 0.12), chronic hypertension (P = 0.51), hyperlipidemia (P = 0.87), diabetes (P = 0.69), nor smoking history (P = 0.99) were significant predictors of postoperative ED. No combination of risk factors was found to be predictive of postoperative ED. Preoperative use of PDE5 was not a significant predictor of postoperative ED (P = 0.33). Neither peak systolic, end diastolic, nor resistive index were significant predictors of ED (P = 0.28, 0.28, and 0.25, respectively). CONCLUSION This long-term follow-up of a large published series suggests that neither preoperative risk factors nor preoperative duplex ultrasound findings are predictive of postoperative ED, thus reinforcing the use of previously published preoperative treatment algorithms.