In vitro Evolution and Engineering for Improved Ribozyme Polymerase Production

According to the "RNA World Hypothesis" the first self replicating molecule formed from the prebiotic chemicals is the ribozyme. A model compartmentalized self replicating system for ribozyme polymerases is designed and used to improve activity, fidelity and generality of the enzyme

Low-valent nickel complexes with sulfur-only and mixed sulfur and phosphorus ligand spheres

Da die Nickel-Komplexe mit Schwefel-Liganden in biologischen Systemen bekannt sind, wird seit vier Jahrzehnten über Nickel-Thiolat-Komplexe in der Oxidationsstufe +II geforscht. Man findet weniger Literaturstellen, wo über die gezielte Darstellung niedervalenter Nickel-Thiolat-Komplexe berichtet wurde. Zu Unrecht, wie wir meinen, denn starke reduzierte Nickel-Thiolat-Komplexe haben ungewöhnliche Bindungsverhältnisse. Die hier synthetisierten Komplexe sind dafür ausgezeichnete Beweise und legen die Vermutung nah, dass sie auch in der Klasse der Metalloenzyme eine gewisse Bedeutung haben könnten.Im ersten Teil der Arbeit stand die Synthese und Charakterisierung von tert-Thiolatliganden bzw. organischen Sulfiden im Vordergrund. Im zweiten Teil wurden die Koordinations-eigenschaften der dargestellten Liganden untersucht. Bei der Untersuchung der Reaktivität der unterschiedlichen tert-Thiolat-Liganden gegenüber Ni(II)-, bzw. Phosphan-Ni(II)-Salzen konnten neuartige zwei- (19-21), fünf- (23, 24), vierzehn- (28) und zwanzigkernige (30) niedervalente Nickel-Komplexe mit ungewöhnlicher trigonal-planarer sowie tetraedrischer und klassischer quadratischer-planar Koordination des Nickels synthetisiert und strukturell charakterisiert werden. Ferner werden diese und bereits beschriebene Nickel-Thiolat-Komplexe[67] [Ni7(7-S)(-StBu)8[BzEt3N] (25), [Ni7(7-S)(-StBu)9]2[Ni7(7-S)(-StBu)8][Ph3P)2N]3 (26), [Ni8(7-S)(-StBu)9] (27) und [Ni17(5-S)3(3-S)2(3-StBu)6(-StBu)9] (29) mittels UV/Vis-Spektroskopie und Cyclovoltammetrie charakterisiert. Einige ausgewälte Nickel-Thiolat-Komplexe wurden durch DFT-Berechnungen untersucht. [Ni5(5-S)(-StOct)5][BzEt3N] (23) [Ni5(5-S)(-StPent)5][BzEt3N] (24) [Ni14(S)6(5-StBu)2(-StBu)10][Et4N] (28)As nickel complexes with sulfur containing ligands are well known in biological systems, research in the last four decades was mainly focused on the synthesis of nickel thiolate complexes in the oxidation state +II. In the literature there is less information on the selective synthesis of low-valent nickel thiolate complexes. We suppose this to be erroneous, particularly because many low-valent nickel thiolate complexes show exceptional bonding properties. The nickel complexes synthesized and characterized in this thesis give an excellent example of these remarkable properties and they are supposed to be important with reference to metalloenzymes. The synthesis and characterization of tert-thiolate ligands as well as organic sulfides is the focus of the first part of this thesis. In the second part the coordination properties of these ligands towards nickel are investigated. In the framework of the investigation of the reactivity of the tert-thiolate ligand with the Ni(II)- or phosphane-Ni(II)-precursor, respectively, new types of two-, five-, fourteen- and twenty-nuclear low valent nickel thiolate complexes with unusual trigonal planar coordination and in some cases additional tetrahedral coordination of the nickel centers were synthesized and structurally characterized. In addition, the new complexes and already described nickel thiolate complexes[67] [Ni7(7-S)(-StBu)8][BzEt3N] (25), [Ni7(7-S)(-StBu)9]2[Ni7(7-S)(-StBu)8][(Ph3P)2N]3 (26), [Ni8(7-S)(-StBu)9] (27) and [Ni17(5-S)3(3-S)2(3-StBu)6(-StBu)9] (29) are investigated by UV/Vis spectroscopy, cyclovoltammetry as well as DFT-calculations for selected complexes. [Ni5(5-S)(-StOct)5][BzEt3N] (23), [Ni5(5-S)(-StPent)5][BzEt3N] (24), [Ni14(S)6(5-StBu)2(-StBu)10][Et4N] (28), [Ni20(S)12(-StBu)10][(NEt4)2] (30), [Ni2(StOct)2(Ph3P)2] (19), [Ni2(StBu)2(Ph3P)2]Tag der Verteidigung: 01.09.2014Paderborn, Univ., Diss., 201

