Miracle-dz/UniFAR-FTUs huggingface dataset:
The global regulator RNase III modulates translation repression by the transcription elongation factor N

Efficient expression of most bacteriophage λ early genes depends upon the formation of an antiterminating transcription complex to overcome transcription terminators in the early operons, pL and pR. Forma tion of this complex requires the phage‐encoded protein N, the first gene product expressed from the pL operon. The N leader RNA contains, in this order: the NUTL site, an RNase III‐sensitive hairpin and the N ribosome‐binding site. N bound to NUTL RNA is part of both the antitermination complex and an autoregulatory complex that represses the translation of the N gene. In this study, we show that cleavage of the N leader by RNase III does not inhibit antitermination but prevents N‐mediated translation repression of N gene expression. In fact, by preventing N autoregulation, RNase III activates N gene translation at least 200‐fold. N‐mediated translation repression is extremely sensitive to growth rate, reflecting the growth rate regulation of RNase III expression itself. Given N protein's critical role in λ development, the level of RNase III activity therefore serves as an important sensor of physiological conditions for the bacteriophage.
Rebuttal from Gerard F. Curley, John G. Laffey and Brian P. Kavanagh

Beitler et al.'s (2013) review of the benefits and mechanisms of avoiding high tidal volume are right on the mark. In addition, they provide a sound biophysical basis for our concern about increasing respiratory rate to offset hypercapnic acidosis (HCA). However, the parallels drawn from other clinical contexts are problematic. For example, the trial of intravenous salbutamol for acute lung injury – stopped early due to harm – is a poor choice. Key concerns regarding salbutamol in that study are rare with moderate hypercapnia such as arrhythmia (Amato et al. 1998; Stewart et al. 1998; Brower et al. 1999), lactic acidosis (hypercapnia reduces it) (Higgins et al. 2009), and impaired oxygen supply–demand balance (hypercapnia improves it) (Wang et al. 2008). Likewise, HCA may certainly worsen pulmonary hypertension, and potentially the outcome; however, it attenuates a key antecedent of pulmonary hypertension, namely oxidant stress (Kantores et al. 2006). Elevated pulmonary vascular pressure in acute respiratory distress syndrome (ARDS) appears not to worsen mortality during low tidal volume ventilation (Osman et al. 2009). Indeed, HCA can augment ventilation–perfusion matching and thereby minimize the need for additional (harmful) ventilatory support (Ketabchi et al. 2009). The sedation issue is confounded as reports exist of HCA increasing (Stewart et al. 1998) or not increasing (Brower et al. 1999) sedative use; in the absence of protocolized sedation the evidence remains deficient. Moreover, the important patient–ventilator dyssynchrony mentioned by Beitler et al. may be due to inappropriate ventilator volume or flow, rather than hypercapnia per se. Immunosuppression from HCA is definitely a concern, especially in sepsis. However, the host response to infection may also contribute to organ injury. It is reassuring that with appropriate antibiotic use HCA does not increase bacterial load or organ injury in experimental pneumonia (Chonghaile et al. 2008); this parallels the conventional use of indicated immunosuppressive therapy in critically ill patients where the risk–benefit ratio is understood and surveillance undertaken. Should HCA during low tidal volume ventilation be treated with buffering agents? Buffering may ablate the protective effects of HCA (Laffey et al. 2000); indeed, while tris-hydroxymethyl amino-methane (THAM) may be preferable to sodium bicarbonate (less intracellular acidosis), the evidence from Dr Hubmayr's laboratory (Caples et al. 2009) indicates that this approach may be harmful. In summary, hypercapnia has beneficial and deleterious effects, depending on its level, timing and context. This is true of most therapies. The cumulative evidence suggests that appropriate use of permissive hypercapnia in ARDS might eventually prove beneficial.
Bacteriophage penetration in vertebrates

