Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into the Structure and Assembly of the Bacteriophage ϕ29 Double-Stranded DNA Packaging Motor

ABSTRACT The tailed double-stranded DNA (dsDNA) bacteriophage ϕ29 packages its 19.3-kbp genome into a preassembled procapsid structure by using a transiently assembled phage-encoded molecular motor. This process is remarkable considering that compaction of DNA to near-crystalline densities within the confined space of the capsid requires that the packaging motor work against significant entropic, enthalpic, and DNA-bending energies. The motor consists of three phage-encoded components: the dodecameric connector protein gp10, an oligomeric RNA molecule known as the prohead RNA (pRNA), and the homomeric ring ATPase gp16. Although atomic resolution structures of the connector and different pRNA subdomains have been determined, the mechanism of self-assembly and the resulting stoichiometry of the various motor components on the phage capsid have been the subject of considerable controversy. Here a subnanometer asymmetric cryoelectron microscopy (cryo-EM) reconstruction of a connector-pRNA complex at a unique vertex of the procapsid conclusively demonstrates the pentameric symmetry of the pRNA and illuminates the relative arrangement of the connector and the pRNA. Additionally, a combination of biochemical and cryo-EM analyses of motor assembly intermediates suggests a sequence of molecular events that constitute the pathway by which the motor assembles on the head, thereby reconciling conflicting data regarding pRNA assembly and stoichiometry. Taken together, these data provide new insight into the assembly, structure, and mechanism of a complex molecular machine. IMPORTANCE Viruses consist of a protein shell, or capsid, that protects and surrounds their genetic material. Thus, genome encapsidation is a fundamental and essential step in the life cycle of any virus. In dsDNA viruses, powerful molecular motors essentially pump the viral DNA into a preformed protein shell. This article describes how a viral dsDNA packaging motor self-assembles on the viral capsid and provides insight into its mechanism of action.
Burow’s solution in the treatment of active mucosal chronic suppurative otitis media: determining an effective dilution

Burow’s solution (13 per cent aluminium acetate) has been found to inhibit in vitro the growth of most commonly occurring bacteria found in the discharging ear. An in vitro study has shown that the minimum inhibitory concentration of Burow’s solution for these organisms lies between a 1:80 and a 1:160 dilution. This paper reports on a clinical trial that incorporated 67 discharging ears to establish the most effective strength of aluminium acetate solution. There was no statistical difference in the effectiveness of full strength Burow’s solution compared to 3.25 per cent aluminium acetate solution (a quarter strength Burow’s solution). Response rates of 80.8 per cent and 75 per cent respectively following a two-week treatment period were achieved using these two solutions. A 1.3 per cent aluminium acetate solution (1/10 strength Burow’s solution) was found to be markedly inferior. Bacteriological and audiological profiles were recorded for each patient.
Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing.
Adaptive neurofuzzy controller to regulate UTSG water level in nuclear power plants

A data-driven adaptive neurofuzzy controller is presented for the water-level control of U-tube steam generators in nuclear power plants. This neurofuzzy controller is capable of learning the control action principles from the data obtained using other methods of automatic or manual control. There are four inputs in the neurofuzzy system, yet only eighty fuzzy rules involved. Therefore, the fuzzy system is versatile and moderately compact. The versatility is due to the higher input space dimension that helps to learn more control principles. The compactness is due to the number of rules being not too many. A 10-h evaluation trial of the trained fuzzy controller demonstrated its capability in regulating the water level under random disturbances and reference level changes.
COMT polymorphism and the risk of endometriosis-related infertility

Estrogens are important factors in the development of endometriosis, and can induce cell proliferation and stimulate cell division. COMT constitutes a crucial element in estrogen metabolism and has been suggested to be involved in the development of endometriosis. This study had the objective of to determine whether the presence of COMT val/met polymorphism (rs4680) increases the risk to endometriosis in infertile patients. A case–control study that included 198 infertile women with endometriosis, 71 infertile women without endometriosis, and 168 fertile women as control group of the Faculdade de Medicina do ABC. COMT (val/met) genotypes were identified by real time PCR (genotyping TaqMan assay) and the results were analyzed statistically by χ2 test. The data showed no statistical difference in the distribution of COMT genotypes neither between infertile patients with endometriosis and control group (p = 0.567), regardless disease degree, nor between infertile patients without endometriosis and control group (p = 0.460). In conclusion, the COMT val/met polymorphism is not associated to endometriosis-related infertility in the Brazilian population evaluated. However, more studies in larger populations are necessary to confirm these results.
Institutional Difference of Antibiotic Resistance of Helicobacter pylori Strains in Korea