Size selectivity in antibiofilm activity of 3-(Diphenylphosphino)propanoic acid coated gold nanomaterials against Gram positive Staphylococcus aureus and Streptococcus mutans

Abstract Biofilm formation by pathogenic bacteria is one of the major threats in hospital related infections, hence inhibiting and eradicating biofilms has become a primary target for developing new anti-infection approaches. The present study was aimed to develop novel antibiofilm agents against two Gram-positive bacteria; Staphylococcus aureus (ATCC 43300) and Streptococcus mutans (ATCC 25175) using gold nanomaterials conjugated with 3-(diphenylphosphino)propionic acid (Au-LPa). Gold nanomaterials with different sizes as 2–3 nm small and 9–90 nm (50 nm average size) large were stabilized by LPa via different chemical synthetic strategies. The nanomaterials were fully characterized using atomic force microscope (AFM), transmission electron microscope, ultraviolet–visible absorption spectroscopy, and Fourier transformation infrared spectroscopy. Antibiofilm activity of Au-LPa nanomaterials was tested using LPa alone, Au-LPa and unprotected gold nanomaterials against the both biofilm-producing bacteria. The results showed that LPa alone did not inhibit biofilm formation to a significant extent below 0.025 mM, while conjugation with gold nanomaterials displayed manifold enhanced antibiofilm potential against both strains. Moreover, it was also observed that the antibiofilm potency of the Au-LPa nanomaterials varies with size variations of nanomaterials. AFM analysis of biofilms further complemented the assay results and provided morphological aspects of the antibiofilm action of Au-LPa nanomaterials

UAV-Empowered Disaster-Resilient Edge Architecture for Delay-Sensitive Communication

The fifth-generation (5G) communication systems will enable enhanced mobile broadband, ultra-reliable low latency, and massive connectivity services. The broadband and low-latency services are indispensable to public safety (PS) communication during natural or man-made disasters. Recently, the third generation partnership project long term evolution (3GPPLTE) has emerged as a promising candidate to enable broadband PS communications. In this article, first we present six major PS-LTE enabling services and the current status of PS-LTE in 3GPP releases. Then, we discuss the spectrum bands allocated for PS-LTE in major countries by international telecommunication union (ITU). Finally, we propose a disaster resilient three-layered architecture for PS-LTE (DR-PSLTE). This architecture consists of a software-defined network (SDN) layer to provide centralized control, an unmanned air vehicle (UAV) cloudlet layer to facilitate edge computing or to enable emergency communication link, and a radio access layer. The proposed architecture is flexible and combines the benefits of SDNs and edge computing to efficiently meet the delay requirements of various PS-LTE services. Numerical results verified that under the proposed DR-PSLTE architecture, delay is reduced by 20% as compared with the conventional centralized computing architecture.Comment: 9,

Drug overdose: a wake up call! Experience at a tertiary care centre in Karachi, Pakistan