Bacteriophages are viruses that infect bacteria. They are the most numerous life forms on earth. As antibiotic resistance is becoming an increasingly worldwide challenge, bacteriophages as potential antimicrobial agents are being more intensively explored. Some very important questions involve their ability to penetrate higher organisms, as this determines potential phage activity in antibacterial treatment. Higher organisms are widely exposed to bacteriophages, which penetrate them quite freely. Bacteriophage activity can be influenced by specific antibodies which, together with the nonspecific immune system, can contribute to their rapid clearance from the organism. Bacteriophages can also interact directly with mammalian cells and even play a role in the development of some nonbacterial diseases, although they are not able to multiply in these cells. All aspects of the interaction between phages and higher organism are of interest and importance for further medical and biochemical applications.
Demonstration of the Renal Venous System at Routine Nephroangiography

The demonstration of renal veins during routine nephroangiography was retrospectively investigated and blindly scored in 60 patients. Three different types of contrast media were used: one high-osmolar ionic monomeric (metrizoate) and two low-osmolar, the non-ionic monomeric (metrizamide) and the ionic monoacidic dimeric (ioxalate). The renal veins and the inferior vena cava were significantly better and more often demonstrated when ioxaglate was used compared with metrizoate and metrizmide. There was no significant difference between metrizoate and metrizamide. Following semiselective renal artery injection, the main renal veins were demonstrated with a diagnostically acceptable quality with ioxaglate in 76 per cent, with metrizamide in 40 per cent and with metrizoate in 29 per cent. On selective renal artery injection the demonstration of renal veins increased to 85 per cent with ioxaglate and remained unchanged with metrizmide (38 %) and metrizoate (26%). Semiselective or selective nephroangiography with ioxaglate at an ordinary dose was in most patients sufficient to allow evaluation of renal vein involvement in disease, rendering high dose selective nephroangiography or selective nephrophlebography unnecessary. A slower diffusion rate of ioxaglate compared with metrizoate and metrizamide is considered to be the major explanation for the better demonstration of the renal veins.
Understanding the genetic architectonics of complex CNS traits: Lost by the association, but found in the interaction?

Recent evidence supports the value of endophenotypes and genome-wide association studies in psychiatric genetics, and their importance for dissecting the neural pathways and molecular mechanisms of complex neuropsychiatric disorders. Continuing this important discussion, here we outline three new mechanisms by which novel classes of genes may facilitate CNS pathogenesis without directly worsening its individual ‘established’ endophenotypes. These putative genetic mechanisms can apply to other human disorders in general, and may also be used for designing novel effective CNS drug treatments.
Reliability of the activities of daily living scale and its use in telephone interview.

Activities of daily living (ADL), a popular outcome assessment tool for studies of disabled populations, was evaluated for use in multicentered studies. The interobserver reliability of a modified Barthel Index of the ADL was evaluated on 18 stroke patients. Reliabilities between administrators of the ADL and between observers of the ADL administrations were r = . 99 for total scores and r greater than . 90 for most of the individual component items. The validity of ADL evaluation based on telephone interviews was demonstrated relative to ADL scores obtained on 72 patients in a direct test of their performance capabilities. The correlations between the performance-based ADL and the interview-based ADL were r greater than . 97 for the total score and r greater than . 85 for most of the individual items. The modified Barthel Index of the ADL is a reliable measure for assessing stable stroke patients, supporting its use in multicenter studies. In addition, the high validity observed in the telephone interview supports its use in longitudinal studies and large surveys where direct performance evaluation is not feasible or too costly.
Phase IIIb, open-label single-arm trial of darunavir/cobicistat (DRV/COBI): Week 48 subgroup analysis of HIV-1-infected treatment-nave adults

COBI, a PK enhancer with no ARV activity is a more selective cytochrome P450 (CYP)3A inhibitor than ritonavir (RTV), does not induce CYP isozymes, and thus has less potential for drug‐drug interactions. COBI boosts DRV PK as effectively as RTV in healthy volunteers.
The contribution of general language ability, reading comprehension and working memory to mathematics achievement among children with English as additional language (EAL): an exploratory study

