Miracle-dz/UniFAR-FTUs huggingface dataset:
Orientational control of fimE expression in Escherichia coli

Phase‐variable expression of type 1 fimbriae is, in part, controlled by site‐specific DNA inversion of the fim switch in Escherichia coli. Of the two fim recombinases (FimB and FimE) that catalyse the inversion reaction, FimE exhibits a strong bias for phase switching from the ON to the OFF orientation. The specificity associated with fimE is the result of two different mechanisms: (i) FimE exhibits a preference for the invertible element in the ON orientation as substrate for recombination; (ii) the invertible element in the OFF orientation acts in cis to inhibit recombinase activity (orientational control). We show here that the invertible element negatively regulates fimE, even though expression of a fimE–lacZYA transcriptional fusion is unaffected by orientational control. The fimE transcript extends into the invertible region and hence switch ON‐specific and switch OFF‐specific mRNA contain different sequences. Furthermore, we show that orientational control is suppressed by the insertion of a structured RNA (tRNAGly) between fimE and the fim switch, indicating that the switch OFF‐specific mRNA is inactivated by 3′ to 5′ degradation. Analysis of the fim switch reveals that it contains two inhibitory elements that exert orientational control independently.
Operative Reduction and Fixation of a Difficult Supracondylar Extension Fracture of the Humerus

We evaluated the results of the operative treatment of a difficult supracondylar fracture of the elbow. A series of 45 consecutive children, the majority presenting initially with a complete dislocation of the humerus, was reexamined. Thirty-two of the patients had undergone an early operation applying the anterior cubital approach and 13 patients had been treated by traction. The lengths of the follow-up periods were 3.1 ± 1.5 and 8.8 ± 2.6 years, respectively. Normal range of extension-flexion and rotation movements was preserved almost invariably by either modality of therapy, whereas the carrying angle of the elbow was reduced significantly more often in the group treated by traction. None of the patients presented with permanent nerve dysfunction, keloid formation, or myositis ossificans. The two preventable early complications, slipping of the osteosynthesis and entrapment of the ulnar nerve, were related to the fixation of the fracture. There were no early or late infectious complications. When the anterior approach was used, operative reduction and fixation of a difficult supracondylar fracture of the humerus proved to be both safe and timesaving. Anatomical results of operation were superior to those attained by traction therapy in our series.
Structure-Guided Systems-Level Engineering of Oxidation-Prone Methionine Residues in Catalytic Domain of an Alkaline α-Amylase from Alkalimonas amylolytica for Significant Improvement of Both Oxidative Stability and Catalytic Efficiency

High oxidative stability and catalytic efficiency are required for the alkaline α-amylases to keep the enzymatic performance under the harsh conditions in detergent industries. In this work, we attempted to significantly improve both the oxidative stability and catalytic efficiency of an alkaline α-amylase from Alkalimonas amylolytica by engineering the five oxidation-prone methionine residues around the catalytic domain via a systematic approach. Specifically, based on the tertiary structure analysis, five methionines (Met 145, Met 214, Met 229, Met 247 and Met 317) were individually substituted with oxidation-resistant threonine, isoleucine and alaline, respectively. Among the created 15 mutants, 7 mutants M145A, M145I, M214A, M229A, M229T, M247T and M317I showed significantly enhanced oxidative stability or catalytic efficiency. In previous work, we found that the replacement of M247 with leucine could significantly improve the oxidative stability. Thus, these 8 positive mutants (M145A, M145I, M214A, M229A, M229T, M247T, M247L and M317I) were used to conduct the second round of combinational mutations. Among the constructed 85 mutants (25 two-point mutants, 36 three-point mutants, 16 four-point mutants and 8 five-point mutants), the mutant M145I-214A-229T-247T-317I showed a 5.4-fold increase in oxidative stability and a 3.0-fold increase in catalytic efficiency. Interestingly, the specific activity, alkaline stability and thermal stability of this mutant were also increased. The increase of salt bridge and hydrogen bonds around the catalytic domain contributed to the significantly improved catalytic efficiency and stability, as revealed by the three-dimensional structure model of wild-type alkaline α-amylase and its mutant M145I-214A-229T-247T-317I. With the significantly improved oxidative stability and catalytic efficiency, the mutant M145I-214A-229T-247T-317I has a great potential as a detergent additive, and this structure-guided systems engineering strategy may be useful for the protein engineering of the other microbial enzymes to fulfill industrial requirements.
Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis

Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states.
Subthalamic nucleus deep brain stimulation improves somatosensory function in Parkinson's disease