OBJECTIVE: To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan.METHODS: A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study.RESULTS: Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married (p = 0.001), 81% needed in-patient psychiatric services (p = 0.016) of whom a significantly high number (38%) refused it. Domestic and social issues were rated highest among DSH group (p = 0.003), depression among females was common (p = 0.028) and Benzodiazepines (41%) was the most frequently used drug (p = 0.021). Sub-group analysis of accidental overdoses revealed mean age of 45.6 +/- 19.6 years, single (75.4%) and males (54.1%). Drugs used were mainly Benzodiazepines (18%) followed by Opioids (11%), Antiepileptics (10%) and Warfarin (10%).CONCLUSION: Our study showed that depressed housewives are at greater risk for DSH. Domestic and social issues were rated highest and Benzodiazepines were the most commonly used agents. Most of our patients refused inpatient psychiatric treatment leading us to believe that general awareness of psychiatric illnesses is imperative in our community. High number of accidental overdoses is alarming in older, single males convincing us to believe that existing pharmacy system needs further evaluation and modification

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BackgroundCohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.MethodsClinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.ResultsWe identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.ConclusionWe suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup

A Comparative Study of Social Media’s Religiopolitical Use by Pakistan Tehrik-e-Insaf (PTI) and Tehrik-e-Labbaik Pakistan (TLP)

The political abuse of social media platforms like Facebook and X (formerly Twitter) has further complicated the religiopolitical dynamics in Pakistan. This study intends to understand the use of Facebook and X in the political journey of Pakistan Tehrik-e-Insaf (PTI), a mainstream political party, and Tehrik-e-Labbaik Pakistan (TLP), a religiopolitical party. A comparative literature review was conducted to critically analyze the peer-reviewed literature to identify the ways PTI and TLP have used Facebook and X to establish and nurture their political ideologies, particularly among youth. The findings of the content analysis revealed that both parties significantly benefitted from Facebook and X to project their political agenda, instill religion (Islam) in their political campaigns, and organize massive (violent) protests. The paper also provides contextual knowledge on social media platforms like Facebook and X being used in religiopolitical discourses and influencing the political attitude of netizens, particularly youth. This study argues that social media has shifted Pakistan’s political dynamics such as electioneering, voter campaigns, and sustaining political control, which has caused increased religiopolitical radicalism among youth

Comparison of oxybutynin and tolterodine in treatment of detrusor overactivity associated with upper motor neuron lesions, based on changes in urodynamic parameters

To compare efficacy of oxybutynin and tolterodine in managing Detrusor Overactivity (DO) in Pakistani patients with different upper motor neuron lesions. Methods: A randomized controlled trial was carried out at Armed Forces Institute of Rehabilitation Medicine, Rawalpindi from January to August 2015 including individuals with a diagnosis of DO as a result of upper motor neuron lesions. Maximal detrusor pressure (MDP) and maximal cystometric capacity (MCC) were measured at baseline and at four months post-treatment. Group-A was treated with tolterodine and group-B with oxybutynin. Results: A total of 60 individuals (mean age: 43.9 ± 15 years) were included. Majority (83.3%) were male and had spinal cord injury as the commonest etiology (56.7%). Group-A had a mean pre-treatment MCC of 188.3 ± 48.2 ml, and a mean post-treatment MCC of 281.5 ± 49.1 ml (p\u3c 0.001). The mean pre-treatment MDP was 83.6 ± 9.5 cm of H2O, and the mean post-treatment value was 40.9 ± 10.2 cm of H2O (p\u3c 0.001). Group-B had a mean pre-treatment MCC of 209.8 ± 60.5 ml, and mean post-treatment MCC of 308.7 ± 65 ml (p\u3c 0.001). The mean pre-treatment MDP was 80.7 ± 10.6 cm of H2O, and the mean post-treatment value was 40.7 ± 10.1 cm of H2O (p\u3c 0.001). The difference in mean reduction in MCC and MDP produced by tolterodine and oxybutynin was statistically insignificant. Conclusions: Both oxybutynin and tolterodine showed similar efficacy in the treatment of DO based on measurable urodynamic outcomes