ABSTRACT An increasing number of high-stakes mathematics standardised tests around the world place an emphasis on using mathematical word problems to assess students’ mathematical understanding. Not only do these assessments require children to think mathematically, but making sense of these tests’ mathematical word problems also brings children’s language ability, reading comprehension and working memory into play. The nature of these test items places a great deal of cognitive demand on all mathematics learners, but particularly on children completing the assessments in a second language that is still developing. This paper reports findings from an exploratory study on the contribution of language to mathematics achievement among 35 children with English as an Additional Language (EAL) and 31 children with English as their first language (FLE). The findings confirm the prominent role of general language ability in the development and assessment of mathematical ability. This variable explained more variance than working memory in word-based mathematics scores for all learners. Significant differences were found between the performance of FLE learners and EAL learners on solving mathematical word-based problems, but not on wordless problems. We conclude that EAL learners need to receive more targeted language support, including help with specific language knowledge needed to understand and solve mathematical word problems.
Structural Adaptation of Trabecular Bone Revealed by Position Resolved Analysis of Proximal Femora of Different Primates

The anisotropic arrangement of trabeculae in the proximal femur of humans and primates is seen as striking evidence for the functional adaptation of trabecular bone architecture. Quantitative evidence to demonstrate this adaptation for trabecular bone is still scarce, because experimental design of controlled load change is difficult. In this work, we use the natural variation of loading caused by a different main locomotor behavior of primates. Using high‐resolution computed tomography and advanced image analysis techniques, we analyze the heterogeneity of the architecture in four proximal femora of four primate species. Although the small sample number does not allow an interspecies comparison, the very differently loaded bones are well suited to search for common structural features as a result of adaptation. A cubic volume of interest of size (5 mm)3 was moved through the proximal femur and a morphometric analysis including local anisotropy was performed on 209 positions on average. The correlation of bone volume fraction (BV/TV) with trabecular number (Tb.N) and trabecular thickness (Tb.Th) leads to the suggestion of two different mechanisms of trabecular bone adaptation. Higher values of BV/TV in highly loaded regions of the proximal femur are due to a thickening of the trabeculae, whereas Tb.N does not change. In less loaded regions, however, lower values of BV/TV are found, caused by a reduction of the number of the trabeculae, whereas Tb.Th remains constant. This reduction in Tb.N goes along with an increase in the degree of anisotropy, indicating an adaptive selection of trabeculae. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Ku80 facilitates chromatin binding of the telomere binding protein, TRF2

The Ku70/80 heterodimer is central to non-homologous end joining repair of DNA double-strand breaks and the Ku80 gene appears to be essential for human but not rodent cell survival. The Ku70/80 heterodimer is located at telomeres but its precise function in telomere maintenance is not known. In order to examine the role of Ku80 fibroblast strain. Following targeted Ku80 knockdown, telomere defects are observed and the steady state levels of the TRF2 protein are reduced. Inhibitor studies indicate that this loss of TRF2 is mediated by the proteasome, and degradation of TRF2 following Ku depletion appears to involve a decrease in chromatin binding of TRF2, suggesting that the Ku heterodimer enhances TRF2 chromatin association and that non-chromatin bound TRF2 is targeted to the proteasome.
Treatment of femur fracture with associated vascular injury.

OBJECTIVE The aim of this study was to determine (1) if internal fixation was associated with a high amputation rate in patients with femur fracture and vascular injury; and (2) if patients who underwent internal fixation before vascular repair had a higher amputation rate. DESIGN This is a retrospective analysis. MATERIALS AND METHODS Twenty-six patients requiring femoral stabilization with injury to the superficial femoral artery, popliteal artery, or common femoral vein were studied. The Injury Severity Score and the Mangled Extremity Severity Score were calculated for each. Nineteen patients underwent internal fixation. Ten patients had internal fixation before vascular repair. RESULTS Sixteen of 19 patients treated with internal fixation had limb salvage. Nine of 10 patients who had internal fixation before vascular repair had limb salvage. Poor outcomes (gangrene, amputation, or death) were associated with a Mangled Extremity Severity Score > or = 6 (p = 0.005). CONCLUSIONS In these patients, poor outcome is associated with severe leg injury, (with a Mangled Extremity Severity Score of > or = 6). Internal fixation can be safely used, and skeletal stabilization can be safely performed before vascular repair. If ischemic time is prolonged, vascular shunts should be used until skeletal stabilization is completed.
A comparison of 99mTc-exametazime and 123I-FP-CIT SPECT imaging in the differential diagnosis of Alzheimer's disease and dementia with Lewy bodies