An established treatment for the motor symptoms of Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Mounting evidence suggests that PD is also associated with somatosensory deficits, yet the effect of STN‐DBS on somatosensory processing is largely unknown. This study investigated whether STN‐DBS affects somatosensory processing, specifically the processing of tactile and proprioceptive cues, by systematically examining the accuracy of haptic perception of object size. (Haptic perception refers to one's ability to extract object features such as shape and size by active touch.) Without vision, 13 PD patients with implanted STN‐DBS and 13 healthy controls haptically explored the heights of 2 successively presented 3‐dimensional (3D) blocks using a precision grip. Participants verbally indicated which block was taller and then used their nonprobing hand to motorically match the perceived size of the comparison block. Patients were tested during ON and OFF stimulation, following a 12‐hour medication washout period. First, when compared to controls, the PD group's haptic discrimination threshold during OFF stimulation was elevated by 192% and mean hand aperture error was increased by 105%. Second, DBS lowered the haptic discrimination threshold by 26% and aperture error decreased by 20%. Third, during DBS ON, probing with the motorically more affected hand decreased haptic precision compared to probing with the less affected hand. This study offers the first evidence that STN‐DBS improves haptic precision, further indicating that somatosensory function is improved by STN‐DBS. We conclude that DBS‐related improvements are not explained by improvements in motor function alone, but rather by enhanced somatosensory processing. © 2013 International Parkinson and Movement Disorder Society
Nuclear architecture and chromosome dynamics in the search of the pairing partner in meiosis in plants

The formation of haploid gametes in organisms with sexual reproduction requires regular bivalent chromosome pairing in meiosis. In many species, homologous chromosomes occupy separate territories at the onset of meiosis. To be paired at metaphase I, they need to be brought into a close proximity for interactions that include homology recognition and the establishment of some form of bonds. How homologues find each other is one of the least understood meiotic events. Plant species with large or medium sized genomes, such as wheat or maize, are excellent materials for the cytological analysis of chromosome dynamics at early meiosis, but genes that control meiosis have been identified mainly in small genome species such as Arabidopsis thaliana. This review is focused on the contribution studies on plants are providing to the knowledge of the initial steps of the meiotic process.
Cochlear implantation in children with large vestibular aqueduct syndrome.

OBJECTIVE This study describes the effectiveness of a multielectrode cochlear implant prosthesis (Cochlear; Cochlear Pty., Lane Cove, Australia) for providing hearing to children with deafness caused by large vestibular aqueduct syndrome (LVAS). STUDY DESIGN The study design was a retrospective study. SETTING All the children attended The Children's Cochlear Implant Center (NSW), which is a specialist center that provides audiologic testing, speech therapy, habilitation, and medical assistance for children with cochlear implants. PATIENTS Ten children were studied who had profound hearing loss and radiologic evidence of a vestibular aqueduct larger than 2 mm in width in its intraosseous portion. INTERVENTION The children received a multielectrode (Cochlear) cochlear implant prosthesis, and the associated programming of the device and habitation were performed postoperatively. No significant problems were encountered at any of the surgeries, although there was an initial gush of perilymph when the otic capsule was opened in 7 ears. MAIN OUTCOME MEASURES Postoperative audiologic performance at six monthly intervals and school performance were assessed. RESULTS The postoperative auditory performance was improved in all children. At 6 months, their average BKB score had increased from 31% to 79%; average word score, from 8% to 43%; and average phoneme score, from 38% to 70%. The older children were able to continue their education in their usual setting with less reliance on hearing support staff. CONCLUSION Children with a deteriorating hearing loss caused by LVAS can derive considerable benefit from a cochlear implant.
NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis. I. Study design and clinical outcomes

A 3-month double-blind and placebo-controlled, phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption efficacy of dietary NovaSil (NS). Volunteers (507 subjects) were clinically screened to evaluate their general health, pregnancy status and blood AFB1–albumin adduct levels. Of these subjects, 177 were randomly assigned to three groups: high-dose (HD), low-dose (LD) and placebo-control (PL) groups receiving 3.0, 1.5 and 0 g NS day−1 in capsules. Trained study-monitors supervised NS capsule administration to participants and recorded side-effects daily. Physical examinations were performed monthly. Blood and urine samples were collected for laboratory analysis. Approximately 92% of the participants (162 of 177) completed the study and compliance rate was over 97%. Overall, 99.5% of person × time reported no side-effects throughout the study. Mild to moderate health events (∼0.5% of person × time) were recorded in some participants. Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. These findings demonstrate that NS clay is apparently safe and practical for the protection of humans against aflatoxins in populations at high risk for aflatoxicosis.
Bicarbonate ion as a critical factor in photosynthetic oxygen evolution.