Goals This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori isolates could be different between 2 institutions, which are located in the different areas in Korea, and to evaluate the effect of antibiotic resistance on the eradication rate of H. pylori. Study H. pylori were isolated from gastric mucosal biopsy specimens obtained from 113 Koreans, who did not have any eradication history. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin were examined according to the agar dilution method by 1 technician. Results All of these patients were treated with the same regimen, proton pump inhibitor-amoxicillin-clarithromycin triple therapy. There was a statistical difference in resistance to metronidazole, levofloxacin, and moxifloxacin among 6 antibiotics between 2 institutions located in Seoul and Gyeonggi province. The rates of eradication were 94.2% for the clarithromycin and amoxicillin-susceptible strains, and 42.8% for the amoxicillin-susceptible and clarithromycin-resistant strains. In contrast, eradication rate was 100% for the amoxicillin-resistant strains. Conclusions These results show that there is institutional difference of antibiotic resistance of H. pylori, explaining the institutional difference of eradication rate of H. pylori. The resistance to clarithromycin seems to be an important determinant for the eradication by proton pump inhibitor triple therapy but resistance to amoxicillin does not have any effect.
Aortic stenting on a type B aortic dissection with visceral and limb ischemia

Aortic dissection complicated with limb and visceral ischemia is a clinical dilemma since surgical intervention carries high risk of morbidity and mortality. The management is further complicated when renal perfusion is impaired and thus associated with severe renovascular hypertension. As catheterization techniques advanced over the past decade, percutaneous endovascular intervention provides a less invasive alternative for management of such cases. We report a case of chronic Stanford type B aortic dissection complicated with visceral and limb ischemia presenting with marked renovascular hypertension, which was successfully treated with percutaneous endovascular aortic stenting. Cathet Cardiovasc Intervent 2001;52:112–115. © 2001 Wiley‐Liss, Inc.
Founders Versus Descendants: Evidence Of The Taiwanese Publicly Traded Firms

This study investigates the performance of founder-controlled firms vis-à-vis firms controlled by founders’ descendants and relatives among Taiwanese publicly traded firms. After adjusting for size, age, growth potential, financial leverage, and industry effects, we find that the Taiwanese descendant-controlled firms underperform the matching founder-controlled firms. In searching for the potential reasons, we find that the average board size for the descendant-controlled firms is significantly larger than that of the founder-controlled firms. In addition, the ratios of familyrelated supervisors and board members of the descendant-controlled firms are significantly higher than those of the matching founder-controlled firms. While the significantly larger board size suggests a potential power struggle between the controlling family and the non-family related board members, the stronger family domination in the board of directors and supervisors for the descendant-controlled firms provides room for entrenchment and tunneling. In light of the absence of large outside blockholders and relatively weaker legal protections, the minority shareholders of Taiwanese firms are dependent upon internal monitoring mechanisms to protect them from the expropriation of the controlling families. However, our results indicate that family control has undermined the internal monitoring mechanism of the Taiwanese descendantcontrolled firms.
Combined Deletion of Macrophage ABCA1 and ABCG1 Leads to Massive Lipid Accumulation in Tissue Macrophages and Distinct Atherosclerosis at Relatively Low Plasma Cholesterol Levels

Objective—The purpose of this study was to evaluate the effect of the combined deletion of ABCA1 and ABCG1 expression in macrophages on foam cell formation and atherosclerosis. Methods and Results—LDL receptor knockout (KO) mice were transplanted with bone marrow from ABCA1/ABCG1 double KO (dKO) mice. Plasma cholesterol levels after 6 weeks of Western-type diet (WTD) feeding were significantly lower in dKO transplanted mice than ABCA1 KO, ABCG1 KO, and control transplanted animals. Extreme foam cell formation was present in macrophages of various tissues and the peritoneal cavity of dKO transplanted animals. Furthermore, severe hypoplasia of the thymus and a significant decrease in CD4-positive T cells in blood was observed. Despite relatively low plasma cholesterol levels dKO transplanted animals developed lesion sizes of 156±19×103 &mgr;m2 after only 6 weeks of WTD feeding. Lesions, however, were smaller than single ABCA1 KO transplanted animals (226±30×103 &mgr;m2; P<0.05) and not significantly different from single ABCG1 KO (117±22×103 &mgr;m2) and WT transplanted mice (112±15×103 &mgr;m2). Conclusions—Macrophage ABCA1 and ABCG1 play a crucial role in the prevention of macrophage foam cell formation, whereas combined deletion only modestly influences atherosclerosis which is associated with an attenuated increase in WTD-induced plasma cholesterol and decreased proinflammatory CD4-positive T cell counts.
Obsessive-Compulsive Disorder following Brain Injury: A Review