ABSTRACT Background: The aim of this study is to investigate the diagnostic value of perfusion 99mTc-exametazime single photon emission computed tomography (SPECT) in the diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) in comparison with dopaminergic 123I-2β-carbomethoxy-3β-(4-iodophenyl)-n-(3-fluoropropyl) nortropane (FP-CIT) SPECT imaging. Methods: Subjects underwent 99mTc-exametazime scanning (39 controls, 36 AD, 30 DLB) and 123I-FP-CIT scanning (33 controls, 33 AD, 28 DLB). For each scan, five raters performed visual assessments blind to clinical diagnosis on selected transverse 99mTc-exametazime images in standard stereotactic space. Diagnostic accuracy of 99mTc-exametazime was compared to 123I-FP-CIT results for the clinically relevant subgroups AD and DLB using receiver operating characteristic (ROC) curve analysis. Results: Inter-rater agreement for categorizing uptake was “moderate” (mean κ = 0.53) for 99mTc-exametazime and “excellent” (mean κ = 0.88) for 123I-FP-CIT. For AD and DLB, consensus rating matched clinical diagnosis in 56% of cases using 99mTc-exametazime and 84% using 123I-FP-CIT. In distinguishing AD from DLB, ROC analysis revealed superior diagnostic accuracy with 123I-FP-CIT (ROC curve area 0.83, sensitivity 78.6%, specificity 87.9%) compared to occipital 99mTc-exametazime (ROC curve area 0.64, sensitivity 64.3%, specificity 63.6%) p = 0.03. Conclusion: Diagnostic accuracy was superior with 123I-FP-CIT compared to 99mTc-exametazime in the differentiation of DLB from AD.
Life Stress and Post-Partum Psychosis: a Preliminary Report

This is a preliminary report from a prospective study of the influence of psychosocial stressors on post-natal relapse in women at high risk of psychiatric disorder after childbirth. Forty-three index subjects with a previous history of psychosis or severe depression were compared with 45 pregnant control subjects without any previous psychiatric disorder. After delivery 51% of index subjects relapsed (RDC diagnoses): 28% were categorised as psychotic and 23% non-psychotic. All psychotic relapses were in women with a previous history of bipolar or schizoaffective disorder (46% of this subgroup). Only the non-psychotic post-partum relapses (mostly depressions) were associated with an increased likelihood of a severe life event in the 12 months preceding illness onset.
Erythrocyte membrane fluidity and red cell cytosolic Ca2+ content during incubation, in normals and in subjects with vascular atherosclerotic disease and non-insulin-dependent diabetes mellitus.

In previous works [3–5] we found, in subjects with vascular atherosclerotic disease (VAD) with and without non-insulin-dependent diabetes mellitus (NIDDM), a significant decrease in erythrocyte membrane fluidity and a significant increase in red cell cytosolic Ca2+ content. These data, associated with the knowledge of the erythrocyte rheological and metabolic alterations accompanying storage [1,2,8,9,11,12], had previously led us to verify the trend of the erythrocyte membrane fluidity and cytosolic Ca2+ content during incubation in normals and in VAD subjects without NIDDM [6]. This research showed that, during incubation, these erythrocyte parameters have an inverse trend (a decrease in membrane fluidity corresponds to an increase in cytosolic Ca2+ content) and that these variations are higher in normals than in VAD subjects. Now we evaluated the trend of these erythrocyte parameters, during incubation, in normals (9 M and 3 W) and in a group of VAD subjects with NIDDM (5 M and 3 W). In this group of patients the vascular disease was demonstrated instrumentally (Doppler, Echo-Doppler, EEG, ECG) and by clinical criteria, while the diagnosis of NIDDM was carried out according to the National Diabetes Data Group [10]. The red cells were separated from fasting venous blood and suspended in isotonic buffer (phosphate buffer saline (PBS) with a glucose level of 2 g/l) at 37◦C. At baseline and after 2, 4 and 8 h we examined the erythrocyte membrane fluidity, marking the intact red cells with fluorescent label 10-(1-pyrene) decanoic acid (PDA) (Molecular Probes, Junction City, OR, USA) and considering the dimer to monomer fluorescence intensity ratio (Iex/Im), and the red cell cytosolic Ca2+
Analytical Methods in the Quality Control of Scientific Publications Part V: The Fraud of Pseudoscientists Based on False Measurements and Method Development