Bicarbonate ion, not dissolved CO(2) gas, is shown to increase 4- to 5-fold the rate of dichlorophenol indophenol reduction by isolated maize (Zea mays) chloroplasts. Glutaraldehyde fixed chloroplasts continue to exhibit bicarbonate-dependent 2,6-dichlorophenol indophenol reduction. Bicarbonate is shown to act close to the oxygen-evolving site, i.e. prior to the electron donation site of diphenyl carbazide to photosystem II. Dark incubation and light pretreatment of chloroplasts in various concentrations of bicarbonate, just prior to assay, indicate that bicarbonate binds to chloroplasts in the dark and is released again as the Hill reaction proceeds in the light. It is suggested that bicarbonate ions may play a critical role in the oxygen-evolving process in photosynthesis.
[The effects of psychosocial skills training on symptomatology, insight, quality of life, and suicide probability in schizophrenia].

OBJECTIVE The aim of this study was to determine the effect of psychosocial skills training (PST) on symptomatology, insight, quality of life, and suicide probability in patients with schizophrenia. METHOD The sample consisted of 22 schizophrenic outpatients diagnosed according to DSM-IV diagnostic criteria. Three PST groups were formed and each group's training lasted approximately 6 months. Nineteen (86%) patients completed the study. The Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Calgary Depression Rating Scale for Schizophrenia, Schedule for Assessing the Three Components of Insight, Quality of Life Scale for Patients with Schizophrenia, and Suicide Probability Scale were administered to the patients before and after PST. RESULTS At the end of the study mean score for the Scale for the Assessment of Positive Symptoms score (baseline 8.5+/- +/- 9.9, post-PST 3.4 +/- +/-6.0, P = 0.004), Scale for the Assessment of Negative Symptoms (baseline 33.7 +/- +/-19.3, post-PST 22.1 +/- +/-15.7, P = 0.001), Calgary Depression Rating Scale for Schizophrenia (baseline 4.2 +/- +/-4.1, post-PST 0.7 +/- +/-1.0, P = 0.001), Schedule for Assessing the Three Components of Insight (baseline 11.1 +/- +/-3.4, post-PST 16.2 +/- +/-1.1, P < 0.0001), and Quality of Life Scale for Patients with Schizophrenia (baseline 53.5 +/- +/-20.0, post-PST 79.6 +/- +/-20.8, P < 0.0001) changed significantly, whereas the change in mean score for the Suicide Probability Scale (baseline 75.1+/- +/- 11.7, post-PST 71.3+/- +/- 8.0, P = 0.06) did not reach statistical significance. CONCLUSION This study demonstrated the effects of PST on the symptoms and functioning of patients with schizophrenia. It can be concluded that using PST for the treatment of schizophrenia, as an adjuvant to pharmacotherapy, could produce significant positive results.
Optimal Operation and Economic Value of Energy Storage at Consumer Locations

We study the optimal operation and economic value of energy storage operated by a consumer who seeks to maximize long-term expected payoff (utility perceived from energy consumption minus energy cost). For a general setting that incorporates random electricity prices and the intertemporal substitution effect in energy demand, we establish a threshold structure for optimal storage operation policies through a dynamic programming approach. For an important special case with inelastic energy demand, we prove that the consumer’s maximum expected payoff is piecewise linear in the storage level; under an additional assumption that both the demand and prices are deterministic, we further establish the equivalence between the optimal storage operation problem and a minimum cost flow problem. These results significantly simplify the (exact) computation of optimal threshold policies. We define the value of storage (VoS) as the consumer’s net benefit obtained by optimally operating the storage. We show that if the consumer can always buy and sell electricity at the same (realized) price, then it is optimal for the consumer to use the storage only for arbitrage, and therefore the VoS does not depend on the consumer’s demand.
Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis

The base excision repair DNA glycosylase MutY homolog (MYH) is responsible for removing adenines misincorporated into DNA opposite guanine or 7,8-dihydro-8-oxo-guanine (8-oxoG), thereby preventing G:C to T:A mutations. Biallelic germline mutations in the human MYH gene predispose individuals to multiple colorectal adenomas and carcinoma. We have recently demonstrated that hMYH interacts with the mismatch repair protein hMSH6, and that the hMSH2/hMSH6 (hMutSα) heterodimer stimulates hMYH activity. Here, we characterize the functional effect of two missense mutations (R227W and V232F) associated with hMYH polyposis that lie within, or adjacent to, the putative hMSH6 binding domain. Neither missense mutation affects the physical interaction between hMYH and hMSH6. However, hMYH(R227W) has a severe defect in A/8-oxoG binding and glycosylase activities, while hMYH(V232F) has reduced A/8-oxoG binding and glycosylase activities. The glycosylase activity of the V232F mutant can be partially stimulated by hMutSα but cannot be restored to the wild-type level. Both mutants also fail to complement mutY-deficiency in Escherichia coli. These data define the pathogenic mechanisms underlying two further hMYH polyposis-associated mutations.
Ultrasound-guided peripheral venous access: a systematic review of randomized-controlled trials

Objective To systematically review the current literature on the effect of using ultrasound (US) guidance for the placement of peripheral intravenous (PIV) catheters in patients with difficult access. Materials and methods A systematic search was performed for the keywords ultrasonography, catheterization, and peripheral vein. A systematic review was performed on randomized-controlled studies comparing the use of dynamic US guidance with the conventional landmark technique. The primary outcome was the success rate of PIV placement and the secondary outcomes included the number of attempts and time to successful PIV placement. Results A total of 1778 titles were identified from the search and the review identified 50 potentially relevant studies that were reviewed comprehensively; six articles were included in the final review. The six studies enrolled a total of 316 patients, 153 in the control group and 163 in the US group. Two of the studies reported a significantly higher success rate for US on the basis of initial success or the overall success rate. The two pediatric studies found that time to successful cannulation was shorter and fewer attempts were required to achieve success for patients randomized to US compared with the traditional method. The six studies included were found to vary significantly in the definition of difficult venous access, recording of procedure time, definition of success rate, and other important factors, making a meta-analysis inappropriate. Conclusion On the basis of this review, routine use of US guidance for PIV placement is not strongly supported by the literature.
Control of power kites for naval propulsion

This paper investigates the application of an innovative technology for high-altitude wind power generation to naval propulsion. The basic idea is to exploit the traction forces exerted by automatically controlled power kites, flying fast in crosswind conditions, to pull a boat. Numerical analyses are carried out employing a mathematical model of the system and an efficient Nonlinear Model Predictive Control (NMPC) law. Differently from existing approaches, the cost function considered in NMPC design is directly the predicted traction force exerted on the kite lines. The obtained numerical results are compared with the data collected during experimental tests carried out in the project KiteNav, undergoing at Politecnico di Torino.
Safety of antiretroviral drug therapy in Jamaican children with HIV/AIDS.

BACKGROUND HIV has been a leading cause of death in Jamaican children aged < or = five years. Antiretroviral drugs (ARVs) are increasingly available in Jamaica through the Global Fund. Adverse effects of ARVs are a major cause for non-adherence to medications. Knowledge of the use and side effects of these drugs are crucial in the management of HIV-infected children as we scale-up the use of antiretroviral therapy, islandwide. We evaluated the adverse events and safety of antiretroviral therapy in children attending four Infectious Disease Clinics in Kingston, Jamaica, a resource limited setting. METHODS Data for children prospectively enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme during September 2002 to April 2005 were analyzed. RESULTS Among 121 HIV-infected children, 77 (64%) were on ARVs, 90% had CDC class C disease, 60% were males and perinatal transmission predominated. AZT/3TC based regimen was utilized in 93%, trimethoprim/sulphamethoxazole prophylaxis was used in 100% and five were completing antituberculous drugs. Anaemia occurred in all patients, with increased severity in those on ARVs. Macrocytosis occurred in 83% and thrombocytopenia in 8% of those on ARVs. Elevation of bilirubin, aspartate transaminase (AST) and alanine transaminase (ALT) levels and reversed albumin to globulin ratio prior to commencing AR Vs, with significantly lower prevalence following use of ARVs emphasized the severity of HIV disease at time of ARV initiation. Clinical adverse reactions were uncommon and included nail discoloration (8%), vomiting (7%), nausea (3%), peripheral lipodystrophy (4%) and abnormal dreams (1%). Ten children required change of ARV medication because of severe adverse effects: three for severe anaemia with repeat blood transfusions, three for severe nevirapine-associated rash and four for indinavir-associated haematuria. CONCLUSIONS ARVs are being successfully initiated in HIV-infected Jamaican children using the public health model. The excellent safety profile, good tolerance and few reported significant adverse effects augur well as antiretroviral therapy is scaled-up islandwide.