Objective: This article reviews obsessive-compulsive disorder (OCD) following acquired brain injury. OCD type symptomatology without any other cognitive, behavioral, or emotional problems following a brain injury appears to be rare. However, the first onset of obsessions and compulsions following a brain injury has been described, but cognitive impairments can potentially color the presentation. Method: This article reviews obsessive-compulsive disorder (OCD) after brain injury, including traumatic brain injury, cerebrovascular accidents, brain tumors and brain infections. Overlapping symtomatology between OCD and brain injury is discussed. Results: Findings regarding the neuro-imaging of OCD after brain injury are reviewed and integrated with neuropsychological data from studies with idiopathic OCD. Conclusion: There appears to be some convergance between findings from studies of the neuropsychology of idiopathic OCD and neuro-imaging of OCD following brain injury.
Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component.

OBJECT Gamma Knife surgery (GKS) has gained increasing relevance in the treatment of metastatic brain tumors, but many metastatic tumors contain a large cystic component and often exceed the size limit for GKS. For such lesions, the authors adopted a procedure in which stereotactic aspiration is first performed and followed immediately by GKS on the same day. In this paper, the authors describe this 1-day combined procedure and evaluate its efficacy. METHODS Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined. RESULTS Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement. CONCLUSIONS The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases.
In silico and in vitro genotoxicity evaluation of descarboxyl levofloxacin, an impurity in levofloxacin

Abstract It is important to establish the safety of impurities in drug substances or drug products. The assessment of genotoxicity of impurities and the determination of acceptable limits for genotoxic impurities was addressed in some recent guidances as a difficult issue. Descarboxyl levofloxacin is an impurity isolated from levofloxacin, which may impose a risk without associated benefit. However, there is insufficient toxic information about descarboxyl levofloxacin. This study investigated the genotoxicity of this impurity by in silico and in vitro methods. We used Derek, a commercial structure-activity relationship software package, as an in silico tool. The results showed that there was a structural alert (quinoline) in this impurity. Then, the in vitro genotoxicity of descarboxyl levofloxacin was investigated by a modified Ames test and by a chromosomal aberration test, using Chinese hamster lung (CHL) cells. Both assays were conducted in the presence or absence of S-9 mix. The results showed that the test impurity was not mutagenic in the Ames test (31.25–500 μg/plate). Whereas there was a statistically significant increase in the number of metaphase CHL cells with structural aberrations at the concentration of 1 mg/mL with S-9 mix, the aberrations rate was 7.5%. It did not significantly increase the number of structural aberration in CHL cells in the presence (at 250 and 500 μg/mL) or absence of S-9 mix. Based on these assays, descarboxyl levofloxacin could be controlled as a nongenotoxic impurity.
Synthesis and Biological Evaluation of 2- and 7-Substituted 9-Deazaadenosine Analogues

A series of 2-halogen and 7-alkyl substituted analogues of 9-deazaadenosine and 2′-deoxy-9-deazaadenosine was synthesized by new efficient methodology involving transformation of corresponding 9-deazaguanosine and 2′-deoxyguanosine, which in turn were synthesized by direct C-glycosylation of 1-benzyl-9-deazaguanine with 1-O -acetyl-2,3,5-tri-O -benzoyl-d-ribofuranose and methyl 2-deoxy-3,5-di-O -(p -toluoyl)-d-ribofuranoside, respectively. Deoxychlorination of C6 and diazotization/chloro- or fluoro-dediazoniation of the sugar-protected 9-deazaguanosine, followed by selective ammonolysis at C6 and deprotection of the sugar moiety, gave 2-chloro- and 2-fluoro-9-deazaadenosine (6 and 9). Substitution of the 7-position of the dihalogen-intermediate with alkyl groups, followed by ammonolysis and deprotection, provided 2-chloro-7-alkyl-9-deazaadenosines (13a–e) and 2-fluoro-7-benzyl-9-deazaadenosine (13f). Catalytic hydrogenation of 13a–e gave 7-alkyl-9-deazaadenosines 14a–e. Similarly, 2-chloro-2′-deoxy-9-deazaadenosine (21), 2-chloro-2′-deoxy-7-methyl-9-deazaadenosine (25), 2′-deoxy-9-deazaadenosine (22), and 2′-deoxy-7-methyl-9-deazaadenosine (26) were prepared from sugar-protected 2′-deoxy-9-deazaguanosine. Among these compounds, 7-benzyl-9-deazaadenosine (14b) showed the most potent cytotoxic activity, with IC50 values of 0.07, 0.1, 0.2 and 1.5 µM, while both 7-methyl-9-deazaadenosine (14a) and 2-fluoro-9-deazaadenosine (9) also demonstrated significant cytotoxic activity with IC50 values of 0.4, 0.7, 0.3, and 1.5 µM, and 1.5, 0.9, 0.3, and 5 µM against L1210 leukemia, P388 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma cells, respectively.
Electronic structure evolution of single bilayer Bi(1 1 1) film on 3D topological insulator Bi2SexTe3−x surfaces