Despite the obvious frauds published in [1] [2] and the involvement of Editors and Editors in Chief of the journals in the publication of these fraudulent papers, the Editors in Chief of publishers have not taken any action to retract the fraudulent papers or to dismiss the corrupt editors. By this passivity, these Editors in Chief are supporting plagiarism, dissemination of fraudulent data, lies and making published information unreliable. In the present paper, we evaluate examples of bold, fraudulent publications and give the names of some Editors directly participating in concealing fraudulent publications, together with the names of Editors in Chief who also concealed and covered the facts of fraud and were reluctant to remove the fraudulent papers from circulation or to remove cheaters from editorial positions. The truth is universal and international; in contrast, the lie is individual and partisan, social, political, confessional, cultural and dirty. Knowledge is a truth that is part of the Universe. Lies are a tool of manipulation and can exist only in distinct environments that produce and support them. In this paper, we will show how artificial prefabricated analytical procedures were used to disseminate false data with the aim of substituting the truth with fraud.
Active and progressive

In this issue of Neurology®, Lublin and over 30 multiple sclerosis (MS) specialists from around the world propose a new consensus framework for MS classification.1 The increasing importance of MRI in clinical management and treatment trials, together with expanding treatment options and improved understanding of the pathophysiology of MS, motivated the present re-examination of MS phenotypic classifications and clinical course descriptions. The new schema supplants the one proposed by Lublin and Reingold2 in 1996 depicting 4 courses of MS that has been widely embraced in research and in clinical practice. The original 4 clinical subtypes were based on an international survey of MS clinicians, and utilized clinical information alone to describe relapsing-remitting, primary progressive, secondary progressive, and progressive-relapsing phenotypes. However, distinctions among the original 4 subtypes are imprecise and do not reflect current capabilities to target MS treatments based on integrated assessment of clinical and MRI data.
A 2-kW Single-Phase Seven-Level Flying Capacitor Multilevel Inverter With an Active Energy Buffer

High-efficiency and compact single-phase inverters are desirable in many applications such as solar energy harvesting and electric vehicle chargers. This paper presents a 2-kW, 60-Hz, 450-V<inline-formula> <tex-math notation="LaTeX">$ _{\text{DC}}$</tex-math></inline-formula>-to-240-V<inline-formula> <tex-math notation="LaTeX">$_{\text{AC}}$</tex-math></inline-formula> power inverter, designed and tested subject to the specifications of the Google/IEEE Little Box Challenge. The inverter features a seven-level flying capacitor multilevel converter, with low-voltage GaN switches operating at 120 kHz. The inverter also includes an active buffer for twice-line-frequency power pulsation decoupling, which reduces the required capacitance by a factor of 8 compared to conventional passive decoupling capacitors, while maintaining an efficiency above 99%. The inverter prototype is a self-contained box that achieves a high power density of 216 W/in<inline-formula> <tex-math notation="LaTeX">$^3$</tex-math></inline-formula> and a peak overall efficiency of 97.6%, while meeting the constraints including input current ripple, load transient, thermal, and FCC Class B EMC specifications.
Adolescents With Conduct Disorder Can Be Mindful of Their Aggressive Behavior

Adolescents with conduct disorder frequently engage in aggressive and disruptive behaviors. Often these behaviors are controlled or managed through behavioral or other psychosocial interventions. However, such interventions do not always ensure lasting changes in an adolescent's response repertoire so that he or she does not engage in aggression when exposed to the same situations that gave rise to the behavior previously. Mindfulness training provides a treatment option that helps an individual focus and attend to conditions that give rise to maladaptive behavior.Using a multiple baseline design,we assessed the effectiveness of a mindfulness training procedure in modulating the aggressive behavior of three adolescents who were at risk of expulsion from school because of this behavior. The adolescents were able to learn the mindfulness procedure successfully and use it in situations that previously occasioned aggressive behavior.This led to large decreases in the aggression of all three individuals. Follow-up data showed that the adolescents were able to keep their aggressive behavior at socially acceptable levels in school through to graduation. Maladaptive behaviors, other than aggression, that the adolescents chose not to modify, showed no consistent change during mindfulness training, practice, and follow-up.