The electronic state evolution of single bilayer (1BL) Bi(1 1 1) deposited on three-dimensional (3D) Bi2SexTe3−x topological insulators at x = 0, 1.26, 2, 2.46, 3 is systematically investigated by angle-resolved photoemission spectroscopy (ARPES). Our results indicate that the electronic structures of epitaxial Bi films are strongly influenced by the substrate especially the topmost sublayer near the Bi films, manifesting in two main aspects. First, the Se atoms cause a stronger charge transfer effect, which induces a giant Rashba-spin splitting, while the low electronegativity of Te atoms induces a strong hybridization at the interface. Second, the lattice strain notably modifies the band dispersion of the surface bands. Furthermore, our experimental results are elucidated by first-principles band structure calculations.
Reduced Frameshift Fidelity and Processivity of HIV-1 Reverse Transcriptase Mutants Containing Alanine Substitutions in Helix H of the Thumb Subdomain (*)

We have analyzed two human immunodeficiency virus (HIV-1) reverse transcriptase mutants of helix H in the thumb subdomain suggested by x-ray crystallography to interact with the primer strand of the template-primer. These enzymes, G262A and W266A, were previously shown to have greatly elevated dissociation rate constants for template-primer and to be much less sensitive to inhibition by 3′-azidodeoxythymidine 5′-triphosphate. Here we describe their processivity and error specificity. The results reveal that: (i) both enzymes have reduced processivity and lower fidelity for template-primer slippage errors, (ii) they differ from each other in sequence-dependent termination of processive synthesis and in error specificity, and (iii) the magnitude of the mutator effect relative to wild-type enzyme for deletions in homopolymeric sequences decreases as the length of the run increases. Thus amino acid substitutions in a subdomain thought to interact with the duplex template-primer confer a strand slippage mutator phenotype to a replicative DNA polymerase. This suggests that interactions between specific amino acids and the primer stem at positions well removed from the active site are critical determinants of processivity and fidelity. These effects, obtained in aqueous solution during catalytic cycling, are consistent with and support the existing crystallographic structural model.
Limitations to vasodilatory capacity and .VO2 max in trained human skeletal muscle.

To further explore the limitations to maximal O(2) consumption (.VO(2 max)) in exercise-trained skeletal muscle, six cyclists performed graded knee-extensor exercise to maximum work rate (WR(max)) in hypoxia (12% O(2)), hyperoxia (100% O(2)), and hyperoxia + femoral arterial infusion of adenosine (ADO) at 80% WR(max). Arterial and venous blood sampling and thermodilution blood flow measurements allowed the determination of muscle O(2) delivery and O(2) consumption. At WR(max), O(2) delivery rose progressively from hypoxia (1.0 +/- 0.04 l/min) to hyperoxia (1.20 +/- 0.09 l/min) and hyperoxia + ADO (1.33 +/- 0.05 l/min). Leg . VO(2 max) varied with O(2) availability (0.81 +/- 0.05 and 0.97 +/- 0.07 l/min in hypoxia and hyperoxia, respectively) but did not improve with ADO-mediated vasodilation (0.80 +/- 0.09 l/min in hyperoxia + ADO). Although a vasodilatory reserve in the maximally working quadriceps muscle group may have been evidenced by increased leg vascular conductance after ADO infusion beyond that observed in hyperoxia (increased blood flow but no change in blood pressure), we recognize the possibility that the ADO infusion may have provoked vasodilation in nonexercising tissue of this limb. Together, these findings imply that maximally exercising skeletal muscle may maintain some vasodilatory capacity, but the lack of improvement in leg . VO(2 max) with significantly increased O(2) delivery (hyperoxia + ADO), with a degree of uncertainty as to the site of this dilation, suggests an ADO-induced mismatch between O(2) consumption and blood flow in the exercising limb.